[Protein evaluation based on intermediary protein metabolism criteria]. The activities of ornithine carbamyl transferase, arginase and glutamic-pyruvic transaminase increase in the liver of the rat if the biological value of the dietary protein decreases. Experiments with pigs revealed in the blood serum an analogous high correlation between the biological value of the dietary protein and the activities of arginase, glutamic-pyruvic transaminase, leucine aminopeptidase and glutamic-oxalacetic transaminase. The most favourable possibility of protein evaluation on the basis of criteria of the intermediary protein metabolism consists in the determination of the blood urea concentration provided that the protein carrier supply is standardized. This procedure which has been elaborated by BERGNER and co-workers in 1968 for the determination of the protein quality was confirmed by TAYLOR and co-workers in 1974 on healthy individuals as a reliable and elegant measuring technique with highly significant correlation. It is concluded that the true biological value of protein carriers or protein mixtures which are intended for human nutrition can on principle be determined only in studies with healthy individuals.


[Evaluation of protein quality in human and animal foodstuffs]. Having mentioned the present criteria for the evaluation of the protein quality, which are almost exclusively based on a numerical value, the author explains and discusses the principles of new criteria suggested since 1969. The following criteria are presented: the "Index d'Equilibre de la Protéine" of Arnould; the criteria "Total Amino Acid Value" and "Essential Amino Acid Value", outlined by GLEM-HANSEN and EGGUM; the "Nitrogen Efficiency Ratio" of EGGUM; the model of a nitrogen balance function, developed by RUFEGER; the multicompartment model for studying the resorption and metabolism kinetics of nitrogen and amino acids, as extended by KRAWIELITZKI; the functional conception of the relationships between the parameters of the nitrogen metabolism and of the laws of growth, according to GEBHARDT, and the method for determining the true amino-acid digestibility according to DAMMERS [7], EGGUM [8], WIESEMULLER [23], POPPE and co-workers [19], UHLEMANN [22] and HERRMANN [12]. Finally, the author gives suggestions for further research on the evaluation of protein quality.


[Digestion and resorption of proteins].

[Digestion and resorption of proteins]. A survey is given of the ultrastructure of the intestinal epithelial cell, especially of its lumenward membrane. Special attention is paid to the peptidases which are located in the ciliated border and within the cell. The authors deal with the purification of the membrane-bound aminopeptidase which is of importance in splitting dietary peptides and illustrate its specificity by the cleavage of casein. The amino acids which are liberated by peptide splitting have in part aminopeptidase-inhibiting properties. The possible digestion physiological consequences are discussed. In vitro experiments were performed to investigate the composition of the content of the distal part of the small intestine of the rat with regard to its possible dependence on the composition of various dietary proteins. The composition of the peptides of the intestinal content is essentially undependent of the amino-acid composition of the diet. There is no enrichment of certain amino acids. The importance of the resorption of the peptides is also evidenced by resorption studies in which enzymatic hydrolysates of proteins (i.e. peptide mixtures) were confronted with a free amino-acid mixture of the same over-all composition. Taking glycyl-glycine-glycine as a model, the authors demonstrate that, in determined ranges of concentration, tripeptides may in part be resorbed without degradation. Finally, the importance of peptide resorption is evaluated and conclusions are drawn as to further studies on the physiology and physiopathology of digestion.


[Interaction between proteins and oxidized lipids]. Oxidized lipids react with proteins to form lipoproteid complexes in which the lipids are bound to the proteins in part by physical forces, in part by covalency. The free radicals resulting from the cleavage by hydroperoxides are the major precursors of the lipoproteid complexes. The interaction is associated with protein denaturation and oligomer formation. The lipids contained in the lipoproteid complexes are only in part extracted by chloroform-methanol; in part not until after acid or alkaline hydrolysis. The nutritive value of the protein moiety is diminished by the reaction of the hydroperoxides with methionine and cysteine and by the reaction of the peroxidic radicals and aldehydes with lysine and other basic amino acids. Secondary reactions of the lipoproteid complexes lead to brown coloured, only partly soluble compounds which often impair the organoleptic value. The rancidity products of the fats are neutralized by the reaction with proteins. The action of highly unsaturated oxidized lipids on proteins results in the development of a fishy aroma.


[Simultaneous isolation of proteins and fats from oil seeds. I. Principle of procedure]. The principle of the procedure for the simultaneous isolation of proteins and fats from oil seeds is illustrated by the isolation of these constituents from sunflower seeds. This procedure is based on the displacement of oil and the extraction of protein by an aqueous electrolyte solution after comminution of the pretreated seeds, removal of the insoluble cell components and separation of the extracts into a fat-containing and a protein-containing phase. The globulins are precipitated isoelectrically; the albumins, by using complexing agents or thermal coagulation. The liberation of the oil from the concentrated fat emulsion is achieved immediately in a mechanical way or after addition of destabilizers. The results are discussed with regard to the yields obtained and the composition of the final products.


[Physicochemical aspects of synthetic food production]. The authors discuss the general approach to the problem of the protein architecture and the working of proteins to synthetic foods. They present the main results from relevant studies on the compatibility and interactions of proteins and polysaccharides in aqueous media and deal with possibilities of influencing the structure formation and the physical properties of gels of given composition.


The stimulatory effect on gonadotropin release of implants of estradiol or progesterone in certain sites in the central nervous system. The sites of stimulatory feedback of ovarian steroids on gonadotropin release were examined. In estrogen-primed ovariectomized rats, estradiol or progesterone was implanted stereotaxically into various hypothalamic and extrahypothalamic areas. Both steroids elevated plasma LH and FSH levels at 6 h when implanted unilaterally into the preoptic-anterior hypothalamic area. Bilateral implants at this site were ineffective; presumably, this was due to the destructive lesion produced by the cannulae since in sham-implanted or anteriorly deafferented rats systemic estrogen was also ineffective. Unilateral estradiol implants in the medial basal hypothalamus elevated LH and FSH at 30 but not at 6 h. Maximum increases of plasma gonadotropins occurred 30 h after implantation of estradiol in the medial amygdaloid nuclei; progesterone implants at this site elevated only FSH at 6 h. Dissociation in the release of LH and FSH was also observed following implantation of estradiol into the hippocampus. Plasma FSH levels were dramatically reduced at 30 h while LH was slightly elevated. Progesterone implants in the hippocampus or medial basal hypothalamus did not alter plasma gonadotropin levels.


Effects of stress on plasma corticosterone and growth hormone levels in rats with median eminence-pituitary islands. The effects of stress on plasma corticosterone and growth hormone (GH) were determined in adult female rats 24 h after forebrain removal in order to study the anatomical substrate essential for stress-induced alteration of pituitary function. Rats with median eminence-pituitary islands (MEPI) showed significant increments in plasma corticosterone levels 15 min after immobilization-blood withdrawal stress. Rats with basal hypothalamic-pituitary islands (BHPI) showed comparable increments, suggesting that the presence of hypothalamic tissue in addition to median eminence did not enhance the steroid response. A subsequent study demonstrated that MEPI rats are capable of a 2nd response, 6 h after the first. MEPI rats also showed a significant 50% increase in plasma GH levels 15 min after immobilization-blood withdrawal. In a final experiment, MEPI rats showed corticosterone but not GH responses to immobilization applied without blood withdrawal. These data offer further evidence that some stressful stimuli can alter pituitary functions under short-term conditions in the absence of hypothalamic or other forebrain neurons.


Compensatory adrenal growth is neurally mediated. We have tested the possibility that compensatory adrenal growth is neurally mediated. Small unilateral electrolytic lesions were made in the ventral hypothalamus of young male rats. Subsequently, unilateral adrenalectomy was performed on the side ipsilateral or contralateral to the hypothalamic lesion. Four days later the animals were killed and the remaining adrenal was weighed; the location and extent of the hypothalamic lesions were determined. Lesions placed on the same side as adrenalectomy prevented compensatory growth of the remaining gland (p less than 0.005), while lesions on the side opposite to the removed adrenal did not interfere with compensatory adrenal growth. We conclude from these findings, and from a review of some anatomical studies, that compensatory adrenal growth is effected through a reflex that involves both afferent and efferent neural limbs.


Lateral asymmetry in patients with nervous and mental disease. A preliminary study. Hand preference and the performance of thumb-to-finger opposition by the right and left hands were tested in four samples: manic-depressives, schizophrenics, nonpsychotic patients with diseases of the central nervous system and normal control subjects. The schizophrenics and manic-depressives both showed significantly more pure dominance (e.g. right-handed, and superior right thumb opposition) than the normal controls, while the nonpsychotic patients with diseases of the central nervous system showed significantly more cross-dominance (e.g. right-handed, but superior left thumb opposition) than the normal control subjects.


Schizophrenia susceptibility and HL-A antigen. The phenotype frequencies of HL-A specificities have been investigated in 47 chronic schizophrenics subdivided in an older and a younger group. The frequency of HL-A 9 was significantly increased in the psychotics as compared to a reference group of 1,263 healthy blood donors, pregnant women and potential kidney donors. Deviations in frequency were also found concerning W 19 and HL-A 5. As HL-A 9 was mainly found in the older group of schizophrenics, it is suggested that HL-A 9 might be associated to some form of schizophrenia with a chronic course.


Hypno-analgesia and acupuncture analgesia: a neurophysiological reality? The effects of hypnosis, acupuncture and analgesic drugs on the subjective experience of pain and on objective neurophysiological parameters were investigated. Pain was produced by brief electric stimuli on the wrist. Pain challengers were: hypnosis (induced by two different video tapes), acupuncture (at specific and unspecific loci, with and without electrical stimulation of the needles), morphine and ketamine. Evaluation of clinical parameters included the subjective experience of pain intensity, blood pressure, puls, temperature, psychosomatic symptoms and side effects. Neurophysiological parameters consisted of the quantitatively analyzed EEG and somatosensory evlked potential (SEP). Pain was significantly reduced by hypnosis, morphine and ketamine, but not during the control seesion. Of the four acupuncture techniques, only electro-acupuncture at specific loci significantly decreased pain. The EEG changes during hypnosis were dependent on the wording of the suggestion and were characterized by an increase of slow and a decrease of fast waves. Acupuncture induced just the opposite changes, which were most significant when needles were inserted at traditional specific sites and stimulated electrically. The evoked potential findings suggested that ketamine attenuates pain in the thalamo-cortical pathways, while hypnosis, acupuncture and morphine induce analgesia at the later CNS stage of stimulus processing. Finally some clinical-neurophysiological correlations were explored.


