Lipid oxidation. Part 2. Oxidation products of olive oil methyl esters.

Olive oil was converted into methyl esters which were autoxidized at 60 degrees C. The composition of oxidized products was determined by the comparison of infrared spectra and NMR spectra of the original and acetylated samples, the sample reduced with potassium iodide and the acetylated reduced sample. Oxidized products were separated by preparative thin layer chromatography on silica gel and characterized by selective detection and by infrared spectrometry of the fractions. The oxidation products consisted of hydroperoxido butyl oleate, substituted hydroperoxides, mono- and disubstituted monomeric derivatives and a small amount of oligomers.


Photometric determination of dithiocarbamate residues by carbon disulphide evaluation method.

A review of analytical methods for determination of dithiocarbamate residues by carbon disulphide evaluation method was made. On basis of KEPPEL method the colorimetric step was modified. For this purpose the reaction of hydrogen sulphide with p-aminodimethylaniline in the presence of ferric and zinc ions to form methylene blue was applied. The coloured compound after a chloroform extraction was measured at 650 nm. The method gives a very high sensitivity of about 2 mug. Recoveries obtained with zineb and maneb for various crops are satisfactory.


[Lysosomal enzymes in starvation after regimen of single or all-day feeding].

The authors studied in rats the effect of starving from 24 to 96 hours after a regimen of single or all-day feeding. They determined in liver homogenate the total activities of beta-N-acetyl glucosaminidase, acid phosphatase and beta-glucuronidase as well as the free activities of the two first-mentioned enzymes. The activity of beta-N-acetyl glucosaminidase was also determined in the blood. It was found that the total activity of beta-N-acetyl glucosaminidase in the liver homogenate increased with the length of starvation. The free and serum activities of the enzymes under investigation showed similar changes. These increases were more marked in rats subjected to a single-feeding regimen before starving. These changes are explained as an expression of the active participation of the lysosomes and their enzymes in the transition to endogenous feeding. The lysosomal membrane was more sensitive in starving animals which had been subjected to a single-feeding regimen.


[Meat quality of broiler rabbits. 2. Chemical composition of meat of valuable cut-up parts of New Zealand white rabbits and hybrids of different body weight].

Studies were carried out on the chemical composition of the meat of valuable cut-up parts in 88 broiler rabbits (51 New Zealand White, 37 hybrids). Muscles of legs and backs differed in nutrient content. The fat content of legs was higher than that of M.long.dorsi, and directly related to increasing carcass weights. As to the varieties mostly insignificant effects on chemical constituents were measured. There were but a few correlations between the analysed qualitative properties.


[New results on migration behavior of benzophenone-based UV absorbents from polyolefins in foods].

The authors deal with the migration behaviour of bezophenone-based ultraviolet absorbents for commodities of low-pressure polyethylene, high-pressure polyethlene, polypropylene and polystyrene. These ultraviolet-absorbent-stabilized plastics (up to 0.5% of ultraviolet absorbent) show a very slight tendency of the light stabilizers towards migration into aqueous, acid or dilute alcoholic foods. Very high migration values are obtained for sunflower oil, Fettsimulans HB 307 or 50% ethanol. The amount of 2-hydroxy-4-octoxybenzophenone which migrates into fat-free foods is only a fraction of the maximum daily dose; a risk to the consumers' health might thus be excluded. In fat-containing foods, the maximum daily dose is also not reached, but the single migration value is higher than the limit value (100 p.p.m.) for total migration. Consequently, the above ultraviolet absorbents should not be used for the ultraviolet stabilization of plastics designed for packing these products. An evaluation of the safety of ultraviolet absorbents of the Dastib type will be possible only if sufficient toxicological data are available.


[Rheology and spinning of alkaline solutions of sunflower seed globulin and casein].

The specific demand of sodium hydroxide is determined for the dissolution of sunflower seed globulin, casein and a mixture of them to equal parts. In low protein-containing solutions it depends for sunflower seed globulin very much on the sodium chloride concentration. From sunflower seed globulin, casein and a mixture of them to equal parts are prepared with sodium hydroxide high protein-containing alkaline solutions. Sunflower seed globulin forms temporally a gel phase. After this phase the solution of sunflower seed globulin shows like casein and a mixture of sunflower seed globulin/casein (I:I) pseudoplastic flow. The flow curves of the pseudoplastic solutions are described mathematically with the OSWALDian power statement. By alkaline solutions of casein and sunflower seed globulin/casein (I:I) the flow exponent n is distributed statistically about 0.9, by solutions of sunflower seed globulin a distribution exists about the mean values n = 0.85 and n = 0.50. lg k depends in all protein solutions on the concentration of protein, sodium chloride, sodium hydroxide and on the temperature and time. For all protein solutions exists a linear relation between the logarithm of viscosity and the reciprocal temperature for lg k and I/T, which is derived normally for NEWTONian flow behaviour. In a suitable scope of spinning for all protein solutions are carried out complete factorial experiment, which guide to regression equations of lg k; in the case of sunflower seed globulin are calculated also a regression equation of the flow exponent n. Going out from the parameters of the spinning process the properties of the spun sunflower seed globulin/casein (I:I) fibers are described.


Volatile sulfur compounds contributing to meat flavour. Part. I. Components identified in boiled meat.

Volatile sulfur compounds from 3 samples of boiled meat (Longissimus dorsi and shoulder meat) have been isolated, separated from the whole flavour complex by mercuric chloride precipitation, regenerated, and examined by gas chromatography. Identification has been carried through by determining Kovats-indices on 4 gas chromatographic columns of different polarity. 29 sulfur compounds have been identified with high certainty, 10 tentitatively. Among 17 thiols, 8 sulfides, 7 disulfides and trisulfides, and 7 heterocyclic compounds only 11 substances have been described previously in literature. The number of mercaptans especially exceeds hitherto knowledge.


Nutrition and flavour-legislation.

Our food laws have to provide for safety of food and to ensure that the consumer is not misled. We are no longer in a position to manufacture food without additives and especially without flavours. For physiological reasons, our food should be offered in a wide variety; an increasing number of food preparations has no natural flavour at all and needs to be flavoured and the industrial manufacture of food requires the flavours to be properly developed in order to withstand the sometimes rather drastic conditions of manufacture. The safety of flavours and flavouring substances is discussed. It is shown that the class of nature-identical flavouring substances has to be treated separately for practical purposes of food control and because the substances of this group offer more certainty with regard to their safety. Some suggestions are made regarding the proper labelling of food which contains flavours. The IOFI (International Organization of the Flavour Industry) model law is discussed which should serve as a basic proposal for the international harmonisation of national food laws.


Changes of sensory value by interaction of alkanals with amino acids and proteins.

Alkanals as carriers of rancid flavour of fat-containing foods were stored in mixtures with nonlipidic substances. The intensity of odour due to alkanals decreased with increasing time of storage, the changes being more pronounced in case of casein than in that of cellulose. Results of sensory tests did not depend on the molecular mass of aldehyde. The water content affected the sensory evaluation only slightly. The formation of aldolization products or polymers and of gluey flavour compounds modified the character of flavour and confused less experienced judges. Both the binding of alkanals and the aldolization reactions were enhanced by presence of primary amino groups.


[Development of fish flavor by reaction of autoxidized lipids with amino acids and proteins].

The rancid fish-oil flavour of autoxidized tetraene, pentaene and hexaene fatty acid esters disappears during storage or heating with free amino acids or proteins. Simultaneously, a flavour of raw, roasted or fried fish develops. The development of this fish flavour is of particular intensity in mixtures containing lysine or some other amino acids. Blocking of the free amino groups in casein or albumin inhibits the development of a fish flavour in mixtures with oxidized lipids. If the mixtures are added with lysine, the fish flavour reappears. The development of a fish flavour is associated with browning reactions.


[Notes about molecular weights of aroma compounds].

Classification of 2000 food aroma compounds as to their molecular weight shows an accumulation in the range of 135 to 155, and an upper limit of 310. Molecular masses of substances with high aroma effectiveness are below 200. As aroma compounds are composed only of the elements C, H, O, N and S, even numbers of molecular masses predominate among these substances. A periodicity with an interval of 7 units of molecular mass observed seems to be caused by the presence of complete homologuous series of compounds within the range of low molecular masses.


[Bouquet qualification of wines by gas chromatography. 1. Experimental method for gas phase analysis].

In the course of our investigations we tried to find a method for the bouquet qualification of wines by gas chromatography. For this purpose, instead of aroma research studies requiring complex equipment and laboursome precise laboratory work, we developed a method for head space analysis functioning with simple experimental instruments and being sufficiently fast for serial routine work. By the method developed, the head space of a great number of samples taken from 7 different wine-types have been successfully examined. Errors of measurement were checked by standard deviation analysis and the values obtained (3,23%) were found satisfactory. According to the above, our head space analysis may provide a satisfactory basis for elaborating a method for the instrumental bouquet qualification of wines.


[Bouquet qualification of wines by gas chromatography. 2. Development of measuring unit for bouquet qualification by determination of relationship of chromatographic peak areas and conditions of application].

In a previous paper we described a method by which routine head-space analysis of wines can be performed with sufficiently accurate results by means of gas chromatography. From the results thus obtained, with application of organoleptic data, chemical and classical analytical parameters of aromatic changes during seasoning and storing wines as well as mathematical-statistical data of the method elaborated, a mathematical relationship has been derived between gas chromatographic peak areas characteristic of different aroma components and the bouquet of wine. Reliability of the method has been verified by the fact that, in spite of the small number of samples, the bouquet of seven different types of wine could be discriminated in 95,45% probalility. The method allows arbitrary choice in the number of samples and in the degree of reliability required, in investigating the quality of a wine. For this purpose, another mathematical relationship has been set up to provide criteria for the distinction of the quality of bouquets. By this method, the bouquet of various types of wines or within an identical type, the bouquet of different vintages and/or bottlings can be determined.


Technological studies on the dehydration of the Nile bolti fish (Tilapia nilotica).

