Bioassay of blood-born tumour cells on in vivo and in vitro systems. Viability and biological integrity of tumour cells circulating in the blood were studied in an experimental system using bioassay methods. Results of subcutaneous and intravenous retransplantation as well as explantation of the blood obtained from tumour-bearing animals previously receiving intravenous inoculation of tumour cell suspension (Yoshida sarcoma, Walker 256 carcinosarcoma and DMBA-induced myeloid ascitic leukaemia), revealed that the tumour cells detected in the blood are not only viable at the time of their transportation in the blood-stream but are also in possession of biologic potentials to proliferate and establish metastatic growths in organs.


Infantile and juvenile cirrhosis of the liver. In 14 years necropsy material 12 cases of infantile and 2 of juvenile liver cirrhosis occurred. In early infancy, diffuse cirrhosis is the most characteristic, whereas in more advanced age cirrhosis of irregular type is more frequent. The posthepatitic, secondary biliary, metabolic and cryptogenic cirrhoses are discussed from aetiological aspects.


The role of heterogeneity of tumour cell populations in biological activity and sensitivity to chemotherapeutics. The biological activity of a rat ascites leukaemia subline isolated by isopycnic centrifugation was compared to that of the original tumour both in vivo and in vitro. The subline had different marker chromosomes, a longer cell cycle time and decreased sensitivity to vinblastine as compared to the original tumour.


Examination of curettage material for the diagnosis of ectopic pregnancy. The histological characteristics of curettage material are described which raise the suspicion of ectopic pregnancy. In the period 1966 to 1975, 464 surgically removed pregnant uterine tubes and in 143 patients curettage material was also examined. On the basis of the curettage material, the suspicion of ectopic pregnancy arose in 109 cases (76%). In 34 curettage materials (24%) no histological sign referring to ectopic pregnancy was detected. Thus in three-fourth of cases examination of the endometrial specimen was of diagnostic value and indicated the necessity of surgery.


A study of hyperlipidaemia induced by ascites tumours. In mice four stages of hyperlipidaemia induced by Ehrlich ascites tumour could be distinguished. Hyperlipidaemia is characterized mainly by increased serum VLDL content accompanied by high triglyceride concentration. The only exception was the regressive stage III where the serum lipid level (VLDL) has temporarily decreased. From the results obtained with the simultaneous examination of the liver, mesenteric fat tissue, tumour cell and ascites plasma lipids, it may be concluded that the endogeneous fat mobilization induced by tumour cells via increased VLDL synthesis and secretion of liver will lead to hyperlipidaemia and to the total depletion of the lipid stores. Rapid and reversible fall in lipid level following the withdrawal of ascites fluid in tumorous animals demonstrated clearly the direct effect of the tumour cells on lipid-lipoprotein metabolism of the host organism.


Studies on the possiblilty of production of immunity against schistosomiasis in experimental animals. In the present work antigenization with somatic and metabolic antigens of adult Schistosoma mansoni worms, their cercariae or eggs has been tried. The study of the immunoglobulin patterns in infected and vaccinated non infected mice showed increase in IgG in all animals, increase in IgM only in the infected and IgA was frequently increased in mice that received metabolic or egg antigens. As regards the degree of resistance of vaccinated animals to S. mansoni infection, 2 groups gave prominent results. 1st the group vaccinated with Schistosoma mansonmetabolic worm antigen in which we got: -- Reduction in the worm load. -- Delayed ovulation and reduction in the number of ova/24 hr stools and/g of liver tissue. -- The histopathological picture of the liver was the best. 2nd the group vaccinated with egg antigen: Although it showed delayed ovulation and reduction in the ova count per 4 hr stools and/g liver tissue, yet the histopathological picture was the worst showing the largest granulomata.


