[The proline content of Sardinian wines (author's transl)]. It has been carried out a study relating the contained in Prolina of Sardinian wines. By the results obtain it has been possible to record that the 5% of samples has a contained in Prolina below 100 mg/1, 29% between 100 and 300 mg/1, an other 29% between 300 and 500 mg/1, the 30% between 500 and 800 mg/1 and 7% has a contained in Prolina superior 800 mg/1.


[Progresses in the concentration of foodstuffs (author's transl)]. The article reports a description and a comparison of three concentration techniques: evaporation, freeze-concentration and reverse osmosis. The discussion is particularly concerned with the problems of aroma losses and retention and, for evaporation, the problems of heat damage and fouling. The increase in viscosity with concentration and the markedly non-newtonian behaviour of most food products are such that only evaporation allows to achieve high concentrations. The major progresses in evaporation plants and techniques are discussed in terms of heat transfer efficiency and residence time. Freeze-concentration and reverse osmosis are suitable for pre-concentration up to 30-35 10Brix of heat sensitive and aromarich products


[Chemical and nutritional evaluation of commercial bakery products for children (author's transl)]. Various bakery products, differing in either composition or processing, all widely consumed in Italy by school children, have been studied. Protein, lipid, reducing and total sugars, amino acid and available lysine contents have been determined, as well as biological parameters have been calculated to verify hypotheses about growth factors. The products examined have low protein biological value and the proteins are considerably demaged by technological processing. Lysine, always the limiting amino-acid in these proteins, is shown to be unavailable in percentages varying from 20 to 60% of the total lysine. Upon describing growth as a function of protein content, the correlation improves considerably. Furthermore, when this variable, protein content, is associated with the corrected chemical score in a linear model, the correlation reaches even higher values.


[Progresses in the preparation of protein hydrolysates for the treatment of diseases related to aminoacid metabolism disorders (author's transl)]. A method is described for the preparation of a protein hydrolysate to be used in diets for the treatment of the diseases primarily related to disorder of amino acid Metabolism. The method is based on the use of ion-exchange resins to avoid the use of mineral acids so that the time of hydrolysis is reduced to 7 hrs and aminoacids destroyed in the usual industrial preparations are protected. Yields of 70% are obtained with an hydrolysis ratio of 90%. These results allow the preparation of hydrolysates with a high chemical score in which the aminoacid responsible for the diseases primarily related to disorder of amino acid Metabolism symtoms have been removed.


[Serum free aminoacid levels in a group of hyperuricemic subjects from the Aosta Valley (author's transl)]. The behavior of serum free aminoacids has been analyzed in a group of 31 hyperuricemic subjects and in a control group of 26 normal subjects. In the hyperuricemic males it has been observed a remarkable decrease of glycine and arginine values, while in the hyperuricemic females it has been noted a decrease in serum glycine and serine. The results are discussed.


[First results of varietal comparison and nitrogen fertilization of rapeseed in Italy (author's transl)]. Some experiments of varietal comparison of various cultivars of rapeseed were carried out, determining the productivity, the oil yield and the analytical characteristics of the oils. Moreover the effects of nitrogen fertilization on the seed production and on oil characteristics were tested. The achieved results have pointed out that, referring to the chosen environment, the cv. "Matador" and "Leonessa" show the highest seed and oil productions, whereas oils extracted from the cv. "Sinus", "Erusine" and "Sinera" contain the minor quantities of erucic acid. It seem that nitrogen fertilization exerts no appreciable influence on rapeseed oil composition. The possibility of the utilization of cv. with law content in erucic acid confirms the practical validity of the cultivation of rapeseed as on oil plant.


[The cholesterol level of egg yolk. A review (author's transl)]. The author, on the basis of research conducted over the last thirty years, demonstrates that the cholesterol content of the egg yolk is 20% less than the level assumed in Italian and French law and based on outdated research. She also shows that the level varies for genetic and environmental reasons and also according to the method of analysis. Finally it is demonstrated that hens' eggs contain much less cholesterol than those of other fowls.


[Progress in food technology: sterilization processes (author's transl)]. The results of the investigations on the behaviour of micro-organisms begun in about 1920 and deepened in more recent years, together with a better knowledge of the mechanism of heat, penetration, have been the basis for the conception and the realization of a large number of sterilization processes, sterilizers and containers allowing a quicker heat exchange to be obtained and higher sterilization temperatures to be used, with the manufacture of preserved food of better quality as a result. Aseptic filling processes, continuous sterilizers with the a can kept rotating or agitated by different means, heat exchangers with mixing of heating medium and food, scraped-surface heat exchangers and containers made of aluminium plastics laminates are being used more and more extensively. The improvement of heat sterilization processes has enabled the use of chemical preservatives to be reduced and to be limited to those surely fase for the health of the consumer. Sterilization by ionizing radiation, which seemed to be so promising at birth, has marked time in these last years and because of the doubts raised as to the harmlessness of radiation-treated foods and other drawbacks it has a present no prospects of application on a commercial scale.


[Rapeseed oil: nutritional aspects and safety considerations (author's transl)]. In this review data are reported on the effects of rapeseed oil feeding to several animal species (mice, pigs, rats, guinea pigs, ducklings, chickens, turkeys) with particular regard to its nutritional value as compared to other vegetable fats, and to physiological and pathological modifications on different organs and tissues, namely: gonads, adrenals, thyroid, liver, myocardium. Finally, the results obtained after administration of regular rapeseed oil (i.e. with high levels of erucic acid) are compared with those obtained using the modern types Canbra, Span, Oro, Zephir (i.e. with low levels of erucic acid). From this comparison it could be inferred that erucic acid could be the major responsible for the observed modifications, but also that other long chain monoenes and the altered ratio between saturated and monounsaturated fatty acids might have a certain degree of pathogenic effects, although in this case the lesions appear later, are less frequent and less severe.


[Chemical characteristics of "artificial wines" (author's transl)]. A wide investigation has been carried out in order to evidenciate the differences of composition between "artificial wines" and genuine wines. "Artificial wines" have been produced by fermentation of mixtures of different amounts of wine making by-products (less, pomaces and press-wines), water and sucrose. The results showed, in particular, that "artificial wines" have a very low content of both malic acid and proline and a high content of nitrates. Significant differences have been also found in the content of polyphenols, alkaline and alkaline  earth metals and citric acid.


[Level of red blood cell phosphorilated compounds in nutritional anemias (author's transl)]. This paper deals with the determination of red blood cell phosphorilated compounds, by automated ion exchange chromatography, in clinically healthy subjects, in two patients with hypochomic iron deficiency anemia and in four patients with macrocytic folic acid deficiency anemia. In the cases of nutritional anemia examined significant variations in the level of glycolitic phosphorilated compounds have been observed. The total acid-soluble phosphate content presents a marked increase in patients with anemia, compared with clinically healthy subjects. Very high increase in the 2,3 DPG, F1, 6DP, R5P, G1, 6DP and IMP red blood cell content is observed. On the contrary, ATP red blood cell concentration presents a marked decrease in all the patients.


[A study of N/H2O ratios in Sprague-Dawley rats under variable conditions and its use for routine NPU determinations (author's transl)]. Nitrogen to body-water ratios were determined in a colony of rats of the Sprague-Dawley strain in order to investigate variations under variable conditions of age and diet. The study was conducted in order to verify the accuracy of body Nitrogen calculation from body-water determinations for the given colony under different experimental conditions. Only male animals were studied. The effect of age was studied for the intevals of 21, 28, 31, 42, 51, 84, and 126 days. N/H2O ratios were shown to increase exponentially with age within the range taken in consideration. Separate regression equations are given for 21 to 31 and for 31 to 51 day old animals relating the N/H2O ratio with age. The relationship between quality and quantity of protein of diets and the N/H2O ratio was investigated in 21 to 31 day old animals only. The N/H2O ratio was significantly higher in the animals fed the protein-free diet and diets with NPU less than 40. For these groups the factor 4.12 was obtained. Animals fed diets with NPU's ranging between 50 and 80 gave a factor of 3.94. For diets with NPU ranging from 50 to 80, the variation of the dietary protein level between 10 and 18% did not appear to influence the N/H2O ratio. NPU values calculated from analitically determined body Nitrogen were compared with NPU value calculated from body Nitrogen estimated using the established N/H2O ratios. The two sets of values are in good agreement supporting the use of the short-cut method for routine NPU determinations, given the appropriate factors are applied. It is recommended that such factors be experimentally determined for each own colony of rats.


[Vitamin "A" and biological membranes. Nota V - Fatty acid composition of erythrocyte stroma in vitamin A deficient rats (author's transl)]. Two groups of albino male rats, were fed for 90 days with a balanced and vitamin A-free diet rispectively, to observed changes, if any, in the fatty acid composition of erythrocyte membranes. The blood was separated with heparin, total lipids from erythocyte stroma were extracted and fatty acids analyzed by gaschromatography. It was noticed an increase in saturated fatty acids; at the same time mono- and, above all, polyunsaturated fatty acids decreased; the results agree with those obtained in rats fed for 30 and 60 days with Vitamin A-free diet as similar changes were observed in liver mitochondrial membranes of the rats, under study, we presume vitamin A modifies, to some extent, the biosyntesis of unsaturated fatty acids.


[Bruises behaviour in canned cling peaches (author's transl)]. Undamaged cling peaches, cv. "Halford", were artificially bruised in three positions of the halves exerting a pressure of 2, 4 and 6 kg/cm2, with a hand penetrometer. These peaches were canned at different times (2, 4, 8 and 16 hours) and stored for five months. The halves were then submitted to a "panel test" which revealed that all the bruised fruits were suitable to give rise to a good canned product.


[Anthropometric nutritional status and food habits of students of the secondary schools of Umbertide (author's transl)]. A survey has been carried out on anthropometric nutritional status and food habits of students of the secondary schools of a little town of Umbria that is now in an economic development. The anthropometric data (body weight and height, skinfolds, diameters, muscle and fat areas and body mass index) show that in the girls the body fat mass is higher than in boys and american girls of the same age. The boys of professional men are fatter than the boys of workmen. The survey of food habits (using the method of frequency of occurrence for three days) shows that milk, eggs, legumes and cheese are not frequently consumed, while meat (particularly beef and veal), alcoholic beverages, animal fats and sucrose occur rather frequently in the diet. The excess of body fat mass and the biological and economic errors in the diet of these children need to be corrected with a nutrition education program. It is well recognized that both diet and physical activity play an important role in the prevention of metabolic degenerative disease and this prevention has to be started as early as possible.