Chemical and microbiological analysis of bolti fish: moisture, chloride, fat, total volatile bases (T.V.B.), thiobarbituric acid value (T.B.A.), total bacterial count and coliforms were estimated in fresh bolti fish, after brining, drying and during storage at room temperature for 3 months. The moisture content decreased after drying but become stable during the storage period. Chloride increased after bringing but no noticeable changes were observed after drying and during 3 months storage. The fat content was not affected by previously processes. T.V.B. and T.B.A. increased after brining, drying and throughout storage period. The rate of increase was higher for dehydrated samples than for sun-dried ones. The reduction of total bacterial count is due to the high salt content and the lack of free water in fish tissues after drying. Coliforms were not present after brining, drying and throughout the storage periods.


Lipids of two Cassia species and Datura stramonium seeds.

The fatty acid constitution of three seed-oils, namely, Cassia alexandrina, Cassia italica and Datura stramonium, were carried out using gas chromatographic analysis. The glyceride structure of these oils was computed using the technique of pancreatic lipase hydrolysis. The phospholipids fraction of these oils were identified using thin layer chromatography, also the fatty acid constitution of the phosphilipids were determined quantitatively by gas liquid chromatography.


[Measurement of emulsion stability].

For the routine assessment of the stability of water-in-oil emulsions, the authors suggest to determine the beginning of de-emulsification or to measure the stability constant at 38 degrees C., since these methods yield fairly reproducible results and require but little time and laboratory outfit. More accurate results will be obtained only by conductance measurements.


[Behavior of various blood parameters of carbohydrate and fat metabolism of light and heavy-weight rats of varying age and different diet groups].

The sera from light and heavy-weight rats varying in age and belonging to different groups on, respectively, pellets or diets containing 3% or 50% of fat were analysed for pyruvate, lactate, aceto-acetate, beta-hydroxybutyrate, free fatty acids, triglycerides and total cholesterol. There were no significant differences in these parameters between light and heavy-weight animals of the same diet group. The total cholesterol content increased with age in the rats which were fed pellets. These findings are compared with previous results of the authors and discussed in the light of recent literature.


[Vitamin B1 determination in ready-to-use infant food].

The authors report of a modification to the vitamin B1 determination (thiochrome method) according to the Specification TGL 18230. Extract purification is considerably simplified by using the KPS cation exchanger. The measurements were performed by means of the Spekol spectrophotometer with fluorescence attachment. In this way, also industrial laboratories with modest outfit are enable to make vitamin B1 determinations. Already after 2-3 months of storage, the thiamine values of the fruit and vegetable baby foods tested lay in part at the lower limit of the stated values. Possibilities of improving the thiamine values are discussed.


[Germ reduction in technical enzyme preparations with special regard to gamma irradiation].

For toxicological and hygienic reasons, the use of enzymes as technical additives is not admitted in various food industries if the germ counts of the preparations to be used exceed the respective tolerance values. In this connection, the authors report some results from attempts to reduce the germ content of a protease preparation, especially by gamma radiation. A gamma ray dose of I Mrad permitted to obtain germ-free preparations without considerable loss of enzyme activity.


[Significance of byssochlamic acid in fruit juice mold].

The authors describe a method for the determination of byssochlamic acid in fruit juice. After extraction and purification, byssochlamic acid is separated by thin-layer chromatography on HF 254 silica gel. The quenching of fluorescence of byssochlamic acid is estimated quantitatively on the plate by means of the thin-layer attachment of a fluorescence spectrophotometer using reference substances. For fruit juices the recovery rate is 80%; the limit of detection lies at 0.5 p.p.m. Byssochlamic acid could not be detected in commercially-available fruit juice and neither in juices produced of fruits which had spontaneously got mouldy.


Characteristics of prickly lettuce seed oil in relation to methods of extraction.

Samples of seed oil of prickly lettuce (Lactuca Sacriola oleifera) which had been obtained by pressing or by extracting with acetone, ethyl ether, petroleum ether or carbon tetrachloride were analysed for the following parameters: viscosity, saponification number, iodine number, thiocyanogen value, unsaponifiable matter, free fatty acids, peroxide number and fatty acid composition. The different parameters varied in part considerably in relation to the method of production (pressing or solvent extraction) and to the solvent. It is tried to interprete these relationships.


Control of postharvest decay in fruits and vegetables by irradiation.

This paper deals with the effect of postharvest gamma-irradiation of strawberries and carrots on their organoleptic quality, storage capacity and chemical composition. Radiation doses of 25 krad for strawberries and 75 krad for carrots were chosen as optimum doses not causing significant changes in the organoleptic quality. We found that strawberries and carrots irradiated at a doseof 25 and 75 krad respectively, retained its microbiological stability even during storage at 12 degrees C (strawberries) and at 25-30 degrees C (carrots), respectively. It was also found that changes in chemical composition depend on storage temperature and time and are not affected substantially by irradiation.


Histochemical, biochemical and ultrastructural studies on the liver of fasted rats.

The subjection of rats with body weight 150 +/- 10 g to complete starvation for a period of four days leads to a diminution of total protein, total lipids, blood sugar, body weight and liver weight. Lipid dystrophy develops in the liver, as well as deposition of lipofuscin-like pigment and atrophy. Lipid dystrophy and desposition of pigment increase during the first three days and abruptly decrease during the fourth. Atrophy is a progressive process. The delineation of three phases in the atrophic - dystrophic process is possible with the application of histological, enzyme-histochemical, morphometric, biochemical and electron microscopic methods: Phase I (first 24 hours) - a common adaptive phase. It engages both the liver, which must utilize the increased nutrients from the organism depots and the homeostatic mechanisms of the organism as a whole. Phase II - (second and third 24 hours) - alterative-restorative, manifested markedly at the liver parenchimal level and especially by autophagic lysosome function. Phase III - (fourth 24 hours) - alterative. Exhaustion of adaptive-restorative liver process (and the hepatocyte in particular), and the organism as a whole as well.


[Behavior of some parameters of lipid and energy metabolism. 1. Behavior of the stationary concentrations of acetyl CoA, acetoacetate and adenosine phosphates in liver, as well as oxygen consumption and P/O ratios in liver homogenates of growing rats on diets differing in fat content].

Young rats were maintained on diets differing in fat content. The determination of certain parameters of the lipid and the energy metabolism in the liver showed that a high-fat diet resulted in a reduction of the stationary level of acetyl CoA, an increase in the concentration of acetoacetate and a reduction of the adenosine triphosphate content and the so-called energy charge. In case of intact respiratory chain phosphorylation, the oxygen consumption of the respective liver homogenates was simultaneously increased. The results obtained with a high-fat diet are indicative of the attainment of a metabolic state which seems to be typical of metabolic regulations in growing rats subjected to anabolic lipometabolism.


[Behavior of some parameters of lipid and energy metabolism. 2. Activity of citrate synthase, ATP citrate lyase, fatty acid synthase, and glucose-6-phosphate dehydrogenase in liver of growing rats on diets differing in fat content].

In continuation of previous investigations, the authors studied the behaviour of the activities of certain enzymes (citrate synthase, adenosine triphosphate citrate lyase, fatty acid synthase and glucose-6-phosphate dehydrogenase) in the livers of growing rats on diets differing in fat content. A high-fat diet resulted in a reduction of the activities of fatty acid synthase, glucose-6-phosphate dehydrogenase and adenosine triphosphate citrate lyase, whereas the activity of citrate synthase increased, which is interpreted in the sense of an acceleration of the introduction of acetyl residues into the citrate cycle for the purpose of oxidative final degradation, and as a removal of acetyl CoA for the purpose of fatty acid synthesis.


[New methods for evaluation and analysis of organoleptic qualities of foods and for calculation of changes. 9. Dependence of irradiation flavor of apple juice and concentrate on the gamma radiation dose].

Various authors have defined organoleptically the concept "cooking flavour" for heat-treated apple juice and concentrate. In a similar way, the "irradiation flavour" caused by gamma radiation is defined in the present paper. It has been found that the irradiation flavour is attributable to low-boiling substances which appear already in the first fraction if the modified MICKO distillation is performed. Tetrahydrofuran (THF) has been identified as the key substance in irradiation flavour. As further evidence may be quoted the similarity of the intensity of off-flavour which was observed also by gas chromatography at the same times of retention, and the removal of the irradiation flavour by means of a THF-specific agent (mercury acetate). In connection with THF solutions added to non-irradiated apple juice, the authors employed the technique of "subjective olfactometry", using the "absolute value scale", to establish mathematical correlations between the intensity of irradiation flavour and the concentration of off-flavour products in apple juice or concentrate. The dependence of the intensity of irradiation flavour on the THF concentration and the gamma radiation dose, respectively, obeyed an exponential function. Thus, it has been possible to calculate the amounts of THF formed by radiation doses varying from 0.64 to 2.55 Mrad. Furthermore, the authors determined the minimum radiation dose for 12% apple juice and for 67% apple concentrate at which the irradiation flavour is first perceived (treshold of perception).


[Biochemical parameters of blood plasma, and body and organ weights of Wistar rats with dietarily-induced experimental obesity].

The authors investigated in rats with dietarily-induced obesity certain biochemical parameters of the blood plasma as well as body and organ weights during the dynamic and the static phase of obesity development. They determined total cholesterol, total protein, albumin, creatinine, urea nitrogen and transaminases. After 4-5 weeks, the animals on a high-diet (50% of fat) had body weights which were, on an average, by 90% higher than those of the control animals. This difference persisted during the static phase. In the animals on a high-fat diet, body length was greater. The high-fat diet (which contains a great proportion of sunflower oil) leads to a decrease of the plasma cholesterol level in obese rats. The plasma-protein bodies, creatinine and urea nitrogen values as well as those for transaminases permit, as parameters for function and damage, to draw conclusions as to kidney and liver damages in the animals on high-fat diet. There were no differences in plasma protein between the control and experimental animals. On the contrary, obese rats showed in some cases high creatinine concentrations during the dynamic phase. Differences in urea nitrogen were not observed between the two groups of animals. Increases in alanine aminotransferase were found in the animals on high-fat diet as a manifestation of fatty degeneration of the liver. A synopsis of weight curves, biochemical parameters and histological findings permits the conclusion that, besides of dietarily-induced metabolic alterations, no additional organic lesions occurred during the present animal experiment on dietarily-induced obesity.


[Feasibility of using meat from swine with diet-related yellow coloration of the fat].