[Experimental and clinical studies on the use of a new suture material: polyglycolic acid]. Experimental and clinical investigation of polyglycolic acid, a new synthetic suture material, is reported. Experimental work was done on single-layer intestinal sutures, while clinical employment of the material was extended to various general surgery operations. There were few signs of inflammation at the site of implant, indicating that the new material has a greater degree of inertness than chronic catgut, restulting in optimal tolerance on the part of the body.


[Use of a new oral antibiotic in surgery]. Results with pivampicillin, a new ampicillin with complete gastric absorption and capable of producing high tissue levels, in the prevention and treatment of postoperative infection in 31 cases are presented. The antibiotic was effective in 29 cases, 4 of which had a prior history of antibiotic intractability. Side-effects consisted of slight gastric disturbances, with suspension of treatment in 1 case only. No clinically significant changes in the laboratory data were noted.


[Residual cystic stump. Its significance in post-cholecystectomy syndromes]. Twelve patients with residual cystic stump syndromes are presented. Since such stumps play a part in the pain symptomatologies observed the day after cholecystectomy, it may be assumed that they are the site of alterations, whether in the stump it self or outside, but in all events in the biliary trunk; the choledochus and Oddi's sphincter are most commonly involved. In the 12 reported cases, the stump was abnormality long, dilated and the scene of chronic inflammation. Association with calculosis of the choledochus presents and aetiopathogenetic difficulty, since it is hard to determine the predominance of either condition; it was, in fact, present in 6 cases. Greater importance must be attached to amputation neuroma or sclerosing odditis. While it cannot always be shown that the residual stump is responsible for post-cholecystectomy syndromes, its removal on diagnosis is recommended when pain and dyskinesis are present.


[Intestinal lymphagiectasis of surgical interest]. Surgical management of a case of intestinal lymphangectasis with unusual features is reported. The view that the picture was one of early segmentary enteritis was supported by some aspects of the course and various anatomopathological features.


[Toxic megacolon].

[Toxic megacolon]. Reference to the literature dealing with idiopathic rectocolitis and its complications, with particular attention to megacolon, is followed by the presentation of two cases of ulcerous colitis complicated by toxic megacolon and a picture of acute abdomen. Emphasis is placed on the clinical features of such complications and the surgical treatment required in accordance with the degree of seriousness of the case.


[Intestinal obstruction in newborn infants. Clinical cases]. Eleven cases of intestinal occlusion (4 personal and 7 culled from hospital records) are presented. The importance of certain symptoms, early diagnosis and the need for minimum trauma in surgical management are discussed.


[Differentiated tumors of the thyroid. Correlations between radicality of the exeresis, recurrence and survival]. An analysis is made of the results obtained in 50 papilliferous and 39 follicular thyroid tumours operated between 1949 and 1969, and forming part of a series of 150 thyroid cancer cases. If not radically managed, papilliferous tumours recur in the neck lymph nodes, though successful reoperation and survival for many years are possible. Follicular forms however, recur in the gland itself in 50% of cases, and prove fatal in one case out of three, even if reoperated. If the first operation is radical, the results are excellent when the tumour is contained in the thyroid, and will be good even when there are already metastases in the neck nodes. Recurrences in this site can be successfully reoperated and a cure obtained. Results will be poor, however, when invasion of the neck itself has begun.


[End-to-end venous graft in cases of femoro-popliteal obstruction]. A series of 112 cases of direct femoropopliteal revascularisation is presented, along with a new method and a description of its somewhat limited indications. The advantages and disadvantages of direct venous graft as opposed to the conventional by-pass are explained. If used in accordance with its specific indications, however, the new method offers results that are fully comparable with those obtained by a by-pass.


[Reimplantation of the gallbladder. Indications and results]. There is no good reason why a gallbladder that has been compressed and displaced by a parasitic or malformative cyst, but is otherwise free of anatomical or irreversible lesions, should be irrevocably sacrificed. Treatment of the primary lesion can thus be followed by re-implantation of the gallbladder. The indications for this surgical technique and its limitations are described with reference to a personal series.


[Study of the therapeutic activity of fentonium in gastroduodenal ulcer]. Personal experience with phentonium, a new synthetic synaptolytic, in the treatment of 26 patients with gastric or duodenal ulcerous conditions and of 4 other patients with gastroduodenitis is reported. Some subjective symptoms (pain, pyrosis, etc.) were taken into consideration and radiographic controls were carried out before and after treatment in order to determine the effect on the evolution of the ulcer niche. Phentonium was administered initially in all cases by the parenteral route (intravenous or intramuscular) in the dose of 10, 20 or 40 mg daily, according to the clinical picture, in one or two divided doses for varying periods (on the average 25 days) and in half the cases treatment was continued by the oral route at the dose of 60-80 mg daily (3-4 tablets) for about 20 days; in 3 cases treatment was continued by the oral route at the dose of 60-80 mg daily (3-4 tablets) for about 20 days; in 3 cases treatment was continued respectively for 5, 14 and 15 months. The therapeutic effect was evaluated as very favourable in 24 cases, discrete in 4 cases, scarce or absent in 2 cases. The time of disappearance or marked attenuation of the symptoms was very brief. The general tolerability of the preparation was excellent. On the basis of the observations made, it is concluded that phentonium represents an effective drug with a high therapeutic index in the treatment of ulcerous disease.


[Clinical use of a new absorbable suture material in general surgery]. Results with a new, completely absorbable synthetic suture material made of polyglycolic acid (Dexon) in abdominal and anorectal surgery are reported. It is considered that this material can usefully be employed in the place of known absorbable materials and, under certain conditions, non-absorbable materials. No complications due to inflammation and mucosa ulceration following transparietal migration of stitches in the sero-serous or seromuscular layer of the intestine were noted. The results obtained when stitches were left in situ in 37 intradermal sutures, on the other hand, were not so satisfactory and some scars were judged cosmetically poor after 6 months. These results are felt to be caused by Dexon's long absorption time. In cases of this kind, therefore, it should only be used in the form of removable, single stitches.


[Treatment of hypertrophic and keloid cicatrices with thiomucase]. As hypertrophic and keloid scars are formed essentially by fibrous connective tissue, the therapeutic response of an enzyme with specific action on mucopolysaccharides of the fundamental connective tissue substance (Thiomucase) was studied. This compound has been used with desamethazone phosphate in the ratio of 1:1 with promising results.


Toxicological and teratological studies of a rapeseed protein diet in rats and mice. Pregnant Sprague-Dawley rats, a fed a rapeseed protein diet (containing 0.2 mg glucosinolates/g protein concentrate) from day 0, showed no teratological effects on the 18th day. However, rats which were permitted to deliver, developed anorexia and weight loss after day 18. A reddish discharge, not blood, from the nose stained the fur of most animals fed rapeseed protein. A similar discharge developed in dams fed on lab chow but fasted after day 18. At delivery, dams would neglect the newborn during the first 24 h but would then resume their diet and litter care. Surviving litters of rapeseed-fed animals were comparable to controls in weight after 3 weeks. Vitamin supplementation did not prevent these effects. Force feeding the diet by gavage aggravated these toxic effects and prolonged the gestation period. No toxic effects were seen until day 18 of gestation when the rapeseed protein diet was fed to rats 3--6 weeks before mating. Control rats given glucosinolates by gavage did not show any adverse effects. The rapeseed protein diet had no effect on NMRI mice during pregnancy and on litter care up to 3 weeks.


Effect of non-ionic detergents on the absorption of fat and alpha-tocopherol in the rat. Malabsorption of rat and alpha-tocopherol was induced in rats by feeding cholestyramine and the effect of Tween 80 and Pluronic F 68 was assessed. Tween 80 did not influence the malabsorption of fat or alpha-tocopherol. Pluronic F68 did not change alpha-tocopherol absorption but did significantly improve fat absorption. The proportion of radioactivity remaining in the liver 5 days after a labelled dose of alpha-tocopherol was increased when Tween 80 or Pluronic F68 was present, perhaps indicating increased absorption via the portal vein. Serum cholesterol levels were not affected by the different diets. The greatly increased excretion of faecal bile salt on dietary cholestyramine was unchanged by the detergents.


Effect of dietary rapeseed oil on hepatic hexobarbital metabolism in mice. The effect of dietary rapeseed oil (RSO) on hepatic hexobarbital metabolism has been studied in short-term experiments in mice by measuring both the activity of mixed function oxidase system in microsomal preparations in vitro and the in vivo hexobarbital-induced sleeping time. Moreover, the fatty acid pattern of liver tissue, with particular regard to erucic and gadoleic acids, was analyzed gas-chromatographically. The hexobarbital metabolism in young RSO-fed (RSO containing 52% of erucic acid and 7.4% of gadoleic acid; 50 cal% for 3 days) is lower by about 44% than in controls treated in the same way with peanut oil, independently of sex. RSO did not have a statistically significant effect of hexobarbital metabolism in adult animals of both sexes. As to the dose-response study, the prolongation of the hexobarbital-induced sleeping time in young male is statistically significant when fed with 30 cal% in RSO for 3 days, while it is not more statistically significant in mice fed 15 cal% in RSO. In RSO mice (50 cal%) erucic and gadoleic acid account both for about 10% of the total fatty acids in the liver tissue, while they are quite absent in controls. It causes a relative deficiency of linoleic and arachidonic acids, known to be essential for synthesis and maintenance of the membranes supporting hepatic microsomal enzymes responsible for the metabolism of some drugs.


An investigation in rats, into the metabolic consequences of early ingestion of dietary carbohydrates. Weanling rats were given diets containing a high proportion of either glucose, sucrose or fructose until they reached 200 g weight, when they were either transferred to a control (chow) diet for 4 weeks or killed. The results were compared with rats receiving a control diet throughout. The triglyceride (TG) and cholesterol levels in liver and in serum had returned to values similar to the control animals 4 weeks after being given the control diet. The fatty acid profile of liver TG and adipose lipid tended to take longer to return to normal.