[Role of tryptophan in the physiological regulation of brain serotonin synthesis (author's transl)]. Tryptophan hydroilase in brain, normally is not saturated by its substrate; therefore the rate of tryptophan hydroxilation in brain is controlled by the concentration  of tryptophan. In the other hand, brain tryptophan content is controlled by the ratio of the concentration of free tryptophan (i.e. not bound to serum proteins) to that of the other circulating amino acids, wich compete for the same transport mechanism from blood to brain. The administration of an amino acid mixture, containing all essential amino acids but not tryptophan, caused a parallel depletion of total and free serum tryptophan and of tryptophan and serotonin in brain. The mechanism of the observed fall in serum tryptophan is a rapid removed of endogenous tryptophan from circulation, secondary to an increased incorporation of tryptophan into proteins by the liver. These results suggest the hypothesis that brain serotonin synthesis is controlled by a perpherical mechanism.


[A gaschromatographic method proposed for sorbitol and sucrose determination in musts and wines (author's transl)]. A rapid method for sorbitol and sucrose determination by gaschromatography of their trimethylsilylderivatives is proposed. Gaschromatographic constants of these compounds are given and method riproducibility has been evaluated.


[Saturated fatty acids determination by GLC after TLC separation (author's transl)]. The determination of fatty acid composition of oils and fats by conventional GLC on polar columns gives satisfactory results for most of the applications. Higher precision is, however, desirable when the content of minor components is of interest. A typical example is the quantitative determination of the percentage of peanut oil in a seed oil mixture, on the basis of the content of lignoceric acid (n-C21). Lignoceric acid, wich is containen in peanut oil in the amount of 1-2%, shows, on polar columns, a very long retention time and, owing to its low percentage, flat and non well measurable peaks. A method was therefore developed which allows an accurate determination of all saturated fatty acids, particulary of those with high molecular weight. The method is based on the separation of satured fatty acids by argentation TLC followed by GLC determination on non polar columns.


[Problems relative to food industries waste water and their available solutions (author's transl)]. In this paper some practical considerations concerning food industries waste water are reported with the view to reduce global pollution and obtain a better utilisation of water supply. General principles and particular options leading to the realisation of an optimal depuration proceeding are set forth, followed by the illustration of some problems connected to waste water issues as well as means actually used for depuration in some typical food industries.


[Level and stability of resistance to SO2 in wild strain of Saccharomyces ellipsoideus (author's transl)]. We have determined the level and the stability of the resistance of SO2 of yeast strains isolated in highly sulfitated musts. The resistance to antiseptic decreases during the storage and successive transfers of strains.


[Techniques for nutrition education in particular for maternal and compulsory schools (author's transl)]. After an introduction on the various factors involved in food habits of humans, the A. is calling the attention on the importance of nutrition education, examining then some of the programs in use. Already in the maternal school the child can learn nutrition with applicative plays. It is compulsory to teach and follow also the in parents. For the compulsory school the nutrition should be taught as such or integrated in other courses as geography, history, mathematics and science. For adults the deep-seated food habits are making more difficult the educational programs. For successful results in nutrition education is essential that the programs are well planned and carried out from well trained personnel not only in nutritional sciences but also in education, cultural anthropology, psicology and sociology.


[Consumer available margarines in Italy. Note 1: Fatty acid composition and trans-isomers content (author's transl)]. The most used consumer available margarines in Italy, showed important differecens regarding composition of the saturated (S.F.A.) and trans-unsaturated (T.U.F.A.) fatty acids. The ratio S.F.A./U.F.A. correlated well to the T.U.F.A. content. The margarines with the higher U.F.A. values presented also the higher T.U.F.A. values and corresponded to those prepared from a single seed oil (peanut, corn, sunflower). The monounsaturated fatty acids are composed of a mixture of geometrical and positional isomers with the unsaturation at any C atom between C6 and C16.


[Sprout inhibition by radiation and chemical treatment in four potato cultivars (author's transl)]. Irradiated and chemically treated potatoes were then stored at 10 degrees C and 80-85% relative humidity. Radiations caused complete inhibition of sprouting and for up to 10 months after harvest the physical and chemical condition of the potatoes remained satisfactory. On the other hand chemical treatment controlled sprouting for up to 7-8 months only. Irradiation and chemical condition of the potatoes rotting. Weight loss was higher in the chemically treated samples. Treatment by radiation did not effect vitamin C and niacin content as compared with chemically treated samples. Irradiation did not cause any change in the sucrose and the total sugar content, as compared with chemical treatment. Total and soluble nitrogen contents were not affected by either treatment. The response to both irradiation and chemical treamtments was only slightly affected by varietal factors provided that the potatoes were healthy and mature at harvest time.


[Food protein quality. 4) Effect of technoligical processing on protein quality of baked products for special dietary uses (author's transl)]. On samples of biscuits for special dietary use and rusks has been determined the protein quality with the method of enzymatic ultrafiltrate digest (EUD) at various levels of industrial production. The results have shown that the baking over again process has determined a decrease on the velocity of digestion "in vitro" against the raw material with large variations in availability of various essential aminoacids. Particularly decreased is the lysine, the limiting aminoacid of these food products.


[Determination of residues of chlorinated and phosphorated pesticides on the fruit of Pesaro province (author's transl)]. The residues of pesticides chlorinated and phosphorated on the fruit of Pesaro province at the moment of its immission on the market has been determined. No pesticides has found to have a residue near to toxicity values, but sometimes more than one pesticide has been found on the same sample. This fact, also if not alarming, must be attentively considered in order to promote a better information campaign and therefore a more rational use of those substances.


[Proline content of Italian wines (author's transl)]. Proline content of genuine wines from different areas is usually over 200 mg/1; a sample contained 1.920 mg/1; some samples has shown a lower content, with a minimum of 76 mg/1. No correlationship has been established between proline content and wine origin and age. Spectrophotometric method gives results markedly higher, in some cases, than give ion-exchange chromatogrpahy.


[Knowledge and opinions on sexuality among young French-speaking Belgians]. We shall limit ourselves to the main topics, leaving the appreciation of the questionnaire to the reader. To evaluate knowledge and opinions on sexuality in young french speaking belgian people, we have questioned : 1210 students at the University of Louvain, 773 in A1 official teaching, 819 in superior free non university teaching and 778 young people being recruted by the belgian army. The following conclusions are global. The mean vocabulary score (rated on 18) in these four samples is 13.22, 14.06, 13.57 and 6.40. This score is in students more than double than the score in young recruted people (and this phenomenon remains even if one includes only boys in higher education). The mean score (13.81) for whole students in higher education type A1 is significantly superior to the one from the University of Louvain. The score observed in official technical teaching A1 is also greater in comparison to free A1. It is also true for free A1 in comparison to the University of Louvain. The words relating to contraception are particularly misknown in the four samples. Regarding the mean score (on 38) on sexual knowledge not related to vocabulary, it is 22.61 at the University of Louvain, 22.53 in free A1 education, 23.72 in official A1 education and 18.535 in young recruted army people. The difference in mean score between official higher education and the University of Louvain is significant ; it is also significant between University of Louvain students and whole students from A1 education (mean : 23.11). There is no significant difference between the score for the University of Louvain and the one for higher free non university education. The mean score in the army, inferior to 50 %, is rather lower than the scores for the other samples, even if limited to boys. Again, questions on contraception are generally misknown. The total score (in %) is 63.98 at the University of Louvain, 64.46 in A1 free education, 67,46 in A1 official education and 44.53 in young army recruted individus. The score is about 20 % lower at the center for recruting and selecting in comparison to the other samples, even if one takes boys only. The difference between the score in A1 official education and A1 free is significant. It is also between total score (65.92) in whole students from A1 technical education and the one at the University of Louvain. It is not significant for the scores in A1 free education versus the University of Louvain. All scores in A1 official education are superior to the one for confessionnal education, even university ; the interpretation of this phenomenon is probably comparable to the influence of the variable "religion". Regarding opinions, we will only indicate that for factors expressing love (tenderness sexuality and mutual esteem) and the possible means of sexual contacts (physical pleasure, a way of expressing love and procreation) : 1...


[Intestinal glucose absorption in rats of different ages (author's transl)]. We studied the intestinal glucose absorption in a colony of rats at different ages. The experiment was carried out on animals of the following ages: 3, 5, 10 and 20 months. All rats were fasted 48 hr prior to the administration of 2 ml. 50% glucose solution by an oesophageal sound. After one hour the animals were killed, the intestine was washed with a determinated quantity of distilled water and homogenized, to find out any trace of glucose in mucose cells. Glucose absorption was calculated as the difference between the quantity introduced and that left in the intestine. The results of this experiment show that glucose absorption expressed as mg/100 gm. body weight/hr decrease significantly during the first 10 months, with no marked changes there after. Absorption rapidly increase during the first 16 month, if expressed as mg/hr. This is probably due to a remarkable weight increase without a proportional increase of intestinal length.


[Riboflavin content of commercial samples of alimentary pastes (author's transl)]. By fluorometric investigation on 42 commercial samples of alimentary pastes, it was established that unlawful custom of colouring these food products with riboflavin is no more performed; in fact, the riboflavin content of the sample examined by use was rather uniform and of the same order of that naturally occurring in these products.


The female prostate updated.

The female prostate updated. The paraurethral glands in the female are the homologue of the male prostate. Inflammation in these in the cause of the very common syndrome of so-called 'recurrent cystitis' in women. Obstruction at the bladder neck, although not so common as in men, does occur. An analysis of the age incidence, clinical presentation, investigations, differential diagnosis and treatment of a personal experience of 88 cases is presented. Seven cases were treated conservatively by catheter drainage or urethral dilatation and 77 by perurethral resection using a Thompson cold punch with very satisfactory results.