The utilization of the flesh of swine objected to because of dietarily-induced yellowing of the fat is an economic problem. The causes of yellowing are explained on the basis of relevant literature and results from studies of the author. The potential use of this flesh in making raw sausages is investigated. The results obtained justify such an utilization. The knowledge acquired permits to recommend this flesh for the manufacture of "Knacker" (a highly seasoned dried sausage) and "Braunschweiger Mettwurst grob" (a kind of Bologna sausage).


Reactions of oxidized lipids with protein. XIII. Interactions of polar groups of lipids with nonlipidic substances.

Contrary to fresh lipids, oxidized lipids form chloroform-insoluble, but methanol-soluble compounds with cellulose. The amount of chloroform-insoluble lipids is significantly higher in mixtures containing cellulose impregnated with albumin. Polar groups of oxidized lipids formed nonextractable compounds with protein more readily than polar groups of a monoglyceride. Compounds insoluble either in chloroform and in chloroform-methanol or methanol were formed in contact of oxidized lipids with protein, contrary to mixtures of lipids with sole cellulose. The formation of these nonextractable compounds is due both to the interaction of protein with hydroperoxides and with non-peroxidic oxidation products.


[New methods for analysis and evaluation of sensory qualities of foods and calculation of changes. 10. Quantitative titrimetric determination of irradiation flavor in apple juice and concentrate and its dependence on radiation dosage].

Irradiation flavour in apple juice and concentrate which is mainly attributable, according to our previous studies, to tetrahydrofuran (THF) that may be quantitatively determined by means of the so-called mercury acetate method. This is based on the fact that the amount of a 4% solution of mercury acetate needed for removing the THF odour is proportional to the THF concentration. Using this method, the amounts of THF produced by various gamma radiation doses (varying from 0.64 to 2.55 Mrad) could be determined titrimetrically. Calculations showed that the THF concentration increases linearly with the radiation dose. Thus, the minimum radiation doses at which the irradiation flavour is first perceived (threshold of perception) may be calculated readily. The mercury acetate method is also a model case of the use of subjective olfactometry for the quantitative determination of flavour key substances in foods so far as they may be quantitatively determined by means of chemical reactions since the endpoint of titration is controlled by the sense of smell.


[Nutritional study of field bean protein isolate and of spun field bean protein-casein fibers].

The amino acid composition of the different field bean protein isolates shows a good correspondence. In relation to casein the content of the whole essential amino acids is low. In the first line the low content of methionine and cystine limits the biological value of this proteins. The content of lysine is relatively high. The enzymatic in vitro-hydrolysis results in a corresponding availability of the amino acids between the field bean proteins and casein. The digestibility is very good, the biological value with less than 50 relatively low. Apart from the low content of the sulphur containing amino acids the amino acid composition of the spun field bean protein/casein(I:I) fibers corresponds with the calculated value; the enzymatic availability of the fibers is also comparable with casein. The digestibility in the nitrogen balance test is very good and the biological value of the fiber corresponds with that of casein.


Neutron diffraction studies of retinal rod outer segment membranes.

Neutron diffraction measurements on isolated retinal rod outer segments show that most of the visual pigment protein, rhodopsin, is embedded in the hydrophobic core of the disk membrane. A very slight outward shift of protein at the cytoplasmic side of the membrane is associated with pigment bleaching.


Model for action of local anaesthetics.

Sodium channels in nerve membranes are postulated to be surrounded by lipid molecules in the gel (or crystalline) phase. Addition of local anasethetics triggers a change in the surrounding lipids to the fluid, liquid crystalline phase, allowing the sodium channel to close with resulting local anaesthesia. The experimental evidence for this model is discussed.


Cellular basis for the T wave of the electrocardiogram.

Differences in action potential duration in different regions of the mammalian ventricle are not systematically present when quiescent tissue is first stimulated, but develop rapidly during repetitive activity. The effects of ouabain and temperature suggest the involvement of the Na+-K+ exchange pump.


Lambda repressor regulates the switch between PR and Prm promoters.

The DNA region containing the Or operator, Pr and Prm promoters and their transcription initiations is sequenced. By binding to Or, repressor turns off Pr, turns on Prm and at higher concentrations turns off Prm, regulating its own synthesis. Prm mRNA is unique in beginning immediately with the initiation of translation, without a preceding leader sequence.


Significance of impulse activity in the transformation of skeletal muscle type.

The changes which follow cross reinnervation of mammalian fast and slow twitch muscles may reflect a capacity of skeletal muscle to respond adaptively to different functional requirements. This interpretation is supported by experiments in which long-term electrical stimulation was used both to reproduce and to oppose the effects of cross reinnervation.


Structure of locust adipokinetic hormone, a neurohormone that regulates lipid utilisation during flight.

Adipokinetic hormone, isolated from locust corpora cardiaca, has been identified as a blocked peptide: PCA-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2. The detailed structure is based on mass spectrometric data, substantiated in part by dansyl-Edman and carboxypeptidase data on thermolytic fragments. This is the first peptide hormone from an insect neuroendocrine organ to be fully characterised.


Complementary base pairing and the origin of substitution mutations.

On the basis of chemical considerations and model building, the Watson-Crick concept of complementary base pairing is extended to a wider range of DNA pairs that A-T and G-C (including A-C, G-T, A-A, G-G and G-A) by invoking imino or enol tautomers (or protonated species) and synisomers. The virtual absence of these additional base pairs from DNA is explained in terms of the low frequency with which these unfavoured forms occur and the two-step mechanism of DNA synthesis, whereby residues are first incorporated by the DNA polymerase and then checked. This base-pairing hypothesis is used to explain the origin, nature and level of spontaneous substitution mutations, their enhancement by base analogues, and the unique effects of certain mutator alleles.


Base pairing and fidelity in codon-anticodon interaction.

Base pairing in codon-anticodon interaction has been investigated in order to understand the basis on which particular base pairs have been selected for or against participation at the wobble position and the basis for codon-anticodon infidelity.


Crystal structure of elastase-substrate complex at -- 55 degrees C.

The structure of a specific acyl-enzyme intermediate in the elastase-catalysed hydrolysis of N-carbobenzoxy-L-alanyl-p-nitrophenol ester has been determined by X-ray diffraction at 3.5 A resolution. The acyl-enzyme was stabilised by cooling the crystal to --55 degrees C during substrate addition and data collection.


The effect of inhibitors of extraneuronal uptake on the distribution of 3H-(+/-)noradrenaline in nerve-free rabbit aortic strips.

1. Nerve-free rabbit aortic strips were exposed to 1.18muM 3H-(+/-)noradrenaline for 30 min. When either MAO or COMT was inhibited, far more O-methylated (MAO inhibited) than deaminated metabolites (COMT inhibited) were formed during the incubation. The accumulation of unchanged amine in the extraneuronal stores was inversely related to the rate of metabolism. 2. After inhibition of both metabolizing enzymes, nerve-free strips were first incubated with the amine and then washed out with amine free solution. Compartmental analysis of the efflux curves showed that two extraneuronal compartments were involved in accumulation (with half times of efflux of 3 and 11 min, respectively). 3. 86muM corticosterone or 30muM phenoxybenzamine greatly decreased the accumulation of noradrenaline in these two compartments. 4. When corticosterone or phenoxybenzamine was added to the wash out solution only, the half time of the efflux from both compartments was greatly increased. However, this effect was seen only after inhibition of COMT and not after inhibition of MAO only (the filling of the extraneuronal stores with unchanged noradrenaline being better after inhibition of COMT than when this enzyme was intact). The effect of corticosterone appeared to be reversible, that of phenoxybenzamine irreversible. 5. Analysis of the efflux of metabolites (in experiments in which only one enzyme was inhibited) indicated that corticosterone affected the efflux of noradrenaline but not that of the metabolites. 6. When either COMT or MAO was inhibited throughout the experiment, very little or no metabolism of noradrenaline occured during prolonged wash out. On the other hand, dis-inhibition of COMT during wash out (by the omission of U-0521 from the wash out solution after it had been present during the initial incubation) revealed that noradrenaline, stored extraneuronally during the initial incubation, is quickly O-methylated during wash out, especially when the efflux of the parent amine is inhibited by corticosterone. 7. The results show that COMT is the major extraneuronal noradrenaline-metabolizing enzyme of rabbit aorta, that inhibition of COMT is a pre-requisite for any corticosterone-sensitive accumulation of noradrenaline, that there are two important extraneuronal compartments (compartments III and IV; Henseling et al., 1976a), and that inhibitors of extraneuronal uptake inhibit both, influx and efflux of noradrenaline.


Lack of epinine formation in adrenal medulla and brain of rats during cold exposure and inhibition of dopamine beta-hydroxylase.

Cold exposure of rats for 4 h and simultaneous inhibition of dopamine beta-hydroxylase by FLA-63 (25mg/kg) led to a reduction of the catecholamine content of the adrenal medulla by 46% and of the brain by 68%. Additional injections of 5 mg/kg FLA-63 4 and 9 h after beginning of the experiments, respectively, kept the catecholamine content on this low level (brain) or decreased it further (adrenal medulla). Administration of 5 mg/kg (-)DOPA together with the mono-amine oxidase inhibitor pargyline (50 mg/kg) 24 h after the first injection of FLA-63 stimulated the resynthesis. It amounted for the adrenal medulla to 20 mug/kg body weight/8 h and for the brain to 45ng/g tissue wet weight/8 h. Paper chromatographic analyses of the extracts of adrenal medulla and brain, respectively, performed at each time of the different injections, clearly identified adrenaline, noradrenaline and dopamine (in traces) in the adrenal medulla as well as noradrenaline and dopamine in the brain; epinine on the contray could not be demonstrated, not even in traces. Since at least 25 ng of epinine can be detected with certainty by our method, it can be concluded that epinine is not formed in amounts greater than 75 ng/pair adrenal glands or 37.5 ng/brain. The present results support the view that the main pathway of adrenaline biosynthesis in the suprarenal medulla and the brain proceeds via noradrenaline and not via epinine.


The molecular weights of plasma and intestinal kallikreins in rats.