Leucine aminopeptidase, Significance of serum elevation in bilharziasis. Leucine aminopeptidase (LAP) activity and creatinine concentration was estimated in serum of twenty five normal adult subjects, twenty four cases with active urinary bilharziasis, eleven cases with active intestinal bilharziasis, ten cases with mixed bilharzial infection (urinary and intestinal), fourteen bilharzial cases with clinical hepato-splenomegaly of bilharzial etiology, thirteen bilharzial cases with clinical hepatosplenomegaly and ascites, and twelve cases with cancer bladder of bilharzial etiology. Significant elevation in the serum enzyme level was found in all bilharzial cases which generally ran parallel to the course of the disease, being more marked in hepatosplenomegalic cases than in cases which showed no clinical signs of liver or spleen involvement. However, it was observed that the enzyme level was lower ascitic than in nonascitic cases. For serum creatinine concentration, no significant variation from normal value was observed in the group of patients with active urinary, active intestinal, mixed infections of bilharziasis and bilharzial hepatosplenomegalic cases. However, a very highly significant decrease in serum creatinine concentration was observed in the group of patients with bilharzial hepatosplenomegaly and ascites. Serum LAP activity and creatinine concentration in the group of patients with cancer bladder of bilharzial etiology showed no statistical variation from normal values.


Urinary leucine aminopeptidase in bilharziasis. Leucine aminopeptidase activity and total protein concentration was estimated in the fresh early morning sample of urine of twenty five normal adult subjects, twenty four cases with active urinary bilharziasis, eleven cases with active intestinal bilharziasis, ten cases with mixed bilharzial infection (urinary and intestinal), fourteen bilharzial cases with clinical hepatosplenomegaly of bilharzial etiology, thirteen bilharzial cases with clinical hepatosplenomegaly and ascites, and twelve cases with cancer bladder of bilharzial etiology. It was found that there is a significant increase in LAP activity in the urine of all groups of patients studied. Again this increase ran parallel to the course of the disease in bilharzial cases. Urine protein concentration was found to be increased significantly in all groups of bilharzial cases studied with the highest value in urine of patients with cancer bladder of bilharzial etiology. However no direct correlation was found between urinary LAP level and protein concentration either within the individual cases or within the different groups.


Chemical control of the sea lamprey: the addition of a chemical to the environment. Construction of the Welland Canal enabled shipping to by-pass Niagara Falls and enter the upper Great Lakes and also eliminated the barrier to the entry to the lakes by the sea lamprey (Petromyzon marinus Linnaeus). Within forty years the commercial fisheries of the Great Lakes was almost eliminated by this parasitic cyclostome. A search for selective chemical control of the sea lamprey was undertaken in the 1950's and culminated with the discovery of TFM (3-Trifluoromethyl-4-nitrophenol). At the request of the International Great Lakes Fishery Commission, the Bureau of Sport Fisheries and Wildlife undertook to assess the hazard of TFM to the aquatic ecosystem, to humans as well as to fish and wildlife. Studies were undertaken in Bureau laboratories as well as by contracts with university and private laboratories. Results of these studies to-date indicate that this material is not subject to biomagnification and does not pose a hazard to man or the the environment.


Long-lived radionuclides in food: 90Sr and 137Cs in the Israel diet. Routine monitoring of Strontium-90 and Cesium-137 levels in the main classes of food consumed in Israel has been carried out for a number of years. Calculations have been made of the intake of these isotopes by various groups in the Israel population using Food Consumption Survey data made available by the Israel Central Bureau of Statistics. More detailed analyses have been carried out to calculate the exposure of groups selected on the basis of demographic, economic and family-size criteria. This was carried out in an attempt to detect "critical groups" in the population who might be overly exposed. Results of these data indicate that in the case of Israel the monitoring of a single food item such as milk or the extrapolation of local fallout data cannot be relied on to give an estimate of radionuclide exposure through food. The relation between high consumption groups and the intake of "average" consumers is discussed in detail and the use of the statistical models developed in these studies for the estimates of radionuclide exposure during periods of high fallout levels which occurred in the past and possible applications with regard to other environmental contaminants is discussed.