[Vitamin "A" and biological membranes. Nota VI-Fatty acid composition of liver mitochondrial membranes in vitamin A-deficient rats (author's transl)]. The results we obtained in studying the fatty acid composition of erythrocyte stroma on vitamin A-deficient rats, led us to repeat the experiment on liver mitochondrial membranes. Two groups of albino male rats, of the Wistar strain, were fed for 90 days with a balanced and a vitamin A-free diet respectively. The animals were killed, total lipid from the membranes of liver mitochondria were extracted and fatty acids separated by gas-chromatography. It was noticed an increase in the percentage of saturated fatty acids; at the same time, mono and polyunsaturated fatty acids decreased. The results agree with those obtained in rats fed for 30 and 60 days with vitamin A-free diet. This seems to support the interpretation that vitamin A modifies, to some extent, the metabolism of polyunsaturated fatty acids.


Bioavailability studies with Digoxin-Sandoz and Lanoxin. Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz tablets have been compared with Lanoxin manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to ""new'' Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz  did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.


Bioavailability of phenytoin. A comparison of two preparations. Plasma phenytoin levels were measured in 60 patients under steady-state conditions for a period of six weeks. During the trial, the preparation of phenytoin was changed from Phenytoin BP (Regent) to Epanutin Infatabs. A significant increase in plasma phenytoin levels following the change of tablet was matched by a decrease in the number of seizures.


Bioavailability of four brands of phenytoin tablets. In order to evaluate the bioavailability of four different brands of phenytoin (diphenylhydantoin, DPH) tablets single doses of 600 mg DPH in acid form were given to six volunteers in a cross-over study. A micronized DPH-acid suspension was used as the reference standard. Significant differences between various products were found. The areas under the serum DPH concentration-time curves (AUC) were 26, 59, 68 and 90 per cent of the AUC of the DPH suspension. The peak serum DPH concentrations using the different tablets were 24, 54, 55 and 80 per cent of the peak value of the DPH suspension. It is likely that the differences in bioavailability of the DPH tablets are of clinical significance.


[Coconut (Cocos nucifera L.) and the preparation of a milk substitute]. Coconut (Cocos nucifera, L.) is an abundant product in Brazil. The authors studied the use of the protein fraction to prepare "milk-substitute" beverages. The analyses were made on albumen, copra and cake. Protein coconut extraction was tried with water; NaCl solutions in different concentrations; HCl and NaOH solutions in different concentrations; HCl and NaOH solutions at different pH values. The extracted proteins were analysed for aminoacid composition and chemical score. The best results of protein extraction were obtained with NaCl 1 M solution using the ratio 100:75 (coconut:solution). The extracted proteins were coagulated with trichloroacetic acid and separated with water and analysed for aminoacid composition and solubility.


Inhibition by dopamine agonists of dopamine accumulation following gamma-hydroxybutyrate treatment. The increase in the dopamine (DA) concentration of rat (whole) brain induced by gamma-hydroxybutyrate was inhibited by the reputed dopamine agonists apomorphine, apocodeine, 2-bromo-alpha-ergocryptine, piribedil, ergocornine and 5,6-dihydroxy-2-dimethylaminotetralin. The last three drugs raised DA levels in saline controls. Haloperidol, which decreased DA in controls slightly, prevented any agonist-induced rise in controls. However, haloperidol antagonized only apomorphine and piribedil in regard to the inhibition of the gamma-hydroxybutyrate induced rise in DA; this neuroleptic did not affect the inhibition by the other agonists. It is concluded that these data provide evidence for local receptor control of DA synthesis and that the DA agonists do not act through a common mechanism.


Status report of Mayo Clinic studies.

Status report of Mayo Clinic studies. Described are primary treatment protocols for 1) those patients with gorssly unresectable stage III or IV ovarian carcinoma, considered reasonable candidates for therapeutic trials aimed at the identification of antitumor activity as determined by the regression of objectively evaluable lesions; and 2) those patients with stage II or III ovarian carcinoma, with little or no visible tumor remaining after surgery, considered reasonable candidates for therapeutic trials involving regimens that may delay or prevent the recurrence of clinically apparent disease. Both protocol involve initially a comparison of cyclophosphamide alone with cyclophosphamide plus adriamycin. A third protocol--an activity-seeking study of two new cytotoxic agents, developed to provide secondary treatment opportunities for patients who have failed on one of the primary chemotherapy protocols--is designed to seek evidence of any cross-resistance between cytembena (beta-4-methoxybenzoyl  beta-cis-bromacrylate) and VP-16 (4'-demethyl-epipodophyllotoxin-beta-D-ethylidene glucoside). Data from all three protocols are so far insufficient to allow meaningful analysis of their results.


Ultrastructural changes in the lungs induced by extracorporeal perfusion. The changes induced in the lungs have been studied, in the course of 15 heart operations with extracorporeal circulation. In each case material was obtained from lungs after the thoracotomy, before starting the perfusion and after its termination. The pulmonary structure showed changes against the control material already prior to perfusion, the most conspicuous alternations of the capillary endothelial cells and of the basal membrane. Examination of the surfactant by ruthenium red demonstrated changes in the reaction; from this circumstance the conclusion has been drawn that affection of the surfactant may have a part in the postperfusion syndrome.


[Neo and postnatal development of the cerebral cortex in mice. Ultrastructural study]. Maturation in the Purkinje cell (Pk) of the cerebellar cortex of developing mice (from birth up to weaning) was investigated by structural and especially ultrastructural studies. In comparison to the adult neuron, four developmental stages were identified by studying selective morphological features (shape and size of the Pk, neuronal environment) as well as specific characteristics of neuronal constituants, particularly the "nucleus-ribosome system". The stages are: early, intermediate and late neuroblasts and young neuron. The neuronogenesis of the Purkinje cell can be summarized as follows: (a) the nuclear maturation occurs early in the development and markedly preceeds that of several organelles in the perikaryon; (b) the cytoplasmic maturation extends gradually until the young neuron state was reached. Some structures such as the granular mass and the "spotted body" in the nucleus, the nuclear envelop including its two membranes, and the ribosomal components either free or attached to the Endoplasmic Reticulum seem to exert an important role during neuronal development. Maturation processes in the Purkinje cell are generally similar in both mouse and rat and, except for some morphological and/or chronological variables, comparable in others developing nerve cells. This model of neuronal maturation is used alone or in comparison to another model of neuro-behavioral evolution which was established concommitantly. Both of these models reveal to be very useful for the evaluation of the effects induced in the developing animal following the administration of neuropsychotropic drugs such as Hallucinogens and Narcotics.


[Long-term syndrome in the treatment of parkinsonism with L-dopa]. A group of 71 patients with Parkinson's disease were treated with L-Dopa and benserazide during periods ranging from 27 to 60 months. In 28% of cases a decline in therapeutic effects and or delayed appearance or increase of secondary actions were observed constituting a long-term syndrome. Its most complex and dramatic expression, the on-off effect, was present in 11% of cases. Those patients with more severe symptoms were studied by means of continuous clinical observation enabling the design of daytime follow-up curves. Observations were repeated with varying dosage patterns, showing variations but no substantial changes or disappearance of the symptoms described. Electromyographic recordings and films were taken in certain cases defining the characteristics of on and off effects. Several procedures were implemented in an attempt to control Long-Term Syndrome manifestations: Change of dosage, variation of L-dopa/decarboxilase inhibitor ratio, association of anticholinergic agents with antidepressants, hypoprotein diets. Improvement was moderate and/or transient, with the exception of Nortriptilline which permitted total or partial control of certain symptoms, especially hypokinetic periods, bouts of tremor and dystonic attitudes. It was occasionally necessary to interrupt administration of L-Dopa, readministering it later with recovery of the therapeutic effect and/or avoidance of undesirable effects for varying periods of time. Loss than optimal doses proved beneficial in reducing or postponing Long-Term Syndrome manifestations. Although L-Dopa does not detain the course of the disease, the persistence of favourable results in most patients for prolonged periods of treatment confirms the long-term therapeutic value of this drug.


Immunological enhancement of chemotherapy in advanced brain cancer. Three hundred C3H mice were used to ascertain the validity of treatment of brain cancer with arsenicals and bacterial polysaccharide. It was found that this method of therapy was efficacious. Also, that a prophylactic effect was demonstrated. 2. In  14 patients with advanced intracranial neoplasm it was found: a) that no curative effect could be brought about once the cancer had spread beyond a certain point. This "point of no return" depends on tumor type, location and degree of brain destruction and general state of debility. b) That subjective and even some temporary objective improvement was possible even in advanced cancer. Necrosis of cancer tissue, that could be attributed to the therapy, was found in a number of cases. c) That some cases of brain cancer showed remarkable response to this form of therapy; more so if radiation therapy was given at the time of administration of the arsenical and bacterial polysaccharide. d) That some cases of brain metastasis showed "complete" destruction of the neoplasms in the brain although the patient subsequently died of the primary neoplasm and multiple metastasis. e) That the principle of enhancing the deposition of the curative material in the neoplasm by the use of bacterial polysaccharide is valid. f) That if this method of treatment (i.e. arsenical, bacterial polysaccharide and radiation) is instituted in the "early" cancer cases we may find it to be an efficacious mode of attack. g) That aresnical by mouth and bacterial polysaccharide by I.M. injection may be useful as a prophylactic to the formation of cancer. This may be contemplated for use in families that seem to show a predisposition to cancer formation. A mode of administration would probably be somewhat similary to the maintencance therapy described in the body of this paper. h) That bacterial polysaccharides have been shown to have the ability to destroy cancers.3,9 This method of enhancing the patients antigen-antibody reaction may eventually be used as a means of gaining an efficient vaccine in cancer therapy. i) Wherever possible definitive surgery should be carried out before the arsenical-bacterial polysaccharide-radiation method is instituted. j) In brain cancer, after craniotomy with removal of all or part of the neoplasm where feasible, the patient should be left with a subtemporal decompression. This will allow for the oedema of the brain that occurs with cerebral radiation therapy. k) That the principle of destruction of the cancer by certain special substances is valid. That the increase of affinity between cancer and destructive (curative) material can be brought about by administering a bacterial polysaccharide at the same time and that radiation therapy may enhance the beneficial effects of this method. 1) That the principle of brining the greatest toxicity to the cancer cells and the least toxic effect to the organism has been applied in the use of this method of treatment. m) That in some cases the cancer may not be destroyed by this therapy but may be made to retrogress or be held in check.