1. The molecular weights of kallikreins of rat intestine and rat plasma have been estimated using gel filtration. 2. Extracts of pooled tissue from rat jejunum, ileum, caecum and colon activated by autolytic processes gave a single peak of kallikrein activity with a molecular weights of 33000. 3. Acid-activated rat plasma gave two peaks of kallikrein activity with molecular weight of 125000 and 61500. 4. Rat intestinal tissue contains a kinin forming enzyme having a molecular weight similar to those of glandular kallikreins and different from those of the rat plasma kallikreins.


Selective noradrenergic denervation of the heart following intravenous injections of vinblastine or vincristine.

1. The progressive effects of a single injection (3mg/kg i.v.) of either vinblastine or vincristine on the innervation of the rat atria have been examined. 2. Functional studies were performed by stimulating electrically the noradrenergic or cholinergic nerve fibres within isolated left atria from treated and control rats. In addition, the effects of the drugs on the ultrastructure of both types of nerve fibre were examined. The noradrenergic innervation was further examined by fluorescence histochemistry and measurement of the noradrenaline content of the atria. 3. On the basis of these studies it appeared that both drugs caused degeneration of noradrenergic nerves; cholinergic nerves seemed to be unaffected. Marked effects were seen 48 h after vinblastine treatment or 30 h after vincristine treatment. 4. Evidence is presented and discussed as to whether or not this action of the vinca alkaloids can be ascribed to their well-established effects on microtubules and intra-axonal transport processes.


Pharmacokinetics of phenprocoumon in man investigated using a gas chromatographic method of drug analysis.

A gas chromatographic method for the determination of phenprocoumon (Marcumar) in serum and urine is described, which facilitates accurate values down to 0.5 mug phenprocoumon/ml serum. After the i.v. administration of 20 mg phenprocoumon in a single  dose to 4 healthy volunteers the following pharmacokinetic data were obtained: After the initial fast decrease (phase 1) of the serum level of phenprocoumon, probably due to the distribution into the different compartments is followed by a subsequent slower fall (phase 2) which occurs with a serum half-life of 157 h. The apparent distribution volume was 6.51. Analysis of the urine demonstrated that 90% of the excreted phenprocoumon detected was in the glucuronide form.


Persistent enhancement of potassium-induced responses of the rat vas deferens by desipramine.

The effect of desipramine on the cumulative dose-response curves of noradrenaline and potassium (K+) was examined on the isolated rat vas deferens. An exposure of 10 min to 10(-7) M desipramine caused a leftward shift and an increase in the maximum response of cumulative dose-response curves of noradrenaline. Desipramine (10(-7) M), in contact with the tissue for 10 min, enhanced responses to cumulative additions of K+ without causing a consistent change in threshold concentrations. Wash-out of desipramine resulted in a rapid loss of enhanced maximum response to noradrenaline while the maximum response to K+ did not show any decrease for up to 120 min after wash-out of drug. One possible explanation for the persistent enhancement of K+-induced responses may be that desipramine causes postjuntional changes which selectively influence contractile responses of this tissue to K+.


Effect of dantrolene sodium upon the activity of the hind leg muscle of the cat with local tetanus.

Cats with local tetanus were i.v. injected with dantrolene sodium. There is no effect of dantrolene sodium on the electromyogram in response to indirect stimulation of the non-poisoned muscle nor on the increased spontaneous activity of the poisoned muscle. The tension of the muscle, however, was strongly reduced.


Differential effect of raised Mg2+ concentration of K+ ion movement and on swelling in the isolated perfused rat liver poisoned by phalloidin.

The K+ release from the isolated perfused rat liver induced by phalloidin was strongly inhibited on raising the Mg2+ concentration of the perfusion medium from 0.5-40mM while, in contrast, the phalloidin induced swelling of the organ and the vasuolisation of the liver tissue was not affected.


Chronopharmacokinetics of ethanol. II. Circadian rhythm in rate of blood level decline in a single subject.

A male human subject administered single, oral doses of ethanol was examined repeatedly for venous ethanol levels. Four separate trials, begun at 03.00, 09.00, 15.00, and 21.00 h, on different days yielded four different estimates of the slope of the apparently linear ethanol disappearance curve. The slopes appeared to exhibit circadian rhythmicity. In a second study of the same subject, the slope was estimated 7 times over a period of 26 h following repeated oral doses. These slopes also appeared to vary in a daily fashion. These preliminary results suggest that pharmacokinetic parameters may not be invariable with time of day.


3-Methoxytyramine as an indicator of impulse-induced dopamine release in rat brain in vivo.

3-Methoxtyramine and dopamine accumulated in vivo in rat brain after monoamine oxidase inhibition with pargyline HCl. A dose of 100 mg/kg i.p. appeared to inhibit monoamine oxidase completely and led to a linear accumulation of 3-methoxytyramine for the first 90 min. Axotomy of the ascending dopaminergic fiber tract by means of a complete transverse cerebral hemisection almost completely blocked 3-methoxytyramine formation provided that catecholamine synthesis was inhibited with H 44/68 (Methylester of alpha-methyl-p-tyrosine). The dopamine receptor agonist apomorphine, 0.5 mg/kg i.p., decreased, while the dopamine receptor antagonist haloperidol, 2 mg/kg i.p., accelerated 3-methoxytyramine formation. gamma-Butyrolactone, 750 mg/kg i.p., not only decreased 3-methoxytyramine formation per se but also effectively antagonized the haloperidol-induced increase in 3-methoxytyramine accumulation. 3-Methoxytyramine formation after inhibition of monoamine oxidase appears to be a reliable indicator of impulse-induced dopamine release and metabolism.


The effects of methacholine and calcium deprivation on the release of the false transmitter, alpha-methyladrenaline, from the isolated rabbit heart.

1. Anaesthetized rabbits were infused for 20 min with 85 mug-kg-1-min-1(+/-)-alpha-methyladrenaline. The hearts dissected 15 min after the infusion contained 1.49 mug/g alpha-methyladrenaline; the endogenous noradrenaline content was correspondingly decreased. 2. Hearts from alpha-methyladrenaline-infused animals were isolated with the right sympathetic nerves intact and perfused. Ventricular rate, right atrial and right ventricular tensions were recorded using the transverse method. 3. Electrical stimulation (10 Hz, 1 ms, 1 min) of sympathetic nerves, perfusion with the nicotinic drug, p-aminophenethyltrimethylammonium (PAPETA) or perfusion with 54 mM KCl (high K+) solution evoked an output of both alpha-methyladrenaline and noradrenaline. The ratio of the amines in the perfusates was similar to that found in the hearts after termination of the experiments or in non-perfused hearts. 4. Methacholine perfused before and during sympathetic nerve stimulation, PAPETA or high K+ inhibited the release of both false transmitter and noradrenaline. These effects were reversed by atropine. Similarly, lowering the calcium chloride concentration of the medium from 1.8 to 0.1 mM decreased amine outputs. This was reversed by washing. 5. Tyramine evoked a preferential release of the false transmitter that was not altered by methacholine or calcium deprivation. 6. These experiments whow that the muscarinic inhibition of neuronal noradrenaline release and the requirement of calcium ions for its liberation by depolarizing stimuli can be extended to a false transmitter amine. It is suggested that the proportion of alpha-methyladrenaline to noradrenaline occurring in the perfusate during administration of tyramine reflects the relative concentrations of the amines in the axoplasm.


Factors determining the rate of relaxation of rabbit aortic strips after an exposure to noradrenaline.

1. When noradrenaline distributes exclusively into the: extraneuronal o-methylation of about one third of the extracellular space (i.e., when both, neuronal and extraneuronal uptake mechanisms are blocked by the presence of cocaine and corticosterone), the response of rabbit aortic strips to noradrenaline is concentration-dependent and relaxation curves (obtained during wash out and starting from different heights) are parallel. Under these conditions the "time required for relaxation to 50 or 20% of the initial contraction" (t50 and t20, respectively) is positively correlated with the initial height of contraction. 2. Measurements of the rate of relaxation that are independent of the height of the initial contraction are obtained either by appropriate correction of the t50 (or t20) or by determination of the "average rate of relaxation down to the 25% level of maximum contraction". 3. Relaxation experiments should a) be carried out with initial contractions of less than 75% of maximum and b) use a measure of the rate of relaxation that is independent of the initial height of contraction. 4. When the experimental conditions favour the extraneuronal accumulation of noradrenaline, corticosterone affects the relaxation of the strips in a way which is consistent with the view that efflux of unchanged amine from extraneuronal stores influences the rate of relaxation. 5. When extraneuonal uptake is operative and accumulation of noradrenaline is poor (i.e., when extraneuronal catechol-O-methyl transferase is intact), corticosterone affects relaxation in a way which is consistent with the view that normally the extraneuronal system serves as a site of loss. Under these conditions corticosterone prevented, during the first 5 min of wash out, the extracellularly distributed amine. 6. It is concluded that the experimental conditions of relaxation experiments determine whether the noradrenaline stores serve as a source of efflux of unchanged amine or as a site of loss.


Factors responsible for reduced pharmacological activity in rats of pentetrazol administered orally.

It was the aim of this investigation to find out why pentetrazol (PTZ) administered orally to rats has considerably lower convulsive effectiveness than PTZ injected parenterally. It could be demonstrated that PTZ is distributed to and eliminated from all organs analyzed, without any sign of storage or of redistribution. Biological halftime was found to be about 3.5 h after subcutaneous injection. PTZ is absorbed slowly from the gastrointestinal tract because PTZ given orally is retained in the stomach for many hours. PTZ absorption is slow from the stomach while it is rapid from the small intestine. Food taken in before and after PTZ administration decreases the rate of PTZ absorption. Retention in the stomach of PTZ given orally is probably due to delayed gastric emptying since PTZ is able to reduce the basal tone and the acetylcholine-induced contractions of isolated preparations of the fundus of the stomach.


[Dynamic characteristics of auditory analyzer neurons and their relation to selective-combination mechanisms of cerebral functional organization].

Neuron responses in the chicken torus and caudal neostriatum to signals with different ecological significance (tones "white" noise, species-specific signals) were studied. It is shown that the frequency band percepted by the acoustic analyzer neurons corresponds to the frequency composition of signals emanated by chickens. Neurons selectively responding to the species-specific signals (song, alarm cries) were found in the forebrain. The specificity of the functional organization of different levels of the acoustic analyzer is considered in the light of the selectively combination principle of the signals integration, which may determine the mechanism of both innate and learned memory.