Selenium content of some foodstuffs and other environmental samples in a mineralized area of Italy. No data are available on Selenium concentration in the Italian environment in spite of its importance as an essential and toxic element. In order to get some information about the concentration and distribution of this element in the environment and in the food-chain, a survey has been made in the Monte Amiata area (Toscana, Italy). Such an area was selected for this study owing to its large mineralization due to many elements (e.g. Fe, Cu, Ag, Sb and particularly Hg). The selenium content has been determined by thermal neutron activaltion analysis and a large volume high-resolution Ge-Li gamma ray spectrometer connected on line to a DEC PDP 8/L computer. The instrumental method requires neither a chemical separation technique nor a pre-or post-concentration of Selenium. The Selenium concentration for wet weight in foodstuffs ranges between a value of 0.008 ppm in milk and a value of 0.2 ppm in chicken. The average Se intake for the population living in the area under investigation has been also estimated. A critical discussion of the data is reported together with a comparison with the Se concentration values referring to other countries.


ECDIN, an EC data bank for environmental chemicals. All environmentally relevant information is computer stored for each organic chemical manufactured in quantities above 1.000 tons per year (whether it is considered as potentially toxic or not), known toxic chemicals (independently of their production figures) and certain classes of inorganic chemicals. The main data fields ("attributes" for each chemical) are: 1. substance identification and physicochemical data; 2. production and use data; 3. handling, transportation, and disposal; 4. environmental involvement (breakdown under biotic and abiotic conditions, average concentrations in environmental matrices); 5. biological effects and toxicity; 6. protection standards, administrative and regulatory data. Structure and substructure codification permits screening for substances with similar structures and coupling to GC-MS-computer analysis units with full or approximative structure outputs. A pilot project has been started permitting queries via direct and inverted file. It will include all available information on a limited number of compounds (some 5.000) from different chemical and use classes. The further software development foresees automatic indexing, automatic encoding of formatted data, automatic query formulation and search on a probabilistic basis for natural-language source data. Easy data flow is ensured by a networking between the central unit at the EC research Centre in Ispra (Italy) and specialised national data centres (ECDIN = European Chemicals Data and Information Network).


Radioisotope techniques in delineation of the environmental behavior of cadmium. Radioisotope techniques are being developed and utilized at Oak Ridge National Laboratory (ORNL) for evaluating the environmental behavior of toxic elements such as cadmium in aquatic and terrestrial ecosystems. Tracer techniques using 109Cd in microcosm, field plot, and stream systems are providing information on biogeochemical cycling and distribution of cadmium in the environment. Parameters being measured include adsorption capacity for cadmium in mineral soils and sediments; uptake rates of cadmium in various plant species from both soils and nutrient solutions as affected by pH, competing cations, and chemical form of cadmium; and distribution of cadmium in various components of both aquatic and terrestrial ecosystems following application of 109Cd to soil vegetation, or directly to streams. Food chain parameters being estimated with 109Cd include uptake, assimilation, and turnover by both aquatic and terrestrial organisms. Information obtained in these radiotracer studies is providing insight into the behavior of cadmium in aquatic and terrestrial ecosystems, especially transport rates of cadmium and potential biomagnification or dilution in food chains. The factors which influence the incorporation of cadmium into vegetative material as well as those affecting residence time in ecosystems have been identified. Use of 109Cd also has permitted evaluation of a cadmium specific electrode as a tool for rapid assay of free cadmium ions in soil solutions.


Technology assessment on the use of pesticides. The extensive use of pesticides in Japanese agriculture was studied as a problem-oriented case of technology assessment with an aim to contribute to the establishment of appropriate procedures of assessing real and potential impacts which modern technologies have or may have on health, industries, economy, society and on the environment and to obtain clues to the development of safer use of pesticides. Direct and indirect impacts, both real and potential, favourable and adverse, were intended to identify and evaluate systematically and comprehensively as their cause and effect sequences were studied. Adverse impacts were divided into tradable and untradable categories, untradable adverse impacts were related mostly to human health. As to the evaluation of impacts, it was suggested that the size of area and population affected, irreversibility and controllability of the impact be considered. It was recognized as urgent and requisite to develop and establish a more efficient and satisfactory method of testing the safety of pesticides and their metabolites over a wider spectrum of organisms and with respect to newer aspects of toxicology as mutagenesis, teratogenesis and cancerogenesis.