[Controlled hypotension with sodium nitroprusside in surgery for cerebral aneurysm]. Sodium nitroprusside given by intravenous drop was infused in 10 patients with cerebral aneurysm in order to achieve the controlled hypotension. The easy beginning of the hypotension was consisted as well as the evanescent action of the drug and the abscense of collateral effects. Morbility and mortality differences were not seen between our cases and those in which normotension was used.


Inclusions in the sural nerve in metachromatic leukodystrophy. A 2 year old girl develops a fever, anorexia and a cough which last three weeks. Following this event, she presented with intention tremor and increasing difficulty with crawling. At the age of 3, a nerve biopsy was done which made the diagnosis of metachromatic leukodystrophy. EM examination of the nerve biopsy revealed large quantitites of abnormal structures in the cytoplasm of Schwann and phagocytic cells. Virus like spheroid bodies were present in a few axons and cytoplasm of Schwann cells.


The lipids of human sciatic nerve by age group. Lipid analysis of normal human peripheral (sciatic) nerve in 18 cases revealed suggestive evidence of quantitative changes in phospholipids and glycolipids at the extremes of life. Total phospholipids were highest in the newborn and lowest over 65 years of age, while glycolipids were lowest in the neonatal period. Cholesterol did not vary with age. Analysis of the major phospholipid components showed their percentage distribution to be age stable, and phosphatidyl serine to be enriched at all ages. The biochemical findings indicate loss of axonal-myelin constituents after 65 years of age. They correlate with histological and physiological studies on peripheral nerve and with the role of the acidic phospholipids as membrane cation-transporters.


Interictal reactivity disturbances in temporal lobe epilepsy. The electrographic study performed on 106 patients with temporal lobe epilepsy and 31 normal subjects showed marked interictal cerebral reactivity disturbances in this form of epilepsy. These disturbances, estimated by testing the orienting reflex and its habituation, were expressed, as a rule, by intensification of somatic, autonomic and electroencephalographic components of the reaction, increase in their resistance to habituation and change in the sequence in which they become habituated. The severity of reactivity disturbances depended on the localization of electroencephalographic focus, clinical form of seizures and characteristics of interictal electroencephalographic abnormalities. The most marked reactivity disturbances were noted in patients in whom the interictal foci were bitemporal, anterior or predominantly anterior (particularly left), accompanied specially by generalized or generalized + partial seizures or by interictal graphoelements of the irritative type. The reactivity disturbances were less severe in epileptics in whom the interictal foci were unitemporal (particularly right), middle, predominantly middle, posterior or associated to partial seizures. In a few patients in whom the interictal bioelectrical activity reflected a nervous hypoexcitability, the reactivity disturbances assumed the appearance of hyporeactivity. The different intensities of reactivity alterations in temporal lobe epilepsy should be related to the different capacity of the epileptogenic lesions to determine interictal changes in diffuse excitability. This capacity depends on he structures involved by the epileptic discharges, which by their morpho-functional particularities, can influence the cerebral excitability.


[Epidemiologic study of myasthenia in Uruguay]. During the period 1960 to 1976 170 cases of myasthenia were analyzed in the Laboratorio de Afecciones Neuromusculares del Instituto de Neurologia de Montevideo. This is an epiderom the total), pregnancy, surgical treatment (Thymectomy, 6%), lethally (13%). It is concluded that myasthenia is an unfrequent disease, with female prevalence (58%); between 30 to 70 years, starting by oculomotor signs (74%) and of severe prognosis in 24% of cases.


[Comparative study of the cognitive functions and symbolic order in temporal and centerencephalic epilepsy of long development of difficult therapeutic control]. The paper is centered in the comparative study of three groups of long-term epileptic patients in which therapeutic control is difficult to achieve, by means of several neuropsychological tests evaluating levels of intelligence, memory, language and praxis. Paget's tests of conservation of physical quantities revealed no significant differences in results obtained from the exploration of operative levels between epileptics with right temporal, left temporal or centrencephalic electroencephalographic foci. There is no parallel decrease of operative level when present, and deficit of mnesic functions, which is constantly observed in the three groups and usually evidenced in short-term memory. The graphic representation of projective space (Cube, house), is parallel to operative weakening. No significant relationship between lateralization of focus and graphic performance is observed. Language exploration by means of Benton and Spreen's battery of tests shows distinctly similar results in the three groups of patients. The location of the epileptic focus shows no relevance with respect to language disturbances. The most outstanding pathologic phenomenon is a certain degree of anomia observed in the naming of objects. Its significance is discussed (Slight degree of amnesic aphasia, deficit of evocative memory, or a lexical level in accordance with the operative deficit). The deficit of the repetition of sentences test and in others including a time element should not be ascribed to a specific language deficit. True aphasia was present in only three patients of the left temporal group after prolonged status epilepticus.


[Comparative study of the structural gramatical performance in dyslalic and dysphasic children]. The comparative performance in the repetition of a set of sentences was investigated in 8 children with developmental aphasia, average 5-7 years and 8 dyslalic ones, average 5-3 years. None presented any hard neurological signs. A battery of sentences was devised for repetition purpose and used as stimulus. Production proved to be less advanced in the group of children with developmental aphasia characterized as follows: highly systematic reduction of the models, lack of consistency in the substitutions both on the phonetic and the lexical levels ill-formed constructions in certain types of structures, high percentage of omission of function words. The dyslalic children's performance however proved to be more advanced and the subjects reproduced well-formed sentences in every single sentence regardless of the sentence length or type. The test devised might turn out to be helpful in practice for the correct diagnosis between patients with developmental aphasia and children with multiple and complex dyslalias.


[Bilateral chronic subdural hematoma associated with hypotension of the cerebrospinal fluid]. A case is presented of a bilateral chronic subdural hematoma complicated in the post-operative evolution by a severe brain-stem suffering associated to a CSF hypotension andan angiographic descent of the brain-stem. The whole picture was made reversible by means of intrathecal injections of saline and the Trendelemburg position. The physiopathology of cerebral hypotension is discussed, considering it as an evolution process that implies both a diminution of the CSF and a descent of the brainstem. This process can be initially free of symptoms.


Serum and red cell cholinesterase activity in duodenal ulcer. Sixty-eight patients suffering from active duodenal ulcer (diagnozed radiologically) were examined for serum cholinesterase (50 patients) and red cell cholinesterase (18 patients) activity. In all these patients serum or red cell cholinesterase activity were found to be significantly low when compared with 56 normal individuals (controls). The low level of cholinesterase activity may be regarded as a pathogenic component of duodenal ulcer.


Study of energy expenditure and food intake of some working class people of Bangladesh. No information is available on energy expenditure and dietary intake of Bangladesh population carried out simultaneously. As a preliminary step in this direction, forty volunteers mostly from the low socio-economic groups were subjected to these studies for a 3-4 day period. Indirect calorimetric method was used for the measurement of oxygen consumption and energy expenditure. Actual weighing of food articles were carried out before consumption and values calculated from standard tables. It was found that values obtained during rest like sitting and lying including basal metabolic rate (BMR) fell within values reported in the literature. Resting energy expenditure, however, tended to rise in the later part of the day and the degree of physical  activity carried out by the subjects. Rickshawpedalling required 6.66 Kcal/min to be expended without passenger and 7.84 Kcal/min with two passengers. Cartpulling required 5.5 Kcal/min without load compared to 6.08 Kcal/min with a load of 350 kg. The small difference was obviously due to a reduction in the speed of cartpulling. This was, however, not true with rickshawpedallers. Dietary intake showed that all the subjects were getting a low protein and low fat diet and that carbohydrates were the main source (over 80%) of calories. The doctors were the only group receiving some animal protein and the cartpullars eating almost none. The number of calories taken were consistent with their activities. One rickshawpedaller had an unusually high intake of over 6000 calories daily.


Use of different saprophytic acid-fast bacilli in complement-fixation test for kala-azar. Complement-fixation tests for kala-azar using antigenic extracts from 4 different saprophytic acid fast bacilli were carried out. It was observed that all the 4 extracts gave positive reactions with sera from kala-azar patients. However, Myco. phlei gave best results and next comes Kedrowsky's bacilli. These two are different strains of the same organism, Myco. phlei. Myco. smegmatis also gave satisfactory results but Myco. butyricum gave weak and false negative reactions in some cases. Last two organisms are the different strains of the same Myco. smegmatis.


Cirrhosis of liver in Bangladesh. (A preliminary report). The incidence of cirrhosis of liver in Bangladesh, its possible aetiological factors and clinical features have been studied. This being the initial report, embraces the population of only two hospitals in Dacca viz., Institute of Postgraduate Medicine and Research (P.G. Hospital) and Sir Salimullah Medical College Hospital situated three and a half kilometers apart. In a population of 5889, a total of 154 cases (2.6%) of cirrhosis of liver have been recorded. Nutritional deficiency has been considered to be the important aetiological factor whereas alcoholism does not appear to have any significant role. Almost all the cases (94.2%) were non-alcoholic. Pattern of clinical features have been compared with those of other authors and variations recorded. Further study on an elaborate scale has been suggested.


Cerebrovascular diseases. (A report of 53 cases). Fifty-three patients suffering from cerebrovascular disease admitted to the Neurology unit of the Institute of Postgraduate Medicine and Research, Dacca, have been analyzed. It has been observed that the age incidence, sex ratio, causes and clinical pattern of cerebrovascular diseases are similar in developed and developing countries.


Some aspects of psychiatric morbidity in the out-patient population of a general hospital. A preliminary report on certain aspects of psychiatric morbidity in persons attending the medical out-patients department of the Institute of Post-graduate Medicine, Dacca, have been presented. Out of 652 cases who have been interviewed, 31% had purely psychogenic conditions, 45% were suffering from purely organic diseases and 14.8% complained of symptoms of both organic and psychogenic features. No apparent underlying aetiology have been detected in 8.6% of cases. Of the psychogenic group, neurotic disorders comprised the  largest number in the sample; anxiety state and sexual neurosis in males were the commonest neurotic disorders. When the mixed groups are included, 44% of males and 49.8% of females had symptoms which were either purely psychogenic in nature or had conspicuous psychogenic component. Reason for such a high percentage of psychogenic component has been discussed. Most of the patients attending the out-patient department were within the age of 21 to 40 years. Attendance in the number of older age persons were less in the psychogenic group than with organic conditions. Further, in females a significant difference was observed between psychogenic and organic group patients above and below the age of 40 years. Patients younger than 40 years were more in purely psychogenic group compared to organic conditions. Most of the patients have been found to be married both in psychogenic and organic group. However, there was significant difference in attendance rate of single males in the psychogenic group were somewhat over-represented in the sample in comparison to purely organic group. There was no relation of marital states in cases of females.