[Responses of neurons of the first and second somatosensory zones of the cortex to peripheral, thalamic and cortical stimulation].

Experiments were performed on cats immobilized with d-tubocurarine or myorelaxin. Neuronal responses were studied in the first somatosensory cortex (SI) to the second somatosensory cortex (SII), ventroposterior nucleus (VP) and contralateral forepaw stimulation. Besides, neuronal responses in SII to SI, VP and contralateral forepaw stimulation were also studied. It was shown that in SII the percentage of neurons excited by afferent volley with two or more synaptic change-overs in the cerebral cortex was larger than in SI. Neurons of SI and SII responded to cortical stimulation ortho- and antidromically, thus confirming the existence of bilateral cortico-cortical connections. Both in SI and SII, PSPs to cortical stimulation were similar in character to PSPs in the same neurons to VP stimulation. In 50.0% of SI neurons and 37.1 of SII neurons the difference in latencies of orthodromic spike potentials to VP and cortical stimulation was less than 1.0 ms. In 19.6% of SI neurons and 41.4% of SII neurons the latency of the response to cortical stimulation was 1.6-4.7 ms shorter than that of the response in the same neuron to VP stimulation. It is supposed that impulses from SI participate significantly in afferent activation of SII neurons.


[Electrophysiologic study of cortico-hypothalamic interrelationships in cats].

In acute experiments on cats anesthetized with nembutal and chloralose the projections of different parts of orbito-frontal cortex, basal temporal cortex and hippocampus to hypothalamic nuclei were studied by focal potential recording. It was found that the proreal gyrus has local projections into the latero-dorsal parts of the preoptical region, rostral parts of the forebrain medial bundle, lateral and posterior hypothalamus with mammilary bodies. The orbital gyrus is projected mainly into latero-dorsal parts of the forebrain medial bundle, latero-ventral part of the preoptical region, and the region of lateral and latero-dorsal hypothalamic nuclei. Projections from the orbital gyrus are of a relatively diffuse character. The basal temporal cortex has diffuse projections into the central part of the preoptical region, latero-ventral part of the forebrain medial bundle and lateral mammilary body. No pronounced foci were observed in the hypothalamic structures during stimulation of the hyppocampus, but diffuse projections were found into ventral parts of the preoptical region and ventral regions of the forebrain medial bundle as well as into lateral hypothalamus and lateral mammilary nucleus.


[Organization of cortico-reticulo-spinal connections in the cat].

Time characteristics of the monosynaptic EPSP evoked by stimulation of the motor cortex in reticulospinal neurons were studied in detail. Negative correlation was revealed between latency duration of EPSP and conduction velocity of the corticobulbar fibres and positive correlation between such characteristics and conduction velocity of axons. Reticulospinal neurons with conduction velocity from 10.8 to 65.0 m/s were activated by fast and slow corticobulbar fibres, but neurons with conduction velocity from 65.0 to 155 m/s were activated only by slow ones. A functional role of different cortico-reticulo-spinal connections is discussed.


[Reticular structures and reticulospinal pathways participating in initiation and inhibition of spino-bulbo-spinal activity].

Efferent discharges in intercostal nerves and activity of reticulospinal fibres during stimulation of the brain stem reticular formation, intercostal splanchnic nerves were recorded in cats anesthetized with chloralose (50 mg/kg). It is found that the structures involved in the transmission of spino-bulbo-spinal activity are located in the medial bulbar and pontine reticular formation as well as in its lateral regions. The structures producing long-lasting (300-800 ms) inhibition of spino-bulbo-spinal reflexes are also wide distributed in the brain stem, especially in the pontine region. Recording of activity of single reticulospinal fibres in the ventral (conduction velocity 16-120 m/s) and lateral (17-100 m/s) funiculi during spino-bulbo-spinal reflexes showed that both medial and lateral reticulospinal tracts may be involved into this reflex mechanism. New evidence is obtained that the inhibition of spino-bulbo-spinal reflexes may be located at supraspinal level.


[Structure of afferent flow in a cutaneous nerve during painful and non-painful mechanical stimulation of cat skin].

Using the colliding impulses method, a quantitative characteristic of afferent flows encoding signals from a receptors totality is given. The frequency spectrum of impulsation in the cutaneous nerve, relative quantity of active A-, Adelta- and C-fibres, and their distribution by impulsation frequency under skin stimulation with pins and needles are found. The afferent impulse flow registered in the nerve under pinning of skin is characterized by a high density determined by the quantity of excited fibres and their impulsation frequency. Nonmyelinated fibres directly excited under painful stimulation generate high frequency impulsation due to which the flow density in the nerve increases. The quantity of active myelinated fibres and the frequency of their impulsation under pricking do not increase considerably in comparison with the same characteristics under unnoxious stimulation of cutaneous receptors.


[Effect of calcium ions on potential-dependent potassium channels in the membrane of the soma of giant mollusc neurons].

The delayed and fast outward currents in the somatic membrane of mollusc giant neurons were studied under voltage-clamp conditions in normal (10 mM) and low-Ca (I mM) saline. At pH 7.2 a tenfold decrease in calcium concentration in the peak conductance vs membrane potential curves for delayed and fast outward currents were shifted along the voltage axis by 10 mV. The shift along voltage axis of the inactivation curve for fast outward current under similar conditions was the same. At pH 9 the shift for a tenfold decrease in calcium concentration was 20 mV. Such an increase in the effect of calcium concentration change at pH 9 is probably due to the increase in the negative charge density in the vicinity of the potassium pathways. The dependence of the rate constants of inactivation alphab and betab for fast outward current upon the membrane potential was studied in solutions with different calcium concentration. The expressions for their calculation were obtained.


[Displacement currents of the sodium channels of the membranes of Ranvier's nodes].

A method to record the displacement current in nodal membrane is described and results obtained on nerve fibres from the frog Rana ridibunda are presented. This current is shown to be due to displacement of charges from an initial state, associated with a large negative membrane potential, to a final state. The dependence of the charge displacement on the membrane potential and degree of inactivation of the sodium channels suggests that the displacement current observed in these experiments is associated with activation of m-gates of the sodium channels. The density of the sodium channels in nodal membrane of Rana ridibunda determined from the density of the charge displaced is about 5000 channels/mum2.


[Decrease in the maximum sodium permeability and slow sodium inactivation in Ranvier's nodes treated with trimecaine].

The effect of local anesthetic trimecaine on sodium permeability was studied in voltage clamped nerve fibres of the frog. Trimecaine affected PNa by means of two different mechanisms: potential independent block (reduction of PNa) and slow inactivation imposed by prolonged depolarization. Trimecaine induced slow inactivation appeared to be qualitatively similar to that produced by externally applied procaine or high external potassium. According to dose-effect curves one molecule of drug per channel reaction is involved for both mechanisms. The drug molecule has greater affinity for the receptor site responsible for slow inactivation.


Preliminary analysis of failures in the radiotherapy of uterine cervix cancer with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure.

Complementary to a previous preliminary analysis of the results obtained in treating head and neck tumors, this paper summarizes observations in testing uterine cervix cancers with a dynamic dose-fractionation regime using Cobalt 60 radiation in combination with oxygen breathing at ambient pressure. A total of 30 cases in different stages are reviewed which had no treatment prior to radiotherapy. In agreement with previous observations, normal tissue reactions were decreased in comparison to those seen after conventional dose-fractionation. Exophytic type of tumors with relatively good vascularization appears to react better to the treatment then less vascularized endophytic tumors. For the evaluation of the possible role of the dynamic fractionation in these results collection of further data is needed.


Peripheral blood lymphocyte counts and survival in breast cancer.

The lymphocytes in the peripheral blood of patients with breast cancer were studied. Peripheral blood lymphocyte counts were found to be significantly lower in the short-survivors when compared with the long survivors. Lymphocyte count may be a host factor, that influences survival in breast cancer.


Chemotherapy of advanced malignant lymphomas comparative evaluation of results with single agent and combination therapy.

86 patients with advanced malignant lymphomas (stage III and IV) were treated either with Vinblastine given as a single agent (49 cases) or with combination chemotherapy MOPP or COP (37 cases). In both, Hodgkin's disease and non-Hodgkin's lymphomas, induction of remission, relaps-free survival and prognostic significance of initial clinical stage were evaluated, in relation to the therapeutic modality. In patients with Hodgkin's disease, combination chemotherapy was found to produce significantly more durable remissions, when compared with single agent therapy. However, difference in the response rate, which was found to be more effective following the combination chemotherapy, was not statistically significant. In patients with non-Hodgkin's lymphomas overall lower response was recorded, regardless of the therapy applied. In all patients, better  response rate and longer lasting remissions correlated with initial stage III.


The metastatic spread of kidney and prostate cancers in man.

This research was performed on 66 autopsy reports of kidney cancers and 58 autopsy reports of prostate cancers. Two alternative hypotheses were tested, i.e. whether metastases spread at random from the primary tumor throughout the body or whether the metastatic spread occurs in steps, referred to as a cascade spread, requiring one or more disseminating sites. It was found that in cancer of the prostate two disseminating sites exist, i.e. bones and lungs. Metastases from the primary tumor appear first in the skeleton and then in the lungs, not vice versa. In cancer of the kidney, the lungs are the major disseminating site. The lymphatic areas did not seem to play a major role in the dissemination of both cancers; on the contrary, the presence of metastases in the lymph nodes seem to depend on the presence of carcinomatous cells in key sites, i.e. the skeleton and the lungs. These results, however, should be interpreted with caution, as explained in the text. Considerations were proposed for future research.


An assay for selecting high risk population for gastric cancer by studying environmental factors.