Effect of dietary substitution of sucrose and its constituent monosaccharides on the activity of aromatic hydroxylase and the level of cytochrome P-450 in hepatic microsomes of growing rats. The effect of dietary substitution of starch by sucrose, glucose, fructose or an equimolar mixture of glucose and fructose on the activity of biphenyl hydroxylase and the level of the major terminal mixed function oxygenase, cytochrome P-450, has been studied in hepatic microsomal preparations from growing rats. The substitution of sucrose for starch depressed the contration and total activity per liver of biphenyl 4-hydroxylase and the concentration, but not the total amount, of cytochrome P-450 in weanling rats. The absolute amount of these enzymes in whole liver was not, however, similarly depressed by the constituents of sucrose, namely glucose and fructose, either when given alone or in equimolar mixture. All these sugars, however, depressed the total activity of biphenyl 2-hydroxylase. The activity of biphenyl 4-hydroxylase in the liver of weanling rats, but not of adults, was reduced when the level of sucrose in the diet was reduced from 60 to 10%.


Effects of calcium solubility on adsorption by rats with induced achlorhydria. Gastric X-irradiated, achlorhydric rats and sham-operated controls were fed diets containing very soluble calcium chloride or calcium gluconate or slightly soluble calcium carbonate or tricalcium phosphate for 3 weeks. Calcium was absorbed more efficiently by achlorhydric rats from the very soluble salts from the slihtly soluble salts. The control rats absorbed calcium from the very soluble and slightly soluble calcium salts with similar efficiency. Achlorhydric rats fed slightly soluble calcium salts developed weaker bones with a lower mineral content than did those fed very soluble calcium. Apparently, the very soluble dietary calcium offset the impaired calcium absorption of achlorhydric rats. Calcium solubility had no significant effect on the bones of control animals.


Role of vitamin B6 on leucine-induced metabolic changes. Administration of leucine at 3% level in the diet has been shown to increase tryptophan oxygenase activity and to decrease kynureninase activity in the liver and to increase quinolinic acid excretion in the urine of rats fed low amounts of vitamin B6 (0.5 mug/g diet). Vitamin B6 at 3 mug/g of diet was able to reverse the effects of leucine on enzyme activities, but not on quinolinic acid excretion. Isoleucine at 0.2% level could counteract the leucine effect on kynureninase but not on tryptophan oxygenase. Administration of leucine also decreased the 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. Simultaneous administration of isoleucine could counteract the effects of leucine on brain 5-HT and 5-HIAA partially at low amount of vitamin B6 but completely at higher levels of vitamin B6 in the diet.


Effect on dietary sucrose and fructose on the metabolism and lipid fractions in liver in the rat. Male and female weanling rats were fed one of the following diets for 26 weeks: 60% (w/w) starch as control (59% of energy content); 20 (20), 40 (39) or 60% (59%) sucrose; or 20% (20%) fructose. With increasing levels of dietary sucrose the livers of male rats but not those of females, were progressively heavier. Livers of rats of both sexes showed progressively higher total lipid levels mainly as a result of high triglyceride levels. The 20% fructose diet produced the same effect as the 40% sucrose diet. The incorporation of 14C-glucose into liver lipids in vitro, and the production of 14CO2 were both depressed by sucrose and fructose feeding in both sexes.


[Effect of dietary magnesium levels on cardiac lesions in rats fed a diet rich in rapeseed oil]. Cardiac lesions (histiocyte infiltration and fibrosis) obtained in rats fed rapeseed oil and 3 magnesium levels (high, low and normal) during 30 or 50 days are quantified by their size. Correspondence factorial analysis is used to compare the results. After 30 days, less cardiac lesions of histiocyte infiltration or fibrosis appear with rats fed a diet high in both rapeseed oil and magnesium than with normal or low magnesium diet. After 50 days, cardiopathogenic effects are less severe with normal magnesium diet than with the others (high or low). In both cases, more severe lesions are seen with low magnesium diet. It is concluded that magnesium overload in the diet does not protect against the cardiopathogenic effects of a diet containing high levels of rapeseed oil. Classical nephrocalcinosis and hypomagnesemia are seen with a low magnesium diet (70 ppm).


Influence of a long or medium chain triglyceride diet on intermediary hepatic metabolism of the rat. Two groups of rats were given, ad libitum, diets containing 20% fat for 4-5 weeks. The fat consisted of either long chain (LCT) or medium chain triglycerides (MCT). A third group of rats was given a low fat control diet. No difference in weight increase could be found between LCT and MCT rats. Total lipids and cholesterol concentrations in the plasma were the same whatever the diet. The high fat diets caused an increase in hepatic acetyl-CoA, citrate, malate and ketone body concentrations. Concentration of ketone bodies in the blood, however, decreased. No ketonuria occurred in any case. Hepatic levels of adenosine 5'-triphosphate, adenosine 5'-monophosphate and inoganic phosphate seemed higher in MCT rats than in LCT rats. The levels of these substrates were increased in both groups compared with the control group. LCT rats had hepatic (NS) and blood (HS) lactate and pyruvate concentrations below the corresponding figures for control rats. Hepatic and blood lactate concentrations in MCT rats were at least equal to or slightly higher (NS) than those of control rats. Hepatic glucose and glycogen and blood glucose concentrations were higher in rats given the high fat diet.


[Effect of unsaturated dietary fats on growth and lipogenesis in rats]. In the growing rats weighting between 70 and 300 g, when 20% of the total daily energy intake consists either of 'lard (with 36% oleic acid) or sunflowerseed oil (with 61% linoleic acid)', lipogenesis, proteinogenesis, feed efficiency ratio and body compositions are identical. With the nutritional conditions used during these experiments, the occurrence of a high level of polyunsaturated fatty acids level in the diet cannot be considered as an exogenous factor able to modify the parameters studied.


Effect of ethanol on the activity of lipoprotein lipase in adipose tissue of male and female rats. The effect of a single large dose of ethanol on the activity of lipoprotein lipase in adipose tissue of previously fasted male and female rats was followed over a 16-hour period. Feeding of ethanol caused an increase in the plasma triacylglycerol concentration in both male and female rats. This has previously been attributed to an increased secretion of triacylglycerols from the liver into the plasma. The present results show that there is probably not any significant increase in the uptake of triacylglycerols in adipose tissue after ethanol feeding in male and female rats, since there was no major increase in the activity of lipoprotein lipase in adipose tissue. This may be a prerequisite for the ethanol-induced increase in the plasma triacylglycerol concentration and shows the unphysiological nature of ethanol as a source of energy.


Long-term effects of starvation-refeeding in the rat. The effects of one vs. two episodes of starvation-refeeding were studied in young male rats as a function of elapsed time between the two episodes of starvation-refeeding. Starved-refed rats ate more and gained weight faster than ad libitum-fed rats. The difference in weight gains could be attributed to the greater amount of body fat in the starved-refed rats. The responses of four NADP-linked liver dehydrogenases:isocitrate dehydrogenase (ICD)/LS-isocitrate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.42), glucose-6-phosphate dehydrogenase (G6PD)/D-glucose-6-phosphate:NADP oxidoreductase (EC 1.1.1.49); 6-phosphogluconate dehydrogenase (6PGD/6-phospho-D-gluconate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.44); and malic enzyme (ME)/L-malate:NADP oxidoreductase (decarboxylating) (EC 1.1.1.40) were studied. Starvation-refeeding caused an overshoot of G6PD, 6PGD, and ME, but not of ICD. A second episode of starvation caused an even greater enzyme overshoot; this difference persisted for 3 weeks with G6PD and for 2 weeks with 6PGD and ME. No significant differences in blood cholesterol were detected.


Patterns of urinary iodine excretion in a newly identified goitrous area of central Sicily. The results of a clinical survey, relative to goiter prevalence and carried out on 2,805 male and female subjects aged from 6 to 15 years, in five small towns in the province of Caltanissetta (Sicily), are reported. Along with clinical examinations, urinary iodine determinations were performed. The identification and classification of goiter have been carried out according to criteria suggested by WHO. Considering both sexes together, 33.6% of the children presented type 1 goiter, and 4.6% presented type 2. Goiter prevalence in the five areas studied appeared to be related to the differences in the iodine content of the various drinking waters. The patterns of urinary iodine excretion, expressed as I/C ratio and derived from determinations performed on 924 of the total number of subjects examined, are reported. An analysis of these data shows that the school population as a whole, in these endemic goitrous areas, presented I/C values significantly different between goiter subjects and non-goiter subjects.


Nutritional regulation of lipid metabolism in rats. VII. Effect of overnight fasting on liver lipids of rats fed different levels of essential fatty acids. Effect of dietary levels of essential fatty acid (EFA), 20% corn oil, 5% corn oil, 20% lard and no fat, on the overnight fasting-induced changes in the concentration and composition of liver lipids of rats was investigated. The increase due to fasting in triglyceride (TG) was not observed when the liver previously contained relatively large amounts of the glyceride. In contrast, phospholipid levels were similarly and significantly increased. Overnight fasting induced increases in percentage of linoleic acid in TG and arachidonic acid in TG and arachidonic acid in phosphatidylcholine, the extents of those being nearly paralleled with decreasing dietary levels of EFA. These changes are interpreted as a reflection of the compensatory action of the body.


Some effects of different dietary carbohydrates on pregnancy and lactation in rats. Female rats were fed from weaning on diets with sucrose, starch, glucose or fructose as the carbohydrate source. Animals were killed at various stages throughout pregnancy and early lactation. Maternal plasma triglycerides (TG), cholesterol, free fatty acids, glucose, insulin and corticosteroids were measured. Lipogenic activity was assayed in the livers, adipose tissue and mammary tissue, and the results compared with those from non-pregnant rats. Insulin, corticosteroids and hepatic lipogenesis were also assayed in the embryos and in newborn pups. Dietary sucrose and fructose produced a significantly higher concentration of plasma TG in the non-pregnant, pregnant and lactating rats than did starch and glucose. All the diets led to an increase in TG concentration at the 20th day of pregnancy, which returned to the original concentration 2 days post-partum. The hypertriglyceridaemia of late pregnancy was accentuated by the feeding of sucrose and fructose. Maternal concentrations of plasma glucose were significantly reduced towards the end of pregnancy in all dietary groups. The replacement of starch by sucrose, or of glucose by fructose, enhanced hepatic lipogenesis. Fructose but not sucrose depressed fat synthesis in the adipose tissue. Hepatic fatty acid synthetase activity was increased in late pregnancy on all diets except that with starch. Late pregnancy intensified hepatic lipogenesis in rats fed sucrose or fructose. The results are discussed in relation to the metabolic changes during pregnancy and to sucrose feeding.