Use and field application of pheromones in orchard pest management programs. Pheromones are recognized as potentially valuable tools in orchard pest management. Their most immediate practical application is in pest monitoring to indicate the need for chemical control. In this role, they can have considerable impact in reduction of pesticide output.


Approaches to insect control based on chemical ecology--case studies. In this article two attempted approaches to control a stored product insect, azuki bean weevil, are discussed based on host selection study and oviposition ecology. The latter study indicated the presence of an oviposition marker, a new kind of pheromone, which was derived from the weevil and was lipid in nature, and suggested its possible use as an oviposition inhibitor.


Experiments on the effect of carbon monoxide on aminolevulinic acid dehydrase (ALAD). The inverse relationship between blood lead concentration and aminolevulinic acid dehydrase (ALAD) is well known. Recently, it has been suggested that a similar relationship exists between carboxyhemoglobin (COHb) and ALAD activity. This study was undertaken to examine more closely the possible effect of carbon monoxide on ALAD. Blood from 19 human volunteers was analyzed for both carboxyhemoglobin and ALAD activity. Smokers had significantly lower concentrations of ALAD than nonsmokers and a rise in carboxyhemoglobin concentration was assocaited with a fall in ALAD activity. The in vitro bubbling of carbon monoxide into human blood did not significantly effect ALAD activity. Four groups of rats (10 per group) wre exposed to carbon monoxide or dietary lead acetate according to the following design: (I) Control--no Pb or CO; (II) 500 ppm Pb acetate in diet; (III) 250 ppm CO four hours/day X 5 days/week X 4 weeks; (IV) Both Pb and CO. Analysis of the rat data showed a significant depression of ALAD by lead. The activity of ALAD in the rats exposed to CO was significantly increased suggesting the possibility of an adaptive phenomenon.


Linkage study on dieldrin resistance and an inversion on the second chromosome of Anopheles stephensi. In a study on the linkage between the gene for dieldrin resistance and an inversion on the second chromosome in Anopheles stephensi, the two factors were found to assort independently. As dieldrin resistance can be assigned either to the third chromosome, or to a position on the second chromosome more than 50 cross-over units from the inversion.


Hut entry and exit by Anopheles gambiae and Anopheles funestus in an unsprayed village near Kaduna in Northern Nigeria. Hut entry and exit by An. gambiae and An. funestus were studied in an unsprayed village near Kaduna in Northern Nigeria. A high turn-over of indoor resting mosquitoes of all blood digestion stages was noted throughout the night. The behaviour of both species was similar. The entry pattern was more uniform than the exit which showed two distinct peaks around sunset and after midnight. Most of the daytime resting mosquitoes left the huts during the first hour after sunset, and therefore the mosquitoes escaping during the subsequent hours of the night were mainly those that had entered the same night and spent only a limited period inside the huts. The significance of the movement of mosquitoes is discussed in relation to entomological evaluation of the impact of residual insecticides.


[Infection of mice with oral administration of trophozoites of Giardia muris]. For the last 9 years we have used Giardia muris for chemotherapy research, passing trophozoites scraped from the mouse small intestine into fresh mice, by gavage. More or less every trophozoite administered orally reproduces in the intestine, as shown by quantitative studies in groups of young, specific pathogen-free mice, treated with 1, 3, 10, 30 or 100 Giardia each. After 7-9 days the number of protozoa in the intestine diminished somewhat, in the groups infected with the largest number of trophozoites.