Gastric cancer mortality incidence data registered in two different areas of Eastern Transylvania (Roumania) were reported related to 325,000 inhabitants from the period of 1951-1972. The findings were compared to some geographical environmental factors deriving from an area of 13,300 km with 905,700 inhabitants. A 2-3.5 times larger incidence of gastric cancer (75-140 per 100,000/year) was found in some selected geographical areas of the intermontane depressions of Gheorgheni and Ciuc in comparison to hilly area of Transylvanian Tableland. The difference might be explained by some unknown environmental gastric cancer risk factors. Of the natural factors, the presence of magmatic substrata shows a significant degree of correlation. The main pedological factor seems to be badly drained pseudoglyied podzolic and peaty soils of low pH and high content of organic matter. Sofs drinking waters also may be involved as risk factor. High altitude, cold climate determining a restricted assortiment of cultivated plants, the successive production of vegetal and animal food on the same soil for livelong periods and several generations, especially in isolated rural areas, seem to represent gastric cancer risk factors. According to authors' opinion a survey of the high-risk population selected on the basis of the environmental factors, especially of the persons suffering from gastric disorders considered today possible precursors of gastric cancer, may offer some progress in detecting early gastric malignancy in the future.


Effect of subarachnoid haemorrhage on micro-circulation in hypothalamus and brain stem of dogs.

In order to investigate the relationship between cerebral vasospasm and microvasculature in the hypothalamus and brain stem, colloidal carbon was infused into the vertebral artery at various time intervals after experimental subarachnoid haemorrhage in dogs. Experiments which demonstrated vasospasm on angiogram were always accompanied by ischaemic changes in serial sections taken from the anterior hypothalamus to the brain stem. However, when it was demonstrated by angiography that the vasospasm had disappeared, the micro-circulation was restored to normal. Electron microscopy of the hypothalamus 48 hours and one week after subarachnoid haemorrhage, demonstrated swelling of the endothelial cells, enlargement of the perivascular glia and increase in number of the pinocytic vesicles in the cytoplasm, thus showing vasogenic oedema in this area. It is assumed that in addition to the vasogenic substance in extravasated blood, changes in irritability of cerebral vessels through the vasomotor pathways in the hypothalamus and brain stem might play an important role in the production of cerebral vasospasm.


Role of the pneumo-encephalogram in the diagnosis of spontaneous subarachnoid haemorrhage.

The authors have collected eighteen cases of primary intraventricular lesions revealed by a subarachnoid haemorrhage. Among these cases, the most important are the choroid plexus papillomas followed by ependymomas; some cases have no precise histological interpretation. Generally speaking, cerebral arteriography gives only indirect evidence of ventricular dilation and thus does not confirm the presence of a lesion. On the contrary, the pneumoencephalogram is consistantly positive, but does not give the differential diagnosis between intraventricular tumours and primary intraventricular haemorrhages. This test should therefore be given the same importance as spinal cord arteriography in the exploration of subarachnoid haemorrhages with negative cerebral angiograms.


Acute spontaneous volume fluctuation in the brain. A contribution to the interpretation of plateau waves. Results of CSF measurements with ventricular drainage.

Primarily the theoretical background of the relation between the intracranial pressure and the volume is discussed. From the definite relationship between volume and pressure it is deduced that with the appropriate equipment intracranial volume changes may be measured instead of the I.C.P. The exact measurement of the volume of CSF drained in relation to the drainage time enable us to differentiate disturbances of the C.S.F. circulation in patients. Furthermore we were able to correlate "plateau waves" with certain amounts of volume fluctuations; these were shown in amounts of drained C.S.F. between 16 and 32 ml. Some scientific aspects of this new method and possible results are pointed out.


Spinal fluid lysozyme in the diagnosis of central nervous system tumours.

C.S.F. lysozyme concentrations were determined in 24 normal subjects and 14 patients with a variety of neurologic diseases. We found absent or very low activity (below 0-5 mg/ml, in 4 out of 24) in normal individuals. Patients with tumours and other neurological diseases had high lysozyme activity in C.S.F. Our findings suggest that lysozyme is not an accurate indicator of the presence of neoplastic disease as suggested by other investigators.


[Functional posterior radiculotomy, in the treatment of cerebral spasticity. peroperative electric stimulation of posterior roots and its use in the choice of the roots to be sectioned].

The authors present a modification of Foerster's Rhizotomy for the treatment of  spasticity in cerebral palsy: functional posterior rhizotomy. The selection of the roots/rootlesses to be sectioned, is accomplished on functional data, based upon the analysis of the reflex responses to the intraoperative lumbar dorsal roots stimulation. With this method it is possible to selectively interfere with the pathological circuits responsible for hypertonia, saving proprioceptive afferences necessary for motor reeducation. The clinical results on hypertonia are the same as for total or partial rhizotomies, but sides effects (ataxia, hypotonia) are considerably reduced.


[Success and failure of the ventriculoperitoneal shunt in the treatment of hydrocephalus].

In ventriculoperitoneal shunting, the intraperitoneal location of the drainage site can be an additional cause of failure. In our series of 70 ventriculoperitoneal shunts, performed in infants and adults for treatment of hydrocephalus from various cause and of various type, failures of this kind manifested themselves usually early in the postoperative period either as a reflux of liquid, not attributable to the operative technique, into the subcutaneous pericatheter tract, or as a reappearance of the intracranial hypertension, without faulty functioning of the ventricular drain. The total success rate was 61% (43/70) but the age of the patient made a clear difference. In patients aged less than 5 months, we observed 11 successes in 33 cases (33%), in those aged less than 1 year, 14 successes in 36 (39%); patients with myelomeninogocele, wherein the shunting was usually done during the first month of life,  fared badly; the role of age seems herein predominant. In patients aged more than 1 year, 29 successes in 34 cases (85%) were obtained; results were notably good in nearly all hydrocephalus of tumoral origin. We think the possible role of the "tightness" of the hydrocephalus has to be invoked as also the possibility of spontaneous remission. Ventriculoperitoneal shunting, devoid of the serious complications of ventriculocardiac shunting, is a simple and effective procedure in many cases of hydrocephalus. Means for more accurate prediction of the chances of success in the individual case are needed.


[Intraspinal meningiomas. A series of 60 cases].

The authors present and compare two consecutive series of spinal meningioma, a total of 60 cases. From the aetiological point of view, the meningioma were more frequent than neurinoma. This study confirms its predominance in the female after the fifth decade. A traumatic factor was sometimes implicated. Anatomically, its localisation predominated in the dorsal region (78.3 p. cent), specially in the first three vertebral segments, and most commonly laterally placed. The strictly epidural meningioma, the multiplicity and the association with a neurinoma were less frequent. On the clinical level, the comparison between the two series illustrated a considerable diminution of the pre-operative evolution of the disease, taking into consideration the existence of spinal deficit less apparent in patients operated after 1963. 54.5 p. cent presented at diagnosis, a total or partial impotence against 81.5 p. cent in the old series. Among the laboratory examinations, the C.D.F. study confirmed slight or even absent cyto-albuminous dissociation, which contrasted markedly with the figures obtained in cases of neurinoma. Plain spinal radiography was usually negative. The radio-opaque myelography revealed a block, sometimes a partial one, very suggestive when bossulated, but which might sometimes mimic a neurinoma or even an epidural lesion. The presence of an arachnoid cyst may give a false level. Surgery was always indicated, regardless of the patients' age. The tumour should be completly removed in a piece-meal fashion with the preservation of the radiculo-medullary elements, which was facilitated by the use of the microscope. To prevent a recurrence, the base of the tumour should be well coagulated or resected followed by a plastic reconstruction of the dura mater. The mortality rate including the late mortality has diminished from 24 p. cent to 11 p. cent. This is essentially due to decubitus in patients who did not improve. The percentage of complete functional recovery rose from 40 p. cent to 66 p. cent of those who survived. The percentage of recovery with sequellae compatible with an autonomous physical activity was stable. The percentage of completly handicaped survivals fell from 28 p. cent to 5 p. cent. The authors conclude that the prognosis for patients with intraspinal menigioma has improved, however the diagnosis is still difficult in the old subject, and there is a serious risk to life when the lesion is in the cervical region.


[Value of the intracranial pressue measurement in the craniosynostoses detected after the age of 1 year].

Notwithstanding the fact that there is a general agreement on the necessity of surgery in the first year of life in craniosynostosis, the problem is more difficult for older children. Deterioration of clinical status is, in general, in relation with an increase in intracranial pressure (ICP), which may happen abruptly following different causes (slight head injury, for example). The purpose of this study was to determine, in different varieties of synostosis, if a high intracranial pressure could exist without clinical signs and consequently, if a surgical opening of the sutures would be necessary. IPC has been measured through a ventricular catheter connected with a transducer and recorder for 24 hours. In half of the cases (11 out of 22) a high ICP (above 20 mmHg) was recorded either permanently or during sleep. This increase in ICP should lead to a surgical decompression, event without clinical signs. On the other hand, psychomotor retardation, abnormal EEG, increased digitation should not be considered as an indication for surgical treatment in cases with normal ICP. The measurement of decreased ICP after operation on a long term basis would be a great value.


[Comparative in vitro action of various antimitotic agents on cell lines established from human brain neoplasms].

The effects of six chemotherapeutic drugs currently used in human gliomas treatment were tested with an in vitro cytotoxicity test. Out of six, VM 26 proved to be the most potent against tumor cells along with a moderate cytotoxicity against normal brain or embryonnic human cells. This specificity did not seem to be related to differences in cellular growth rates.


[Giant aneurysm of the sylvian artery in a 4-year old child (exeresis, remission)].

The AA. describe a case of a giant aneurysm 6 centimeters in diameter in a child of 4 years old. The lesion was made evident on the occasion of an hemorrhage that has caused an insular hematoma. The patient has undergone an operation with favourable outcome. The lack of neurologic symtomatology until the moment of the hemorrhage lead the AA. to think that this lesion was of the notables proportions from the moment of birth, so that the cerebral parenchyma was modeled on it. Unlike others cases in litterature recogniset, the wall of the aneurysmatic bag did not present fibrotics thickenings, and besides the blood-clot included in it seemed histologicaly of recent formation.


[Sensory organization of the reticular formation: Specific integrative activity].