Effect of pantothenic acid deficiency on microsomal lipids of rat liver. Microsomal lipids of the liver from control rats and pantothenic acid (PA)-deficient rats, kept on a diet for a period of 75-116 days, were examined. Separation of individual phospholipids revealed a significant decrease in phosphatidyl choline in PA deficiency.


[Morphology of myometrial and decidual arteries in normal pregnancy, in toxemia of pregnancy, and in maternal diabetes (author's transl)]. 127 specimens, obtained by different methods from the myometrium and the placental bed after parturition, are investigated histologically. This material includes normal pregnancies as well as cases of maternal diabetes with and without hypertension and cases of hypertension in EPH-gestosis. The different parts of the arterial system (spiral arteries, basal arteries, radial arteries) are separately investigated. Physiologically, the pregnancy induces changes in the wall of the decidual arteries and possibly in the distal part of the radial arteries. The fibromuscular layer including the elastic fibers were destructed and replaced by fibrin and connective tissue. For this reason, in these parts of arteries it is very difficult to separate pathological from physiological changes.


[The "small airways disease" and its early diagnosis]. The "small airways disease" constitutes the initial, silent step of chronic obstructive bronchopneumopathies and remains misknown for a long time. Discussion is made of an anatomic and physiologic definition of these small airways and authors insist on the concept of MEAD's equal pressure point. The classical technics of functional study (spirometry, determination of the resistances in the airways) are of poor help for evidencing the lesions of these airways; more specifical technics have been advanced (flow-volumes curves, frequency-dependence of the compliance...). Their meaning and their place in the detection and diagnosis of chronic obstructive bronchopneumopathies is presently object of numerous discussions.


[The small airways obstruction: an assay of structure-function correlation]. A review is made of the structural lesions responsible of the small airways obstruction: stenosis of the peripheral membranous bronchioles, either segmental stenosis or diffuse narrowing; loss of bronchioles consecutive to the inflammatory destruction of their walls; mucus plugs; fine or metabolic modifications of the distal bronchiolar epithelium. It is probable that these two latter lesions,--mucus plugs and lesions of the bronchiolar epithelium--, are reversible. Nevertheless, we don't know presently what are among these various bronchiolar lesions those responsibles for the alteration of the functional tests used in the study of early obstruction of the small airways.


[Regional distribution of ventilation and perfusion in the beginning chronic bronchopneumopathies]. The regional distribution of lung ventilation and perfusion was determined in five normal subjects and in patients suffering from chronic bronchitis or asthma with variable functional repercussion, and also in some cases of beginning lung emphysema. The system of detection under use is a scanning camera coupled with a computer. In the case of chronic bronchitis or of asthma, there exists, the more often, a redistribution of lung ventilation and perfusion from the bases towards the vertices. The alterations are less evident in the cases of emphysema submitted to study. The limits of the method are object of discussion. Its application to the early detection of bronchopneumopathies does not appear as possible.


[Determination of the closing volume and its value in the early detection of chronic obstructive lung disease]. The determination of the closing volume appears as a good test for the early detection of obstructive lung diseases and of disorders in the ventilation distribution. Easy to perform, its use should become extensive. To make use of this investigation under the better possible conditions, it is strictly necessary to respect methodologic norms and an excellent technology and to be aware of some morphologic anomalies in the curves.


[Frequency dependance of compliance].

[Frequency dependance of compliance]. Resistance of peripheral or "small" airways is only a small part of the total pulmonary resistance (Raw). Even considerable obstruction in these airways will have little effect on total resistance. Conversely this will lead to inequality in the time constants of units in parallel, and dynamic lung compliance (C dyn) shall fall as respiratory frequence increases. C dyn is measured from simultaneous recordings of transpulmonary pressure (esophageal balloon) and volume obtained from a volume displacement plethysmograph. If Raw and static compliance are found to be normal, the frequency dependance of compliance will result from peripheral airway obstruction only. Early stages of chronic airway obstruction can be established by this method. However this appear not suitable for wide-scale studies.


[The maximary expiratory flow-volume curve]. The maximal expiratory flow-volume curve is obtained by recording simultaneously, in the course of a forced expiration, the volume in abscissa and the flow in ordinate. Mention is made of the various recording technics and also of the ways for quantifying the results (determinations of the instantaneous flows at various volumes). The clinical applications of the flow-volume curves are taken in consideration. The advantages and inconvenients of this method are discussed.


[Determinations of the carbon monoxide diffusion at the early stages of chronic obstructive lung disease]. The determinations of the diffusion capacity of lungs for carbon monoxide (DLco) with single breath or steady state methods find their elective indication in the diseases affecting electively the alevolar-capillar membrane, particularly in the cases of fibrosis. In the course of chronic obstructive bronchopneumopathies, they are more or less disturbed by the anomalies in the distribution of lung ventilation and perfusion that coexist with them in a constant mood. Nevertheless, it has been proved that the fall in DLco and in the relation DLco/alveolar volume is one of the elements that contribute to recognize lung emphysema and to make the distinction between the same and chronic bronchitis or asthma. It is also well established that DLco is lowered in the smokers, but the meaning of this fact is presently bad known: artefact due to the presence of carboxic-hemoglobin; lesion of the alveolar-capillar membrane or anomaly in the bronchiolar permeability. DLco is also diminished in some asymptomatic subjects bearers of a deficiency in alpha-l-antitrypsin and may be also encountered in the course of beginning lung emphysema with anatomic authentication. In some cases, the fall in DLco might therefore bear witness, prior to any spirographic alteration, of the involvement of the alveolar-capillar membrane, but not of the true bronchial obstruction.


[Comparison between the closing volume comportments and the Vmax/V curve in patients with obstruction of the small airways]. Three groups of patients with obstruction of the small airways and normal main airways were submitted to study by determining the closing volume and the V max/V curve. In the first group (beginning chronic bronchitis) was noted an alteration of the curve with normal closing volume in almost all the cases; in the second group (asthma in the remission phase) the closing volume was increased and the curve normal in a part of the patients, -while in the other part the closing volume was normal and the curve altered; in the third group (recent heart infarct), a significative increase in the closing volume was noted with a slightly altered curve: improvement of the tests was obtained after administration of diuretics, the improvement being far more noticeable for the closing volume than for the V max/V curve. The closing volume is therefore an extremely sensitive test of the obstruction of the small airways when the obstruction interests before all the basal zones of the lungs. When the resistances of the small airways are irregularly distributed, the determination of the V max/V curve is, conversely, more useful.


[Modifications in the closing volume due to the inhalation of tobacco smoke]. Two methods, the one making use of nitrogen and the other of body plethysmography were applied to a group of normal young subjects in order to value the effects of the inhalation of tobacco smoke on the "closing volume". The results obtained with the two methods are different; according to authors, this phenomenon may be explained on the base of the physiopathologic meanings of the closing volume, under the condition to admit that tobacco smoke may promote an early closure and before all disorders in the distribution of the residual volume.


[Comparison in patients with chronic bronchitis of the data offered by the output-volume loop and the transfer capacity of CO]. The present study concerns 78 cases of chronic bronchitis (mean age : 55,3 years) submitted to a complete enough functional respiratory study (spirometry, RV, blood gases) and distributed into three groups:--Group I: 78 cases, mean age : 55 years. All these patients were submitted to spirometry, blood gases determination and determination of the transfer capacity of CO (by making use of the method under single breath : 54 cases,--or the method with steady state : 24 cases).--Group II : 15 cases, mean age 54 years. All these patients were submitted to spirometry, blood gases determination, determination of the transfer capacity of CO with the method under single breath and to a determination of the V (60-70%) CT output on the output-volume loop.--Group III : 13 cases, mean age 53,9 years. All these patients were submitted to spirometry, blood gases determination, determination of the transfer capacity of CO with the method under steady state and a determination of the V (60-70%) CT output on the output-volume loop. The comparison of the data and the study of the eventual correlations between the various parameters determined suggests that the determination of the V (60-70 %) CT on the V/V loop is a more reliable parameter of the obstructive ventilatory syndrome than the determination of the disorders in the transfer capacity of CO. This latter method of study under steady state appears often modified when there exists an alveolar (as yet mentioned by other authors); however, this is not the case when the test is performed under single breath. In the detection of chronic bronchitis, the informations obtained with the determination of the V (60-70 %) CT output appear thus to assume a great value, but these results necessitate to be verified in a greater number of patients.


[Normal value and age and sex correlations of mean expiratory output (25-75%). Diagnostic value in early obstructive bronchopneumopathies]. The maximum output of half-expiration (MMFR) or DME 25-75% is studied in 136 subjects, evalued as non obstructive, after the determination of the MEVS/VC X 100. The values noted are reported to the body surface (S) in order to eliminate the biometric differences. A highly close correlation, of the exponential type, is thus put in evidence for each sex between the DME/S and the age of the subjects. The study of the DME in subjects with obstructive Tiffeneau makes possible: a) to determine an inferior limit of the normal condition; b) to bring confirmation of the fiability of the test. The study of the determination of the DME/S is then performed in subjects with normal MEVS/VC X 100 and clinically suspect of bronchial obstruction (tobacco addicts, patients at stage I of chronic bronchitis, asthmatic patients outside the attacks). The DME determination lets appear the presence of a bronchial obstruction in almost one half of the subjects submitted to study.


[Pediatric spirometry as a prognostic test of adult obstructive bronchopneumopathy]. Authors study the spirometry of 40 asthmatic children between 6 and 12 years in age. Spirometric determination was performed immediately after the asthmatic attack and also at least 15 days after the last attack. The cases have been subdivided into four groups for what concerns Tiffeneau's index and Mottly's index. The group of subjects with abnormal Tiffeneau's and Mottly's indices is of particular interest. There exists probably in such subjects a beginning emphysema that might lead up, at the adult age, to a picture of obstructive bronchopneumopathy.