[New faunal and biological observations on ticks in Abruzzo]. Ticks collected during the years 1975-76 in Abruzzo (Prov. l'Aquila and Chieti) Italy are reported. The following species have been identified: Ixodes canisuga, Ixodes frontalis, Ixodes hexagonus, Ixodes ricinus, Dermacentor marginatus, Haemaphysalis sulcata, Rhipicephalus bursa, Rhipicephalus sanguineus, Hyalomma marginatum. New hosts are: Felis catus for Ixodes canisuga; Scolopax rusticola, Motacilla flava, Corvus cornix for Ixodes frontalis; Sciurus vulgaris for Haemaphysalis punctata; Garrulus glandarius for Haemaphysalis sulcata. For Italy the following records are new: hosts: Corvus frugilegus for Ixodes frontalis; Coturnix coturnix and Alauda arvensis for Haemaphysalis sulcata; immature stages: Ixodes canisuga on Vulpes vulpes; Ixodes frontalis on Turdus merula; Haemaphysalis punctata on Coturnix coturnix, Phasianus colchicus, Erinaceus europaeus, Lepus europaeus; Accordingly numerous species, hosts and seasonal records are new for Abruzzo.


[A new species of Plagioporus (Caudotestis) tyrrhenicus sp.n. and its 2 new parasitologic findings in Blennius pavo Risso, 1810]. In a survey of the helminth parasites of Blennius pavo Risso, 1810 three different species of digenea were collected. Plagioporus (Caudotestis) tyrrhenicus sp.n. is described, figured and compared with other species of the subgenus Plagioporus (Caudotestis) Issaitchikov, 1928. Plagioporus (Caudotestis) tyrrhenicus differs from P. (Caudotestis) azurionis Yamaguti, 1951 in the position of cirrus sac, in sucker ratio and size of the eggs; from P. (Caudotestis) sinitzini Mueller, 1934 for extent of excretory bladder and size of the eggs; from P. (Caudotestis) synagris Yamaguti, 1952 for size of the pharynx and oesophagus, extent of the vitellaria and size of the eggs. Lepocreadium album (Stossich, 1890) Stossich, 1904 is redescribed, figured and recorded for the first time in Blennius pavo. Deretrema sp. is figured and recorded for the first time in the same host.


[Protostrongylus (Protostrongylus) rufescens boevi, a new subspecies, parasite of the respiratory apparatus of chamois]. A nematode parasitic of bronchial system of Rupicapra rupicapra (chamois) of Parco Nazionale del Gran Paradiso (Italian Western Alps) is described and the name Protostrongylus (Protostrongylus) rufescens boevi subspecies nova, is proposed.


[Natural galactogenic infestation of the foal by Strongyloides westeri]. Strongyloides westeri larvae transmission by mare milk in foals has been studied; the results show the importance of this route for parasite penetration.


[Parasitic fauna of Salmo trutta L. of the Tirino river. I. Redescription of Dentitruncus truttae Sinzar, 1955 and considerations on the genus Dentitruncus Sinzar, 1955]. Dentitruncus truttae Sinzar, 1955 is redescribed and figured from specimens from Salmo truttae L. collected in the Tirino river (L'Aqula-Italy). The diagnosis of the genus Dentitruncus is completed and the characteristics separating Dentitruncus Sinzar, 1955 from Pseudorhadinorhynchus Achmerov e Drombrowskaja-Achmerova, 1941 are discussed.


[Irregularity of spicules of the genus Spiculocaulus Schulz, Orlow and Kutass, 1933]. The accurate measurement of the length of the spicules of 100 male specimens of a lung nematode belonging to a species of the genus Spiculocaulus collected from trachea and bronchi of chamois (Rupicapra rupicapra) of Parco Nazionale del Gran Paradiso--Italian Western Alps--shows that the spicules are constantley inequal: the left spicule is the longer. The original description of the species Spiculocaulus austriacus (Gebauer, 1932) found in trachea and bronchi of Rupicapra rupicapra from Austrian Alps state to the contrary that in this species spicules are equal in length. New investigations are necessary to establish if the species S. austriacus has to be redescribed for this important character or if our specimens belong to a new species.