On the basis of personal investigations including 1) electrophysiological methods (EEG, averaged evoked potentials), 2) behavior methods, 3) destruction of various parts of the brain (mesencephalic reticular formation, auditory pathways) and 4) pharmacological methods, conducted in the years 1953-1974 the author put forward a concept of sensory organization of reticular formation postulating existence of special systems in the reticular formation differing in their relative physiological and chemical specificity. This relative specificity is, in this concept, the ability of the so-called non-specific neurons in the reticular formation to be included under certain experimental conditions into specific functional systems. The author suggests the term "paraspecific systems" for designating these relatively specific systems. It seems that these systems determine the integrative role of reticular formation in the process of learning. In contrast to this important role the reticular formation is without any greater importance for the process of memory storage. The dynamic and relatively specific functional organization of reticular formation provides potential possibilities of its utilization in the processes of reeducation or rehabilitation in central nervous system damage and in pharmacological treatment of psychic disturbances.


[Gasometric studies of arterial blood in patients with stroke].

Gasometric determinations of pCO2, pO2, HCO3 and SO2 were performed in arterial blood in 100 patients with brain stroke. The following conclusions have been drawn. 1. In 2/3 of cases of brain stroke decreased partial oxygen pressure and in 1/3 of cases acid-base equilibrium disturbances are observed. 2. Hypoxia occurs in brain stroke mainly in patients with consciousness disturbances, which suggests that impaired airways patency plays a role in the pathomechanism of this disturbance. 3. Acid-base equilibrium disturbances in cases of brain stroke have in most patients the character of respiratory alkalosis which seems to be due to hyperventilation determined by central nervous mechanisms as well as to hypoxia caused by insufficient patency of airways. 4. Gasometric investigations of arterial blood in brain stroke are important for establishing the degree of homeostasis disturbances and for choice of methods of therapeutic management.


[Usefulness of electromyographic examinations of paravertebral muscles in patients with lumbosacral root compression syndrome].

The author studied electromyographic findings and surgical exploration results in 37 women and 63 men operated upon for nucleus pulposus prolapse. EMG investigations of paravertebral muscles were found to be useful in the diagnosis of motor root lesions. A correlation was found between the size of prolapse and the area of denervation potentials in paravertebral muscles. On the other hand, it was found that these investigations do not indicate accurately the level of nucleus pulposus prolapse.


[Fatigability of stapedius muscle in myasthenia].

The fatiguability of m. stupedius was studied in 20 patients with myasthenia and 16 controls determining the reflex of this muscle by means of electroacoustic bridge. In half of the patients group the fatiguability of stapedius muscle was increased and in some cases the reflex threshold of the muscle was raised. The authors suggest continuation of these investigations especially for determination of the clinical importance of these observations.


[Our modification of ergograph for studying muscle fatigability in myasthenia].

The authors designed and made an ergograph of own modification and elaborated normal values of fatiguability half-time on the basis of 51 healthy subjects comparing the results with those in a group of 41 myasthenics subjected to thymectomy. The fatiguability half-time was determined in groups of muscles in the hand, axilla and popliteal area and masseters before and 14 days after thymectomy. The ergographic record was obtained without application of drugs as well as at the peak of activity of drugs and at the peak of activity of those after 5 mg Tensilon dose. The investigation made it possible to determine the muscle power before and after tymectomy. The Tensioln test at the peak activity of drugs permitted to establish the necessary dose of anticholinesterase drugs, especially after the operation.


[Improving radiographic diagnosis of the sella by means of direct magnification technics and autotomography].

On the basis of personal experiences with 30 cases and a survey of literature the authors discuss the value of radiological diagnostic assessment of sella using a technique of direct magnification and autotomography. The superiority of these techniques over the information obtained from plain films of the skull has been demonstrated. These techniques are easy, not time-consuming, they do not require complex apparatus and their costs approximate those of plain radiograms.


[As yet unknown sign in internuclear ophthalmoplegia: unilateral eyelid retraction occuring during abduction or adduction of the  eye bulb].

The author presents 2 cases of internuclear ophthalmoplegia with unilateral upper lid retraction and widening of the palpebral fissure of the adducted eye with a simultaneous narrowing of the palpebral fissure of the other eye. In the 3rd case of internuclear ophthalmoplegia with paralysis of the lateral rectus muscle, the sign of upper lid retraction was present in the adduced eye.


[Analysis of clinical and social features in a group of epileptics with frequent seizures].

A group of 50 epileptics (group C) with frequent seizures refractory to treatment was studied. The control group (R) comprised 50 cases with rare seizures. It was found that despite systematic treatment (with full therapeutic doses) and frequent changes of drugs the frequency of seizures was not reduced in group C. The analysis of clinical features of both groups showed that group C as compared with group R had more patients with temporal lobe seizures, neurological abnormalities, low intelligence quotient, changed background activity in EEG and longer duration of the disease. These data may suggest a greater number of cases with detectable organic brain lesions among patients with frequent seizures.


[Evaluation of selected parameters of calcium metabolism in epileptics on long-term treatment with diphenylhydantoin].

In 11 epileptics treated with DPH for 10-20 years a significant fall was observed in the serum levels of calcium, phosphates, and ionic index, with a significant rise in the serum magnesium concentration. No detectable changes were observed in the radiological appearance of bones and alkaline phosphates activity was within normal range. In two cases histological examinations demonstrated signs of osteomalacia. The authors postulate the necessity of monitoring selected parameters of calcium metabolism in patients on long-term treatment with diphenylhydantoin.


[Clinico-morphological analysis of clinically unrecognized subdural hematomas].

The authors report clinical and morphological analysis of 31 autopsied cases of subdural haematomas unrecognized during life. The most frequent erroneous clinical diagnosis was cerebrovascular brain disease, psychiatric syndrome or brain tumour. The greatest diagnostic difficulties were encountered in cases of subdural haematoma developing in elderly subjects (in this material 24 patients were aged above 60 years). Brain atrophy delayed in them the appearance of intracranial raised pressure syndrome, coexistence of vascular changes masked the signs of subdural haematoma and frequent memory disturbances made history taking difficult. Brain atrophy in elderly subjects may be also a factor contributing to development of subdural haematoma. Widening of subdural space causes greater tension of bridging veins and their easier rupture when the brain is displaced during trauma. Absence of inflammatory changes in the neuropathological findings in cases of subdural haemorrhage suggests that the term "chronic subdural haematoma" is better than the older term "pachymeningitis haemorrhagic interna".


[Preliminary evaluation of Rivotril in epilepsy].

Treatment with Rivotril in doses of 2-10 mg daily was given to 26 patients with various forms of epilepsy, mostly refractory to previous treatment. In 2 cases the drug was withdrawn on account of intolerance, in 4 cases treatment was stopped after several days in view of greatly increased frequency of seizures. In the remaining cases the drug was administered during 2 to 27 months, (mean 7 months) in 3 cases as the only medication and in 17 with other anticonvulsants. The best therapeutic results were obtained in patients with partial seizures of complex symptomatology and in generalized non-convulsive seizures, the worst results in generalized seizures. Electroencephalographic findings included particularly disappearance of seizure activity, while focal changes persisted and even grew worse in some cases. Apart from 2 cases of acute intolerance in another 4 cases side effects were observed with somnolence, dizziness, equilibrium disturbances, and in one case granulocytopenia developed. Allergic changes and liver or renal damage were never observed. The authors suggest introduction of the drug in treatment of epilepsy in view of its favourable clinical effect even in cases refractory to previous treatment, especially since the drug is relatively well tolerated.


[Hospital infections and their control in neurology departments].

The authors discuss briefly the problem of hospital infection, its nature, routes of spread and types of causative bacteria. A particular emphasis is laid on the problem of high risk neurological patients. Discussing the methods of hospital infection control in neurological departments the authors stress the importance of the room for minor diagnostic and therapeutic procedures since a real danger to the neurological patients is the possibility of infection during lumbar tap.


[Effect of deep hyperventilation on lactate concentration in cerebrospinal fluid and brain tissue].

Deep hyperventilation (HV)--pCO2 less than 15 mm Hg--was applied in rabbits with normal intracranial pressure (ICP) and in cats with experimental brain oedema developed after epidural balloon compression. In animals with normal ICP there was an increase of CSF and tissue lactate concentration as soon as after 45 min. of HV. The lactate concentration was increasing all the time during HV. The resumption of normoventilation (2 h) after 10 h of HV was sufficient to bring the lactate level down near normality. Electron microscope studies showed only slight ultrastructural changes without destruction, even after 10 h HV. In animals with increased ICP, brain oedema was the main factor raising the lactate level, while the effect of HV was negligible.


[Hyperventilation and mannitol administration during surgery in patients with space-occupying intracranial lesions].

The aim of this work was to evaluate the effect of hyperventilation and mannitol on brain volume during neurosurgical operations. The material comprises 30 cases of supratentorial tumours. pO2, pCO2, pH and lactate concentration were determined in the arterial blood and in 7 cases also in the CSF. It was established that hyperventilation sometimes fails to decrease ICP; it was observed that hyperventilation was more effective in decreasing brain volume of the pCO2 level decreased by 14,6 mm Hg on the average. The joint use of hyperventilation and hypertonic mannitol was found to be more effective. Neither of the above methods was effective in the case of cystic tumors.


The possible role of histamine in the control of prolactin and gonadotropin release.

To evaluate a possible role of histamine in the CNS control of prolactin and gonadotropin release, adult ovariectomized rats, with stainless steel cannulae implanted in the 3rd ventricle, were given s.c. injections of 10 mug of estradiol benzoate. 48 h later, 2 mul of 0.9% NaCl alone or of saline containing 1, 5, 25 or 125 mug of histamine dihydrochloride was microinjected into the ventricle. Immediately before and then 15, 30 and 60 min after, blood samples were withdrawn from etherized rats for radioimmunoassay (RIA) of serum prolactin, LH and FSH. In the histamine-injected rats, an increase in prolactin titers was observed and was highly significant in groups receiving the higher doses. A small yet significant release of LH, but not of FSH, was also observed. When 25 mug of histamine was injected directly into the pituitary or into the jugular vein, no elevations were observed, indicating a site of action in the brain. Restraint stress elevated serum prolactin and lowered serum LH and FSH in ovariectomized rats. These responses were blocked by the intrajugular injection of diphenhydramine (5 mg/kg). It is suggested that histamine may be involved in the hypothalamic control of prolactin release and possibly of gonadotropin release.


Differential effects of dopamine agonists and haloperidol on release of prolactin, thyroid stimulating hormone, growth hormone and luteinizing hormone in rats.