Incidence of important blood groups in Bangladesh. Different blood groups were determined in the Bengalee population. The prominent blood group was B in the ABO system, Rh. D negative was only 2.56% whereas Kell was 0.8%. These results have been compared with the Caucasians, Chinese and the Negroes.


Ulcerative colitis in Bangladesh.

Ulcerative colitis in Bangladesh. A total of 100 cases with chronic diarrhoea having no apparent cause were investigated. Fifty seven of these cases fulfilled the diagnostic criteria of ulcerative colitis. Fortyone of these 57 patients were treated for acute amoebic dysentery during the initial episodes of their illness. Since attack of acute amoebic dysentery is liable to produce post-dysenteric ulcerative colitis, it is possible that ulcerative colitis exist in this country in at least 2 forms, idiopathic and post-dysenteric.


Incidental discovery of an unusual secretor status of patient group A2B with anti-A1 antibody in the serum. A variant of AB blood group (A2B) in a patient is described. Anti-A1 agglutinin was demonstrated in the serum and the saliva of secretor contained BH but no A substance. This is the first report of abnormality regarding  secretor status of group A2B, individual from Bangladesh.


Cholelithiasis--areview of 130 cases.

Cholelithiasis--areview of 130 cases. One hundred and thirty cases of cholelithiasis were studied in the surgical wards of the Institute of Postgraduate Medicine and Research, Dacca. Geographical distribution, pattern of clinical features, results of biochemical, microbiolgical, histopathological and other investigations have been recorded.


Malignant neoplastic lesions in Bangladesh (an analysis of 2064 cases). Analysis of 2,064 cases of malignant neoplasms was done to determine the male/female ratio and site distribution. Attendance of female patients with malignant conditions were less in number and the male/female ratio was 2.3:1. In the females malignant neoplasms of the sex organs (cervix uteri and breast) were more prevalent and in the males malignant neoplasms of the trachea, bronchus, lungs, larynx and oropharynx were more frequent.


Menstrual regulation (M.R.) service (a preliminary report). One hundred and twentythree women utilised the M.R. service at the Out-Patients Model Clinic at Mohammadpur and at a privately owned clinic. The pertinent data about these clients are discussed.


Brain-weight/liver-weight ratio as an index of nutritional status in perinatal deaths. Brain-weight/liver-weight ratio has been suggested to be a good indicator of nutritional status in new-born babies. But no evidence except low blood sugar and low hepatic reserve of carbohydrate have been presented to support this. In the present study babies dying in perinatal period have been compared by dividing  them arbitrarily into two groups according to a fixed B/L ratio of 3.5. The results showed that the nutritional status of babies with high B/L ratio was comparatively poorer than babies with normal B/L ratio in terms of weight, length and hepatic reserve of iron, folate and vitamin A, and thus provide evidence to the hypothesis.


Chrysotile asbestos: biological reaction potential. Evidence is presented indicating that chrysotile asbestos induces rapid cellular ageing in lung fibroblast cultures. Depending on the dose of asbestos given to these cultures the formation of fibrous collagen is enhanced or suppressed. The reaction of chrysotile at the cellular and molecular level is discussed and is considered to be determined by the organic coating it receives or the manner in which the surface absorbed material is modified. Studies are included of the ability of chrysotile to adsorb and retain serum proteins, pulmonary surfactant and lysosomal enzymes. Finally, a critical appraisal is given of the theories accounting for chrysotile-induced fibrogenesis particularly related to the lung fibroblast system studied.


Tryptophan metabolism and recurrence rates of patients with breast cancer after mastectomy. Women with early breast cancer were given a loading dose of L-tryptophan after mastectomy and a comparison made between their excretion of metabolites of the kynurenine pathway and the rate of recurrence of the disease.


The excretion of 3-hydroxyanthranilic acid in patients with bladder and kidney carcinoma. In comparison with healthy age- and sex-comparable subjects, a significantly higher concentration of unconjugated 3-hydroxyanthranilic acid was detected in the urine of untreated bladder and kidney carcinoma patients. Because of tryptophan metabolite 3-hydroxyanthranilic acid is suspected to be involved in the carcinogenesis of bladder tumours, it is of importance to know if the concentration will normalize to the level of the control group after curation of the tumours, indicating that the aberration was a result of the disease itself. The first results from a study in bladder carcinoma patients during the follow-up after curation of the tumours suggest a persistent increase in the urinary concentration of free 3-hydroxyanthranilic acid.


The action of 3-hydroxyanthranilic acid and other tryptophan metabolites on stimulated human lymphocytes. Short term cultures of phytohemagglutinin stimulated lymphocytes were used to study effects of tryptophan metabolites of the kynurenine pathway at the cellular level. Only the metabolites 3-hydroxyanthranilic acid and 3-hydroxykynurenine demonstrated an effect when (3H) thymidine was used to monitor the response. Morphological examination of the cultures did not clearly reveal an effect. Because the adenosine triphosphate level was also decreased upon the addition of 3-hydroxyanthranilic acid the possibility is considered that the mechanism of action of the metabolite on cultured lymphocytes can be explained by a suppression of the oxydative phosphorylation.


Studies on tryptophan metabolism in Danish bladder cancer patients. Urinary excretion of metabolites of the kynurenine pathway before and after a loading dose of 2 g L-tryptophan was studied in 31 bladder cancer patients from the Copenhagen area. Only 2 patients (6 per cent) showed abnormal tryptophan metabolism, and both patients excreted increased amounts of only 3-hydroxykynurenine after a loading dose of 2 g L-tryptophan. The percentage of bladder cancer patients with abnormal tryptophan metabolism is compared with the percentage found in other parts of the world. It is suggested that these findings may indicate that tryptophan metabolites do not play a major role in the genesis of bladder cancer among bladder cancer patients from the Copenhagen area. Other etiologic factors should be looked for.


The excretion of tryptophan metabolites in patients with different forms of haemoblastosis. The urinary excretion of kynurenine, 3-hydroxykynurenine, kynurenic and xanthurenic acid has been determined by bidimensional paper chromatography in 61 patients with different forms of haemoblastosis (27 cases of Hodgkin's disease, 10 cases of non Hodgkin's lymphomas, 8 cases of acute leukaemia, 11 cases of myeloproliferative disorders, 5 cases of lympho-immunoproliferative disorders). An abnormal urinary excretion of some metabolites of tryptophan's kynurenine pathway is frequent but not constant in all the neoplasias of the myelolymphopoietic system studied so far. In Hodgkin's disease the correlative test between urinary excretion of tryptophan metabolites and clinical stage, histological type and treatment enabled us to point out that the anatomo-clinical diffusion of the lymphoma interferes only through kynurenine and 3-hydroxykynurenine excretion. The histological type seems to influence the 3-hydroxykynurenine excretion. On the contrary, the metabolic alterations present are not affected by treatment. We believe that the metabolic alteration of tryptophan is secondary to a deficit of pyridoxal phosphate and nicotinamide-dependent enzyme activities.


Effect of phototherapy on the urinary excretion of tryptophan metabolites in neonatal hyperbilirubinemia. The 24 hours urinary excretion of tryptophan metabolites after an aminoacid loading (50 mg/Kg body-weight) was studied in a group of hyperbilirubinemic infants with or without light exposure treatment, in comparison to normal newborn babies. Kynurenine was the main metabolite in the urine of the control subjects. In the hyperbilirubinemic infants a high urinary excretion of kynurenine and 3-hydroxyanthranilic acid was observed. In the ones treated with phototherapy these two substances were markedly decreased. Besides 3-hydroxykynurenine was almost always absent. The effect of the light exposure was studied on kynurenine and 3-hydroxykynurenine "in vitro". Kynurenine did not present any photodecomposition. On the contrary, 3-hydroxykynurenine was easily decomposed. This fact can explain the decreased excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid observed in urine of hyperbilirubinemic newborn infants treated with phototherapy. The decrease of kynurenine in these infants probably is a consequence of the photodecomposition of 3-hydroxykynurenine.


Effects of oral contraceptives on tryptophan metabolism and vitamin B6 requirements in women. To evaluate the effect of oral contraceptive usage on the nutritional requirement for vitamin B6, control women and oral contraceptive users were depleted of vitamin B6 for 1 month followed by a month of repletion with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride per day. At weekly intervals a number of indices of vitamin B6 nutrition were measured. Marked elevation in excretion of tryptophan metabolites occurred in oral contraceptive users after tryptophan loads. However, other indices of vitamin B6 nutritional state, including urinary 4-pyridoxic acid excretion, urinary cystathionine excretion, plasma pyridoxal phosphate concentrations, and erythrocyte aspartate and alanine aminotransferases were not different between controls and oral contraceptive users. The excretion of metabolites after oral loading doses of L-kynurenine (which bypasses tryptophan oxygenase) was elevated in oral contraceptive users indicating that abnormal metabolism of tryptophan was not due only to induced tryptophan oxygenase. The data indicate that use of oral contraceptives does not generally change the requirement for vitamin B6 but rather produces a specific change in activity of enzymes beyond kynurenine in the pathway of tryptophan metabolism.


Research on tryptophan metabolites "via kynurenine" in epidermis of man and mouse. The pattern of tryptophan metabolites "via kynurenine" was determined in the epidermis of man and mouse using semiquantitative method of one- and two-dimensional thin-layer-chromatography. In the epidermis of healthy man the following metabolites were present: tryptophan, kynurenine, anthranilic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, kynurenic acid, nicotinic acid; the same metabolites, with the exception of kynurenine, were present in the epidermis of healthy mouse. In the epidermis of patients with porphyria cutanea tarda and of those with pellagra, the above pattern was modified and resulted similar to that found in the urine. In the epidermis of patients with pellagroid erythema an alteration of "via kynurenine" metabolites was present. In epithelioma tissues all the above mentioned metabolites were increased while in keratoacanthoma were normal. In burnt epidermis xanthurenic acid was present. In the epidermis of mouse with DDC-porphyria the pattern was characterised by absence of tryptophan, anthranilic and nicotinic acids. These data and those obtained by determination of tryptophan-pyrrolase and kynureninase activities are presented and discussed.