[Lung ductances and the determination of lung diffusion capacity in silicosis]. A study of the behaviour of global and partial lung ductances for CO having for aim to value the lung diffusion function in 97 silicotic workers was undertaken by authors. The workers were divided into three groups according to the Cincinnati classification. The mean values of the global ductance for CO let appear a fall in all the groups when comparison is made with the standard values previously registered in a group of normal subjects. The partial ductances have put in evidence a fall in the mean values below the normal values, only for what concerns the alveolar-capillar ductance for groups 2 and 3. The study of partial ductances in bronchitic and non-bronchitic silicotic subjects lets appear in the first ones a fall in the ventilatory and alveolar-capillar ductances,-- and in the second ones an isolated fall in the alveolar-capillar ductance.


[Functional state of the thyroid gland and thyrotropic activity of the hypophysis in patients with dyspituitarism of the puberto-adolescent period]. The authors report the results of study of the thyroid gland function in 72 patients with dyspituitrism of the puberto-juvenile period; the thyrotropic activity of the hypophysis was also studied in 37 of these patients. It was revealed that the TTH level could change both in the direction of decrease and of elevation; the inorganic phase of the iodine metabolism was reduced and the organic one--elevated. Such disproportion between the inorganic and organic phases of iodine metabolism in this disease was attributed to the hormonal disbalance, the excess in the organism of glucocorticoids and estrogens.


[Study of the level of lipids in the blood serum of patients with Shereshevsky-Turner syndrome]. A comparative study of serum cholesterol, total lipoprotein and triglyceride level in patients with the XO karyotype and in normal subjects (XX) showed cholesterol and total lipoprotein to be increased in these patients; as to triglyceride level--it proved to be unchanged. The type of hyperlipoproteinemia was established in 7 of 18 patients examined; all of them under 30 years old. Thus, the incidence of hyperlipoproteinemia in the XO patients was sharply increased; this seems to be related to the low estrogen level.


[Excretion of estriol in pregnancy complicated by diabetes]. A study was made of estriol excretion in the urine of women during normal pregnancy and in pregnancy against the background of diabetes. It was revealed that estriol secretion was decreased in pregnant women suffering from diabetes. As supposed there existed an interrelationship between the diabetic status and the level of estriol excretion.


[Dynamics of inhibition of the hypophyso-adrenal function in the administration of isotonic solutions of hydrocortisone into various hypothalamic nuclei]. Injection of 1% hydrocortisone solution into the arcuate, ventromedial or supraoptic nucleus of the hypothalamus inhibited the activity of the hypophysis-adrenal system. This inhibition began 0.5 hours after the administration of the hormone into the microcellular nuclei and reached the maximum in 2 hours when the corticosteroid secretion was cut by about half. After the injection of hydrocortisone into the supraoptic nucleus inhibition of the hypophysis-adrenal system began later than in its administration into the arcuate or the ventromedial nucleus. In this case the level of corticosteroids began to decrease two hours after the injection, and in 3 hours it was half of the initial one. Apparently hydrocortisone retarded the synthesis of the corticotropine-releasing factor in the hypothalamic nuclei.


[Influence of DOPA, dopamine and melatonin on adrenal function in rats]. Experiments were conducted on Wistar rats, 160 to 180 g in weight. Epiphysectomy and pseudoepiphysectomy were carried out 14 days before the main experiment. Adrenal gland function was assessed by the rate of secretion of aldosterone and corticosterone into the adrenal vein and by the content of adrenaline in the adrenal glands. DOPA, dopamine and melatonine were administered into the third cerebral ventricle in a dose of 1 gamma per 100 g of weight, and intravenously in a dose of 100 gamma per 100 g of weight. Intraperitoneally melatonin was injected in a dose of 1 mg/100 g twice a day for 3 days. It was shown that administration of DOPA to males and of dopamine to females into the third ventricle of the brain increased the rate of aldosterone secretion in the intact rats. With different methods of administration melatonine decreased the rate of aldosterone and corticosterone secretion in the intact rats. Intravenous injection of melatonine to epiphysectomized rats stimulated the rate of secretion of the mentioned hormones.


[Excretion of testosterone in men with various forms of hypogonadism]. A reduction of testosterone excretion in men with hypogonadism is reported in literature; however, the clinical peculiarity of its individual forms are not considered in these works. This paper treats of testosterone excretion in 43 patients with various forms of hypogonadism, of this number in 36 before and after a single testosterone-propionate loading. There was seen a reduction of testosterone excretion in hypogonadism. Secondary hypogonadism coursed against the background of a more marked insufficiency of testosterone excretion than the primary one. In a number of hypogonadism cases testosterone excretion remained unchanged and their clinical signs were caused by an inadequate realization of the androgenic effect. In hypogonadism an increase of the urinary excretion following its administration did not always correspond to the dose of the administered hormone, which could serve as one of the pathogenetic mechanisms of development of the disease.


[Excretion in the urine of glucuronides of testosterone and androstenedione in women with climacteric neurosis and without neurosis]. The author elaborated a method of study of the urinary excretion of the testosterone and androstendione glucoronides and applied it in 20 women (4 healthy women of reproductive age, 10 women at the postmenopause with a climacteric neurosis, and 7 healthy women during the climacteric). In healthy women the mean values of testosterone and androstendione urinary excretion showed no significant difference from those in women of the reproductive age and during the climacteric. It is supposed that the level of urinary excretion of these hormones showed but little change with the progress of age. As to women with a climacteric neurosis, there was no significant change of the mean values of urinary excretion to testosterone and androstendione in comparison with healthy women of the same age. This suggests that the androgenic function of the adrenal glands in this neurosis showed no significant change. Patients with a climacteric neurosis displayed higher variations in the values of the urinary excretion of testosterone and androstendione glucoronides, which was possibly associated with disturbances of regulation of the production of the androgens by the hypothalamic centres.


[Influence of destruction of the subcommissural organ on the glomerular zone of the adrenal cortex]. Experiments were conducted on 30 rats; a study was made of the morphometric and quantitative enzymatico-chemical changes in the glomerular zone of the adrenal cortex in stereotaxic disturbance of the subcomissural organ; there was established a marked atrophy of the glomerular zone, a significant reduction of the diameter of the nuclei of the adrenocorticocytes and depression in these structures of the enzymatic activity of the energy metabolism. Histophysiological characteristics of the glomerular zone can be assessed as its hypofunctional condition and indicates an association between the functional activity of the subcommissural organ and the production of aldosterone.


[Autoregulation of the somatic function of the adenohypophysis in intact and thyroidectomized rats]. Experiments conducted on male rats showed exogenous STH (2 mg daily for 10 days, subcutaneously) to cause a reduction in the STH content in the adenohypophysis and in the incorporation of labeled amino acids into the SHT in vitro both in intact and in thyroidectomized animals. Exogenous STH somewhat normalized the increase in body weight and the weight of the adenohypophysis of the thyroidectomized animals. A conclusion was drawn that autoregulation of the somatotropic function of the adenohypophysis persisted under conditions of a marked thyroid hormone deficiency.


[Organotropicity and the dynamics of the clearance of exogenous labelled TSH from the blood under conditions of stimulation and blockade of the thyrotropic function of the hypophysis]. Experiments were conducted on male Wistar rats. Incorporation into the kidney, the liver and the thyroid gland of I131-TSH and its elimination from the blood was studied. The rate of I131-TSH elimination from the blood plasma varied depending on the level of the endogenous TSH in the circulating blood of the recipient rats. The half-elimination period of the I131-TSH from the blood plasma of the intact rats constituted 10.4 minutes. In these animals the labeled hormone accumulated in the thyroid gland only 30 minutes after its administration. In case of an increase of the blood level of endogenous TSH following thyroidectomy the period of half-elimination of the I131-TSH from the plasma fell to 3.6 minutes; with reduction of the endogenous hormone level due to the block of the hypophysial secretion by triiodothyronine the period of the I131-TSH half-elimination rose to 39.4 minutes. In the latter case the labeled hormone failed to be incorporated into the thyroid gland. A conclusion was drawn on a possibility of assessing the level of the thyrotropic activity of the hypophysis on the basis of the changes in the period of the I131-TSH half-elimination from the blood plasma of the recipient animals.


[Blood sugar level and immunoreactive insulin in the blood plasma in pregnant women with supposed prediabetes in the dynamics of a normal glucose tolerance test]. A study was made of the blood sugar level and blood plasma immunoreactive insulin (IRI) on fasting stomach and in the GTT dynamics in 33 pregnant women with a possible prediabetes and also in 8 nonpregnant women and 20 pregnant women of the control group. GTT proved to be normal in all the women under study. There proved to be no significant difference between the blood sugar level on fasting stomach and in the GTT dynamics in pregnant women of both groups and in the nonpregnant women. In comparison with nonpregnant women, pregnant women of both groups displayed a higher mean blood sugar elevation during the whole GTT period--in the II and III trimesters. Blood plasma IRI in the pregnant women with a possible prediabetes and in the pregnant women of the control group on fasting stomach and in the GTT dynamics showed no significant difference between one another. In comparison with nonpregnant women, pregnant women of both groups showed an increase in IRI content of fasting stomach and in the GTT dynamics beginning from the II trimester and reaching the maximal level during the III trimester of pregnancy. IRI over glucose index did not differ in pregnant women of both groups from the nonpregnant women. Thus it was revealed that hyperinsulinemia in pregnancy in practically healthy women and in women with a possible prediabetes was compensatory in character.


[Influence of DOPA on the reactions of fetuses of adrenalectomized and ovariectomized rats to adrenaline stress]. It was shown that administration of noradrenaline precursor--L-DOPA (45 mg/kg) to pregnant adrenal- or ovariectomized rats restored the reaction of their fetuses to stress to the level characteristic of fetuses, whose mothers were falsely operated with their adrenal glands and ovaries remaining in situ. It is supposed that during the prenatal development in rats stress-reaction was realized with the participation of noradrenaline of the maternal CNS.


[Influence of epiphysectomy on the metabolism of electrolytes]. On the 5th day after epiphysectomy rats displayed a reduction of the kidney excretion of Ca and Mg with a simultaneous increase of these elements in the tissues. By the 10th day after the operation the mentioned indices were restored to the preoperative level, but there occurred an increase in the urinary excretion of Na and a reduction of its tissue content. DOCA administration to the epiphysectomized rats eliminated the changes in the Mg and Ca excretion, but failed to influence the Na excretion. Apparently, the hormones of the epiphysis are necessary for the manifestation of the Na-retention action of the mineralocorticoids.