The dose-response effects of apomorphine and ET-495 (piribedil), 2 specific dopamine (DA) receptor stimulators, and haloperidol, a DA receptor blocker, were tested on the secretion of prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH) and luteinizing hormone (LH) in male rats. Both apomorphine and piribedil reduced serum PRL and TSH levels, stimulated GH release at low but not at high doses and either had no effect or tended to reduce serum LH levels. The minimal effective dose of apomorphine for reducing PRL by 30 min was 0.01 mg/kg; TSH inhibition was observed with a dose of 0.1-0.3 mg/kg. The inhibitory effects of apomorphine (1.0 mg/kg) on PRL and TSH levels were maximal by 15 min and diminished by 120 min; plasma GH was highest 120 min after injection. Thyroidectomy (10 days) markedLH elevated serum TSH, had no effect on serum PRL and inhibited the ability of apomorphine (0.1 or 0.3 mg/kg) to reduce TSH but not PRL levels. These observations may indicate that separate dopaminergic control mechanisms exist for TSH and PRL secretion. Administration of haloperidol elevated serum PRL, tended to lower TSH, dramatically reduced GH and had no effect on LH levels. Haloperidol pre-treatment blocked the effects of apomorphine on PRL, TSH, and GH secretion. The overall results of this study indicate that DA agonists inhibit PRL and TSH, stimulate GH but do not stimulate LH release in male rats.


[Chronic Horton's neuralgia treated successfully with indomethacin].

The author describes a case in which different types of headaches occurred in life. In childhood the patient had typical attacks of ophthalmic migraine, at the age of 45 years classical Horton's neuralgia developed lasting 5 months, occurring 3-4 times daily and 2-3 times in night time. The pains were intense, their location was always identical and their duration was 15-20 min. It seemed at the time of observation that they represented a form intermediate between that described by Ekbom and Olivarius and that reported by Sjaastad and Dale. After treatment with Indomethacin immediate improvement was obtained with disappearance of pains.


[Surgical treatment of hypophyseal adenomas using the nose and sphenoid sinus approach].

A method of hypophyseal adenoma removal through the nose and sphenoidal sinus is described. The method was used in 26 patients and no postoperative complications were observed. The approach to the sella from the sphenoidal sinus makes it possible to remove the tumour from the sphenoidal sinus and from the area below and behind optic chiasm.


Accumulation of 3H-testosterone in nuclear and cytoplasmic fractions of rat brain during postnatal development.

The accumulation of 3H-testosterone and its metabolites in the brain of neonatal and prepubertal rats was measured following injections of the hormone in vivo, or after incubation of minced brain tissue with 3H-testosterone in tissue culture medium. Radioactivity associated with purified nuclei and various cytoplasmic fractions of brain tissue was determined in 2-5-day, 10-12-day, and 25-32-day-old animals. Comparisons of radioactive steroids, accumulated 2 h after s.c. injections of 3H-testosterone or 3H-estradiol, showed that testosterone (T) is accumulated to a lesser extent than estradiol (E), but the age-related patterns of uptake are similar for both steroids. A continuous decrease in radioactivity was observed in nuclear and cytoplasmic fractions from the brains of 2-, 4-, and 12-day-old animals that were given injections of 3H-testosterone in vivo. This age-related pattern of decreasing uptake of radioactivity was not observed when excised brain tissue was incubated with 3H-testosterone in tissue culture medium. Thus, it appears that the age-related responsiveness of neonatal rats to T may be due more to the fact that decreasing amounts of the hormone reach the brain in older animals than that an inherent difference exists in tissue susceptibility during this period. Most of the radioactivity accumulated in the brain was associated with cytoplasmic fractions. Less than 1% of the homogenate radioactivity accumulated in purified nuclei. This restricted uptake and the kinetics of 3H-testosterone nuclear accumulation suggest that a nuclear site of action of T and/or its metabolites exists in the neonatal rat brain.


The effect of surgical isolation or ablation of the medial basal hypothalamus on serum prolactin levels in male rats.

Complete isolation of ablation of the medial basal hypothalamus (MBH) was performed in adult male rats, and non-stress prolactin levels were measured by radioimmunoassay in blood collected by decapitation at 24h, 2 weeks and 6 weeks following surgery. 24 h after surgery, medial hypothalamic ablation (MHA) markedly elevated prolactin levels compared to those of intact control rats; prolactin levels subsequently declined to normal resting values 2 to 6 weeks following surgery. Circulating prolactin levels following hypothalamic isolation were not different from those of controls at either acute or chronic sampling intervals. These data suggest that chronic isolation or destruction of the MBH does not alter basal prolactin secretion in male rats, provided that circadian and stress-induced variations in control animals are properly considered.


[Progressive spinal muscular atrophy of proximal location in adults].

The authors report two cases of familial progressive muscular atrophy of proximal localization, with late onset of signs which was associated with involvement of the motor nucleus of trigeminal nerve and hypoglossus nerve nucleus as well as with presence of gynaecomastia. Cases of coexistence of gynaecomastia with spinal muscular atrophy are rare in the literature and the present report may serve for explanation whether the association of these signs is accidental or whether it is a separate nosological entity.


Effects of ovariectomy on dexamethasone suppression of the adrenal axis in adult rats.

Three weeks after ovariectomy, adult female rats had lower basal levels of serum corticosterone (B), which did not display a daily rhythm, and reduced responses to ether stress, measured by blood levels of B 15 min after ether exposure. Ovariectomized (OVX) females were more sensitive to dexamethasone (DEX) suppression of the ether induced stress response, reaching basal levels at a dose of 50 mug DEX/100 g b.w. At this dose, B levels were reduced by only 30% over saline-control values in intact rats. DEX-treated intact rats displayed a short-term suppression, reaching a maximum 2 h after the injection followed by a rebound 7 h post-injection and a second suppression period evident by 11 h post-injection. OVX rats showed a steadily increasing suppression that began 1 h after injection and persisted to the last sample time at 11 h post-injection. The disappearance of DEX from peripheral blood was followed by means of radioimmunoassay and no difference was found between intact and OVX rats either in the basal state or 15 min after ether stress. It can be concluded that ovarian steroids condition the sensitivity of the adrenal axis to DEX suppression and that the differences in DEX sensitivity  we have previously noted between prepubertal and adult rats can be accounted for by a change in gonadal status rather than by a critical developmental event in the adrenal axis itself.


[Development of papilledema in cases of tumors of the lower segment of the vertebral canal].

The author discusses the problem of the mechanism of intracranial hypertension developing with papilloedema in cases of tumours situated in the lower parts of vertebral canal. The author discusses the present data in literature and an own case in which manifestations of intracranial hypertension with papilloedema developed in a 48-year-old man with neuroma situated in the vertebral canal at the level of 11th thoracic vertebra. In a discussion on the problem the author stresse that his case failed to confirm the accepted view that the cause of intracranial hypertension in cases of tumours in the lower part of the vertebral canal should be sought in increased protein level in the cerebrospinal fluid. Attention was called also to the fact that in most cases described as yet presence of gliomas was demonstrated and the cerebrospinal fluid pressure was never so high (700 mm H2O in lying position).


Responses of plasma "estradiol" and plasma LH to ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection at various ages.

Plasma LH and "estradiol" were measured by radioimmunoassay in female rats 5, 10, 15, 20, 25, 30, 40, and 80 days of age, and the changes in these hormone levels 24 h after ovariectomy, ovariectomy plus adrenalectomy, and estrogen injection were determined. Plasma "estradiol" was high at 5 days of age; it increased further to a peak at 15 days of age, and declined thereafter to the low levels seen in adult rats. At each age, plasma "estradiol" declined about 50% 24 h after ovariectomy, whereas it fell to undetectable levels 24 h after ovariectomy plus adrenalectomy at 20 and 80 days of age. Plasma LH did not increase 24 h following ovariectomy at 5 days of age, but it did at all ages thereafter. The peak increase occurred 24 h after ovariectomy at 15 days of age, and the increment was progressively smaller at older ages. Ovariectomy plus adrenalectomy did not cause a significantly greater increase in plasma LH than ovariectomy alone. Injection of estradiol caused a decrease in plasms LH at all ages except in the animals ovariectomized at 5 days of age. The greatest decrease was seen in animals ovariectomized at 15 days of age, with a progressively smaller negative feedback response as age increased. In addition to providing systematic data on changes in the negative feedback effect of estradiol at various ages, the results indicate that, especially in immature animals, there is a circulating substance which cross-reacts with antibodies to estradiol but which does not appear to be a biologically-active estrogen. It does not come from the ovaries and disappears from the circulation if the adrenals as well as the ovaries are removed.


[Traumatic injury of ciliary ganglion].

The authors report a case in which slight cranial trauma was followed by manifestations of damage to the right ciliary ganglion. After 3 weeks the signs of damage began to regress and disappeared completely. Laboratory investigations failed to demonstrate any abnormalities. Apart from this trauma there were no other detectable causes, and especially there were no history data suggesting past infection, botulism or syphilis. The mechanism of ciliary ganglion injury is not known (contusion, haematoma, oedema etc.).


[Malignant meningioma with extracranial metastases].

The authors report a case of primary malignant meningioma of meninges in the right frontal area with metastases to meninges in the right temporal area and left atrial endocardium and with emboli composed of malignant cells in the vessels of the myocardium, spleen, liver, lungs and pancreas in a 49-year-old woman after commissurotomy performed for rheumatic valvular heart disease.


The megadolichobasilar artery anomaly and expansion of the internal auditory meatus.

A case of megadolichobasilar artery anomaly (MDBA) with expansion of the internal auditory meatus is presented. There was no associated hearing loss and it is postulated that IAM expansion without hearing loss may occur with this anomaly.


Rare carotid-vertebrobasilar anastomoses with notes on the differentiation between proatlantal and hypoglossal arteries.

Two cases of persistent anastomoses between the carotid and vertebrobasilar systems which have only once been previously reported are described. These are a proatlantal intersegmental artery which arises from the external carotid artery and a primitive trigeminal artery with direct anastomosis to the superior cerebellar artery. Angiographic criteria for differentiation of the proatlantal and more common hypoglossal arteries, as well as the rare persistent cervical intersegmental artery are also presented.