Tryptophan metabolism in skin diseases.

Tryptophan metabolism in skin diseases. In a number of skin disturbances conditioned or aggravated by sunlight and/or mainly diffused to the cutaneous connective tissue (present acquired pellagra, lupus erythematosus, porphyria cutanea tarda, actinic reticuloid, Rothmund-Thomson syndrome, lymphocytoma cutis, scleroderma, dermatomyositis, burns, linphomas, parapsoriasis, acrodermatitis enteropathica) excretive changes were found only in the "via kynurenine" metabolites. As a rule kynureniase activity was reduced and tryptophan-pyrrolase activity was increased. In the epidermis tryptophan leads to niacin pathway was found to be present and sometimes autonomous.


Influence of iron and ascorbic acid on tryptophan metabolism in man. South African Bantu patients with a scurvy-type skin, which developed after a prolonged, iron-induced hemosiderosis, were studied with ascorbic acid-1-C14 and the 2 gm tryptophan load test. The metabolism of the two compounds was found to be abnormal in these patients. The data suggested that ascorbic acid was rapidly (iron accelerated) metabolized to monodehydroascorbate, a compound that rapidly reacts with tissue DPNH to form DPN. This mechanism could reduce tissue levels of DPNH such that the feed-back control of tryptophan pyrolase enzyme was depressed. The change in control level of the pyrrolase enzyme permitted large quantities of tryptophan to be converted into the kynurenine pathway products, and a smaller quantity for the serotonin pathway. This mechanism could contribute to the abnormal tryptophan metabolism found in chronic pellagrins with dementia.


Tryptophan metabolism in nervous disease. The paper describes effects of tryptophan loading on tryptophan metabolism in healthy persons as well as alterations of tryptophan metabolism observed in varians diseases associated with nervous symptoms, i.e. Wilson's disease, Hartnup disease, phenylketonuria and acute intermittent porphyria. The results are discussed.


Tryptophan metabolism in various nutritive conditions. In phenylalanine administered rat, tryptophan chiefly metabolized to xanthurenic acid and in nicotinic acid administration to 5-hydroxy indole acetic acid mainly. MAO reaction inhibited by quinoline compound and the inhibition of kynurenine aminotransferase activity through the injection of epinephrine or serotonin were observed. And also the induction of tryptophanpyrrolase in starvation was discussed.


Tryptophan metabolism in the joint diseases. Tryptophan metabolites through kynurenine pathway and 5-hydroxytryptophan pathway in the synovial fluid, blood and urine of patients with rheumatoid arthritis and those with osteoarthritis were investigated in order to know the specificity of the tryptophan metabolism, especially the role of serotonin in the joint diseases. A metabolic map of tryptophan in the synovial fluid was also made. It was found that tryptophan in rheumatoid arthritis was metabolized mainly to anthranilic acid through kynurenine in the kynurenine pathway, whereas in osteoarthritis the pathway of kynurenic acid and nicotinic acid was characteristic. Otherwise in 5-hydroxytryptophan pathway there were no significant differences in the levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid in the synovial fluid between rheumatoid arthritis and osteoarthritis but the activity of monoamine oxidase in the synovial fluid was higher in osteoarthritis than in rheumatoid arthritis.


Tryptophan/nicotinic acid pathway during levodopa treatment of Parkinsonism. The behaviour of some urinary metabolites of tryptophan/nicotinic acid pathway was studied in 7 patients with Parkinson's disease during a 24-day period of levodopa treatment. Corresponding to the appearance of side-effects (agitation, anorexia, dysphagia, glossitis, abdominal pains) in 5 patients there was an increase in urinary Ky, AA, AAG, o-AHA, and 3-HK, while 3-HAA excretion fell. Since no other drugs were given, it was presumed that this effect was due to levodopa administration.


Nature and biosynthesis of ommochromes in Locusta migratoria cinerascens Fabr. (Orthoptera, Acrididae) and its albino mutant. The identification and localization of the 4 ommochromes present in locust body were established. 2 new chemical species were isolated: acridiommatins 1 (under crystalline form) and 2 (perhaps a xanthommatin ester). The course of their biosynthesis was studied with 2 different methods: quantitative analysis of the ommochrome content in organs during the 2 last larvel instars and the whole imaginal life and measurement of the tryptophan pyrrolase activities during the same period in the normal strain and in an albino mutant strain. With these 2 methods a cyclic activity related to the moulting cycle was found in the ommochrome pathway without any notable difference beween the 2 strains.


Yellow pigments in the wings of Papilio xuthus (papilionid butterfly). The yellow pigment (Papiliochrome II) of the wings of Papilio xuthus (papilionid butterfly) were extracted, purified with column chromatographies, and examined for chemical and physical properties. Furthermore, the decomposition-products of the pigment were isolated with columm chromatographies and identified. It was found that the pigment readily decomposed on heating to a DOPAmine derivative (SN-1) and kynurenine and that the SN-1 substance was broken down into a DOPAmine derivative (SN-1a) and beta-alanine by hydrolysis in 1 N HCl. These results were confirmed by the injection-experiments of 14C-tryptophan, 14C-DOPAmine, and 14C-beta-alanine. It has been concluded that Papilio-chrome II contains a beta-alanyl DOPAmine derivative and kynurenine as constituents.


Studies on melanogenesis of tryptophan in Harding-Passey mouse melanoma. D,L-tryptophan[benzene ring-14C (U)] and D,L-tryptophan (methylene-14C) are incorporated significantly into melanin of Harding-Passey mouse melanoma. D,L-5-hydroxytryptophan (methylene-14C) and 5-hydroxytryptamine-3-14C (serotonin) gave an incorporation of radioactivity into melanin significantly lower than tryptophan. D,L-tyrosine-2-14C was incorporated into melanin as well as tryptophan. Therefore tryptophan must be considered an important precursor in the biogenesis of melanins too.


Effect of tryptophan and its metabolites on gluconeogenesis in mammalian tissues. In parenchymal cells from starved mice L-tryptophan is a potent inhibitor of gluconeogenesis from substrates giving rise to oxaloacetate. Quinolinate yields a different pattern of inhibition and is generally much less effective. Tryptamine, indole 3-acetaldehyde and indole 3-acetate are equally as effective as tryptophan. Tryptamine inhibition alone may be overcome by pargyline; serotonin does not prevent the inhibition due to tryptophan. In kidney slices from starved rats, however, tryptophan has no effect on gluconeogenesis. Indole 3-acetate is also relatively ineffective, but quinolinate is signficiantly more potent than in liver; at 0.1mM, glucose production from lactate is 50% inhibited. Quinolinate is less effective with citric acid cycle substrates; the pattern of inhibition is consistent with a direct action on phosphoenolpyruvate carboxykinase. There is no evidence that glutamate dehydrogenase is simultaneously inhibited.


Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA). 1) Xanthurenic acid-insulin complex reduced insulin activity. 2) The antigenicity of xanthurenic acid-insulin was almost same as native insulin. 3) Saturated fat increased urinary xanthurenic acid in vitamin B6 deficiency.


Purification of xanthurenic acid-insuline complex. Tritium labeled xanthurenic acid (XA)-insulin complexes A and B were obtained. These were shown to be one component by the disc electrophoresis, and bound XA was not liberated by the electrophoresis from the paper electrophoresis experiment. The result of the gel filtration showed that the molecular weight of the complex A and B was 24,000. But there is still a possibility that complex B might be contaminated with free insulin.


Selective separation of tryptophan derivatives using sulfenyl halides. Upon reaction of tryptophan containing proteins with 2-nitrophenylsulfenyl chloride (NPS-Cl) the nitroaryl chromphore (lambda max 365 nm, epsilon 4000) is covalently linked at the 2-position of the indole ring of tryptophan. From the mixture of peptides obtained by enzymatic or chemical fragmentation of the labelled protein, the yellow tryptophan peptides are much more easily separated by column as well as paper chromatographic techniques, since their easier detection by spectrophotometry. Tryptophan peptides have been also isolated by diagonal electrophoresis, upon introduction of a carboxylate anion in the peptide by reaction with the carboxy-substituted reagent 2-nitro-4-carboxyphenylsulfenyl chloride. Sulfenl halides have been also used for the selective chemical coupling of tryptophan peptides to a solid support, thus facilitating their separation. N-acetyl-tryptophan has been covalently coupled to an amino-resin (aminoethylated Bio-Gel), and the resulting polymer reacted with a mixture of peptides in presence of 4,6-dinitrophenyl-1,3-disulfenyl chloride in glacial acetic acid. Selective covalent binding of tryptophan peptides has been checked.


Microbiological synthesis of L-tryptophan and its related amino acids. Crystalline tryptophanase from Proteus rettgeri was shown to catalyze the synthesis of L-tryptophan from pyruvate, ammonia and indole, at maximum velocity approaching that of the degradative reaction. Based on the results obtained with the crystalline tryptophanase, an enzymatic method for preparation of L-tryptophan and its related amino acids was developed. The cells of Proteus rettgeri containing high enzymatic activity were used directly as the enzyme. This method is simple and is one of the most economical processes to date for preparing L-tryptophan related amino acids from starting materials: sodium pyruvate, indole and its derivatives.


Applications of gas chromatography and mass spectrometry in neurochemical studies: determination of indole amine profiles at the picogram level. Work is presented on the application of sensitive and specific analytical methods for the simultaneous assay of tryptophan and its indolic metabolites (5-hydroxytryptophan, serotonin, 5-hydroxy-indole-acetic acid, tryptamine and indoleacetic acid). Due to their small concentrations in selected areas of the central nervous system, suitable derivatives have been prepared for separation by Gas Chromatography (GC) and detection by electron capture (ECD). Carboxylic acid groups have been methylated with BCl3-methanol and phenolic and amine groups have been acylated to pentafluoropropionyl derivatives. This type of derivatives allow a detectability limit of 5 picograms (5 x 10(-12) gr) if the corresponding reaction kinetics and yields are properly optimized. Response curves are presented. Identifications have been obtained by combined GC-MS and by the use of Kovats indeces in two GC stationary phases. The GC separation of the six compounds indicated above can be performed in less than 5 minutes with quantitative reproducibility. This work opens the possibility of performing comparative studies ("screening") of various physiological and pathological conditions by detecting any changes in the profile representative of a whole metabolic pathway, such as that of the indolic compounds in this case.