[Study of the characteristics of transcortin and the progesterone binding protein of the plasma of pregnant guinea pig]. Experiments were conducted with the plasma of pregnant guinea pigs; it was shown that the corticosteroid-binding protein (CBP) of the plasma in a pregnant guinea pig (in difference from the CBP of other species) bound cortisol only, and not progesterone. Progesterone-binding protein (PBP) of these animals bound progesterone, but not glucocorticoids and their metabolites. The binding capacity of CBP proved to be several hundred microgram per cent of cortizol and of PBP--about 100 microgram per cent of progesterone. The association constant of the CBP with cortisol constituted 10(6) M-1, and of the PBP-10(-8) M-1. These proteins are also analysed according to a number of other parameters.


[Hormonal and pyridoxine induction of threonine dehydratase in the rat liver]. The activity of threonindehydratase in the liver of intact and adrenalectomized rats increased considerably after the administration of cortisol. A simultaneous with cortisol administration of insulin or testosterone led to inhibition of the corticosteroid induction of the enzyme. On the contrary, thyroxin increased both the basal activity of the enzyme and its response to the administration of cortisol. Besides the hormone, threonindehydratase cofactor (in the form of pyridoxine) led to an increase in the enzymatic activity. However, cofactor induction was expressed only in rats with intact adrenal glands.


[Influence of glucocorticoid hormones on the pool and intracellular distribution of ubiquinone in the tissues of rats]. Experiments on the study of the effect of glucocorticoids on the content and intracellular distribution of oubichinon in the liver, heart and spleen were conducted. Hydrocortisone (2.5 and 5 mg/100 g) and cortisone (5 mg/100 g) was injected subcutaneously for 10 days. It was found that hydrocortisone in a dose of 2.5 and cortisone in a dose of 5 mg/100 g failed to influence the total level of oubichinon in the tissues under study. Administration of hydrocortisone in a dose of 5 mg per 100 g of weight was accompanied by an increase in the oubichinon concentration in the spleen. A study of the intracellular distribution of the coenzyme indicated an elevation of its content in the hyaloplasma and its reduction in the mitochondrial fraction. On the basis of the data obtained it could be supposed that glucocorticoid regulation of the oubichinon level was realized at the subcellular level. Possibly, glucocorticoids altered the membrane permeability for oubichinon causing its redistribution in the cell.


[Restoration of antibody synthesis by means of thymus extract in neonatally thymectomized animals]. One of the fractions of the thymus extract of a calf obtained by the authors restored the synthesis of antibodies to sheep erythrocytes in neonatally thymectomized mice and rats. Fractions isolated anologously from the tonsils and the lymph nodes failed to influence the antibody genesis. The data obtained are in favor of the endocrine function of the thymus of significance in the establishment and regulation of the immunological reactivity.


Central metabolic and humoral factors involved in the neural regulation of feeding. Evidence is summarized for the theory that long-term regulation of energy balance is elaborated by an interface between matabolism and brain activity within the medial hypothalamus, while short-term satiety effects are a more direct consequence of dampened activity in lateral hypothalamic feeding circuits. Possible relationships of these functions to autonomic control circuits are discussed.


Cholecystokinin: a putative satiety signal. The intestinal hormone cholecystokinin (CCK) elicits satiety in rats and inhibits food intake in rhesus monkeys. This behavioral effect is specifically related to the C-terminal octapeptide structure of CCK and is a new biological effect of the hormone. Endogenous CCK released by food entering the duodenum may inhibit feeding and elicit satiety under physiological conditions, but no experimental evidence is availabe on this point. Until such evidence becomes available, we believe that CCK should be considered a putative satiety signal. The satiety effect of CCK suggests a therapeutic role of CCK for human hyperphagia and obesity. An interesting therapeutic alternative to administration of exogenous CCK is the release of endogenous CCK by nutrients such as amino acids. These nutrients can be ingested as preloads which are calorically trivial, but which release significant amounts of CCK. Such preloads inhibit food intake in rhesus monkeys. Their efficacy in man has not been determined.


Studies on the nervous regulatory mechanism of blood sugar levels. Intraarterial injection into the carotid artery or intravenous injection of glucose caused a decrease in efferent discharge rate of the adrenal nerve and an increase in discharge rate of the pancreatic branch of the vagus nerve. Decrease in blood sugar level following administration of insulin increased adrenal nerve activity and caused a decrease in the activity of the pancreatic branch of the vagus nerve. Administration of 2-DG resulted in an increase in adrenal nerve activity and a decrease in pancreatic nerve activity. Glucose also caused a decrease in discharge rate of afferent nerve fibers from glucoreceptors in the liver. The results suggest the existence of a nervous regulatory mechanism of blood sugar levels.


Triglyceride metabolism in epididymal adipose tissue of obese animals. Experiments were carried out to elucidate the mechanism of triglyceride accumulation in epidiymal adipose tissue of obese mice made by goldthioglucose injection. Specifically, fat mobilization and its deposition were investigated. In goldthioglucose-treated mice, the weight of the epididymal adipose tissue was 1,200 percent of that of control mice, while adrenaline-induced lipolysis and lipase activity of the tissue were 272 and 450 percent of control respectively. These results suggest that deposition of fat far exceeds fat mobilizing activity in the adipose tissue of the obese mice. It was found that triglyceride synthesis from glucose increased in the adipose tissue of these mice. Therefore, it is suggested that obesity in gold thioglucose-treated mice may not be due to decrease in fat mobilization but to increase in triglyceride synthesis from carbohydrate.


Direct fiber connections between the frontal cortex and the hypothalamus in the rat: an electron microscope study. The direct fiber connections between the frontal cortex and the hypothalamus, especially the ventromedial nucleus and the lateral hypothalamus have been studied by electron microscopy using the orthograde terminal degeneration technique. The results obtained are as follows: Typical electron dense degeneration of the axon terminals is constantly recognized in the neuropil of the lateral hypothalamus on the same side following a lesion of the frontal cortex. On the other hand, the degenerating terminals are found in the field of the neuropil of the frontal cortex following the lesions of either the VMH or the LH, exclusively ipsilaterally. The present study demonstrates the existence of direct fiber connections from the frontal cortex to the LH and from the LH to the frontal cortex in the rat, and suggests the possible existence of a direct projection from the VMH to the frontal cortex.


Role of sensory factors in chewing and feeding behavior. Since feeding behavior has a complex physiological background, in the physiology of feeding behavoir not only the mechanisms in the hypothalamus, but also input and output physiologic factors which stimulate and/or inhibit the central network for feeding and aversion behavior, must be considered. Normal feeding and aversion behavior are accomplished by a series of highly co-ordinated physiological functions involving various parts of the body, and humoral, hormonal, metabolic, and sensory and motor functions for feeding behavior must be well considered from a wider wiew point. For this purpose, morphological, biochemical, and neurophysiological extensive approaches to study the feeding behavior mechanisms are essentially important. In the present paper, neurophysiological network concerning feeding and aversion behavior was under discussion. Particularly, relations between input, central and output factors for these behaviors were considered. As an input factor, a role of the nerve impulses of the chorda tympani and lingual nerves was evaluated. As a central factor, involvement of the neurons in the cortical taste area was discussed, and response patterns of cortical taste neurons to negative and positive taste information was analyzed with regard to taste perception mechanisms. In addition, mechanisms in the posterior hypothalamus for the taste aversion behavior were explained through ablation and recording techniques in the rat; and the neuromuscular mechanisms of chewing, which complete the feeding behavior, were also discussed. Importance of such comprehensive systematic approach to proper understanding of feeding and aversion behaviors was emphasized.


Excitatory and inhibitory effects of globus pallidus and substantia nigra on the lateral hypothalamic activity in the rat. Stimulation of the rat globus pallidus (GP) and substantia nigra (SN), while recording in the lateral hypothalamus, revealed mutual interconnections. Stimulation of GP produced an EPSP-IPSP sequence, while SN stimulation produced EPSP only. Antidromic LH spikes were obtained with either stimulation. Inhibitory interneurons responsible for the IPSP are located in the dorsolateral part of the LH. In the LH, only glucose sensitive neurons were specifically facilitated by SN stimulation and inhibited by GP stimulation. Dopamine and noradrenaline, applied electrophoretically to these neurons, yielded inhibition in a dose response manner, denying the possibility of dopamine as an excitatory transmitter substance. The mutual interrelationship between the LH and other centers, including the frontal cortex, may well influence motivation of feeding and other behavior.


Excitatory control of hypothalamic ventromedial nucleus by basolateral amygdala in rats. Effects of single and repetitive stimulation of the basolateral amygdaloid nucleus (AL) on the rat hypothalamic ventromedial nucleus (VMH) activity were investigated. Extracellular single unit discharges and evoked potentials were recorded in the VMH and stria terminalis using microelectrodes. Three effects of AL stimulation on the VMH were observed: exitation, inhibition, and disinhibition. Disinhibition may, in fact, be inhibition of inhibitory interneurons within the VMH. Finally, a tentative concept of the neural network within the VMH is discussed.


Organization of some brainstem and limbic connections of the hypothalamus. Electrophysiological and anatomical studies allow the formulation of some features of organization of the lateral hypothalamus: (1) The HVM is the major source of modulatory inpur to the lateral hypothalamus; (2) There is a high degree of convergence of afferent paths in the lateral hypothalamus resulting in the same type of postsynaptic firing pattern, whether it be inhibition or excitation; (3) The response to afferent activation is usually quite simple, consisting of either a brief excitatory period or a fifty to several hundred millisecond inhibition. Complex firing patterns in a response to afferent stimulation are rare; (4) Descending hypothalamic output activates two classes of neurons in the midbrain; (a) an output with a strong synaptic drive acting upon cells which are not spontaneously active and which do not respond to arousing stimuli, and (b) an output with moderate to weak synaptic drive acting upon cells that are spontaneously active and excited by peripheral arousing stimuli.