[Influence of temperature and humidity on the reproductive efficiency of Ixodes ricinus (Linnaeus, 1758) and Hyalomma marginatum Koch, 1844 (Ixodoidea, Ixodidae)]. Laboratory studies have been carried out on two species of ticks, I. ricinus and H. marginatum, showing different seasonal activity and different geographical distribution in nature. The purpose of the present study has been to investigate the effect of different combinations of temperature and humidity on the oviposition of I. ricinus and H. marginatum. An index of reproduction efficiency (no. eggs/wt female), established to relate the capacity of the females to produce eggs to their body weight, has been calculated; for I. ricinus 5 temperatures (18-20-25-27 and 30 degrees C) have been studied (Fig. 1), for H. marginatum 3 (25-30 and 32 degrees C) (Fig. 2) and for both species 2 R.H. (75-95%). An optimal range of temperature, within which the value of such an index doesn't change, has been demonstrated for both species by statistical testing (Table 1). A critical weight value as the minimum engorged female weight required for egg deposition has been identified with the weight of first female which has laid eggs. This weight, different in each species, is influenced by temperature and humidity.


[Observations on the species Stefanskostrongylus soricis (Soltys, 1954)]. A short redescription of Stefanskostrongylus soricis (Soltys, 1954) parasite of Sorex minutus from Bialowieza forest (Poland) and Parco Nazionale Gran Paradiso (West Italian Alps) is given.


The salivary gland chromosomes of Anopheles labranchiae Falleroni 1926. The salivary gland chromosomes of Anopheles labranchiae Falleroni, 1926 are described and figured. A. labranchiae is the sibling species of the maculipennis complex most closely related to A. atroparvus and the map of A. labranchiae is generally comparable to that of A. atroparvus. The chromosomal areas which are asynaptic in the hybrids between the two species are also described.


Transmission patterns of onchocerciasis in southwest Ethiopia. The three transmission patterns found till now in Ethiopia are described. The forest area contains ideal conditions for the breeding of Simulium, but the sparse human population makes the transmission rate low. Only a few people were found to be infected. The subsistence crop farming area is a less ideal habitat for the vector due to the scarcity of bush and shade. However the presence of a largest population can explain the slightly higher prevalence of the disease than in the forest. The coffee farming area is densely populated, rich in bush and shade, with heavy rainfall and numerous rivers. Here the number of Simulium and their chance to reach the infective stages, are considered to be high. A high prevalence of the disease was found in this zone.


Caffeine content of beverages as consumed. Quantitative analysis of beverages prepared at home by staff of the Addiction Research Foundation revealed a lower and much more variable caffeine content of both tea and coffee than had been reported in earlier studies, most of which were based on analysis of laboratory-prepared beverages. Median caffeine concentration of 37 home-prepared samples of tea was 27 mg per cup (range, 8 to 91 mg); for 46 coffee samples the median concentration was 74 mg per cup (range, 29 to 176 mg). If tea and coffee as drunk contain less caffeine than generally supposed, the potency of caffeine may be greater than commonly realized, as may the relative caffeine content of certain commercial preparations, including chocolate and colas. The substantial variation in caffeine content emphasizes the need to establish actual caffeine intake in clinical, epidemiologic and experimental investigations of caffeine effects.


In vitro estrogen-binding by human breast carcinomas. Patients whose breast carcinomas possess only low concentrations of a receptor molecule that binds estrogens with high affinity are unlikely to respond to hormonal manipulative therapy when the disease recurs. The estrogen-binding capacity of 106 breast carcinomas was measured by an in vitro method and was expressed per milligram wet weight and in some cases related to the concentration of deoxyribonucleic acid (DNA) of the tumours. The ability of tumors to bind 3H-estradiol ranged from 0 to 1.3 fm/mg in pre- and perenopausal women, and from 0 to 16.8 fm/mg in postmenopausal women. Menopausal status or serum concentrations of endogenous estrogen, or both, should therefore be considered when tumours are classified into low and high estrogen-binding capacity. It is not necessary to carry out Scatchard analysis for every tumour, and expressing estradiol binding on the basis of DNA concentration may be preferable to expressing in on a wet-weight basis.


Decreased anion gap associated with monoclonal and pseudomonoclonal gammopathy. Nine patients with monoclonal and one with pseudomonoclonal gammopathy were found to have a decreased anion gap. Eight of the patients had multiple myeloma, one has plasma cell leukemia and one had chronic active hepatitis. In all of the the decreased anion gap was associated with an increased concentration of IgG greater than 5 g/dl.