The influence of antiepileptic drugs on vitamin B6 metabolism. Vitamin B6 nutriture was measured by means of determination of activity of EGOT in 30 and of serum pyridoxal phosphate in 27 epileptic children under antiepileptic treatment with various antiepileptic drugs and with hydantoin and succinimide alone, 25 healthy infants and children were controls. Under the treatment with antiepileptic drugs, especially with hydantoin and succinimide a depression of the activity of EGOT and the level of pyridoxal-phosphate in serum followed. As an induction of vitamin B6 dependnet enzyme activity can be excluded a possible explanation for the disturbance in vitamin B6 metabolism could be the inhibition of activity of pyridoxalkinase. We consider the administration of vitamin B6 in addition to hydantoin and succinimide as appropriate.


Free and bound tryptophan in the blood of depressives. In in vitro studies, the influence of pH and the concentration of albumin on the binding of tryptophan to this protein is shown. Addition of palmitic acid to human plasma decreases specifically bound and increases free tryptophan. In separate experiments, free and bound tryptophan, tyrosine, free fatty acids (NEFA) and albumine were studied in healthy volunteers and depressives treated by sleep deprivation.


Labelling of the indole nucleus of tryptophan at the 2-position. Tryptophan may be converted in high yields to the 2-hydroxy-derivative by reaction of sulfenyl halides and subsequent hydrolysis in 20% acetic acid at high temperature of the 2-thioaryl-compound. 2-Thiol-tryptophan and related compounds have been obtained by reduction of the tryptophan dimers obtained by reaction with sulfur dicholoride (S2Cl2). Novel methods of isotopic labelling the indole moiety at the 2-position have been also developed. 2-Thioaryl-indole derivatives with a propionic acid side chain at the 3-position are converted by one equivalent of N-bromosuccinimide in bicarbonate solution to lactones, which upon reduction with NaBH4 (or NaBD4 or NaBT4) give indole-propionic acid derivatives (or 2-labelled compounds thereof). The incorporation of deuterium or tritium was approximately 80%.


Tryptophan metabolism in Cicer arietinum. Crude extracts of Cicer arietinum seedlings contain enzymes that mediate the oxidation of tryptophan. The most active is formylase followed by tryptophan oxygenase and kynureninase. Tryptophan is also utilized for the synthesis of indolyl-3-acetic acid. The stimulation of tryptophan oxygenase in seedlings incubated in presnece of indolyl-3-acetic acid has been shown by specific labelling of haem moeity and the apoenzyme not to involve de novo synthesis.


Studies on the metabolic pathway of anthranilic acid in rats. Recent experiments with administration of anthranilic acid in rats afforded two new metabolites; anthranilamide and a light blue fluorescent substance. Administration of anthranilamide to rats resulted in urinary excretion of two main metabolites which were isolated from urine as 3-hydroxyanthranilamide-O-sulfate and 5-hydroxyanthranilamide-O-sulfate. This fact showed that anthranilamide is hydroxylated and then conjugated in vivo. Hydroxylation of anthranilamide was found to be catalyzed by drugs hydroxylation system but not by the microsomes alone, and is a specific reaction activated by a protein component contained in the soluble fraction. The purified protein component was recongneized that it was bluish green protein containing copper and zinc, and its molecular weight was 25,700. This protein component had no effect on the metabolism of drugs by liver microsomes but showed specific activation of hydroxylation of 2-aminobenzoyl compounds.


Activation of tryptophan pyrrolase by benzylhydrazine. The mechanism responsible for the activation of tryptophan pyrrolase (TP) by benzylhydrazine (BZH) was investigated. The increase in holo/apo ratio of rat TP activity after addition of BZH in concentration of 1 x 10(-4)M, which is a major metabolite of isocarboxazid (ISOC), was higher than those in mice and guinea pigs. In addition, treatment with ISOC to rats (50 mg/kg i.p.) resulted in a significant increase in TP activity. These results suggested that the BZH-induced elevation of TP is at least in part due to a stimulation of conjugation step of TP activity.


Triamterene and mouse liver tryptophan pyrrolase: possible activation of cytosol by the pteridine in enhancing enzymic activity. Triamterene (2,4,7-triamino-6-phenylpteridine), a diuretic drug, affects the hepatic endogenous holotryptophan pyrrolase (EC 1.13.1.12) in the mouse, with stress from sham-operation as a preconditioning factor; under these conditions, maximum levels of enzymatic activities are obtained. These values range from 6.87 to 9.84 units with a mean value of 8.252 mumoles of kynurenine per gram tissue per hour. Employing similar experimental designs, the effects of cortisol were studied for comparative evaluation; these activities range from 4.154 to 4.999 units with a mean value of 4.49. The significance and the possible mechanism of action of triamterene are discussed.


The rate of tryptophan oxidation by tryptophan pyrrolase in the rat: effect of tryptophan loads and changes in tryptophan pyrrolase activity. The in vivo assay of tryptophan pyrrolase gives best results when [ring-2-14C] tryptophan is used and rates of labelled CO2 production are measured at short times after the labelled tryptophan injection. Using this technique in conjunction with in vitro measurements, we find that both tryptophan pyrrolase activity and the liver tryptophan concentration are important factors in controlling the rate of tryptophan breakdown by pyrrolase. Tryptophan in the liver has a very high turnover rate, and the enzyme activity and the liver tryptophan concentration interact. Thus a high liver tryptophan increases the enzyme to speed tryptophan breakdown, while a high pyrrolase activity may tend to lower liver tryptophan, thus tending to decrease both the rate of tryptophan catabolism and possibly the enzyme activity.


Subcellular distribution and properties of rat liver kynurenine transaminase. Kynurenine transaminase activity in rat liver was found in both the mitochondrial and supernatant fractions. The mitochondrial and supernatant fractions contained (a) kynurenine pyruvate transaminase which showed a preference for pyruvate as amino-acceptor and a pH optimum between 8.0 and 8.5 and (b) kynurenine alpha-ketoglutarate transaminase with a preference for alpha-ketoglutarate and a pH optimum between 6.0 and 6.5.


Kynurenine pyruvate transaminase and its specific inhibitor in rat intestine. Kynurenine pyruvate transaminase was partially purified and characterized. The enzyme catalysed the conversion of L-knurenine to kynurenic acid. Transamination rates of 3-hydroxy-DL-kynurenine and 5-hydroxy-DL-kynurenine by the enzyme were 1/2.9 and 1/2.6 of kynurenine. The enzyme showed a higher preference for pyruvate than 2-oxoglutarate as aminoacceptor. The pH optimum of the reaction was 8.0 and 8.5. It was shown that the inhibitor of kynurenine pyruvate transaminase was present in the intestine.


Factors affecting the access of mitochondrial kynurenine aminotransferase to its substrates. The kynurenine aminotransferase activity of isolated rat kidney mitochondria is enhanced several-fold by membrane disruption or by the addition of 1 mM CaCl2. The addition of CaCl2 can thus be used conveniently to obtain full expression of the mitochondrial enzyme activity. CaCl2 apparently stimulates the activity by facilitating the penetration of the mitochondrial inner membrane by the substrate, alpha-ketoglutarate. Consistent with this view, two inhibitors of dicarboxylate translocation, benzylmalonate and quinolinate, inhibited the activity of the isolated mitochondria but not that of the disrupted mitochondria. Both inhibitions were prevented at higher Ca++ concentrations, suggesting that thes compounds inhibit by complexing Ca++ needed for the translocation of alpha-ketoglutarate. This action of quinolinate may explain its ability to interfere in vivo with the mitochondrial translocation of dicarboxylates as reported by Spydevold et al.


Relationship between pyridoxal phosphate and some synthetic oestrogens, gonadotropin and thyroxine in their effects on kynurenine hydrolase and kynurenine aminotransferase enzymes of normal mouse liver. The interrelationship between pyridoxal phosphate and gonadotropin and thyroxine in their effects on kynurenine metabolism was studied in the whole liver homogenates from male mice. These in vitro studies were planned to investigate the effects of these hormones on the vitamin B6-dependent enzymes, kynurenine aminotransferase and kynurenine hydrolase. It was found that gonadotropin (from serum of pregnant mares) inhibits both enzymes, whereas thyroxine inhibits the kynurenine aminotransaminase enzymes only. There was evidence indicating that pyridoxal phosphate was not the factor directly responsible for the observed inhibition. Increasing concentrations of pyridoxal phosphate were unable to counteract the inhibitory effects of these hormones.


Hydroxykynureninase and the excretion of 3-hydroxyanthranilate by yeast. A comparative analysis of the kynureninase-type activity found in various organisms has demonstrated two forms of enzyme. One, inducible by tryptophan, has a relatively low Km for L-kynurenine, and is found in microorganisms such as Pseudomonas fluorescens and Neurospora crassa. The other, unaffected by tryptophan, has a low Km for L-3-hydroxykynurenine and is found in a wide variety of organisms, including molds, amphibia, birds and mammals. The yeast Saccharomyces cerevisiae lacks the inducible kynureninase but contains the constitutive enzyme termed an hydroxykynureninase. As a result, the yeast, unlike M. crassa, excretes 3-hydroxyanthranilate in response to L-tryptophan. However, initial studies indicate that little if any 3-hydroxyanthranilate accumulates in beer, wine or bread. Although 3-hydroxyanthranilate is suspect as an endogenous carcinogen, its carcinogenicity as an exogenous agent has not been shown.


Regulation of the activity of microbial kynureninase by transamination of the enzyme-bound coenzyme. Kynureninase was purified to homogeneity from the extracts of Pseudomonas marginalis and Neurospora crassa. The active kynureninase containing pyridoxal 5'-phosphate transaminates with L-ornithine or L-alanine to form the inactive pyridoxamine 5'-phosphate form of enzyme and delta1-pyrroline-2-carboxylate or pyruvate. This inactive enzyme transaminates with pyruvate to restore the active pyridoxal 5'-phosphate enzyme and L-alanine. The activity of kynureninase is regulated in this manner by transamination of the coenzyme moiety.