Innervation of hypothalamic and limbic areas by the cholinergic, the GABA-ergic and the catecholaminergic nerve fibers; a quantitative analysis. By measuring activities of enzymes involved in synthesis of acetylcholine, gamma-aminobutyric acid (GABA), dopamine or noradrenaline, extent of innervation of cholinergic, GABA-ergic, dopaminergic and noradrenergic fibers were analysed in discrete brain areas and subareas of the baboon and the rabbit with a special reference to the hypothalamus and the preoptic ares. In the latter area, cholinergic and dopaminergic innervation increases medio-lateraly on the one hand, and noradrenergic innervation reversed on the other hand. GABA-ergic innervation is almost evenly distributed in this structure. By placing electrical lesions in the lateral hypothalamus, an analysis was made of inputs of these innervations.


Brain mechanisms in the control of feeding: a new neurochemical profile theory. A new theory is presented in which two profiles of chemical activity are postulated to regulate the intake of food. One is a peripheral profile which consists of the ratio of all blood-borne substances, one to another, that are involved in energy balance, lipid deposition, and other aspects of long and intermediate term regulation. The changes in the ratio are presumably monitored by structures in the CNS. The second profile consists of the chemical activity of transmitter and other neurohumoral factors within the same structures in the CNS. The ratio in their release provides appropriate neural signals which serve to activate or inhibit the various events of the feeding mechanism. The preliminary attempts to characterize, by GC-mass spectrometry, profile constituents in samples of fluid collected from the fasted and satiated cat are described. The recent results of experiments on the role of the forebrain catecholamines in food intake are also presented.


Effects of essential amino acids on central neurons. Effects of eleven essential amino acids ejected by means of electrophoresis through five barrel glass microelectrodes on the frequency of extracellularly recorded action potentials of brain cells were determined. Data were collected on 129 cells from four different parts of the brains of 22 female hooded rats anesthetized with a mixture of chloralose and urethan. Eleven cells were tested in the cerebral cortex, 57 in the thalamus, 33 in the zona incerta, and 28 in the lateral hypothalamus. Of the eleven amino acids tested, cells of the zona incerta and lateral hypothalamus appear to be the most responsive and increases in discharge frequency were observed for all the amino acids except lysine and cystine. Cystine seems to be unusual in that it is the only amino acid tested which produces a decrease in the spontaneous discharge frequency. Cells of the cerebral cortex were not considered responsive in terms of the criteria of this study and displayed relatively high thresholds to all the essential amino acids. These results indicate some differential sensitivity of certain cells of the brain to essential amino acids which might be related to the centrally mediated anorexia which develops when rats are fed disproportionate amounts of these same amino acids in the diet.


Comparison of the effects of intracranial injections of 6-OHDA and guanethidine on consummatory behavior and monoamine depletion. 6-Hydroxydopamine (6-OHDA) has been used extensively to study the effects of catecholamine depletion on feeding and drinking behavior. The results from these experiments are variable and do not clarify the involvement of catecholamines in these behaviors. Guanethidine, which has been used in studies of the peripheral autonomic nervous system, provides an alternative method of catecholamine depletion. In the experiments reviewed here the effects of injections of 6-OHDA and guanethidine into the rat brain on consummatory behavior and temperature regulation have been compared and related to changes in monoamine levels as shown by fluorescence histochemistry. Injections of 6-OHDA into anterior hypothalamic areas have lethal effects on food deprived animals. This effect may be explained in terms of loss of ability to regulate temperature. Animals whose catecholamines were depleted by guanethidine injections into anterior lateral hypothalamus showed a consistent reduction in food and water intake and an elevation of body temperature. Reconciliation of these findings appears difficult. However, a comparative study of the intracranial diffusion patterns of guanethidine and 6-OHDA has revealed marked differences in the extent of diffusion as seen with the fluorescence histochemical method when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage extended up to 1 mm in diameter. Generalized damage was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). At the doses used guanethidine, but not 6-OHDA caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm from the cannula tip. Guanethidine was less selective for dopaminergic compared to noradrenergic neurons. These differences between the effects of the two drugs are explained in terms of their unique pharmacological properties and their estimated decay in CNS tissue. An attempt has been made to account for the differences in behavioral data and in particular the variability of the 6-OHDA data in terms of the differences in the type of damage produced by the two drugs and the extent of their diffusion. It is also argued that the different patterns of damage would not easily be distinguished by biochemical analysis, and further, that changes in injection volume and concentration may lead to different damage patterns.


The child, vulnerable in the mother's desire. In this paper, by presentation of some clinical material, the author wishes to demonstrate that in some cases it is possible to detect very early in the phantasies and/or the psychosomatic manifestations of expecting mothers what later will be experienced by the infant as the loss of the first object of love. This loss, with its deeply destructive consequences (in terms of personality development) is one of the factors that can possibly sign the entrance to child psychosis. Although one can rarely attribute, with certainty, the onset of such severe emotional disturbances to only one factor, the hypothesis can be maintained that the desires and wishes of the woman, while expecting a baby, play a determining role on the fate of child. One should also add that it is not infrequent to observe various changes and fluctuations in the attitudes of mothers after the child is born. Still, the material of the cases under discussion (of which only two will be presented here) seems to point towards a development in which the pre-birth way of experiencing the child on the part of the mother puts a definite and particular sign on the object relations to follow.


Muscular tension and psychopathology. A comparison of four psychopathological groups by general physiotherapeutic examination of muscular tension. From 1968 to 1970, 136 test patients divided in four groups have been examined by general physiotherapeutic muscle tension examination. Group 1 were psychotic patients, group 2 were neurotic patients, and both groups were inpatients in a psychiatric hospital. Group 3 were ambulant patients at a physical institute and group 4 were healthy control persons. Each group was examined by five different, independent clinical muscle tension investigations: (1) examination of posture when standing and lying supine; (2) examination of respiration standing and lying supine; (3) examination of resistance to passive movements; (4) examination of muscle elasticity on palpation, and (5) examination of the patients reaction to the palpation. Altogether 47 variables were investigated, and of these 34 gave results which were statistically significant. This study confirms that there is a systematic connection between muscle tension and psychic conditions and the physiotherapeutic muscle tension investigation can contribute to diagnosing the degree of psychopathology and could be an aid in the selection of treatment. It is of interst to find out whether there is a connection between tension of the skeletal muscles on the one side and psychopathology on the other. A possible connection between the two might open the door for a comprehensive understanding of somatical and psychological illnesses, and offer the possibility for a more concise and direct treatment.


Combined inpatient and outpatient group psychotherapy: a therapeutic model for psychosomatics. A special strategy of psychotherapeutic approach to psychosomatic patients is described including a 3-month period of inpatient and a 2-year period of outpatient group psychotherapy. Additional therapeutic procedures applied during the time of hospitalization are a special kind of sensitivity training ('sensual awareness' -- 'konzentrative Bewegungstherapie') and analytic ergotherapy. The therapeutic techniques used are psychoanalytic with special regard to the scenic figures which arise during the course of a session. The 'scenic function of the ego' represented in, e.g., certain body movements, sitting-arrangments, and talking-sequences offers the opportunity of a possible access to the often poor phantasy life of the psychosomatic patient, suffering from what we call the Pinocchio syndrome. The key structure of the model implies the arrangement fixed prior to the onset of therapy between patients and therapist, to stay together as a closed in- and outpatient group for 2 years. This enables the patients to take the risk of new emotional experiences under the cover of protected living conditions in the hospital, as well as the chance to check and confirm these experiences under the pressure of the regular social conditions they live in.


[Studies of the circulation in patients with essential hypertension during the 1st and 2nd standard exercises of autogenic training]. A group of ten hypertensive patients were examined as to their circulation at rest, before, and during, the first and second standard exercises of autogenic training. During the exercise there was a significant reduction in cardiac time volume. The expected simultaneous decrease in the total peripheral resistance could not be demonstrated by our methods. Its apparent rise is interpreted as a result of its dependence on the heart beat volume, but can also be understood as an abnormal reaction of a pathological functional state. To clarify this further it would be necessary to establish an isolated determination of that circulatory parameter. It could be shown that the minute-volume component of hypertension can be affected by autogenous training.


[Stereotyped movements and autonomous rhythms]. The present study is concerned with the pathogenesis of jactatio capitis, of the stereotyped movements of oligophrenics, of dements, and of long-stay hospitalized defect schizophrenics, as well as with stereotyped movements in domestic animals. This leads to a discussion of the significance of rhythmically alternating innervation for pathological and normal movements. The relevance of rhythmic events for movements in inanimate systems is emphasized and the analogies which exist between movement in the organic and in the inorganic sphere are pointed out.


Plasma and erythrocyte concentrations of lithium. The authors have studied the clinical response, EMG and EEG changes in 12 depressed patients after 28 days of lithium carbonate treatment of 1,200 mg daily. The findings confirm: (1) a high correlation between the degree of improvement and the RBC lithium: plasma lithium ratio on the 28th day; (2) a slight decrease in motor conduction velocity (m.c.v.) and increase of M-response duration during lithium treatment; (3) no correlation between EEG and lithium levels and percentage of improvement.


The effect of trance on memory content.

The effect of trance on memory content. In a Yucatecan crisis cult of short duration, the millenary expectations are remembered long after the dissolution of the cult. So is Satan who, it is felt, tempted the congregation. The cultural innovations instituted during the cult, however, are almost immediately forgotten. The differential recall is shown to be related to the quality of the trance behavior during the cult and to the threatening versus neutral content of the memory material.


beta-Hydroxy fatty acid production during fatty acid oxidation by heart mitochondria. The effect of various incubation conditions on the production of beta-hydroxylaurate, -myristate, and -palmitate by isolated rabbit heart mitochondria oxidizing palmityl carnitine was studied. A gas chromatographic-mass spectrometric method was developed to identify and measure submicrogram quantities of methyl esters of these beta-hydroxy fatty acids (FA). Alpha-Deuterated esters of beta-hydroxy-FA served as internal standards. The total amount of the three beta-hydroxy-FA in fresh mitochondria was 0.045 mug/mg of protein. Malate, ATP, rotenone, and 1-carnitine together effected an NADH:NAD ratio of 8 and the accumulation of 0.896 mug of beta-hydroxylpalmitate. Omission of carnitine decreased the beta-hydroxy-FA by 65 percent. Omission of palmityl carnitine resulted in no beta-hydroxy-FA. Without rotenone the NADH:NAD ratio was 0.5 and there accumulated only 0.085 mug of beta-hydroxy-FA/mg of protein/10 min. Succinate, in place of malate, effected an NADH:NAD ratio greater than 10 but only 0.465 mug of beta-hydroxy-FA/mg of protein/10 min. We conclude that elevated mitochondrial NADH:NAD ratios facilitate beta-hydroxy-FA accumulation by slowing beta-hydroxyacyl-CoA oxidation. Cardiac hypoxia may prompt beta-hydroxy-FA accumulation and/or release.