Studies on 3-hydroxykynureninase from rat liver. Kynureninase (L-kynurenine hydrolase E.C. 3.7.1.3.) was purified about 200 times from rat liver. The purified enzyme catalyzes the L-3-hydroxykynurenine leads to 3-hydroxyanthranilate reaction more favorably than the L-kynurenine leads to anthranilate reaction, with Km values of 1.67 x 10(-6) M for L-3-hydroxykynurenine and of 1.67 x 10(-4) M for L-kynurenine. Besides, this enzyme did not produce 5-hydroxyanthranilate from D,L-5-hydroxykynurenine. Therefore we think it is mainly a 3-hydroxykynureninase regulating the tryptophan degradation towards the formation of nicotinic acid necessary to NAD synthesis, rather than towards the accumulation of anthranilate.


Development of analytical methods for the detection and determination of kynurenic and xanthurenic acids. A survey was carried out on the techniques developed by numerous research workers in this important field since Liebig discovered the presence of kynurenic acid in the urine of dogs fed on meat and Musajo that of xanthurenic acid in the urine of rats on a fibrin diet. The survey starts with the old methods of assay by precipitation of kynurenic acid and goes on to include the more recent ones of colorimetric assay of xanthurenic acid with ferrous sulphate or ferric chloride and of kynurenic acid by means of transformation into a chloro-derivative of the type of Besthorn dyes. Chromatographic techniques including paper chromatography, thin-layer chromatography, column chromatography nad gas chromatography, enabled researchers to detect the slightest traces of the two quinolincarbonic acids in the biological fluids together with the other metabolites of tryptophan. Among the techniques adopted for this purpose electrophoresis, automatic analyzers, polarography and, finally, the use of labelled substances, in particular L-tryptophan-3-C14, are included.


A thin layer chromatographic method for the separation and identification of the tryptophan metabolites present in whole human urine. This paper reports a new thin layer chromatographic system which is able to separate a total of thirtyeight (38) tryptophan metabolites from a synthetic mixture in a period of three hours. The system consists of thin layers of silica gel GF254 which are eluted in two dimensions, employing in the first dimension a mixture of propanone, 2-propanol, water, ammonia (0.88) (50 : 40 : 7 : 3 V/V) and in the second dimension a mixture of chloroform, glacial acetic acid, methanol and water (65 : 20 : 10 : 5 V/V). A method whereby the separated tryptophan metabolites may be unambiguously identified in situ following the thin layer chromatography is also presented and discussed. This method utilises the effect of ultraviolet light, at 254 and 350 nm, and the colour reactions between the metabolites and four reagents namely, a modified Ehrlich, o-phthaldehyde, Pauly and Ninhydrin-cadmium acetate. A summary of the unsuccessful attempts to quantitate the modified Ehrlich positive metabolites by in situ reflectance densitometry is also given. Finally, it is demonstrated that the new system may be used to advantage to separate and identify tryptophan metabolites in studies of whole human urine.


Quantitative analysis of tryptophan metabolites in urine of normal and endotoxin poisoned mice. We have developed methods for quantitatively monitoring the in vivo flow of tryptophan between the kynurenine and serotonin pathways. Our data suggest that endotoxin-poisoned mice have more tryptophan flowing into the serotonin pathway than normal mice both with and without tryptophan load. It appears that the distribution of tryptophan between the serotonin and kynurenine pathways in vivo is constant over a very wide dose range and that substrate availability rather than tryptophan oxygenase activity determines the precise amounts of tryptophan which flows into the two pathways.


A study of urinary tryptophan metabolites in relation to the phenylalanine content of semi-synthetic diets in a patient with phenylketonuria. The influence of different phenylalanine (Phe) levels in semi-synthetic diets on the urinary excretion of tryptophan (Try) metabolites was studied in one untreated phenylketonuric (PKU) patient. Low dietary Phe decreased the excretion of indoleacetic acid, indolelactic acid, indican and Try but did not increase 5-hydroxyindoleacetic acid. Under the low Phe diet, the excretion of N-acetyltryptophan, kynurenic and xanthurenic acid are greatly increased in the urine after a Try load. The possible significance of the extensive acetylation of Try and Phe is discussed in relation to the low blood levels of Try and PKU and to the phenomenon of decreasing blood Phe levels in PKU.


Regulation of plasma free 5-hydroxytryptamine level. In this study we investigated the mechanisms which control the level of free 5-hydroxytryptamine in plasma. Results indicate that both degradation by monoamineoxidase and uptake by platelets are important for this control. On the other hand, results show that an increase of plasma free 5-HT induces cardiovascular disorders.


The control of brain tryptophan concentration. Addition of linoleic acid to rat plasma caused increased uptake of radioactive tryptophan by incubated brain slices. Addition of competing amino acids within the physiological range of their concentrations had negligible effect. Rat midbrain tryptophan concentration in vivo correlated significantly with plasma free tryptophan. These results are consistent with previous work indicating the importance of plasma free tryptophan as a determinant of brain tryptophan concentration.


Tryptophan-free diet: a new means for rapidly decreasing brain tryptophan content and serotonin synthesis. Changes in the synthesis rate of brain serotonin are positively correlated with changes in the concentration of brain tryptophan, indicating that the concentration of tryptophan in the whole brain reflects that at sites of serotonin synthesis. In turn, the concentration of brain tryptophan is positively correlated with that of free serum tryptophan (tryptophan is the only amino acid bound to serum proteins) and negatively to that of other amino acids competing with tryptophan for the same transport from blood to brain. Consistently, experiments in rats have shown that treatments which increase free tryptophan in serum (in respect to competing amino acids) also increase brain tryptophan and serotonin turnover. Conversely, the ingestion of diets containing all amino acids except tryptophan cause a dramatic fall in free serum tryptophan and a parallel decline in brain tryptophan and serotonin synthesis. In man the administration of an amino acid mixture lacking trytophan produces a marked depletion in serum tryptophan concentration.


Effect of clozapine on 5-HIAA excretion in urine and CSF of psychotic patients and on serotonin metabolism in rat brain. In a clinical study and with experiments in rats Clozapine showed a sedative effect, which diminished during the treatment, and indicated a development of tolerance. 5-HIAA in urine and CSF of patients was elevated after 10 days of treatment. 5-HT and 5-HIAA were elevated in the brains of rats in acute experiments as well as in chronic experiments.


Effect of hypophysectomy and growth hormone on tryptophan and serotonin metabolism. The present study reports data on brain serotonin (5-HT) metabolism in two experimental conditions which have in common a lack of pituitary growth hormone (GH) and refers also the effect of a GH replacement therapy. In hypophysectomized female rats or genetically dwarf mice, which have a more selective deficiency of GH, brain tryptophan (TP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were significantly higher than in age-matched controls. Brain levels of 5-HT were practically unchanged. A GH replacement therapy resulted in both hypophysectomized rats and dwarf mice in a significant reduction of brain TP and 5-HIAA concentrations. These results suggest that GH may exert an inhibitory action on 5-HT metabolism. Consonant with this view are the preliminary findings that in 7 individuals with elevated plasma GH levels for acromegaly, plasma TP levels were lower than in control subjects.


Gradients of concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). CSF from neurological and other patients was analyzed for its content of tryptophan, 5-HIAA and homovanilic acid (HVA). The gradients of concentration of these substances from ventricular spaces to lumbar sac indicate that tryptophan and 5-HIAA probably enter the CSF from all levels of the nervous system, but that HVA originates entirely in the brain. A study of CSF tryptophan in patients with hepatic cirrhosis provided no support for theories which implicate abnormal tryptophan metabolism as a cause of hepatic coma.


Serum gastrin level in early childhood.

Serum gastrin level in early childhood. Serum gastrin concentration was measured in newborns and infants with no gastrointestinal disorders, in the fasting state and after food stimulation. Mean fasting concentration in 14 newborns aged 1 to 12 days (130 . 4 pg/ml +/- 11 . 4 SE) was significantly higher than the mean value in 23 infants aged 1.5 to 22 months (101.4 +/- 6.6 pg/ml). Ingestion of the usual milk meal resulted in a definite rise of the serum gastrin level in the 5 subjects tested (3 newborns and 2 infants). The mean fasting serum gastrin level in 6 babies with hiatus hernia and gastro-oesophageal reflux was found to be no different from the corresponding value in 8 age-matched controls. However, a conspicuously raised fasting gastrin concentration was observed in one infant with lower oesophageal dyskinesia. The results indicate that the release of gastrin and the reactivity of the hormone-producing sites to food stimulation in early life are similar to those in adult humans. No defect of gastrin release was shown in patients with gastro-oesophageal reflux.


The VDRL test in a blood transfusion service. A survey has been made of the results of 12 months' VDRL screening in a blood transfusion service. Positive VDRL tests were found on 318 of the 73 350 blood donations collected during 1974. Thirty-four tests confirming specific treponemal infection were found in 24 donors. A battery of confirmatory tests showed the remaining 284 positive VDRL reactions from 235 donors to be biological false positive (BFP) results, and, of these, one-third were considered entirely negative by the reference laboratory. BFP reactions were commoner in female donors than in males, and a higher incidence than expected was observed in younger female donors and older male donors. A marked seasonal incidence was noted, 65% of all BFP tests from the transfusion service being found in the four colder months of May to August. Although some differences exist between the group as a whole and the 36 donors (15.3%) found to have BFP results on more than one occasion during the year, there is little evidence from these studies to suggest that regular blood donation per se is a contributing factor to the finding of a BFP result in VDRL screening. It is probable that the population tested regularly  by the blood transfusion service reflects a small but representative sample of the community as a whole.


[Lack of beta-adrenergic stimulation of membrane bound adenyl cyclase in psoriasis as compared to normal epidermis (author's transl)]. Glucagon and beta-adrenergic compounds such as 1-isoproterenol stimulated the low activity of an ATP-utilizing enzyme located on the cell membranes of normal keratinocytes. Addition of beta-antagonist propranolol to the incubation medium prevented the stimulatory effect of 1-isoproterenol. We considered, therefore, the reaction product being due to epidermal membrane-bound adenyl cyclase activity. In psoriatic epidermis the basal adenyl cyclase activity was low, similar to normal epidermis, however, glucagon and 1-isoproterenol failed to stimulate the enzyme activity in psoriasis under the same conditions. It seems, therefore, that the beta-adrenergic-cAMP cascade as a regulatory epidermal control mechanism of induced proliferation is ineffective in this disease.