Inhibited adenine nucleotide translocation in mitochondria isolated from ishcemic myocardium. Experiments conducted in healthy mongrel dogs indicate that acyl-CoA levels are raised and adenine nucleotide translocase is inhibited during ischemia. The biochemical findings are accompanied by ultrastructural evidence of myocardial cell damage. These results raise the possibility that the inhibition of adenine nucleotide translocase may be a key disturbance in cellular metabolism.


Energy metabolism in the infarcted cardiac muscle: the interaction of contractile protein and mitochondria. In order to investigate the behavior of the energy-converting system in the myocardium, an experimental in vitro model was developed which consisted of contractile protein (myosin B) and mitochondria (Mit) prepared from canine cardiac muscle. In this system, ATP produced in Mit from added ADP caused the superprecipitation of the myosin B (My-B). One hour after the onset of experimental myocaridal infarction in the dog, the superprecipitation was very low in the system if Mit prepared from the infarcted myocardium were used, regardless of the origin of the myosin B. The respiratory control index of Mit prepared from infarcted was lower than that from noninfarcted myocardium, but the ADP:O ratio in Mit from infarcted myocardium, was little deteriorated. The findings indicate that a transferring process of an energy source from Mit to myosin B was markedly impaired in the infarcted myocardium. They also throw light on the mechanism by which the myocardium ceases its contraction at an early stage of infarction.


Correlation between coronary venous inosine concentration and myocardial wall thickening during regional ischemia. Correlations between local mechanical and metabolic events were studied during partial decrease in flow in the left anterior descending coronary artery in the open-chest pig. During ischemia, systolic ventricular wall thickening decreased. Concomitantly, the concentration of inosine, hypoxanthine, lactate, and potassium in the regional anterior coronary vein increased, whereas the concentration of these compounds in the femoral artery did not change. A negative correlation was observed between the venous inosine concentration and the decreased myocardial wall thickening during ischemia. This study indicates that the local venous inosine concentration is a sensitive indicator of regional myocardial ischemia in the pig.


Correlation between biochemical and contractile changes after myocardial ischemia and revascularization. Regional contractility measured as myocardial fiber shortening ceased 15-30 sec after coronary occlusion; myocardial ATP content was unaltered at this time. Contractility returned promptly if occlusion was released within 45 min. With occlusion of 1-3 hr, delayed recovery of contractility was observed 2 weeks after reperfusion; the extent of recovery diminshed with increasing period of occlusion. Concomitantly, there was parallel recovery of synthesis of ATP and creatine phosphate (CP) in reperfused myocardium.


Release of (14C) adenosine from the guinea pig heart during autoregulation. The radioisotope method applied in the studies presented appears to be of particular advantage for the sensitive measurement of changes in adenosine release from the myocardium. The data obtained provide evidence that conditions which alter the oxygen supply to the heart such as lowering the perfusion pressure, temporary interruption of coronary inflow, and reducing oxygen content in the perfusion medium are accompanied by an enhanced release of adenosine. These results further support the concept that adenosine is a mediator in the regulation of coronary flow.


Creatine release from the isolated perfused rat heart. Creatine release from the isolated perfused rat heart decreases during the first 40 min of perfusion to a constant rate which is maintained for at least a further 50 min. Reoxygenation after a period of 15 min of anoxia is accompanied by an increase in creatine release. The highest rate of release occurs during preperfusion after the excision of the heart. These losses might contribute to impairment of function after anoxia.


Uptake and phosphorylation of (14C) creatine by mouse cardiac muscle in vivo. Tracer doses of [1-14C]creatine were given intravenously to mice and the total activity of cardiac muscle compared with skeletal muscle and diaphragm were determine periodically thereafter for up to 5 days. An inverse relationship was found between the rate of uptake, i.e., turnover of creatine in vivo and total muscular creatine, cardiac muscle exhibiting the most active turnover of all muscles. Similarily, the in vivo labeling of intracellular creatine phosphate of cardiac muscle proceeded at a rate much faster than in skeletal muscle. Hypoxia (10 percent O2--90 percent N2) during the equilibration of the pulse label inhibited both the uptake of creatine and its intracellular phosphorylation. We suggest that the rapid metabolism of creatine is related to the predominance of mitochondrial oxidation in cardiac muscle, creatine serving as a carrier of high energy phosphate groups from mitochondria to myofibrillar ATP and reflecting a directed intracellular energy flux.


Myocardial high energy phosphates in experimental thyrotoxicosis in guinea pigs. Experimental thyrotoxicosis was produced in guinea pigs by daily intraperitoneal injection of 0.7 mg/kg thyroxine (T4) or 0.15 mg/kg triiodothyronine (T3), as shown by an increase of PBI over 50 gamma percent, weight reduction of 20--30 percent, and increase in heart rate of 30--50 percent. Control animals received solvent only. Metabolites were determined in heart muscle on the 1st, 3rd, and 7th day using freeze-stop technique and enzymatic methods: creatine phosphate (CP), ATP, ADP, AMP, glucose 6-phosphate (G-6-P), fructose diphosphate (FDP), pyruvate, lactate, and inorganic phosphate (Pi). In thyrotoxic animals there was a decrease in CP which became significant after 3 days and more pronounced after 7 days. The ratio of CP to Pi decreased. G-6-P and FDP levels increased. The results were identical after administration of T4 and T3. ATP decreased slightly and ADP increased slightly after T4. Propranolol up to a dose of 3 mg/kg or practolol up to 10 mg/kg given daily i.p. on the 4th to 7th day did not prevent either the T4-induced decrease in high energy phosphates or the increase in G-6-P.


Effects of changes in the concentrations of substrate and oxygen on the perfused rabbit heart. Rabbit hearts were perfused with bicarbonate-buffered fluid containing 1.0 mM glucose and 1.5 mM lactate. Pairs of redox substrates were measured in the perfusion fluid and the heart after perfusate concentrations of beta-hydroxybutyrate (beta-HB) and oxygen were varied. The perfusate lactate to pyruvate ratio was shown to accurately represent the tissue ratio. The intracellular redox state varied independently of changes in substrate uptake. Increasing perfusate beta-HB concentration caused increased beta-HB uptake, decreased lactate uptake, and unchanged glucose uptake. Decreased perfusate oxygen tension caused inhibition of lactate and beta-HB uptakes and, when exteme, caused increased glucose uptake. The combination of a modest reduction in oxygen tension and increased perfusate beta-HB concentration caused a more reduced environment in the tissue than either change by itself. This combination of changes may have additive deleterious effects as suggested by clinical observations.


Utilization of endogenous lipids and glycogen in the perfused rat heart: effects of hypoxia and epinephrine. The interaction of hypoxia and catecholamines in the regulation of heart tissue lipid and glycogen utilization was studied in isolated perfused rat hearts with lipids prelabeled in vivo with [1-14C]palmitate. In well oxygenated hearts, epinephrine stimulated triglyceride mobilization by approximately 2-fold. In hypoxia, net mobilization of triglycerides was negligible with or without added epinephrine. Thus, the effect of hypoxia to reduce triglyceride mobilization would favor the accumulation of neutral lipid in the myocardium Glycogenolysis was markedly enhanced in hypoxic hearts and epinephrine produced little further stimulation. In well oxygenated hearts, epinephrine increased glycogen mobilization by 3-fold.


Transmural gradients in the ischemic dog left ventricle: metabolism of endogenous triglycerides and glycogen. Regional differences in glycogen and triglyceride metabolism were found in the ischemic dog left ventricle. Under these conditions, the subendocardium was characterized by a faster rate of glycogenolysis and the least ability to mobilize tissue triglycerides relative to subepicardial and midventricular zones.


The uptake of free fatty acid in the rat heart. During the perfusion of isolated rat hearts with [1 - 14C]palmitate or [1 - 14C]oleate the rate of incorporation of label into lipids is greater in the microsomal fraction, less in the mitochondrial fraction, and least in the cell sap fraction. The degree of esterification is greatest in the microsomal fraction and greater for oleate than for palmitate. There is an early and high degree of labeling of phospholipid in the microsomal fraction. The specific activity of mitochondrial free fatty acids is higher than that of microsomal or cell sap free fatty acids.


Effect on myocardial metabolic pattern of local complete and incomplete ischemia. After local complete ischemia at normothermia of 60, 100, 140, and 180 min duration the status of the adenylic acid-creatine phosphate system in the canine myocardium recovered to 98, 85, 74, and 30 percent of the control values, whereas glycogen was restored even more. In the infarcted myocardium the extent of alterations of the metabolic status was a function of the residual blood flow. Deviations from a regular metabolic status developed if the blood flow dropped below about 35 ml/min/100 gm. This critical flow rate is expected to vary with the energy requirement of the heart, but it is in keeping with results obtained by Rudolph and coworkers (personal communication) who found that patients with a myocardial blood flow below 30 ml/min/100 gm had a life expectancy of less than 1 month. In the nonaffected myocardium, both in experiments with local complete ischemia and in experiments with infarction, the metabolic status was always within normal ranges. This is in contrast to results published by Gudbjarnason (1971/1972) and Gudbjarnason, Puri, and Mathes (1971), who found that in noninfarcted myocardium tissue levels of ATP and creatine phosphate decreased to about 50 percent of the control values and that there was no restoration to normal values within 10 days after infarction.


Metabolism of norepinephrine in noninfarcted heart muscle after experimental myocardial infarction. A marked, reversible decline in cardiac norepinephrine (NE) stores was noted after experimental myocardial infarction. Uptake and accumulation of tracer dose of dl-[7-14C]norepinephrine appeared to be unchanged as well as the rate of degradation. Despite marked variations in pool size the subcellular distribution appeared to be unchanged, and no preferential uptake into any subcellular fraction was observed.