Technique evaluation of foster care in chronic psychiatric disorders. Foster care received by 178 patients with chronic psychiatric disorders discharged from Hamilton Psychiatric Hospital in the years 1966 through 1969 was studied by technique evaluation. Residents were followed for 3 years by means of health records. The achievement of operational objectives of the program (Homes for Special Care) was compared with two types of outcome--emergency readmission to hospital and discharge to the community. Emergency readmission was associated with rural location of the foster home, inferior quality of the home operator and smaller size (i.e., fewer residents) of the home. Discharge to the community was more common among younger, female residents whose previous psychiatric hospitalization had been relatively brief. In general, prescription audit was not a fruitful way of evaluating quality of health care.


Analysis of neocortical electrical responses evoked by stimulation of various hypothalamic structures. Evoked potentials (EPs) and extracellular unit activity were recorded in various parts of the neocortex of unanesthetized cats immobilized with succinylcholine. During hippocampal stimulation EPs of maximal amplitude are recorded in the anterior sigmoid gyrus with a latent period (LP) of 0.5-2.5 msec. The first component is a fast positive spike with a duration of about 1.5 msec. In the middle suprasylvian gyrus, hypothalamo-cortical (HC) EPs have a monophasic surface-negative configuration and are recorded after an LP of 2-6 msec. HC EPS in the anterior sigmoid gyrus can bind a rhythm of stimulation of up to 200 pulses/sec and are characterized not only by high functional mobility, but also by the property of posttetanic potentiation. The main positive wave appears to a testing stimulus with an interval of 7-10 msec. Complete recovery of all components of HC EP takes place at an interval of 50-150 msec. In response to the conditioning stimulus a biphasic change in excitability of the neurons is observed in the association areas of the anterior sigmoid and middle suprasylvian gyri of the neocortex. The maximal number of responding neurons in the deep layers of the cortex discharges in the period of development of the initial spike and the main positive wave of the HC EP.


Analysis of the role of central noradrenergic structures in memory trace recall. During the reproduction of a conditioned passive avoidance response by albino rats and also during the action of a conditioning stimulus in animals trained by invariable reinforcement of the conditioning stimulus, a significant decrease was found in the noradrenalin content in nuclei of the limbic system and anterior hypothalamus compared with the control. In untrained animals, and also in trained animals subjected to repeated testing in the course of 4 days, the decrease in the noradrenalin content was less marked. Reproduction of the conditioned active avoidence response in a shuttle box did not induce changes in the noradrenalin content.


Histochemical study of lipid absorption in two teleost fishes. Absorption of lipid in the different regions of the intestine of two teleost fishes has been studied histochemically at different time intervals of 4, 10 and 20 h. All the three portions of the intestine have the absorptive capacity. However, it varies from one region to another. The lipid has been absorbed in the form of lipoid particles and lipoid goblets. It is also recorded here that some lipoid droplets are absorbed by pinocytosis across the brush border membrane. The lipid absorbed was localized in the brush border cells, in intercellular spaces of connective tissue, in submucosa, in between serosa and muscularis, in the lumen of blood capillaries and mesentric lymphatic vessels but was absent in muscularis and serosa.


Studies on the oogonial cycle in Puntius ticto (Ham.) II. Formation of mature follicles. During the formation of maturing oocyte and mature follicle most of the changes are observed in the ooplasm while nucleus gets reduced in size and finally vanishes in the ooplasm. Few of the nuclei migrate into the ooplasm (yolk nucleus) which is responsible for the yolk accumulation. The mature follicle is covered by the theca, granulosa and zona rediata.


Ultrastructural observation on the rectal gills of Zygoptera larva. The zygoptera larvae have tracheal gills. Both outer and inner epicuticles of damselfly larvae (Zygoptera) are pierced by pores of about 200...250 A thickness. The pores are distributed at a distance of about 500...600 A apart. Their endings are noticed upto the lower portion of exocuticle. The endocuticle is a big area in which the respiratory epithelium have flat apical and basal sides, plasma membrane is not folded. Glycogen granules are distributed in the cytoplasm and a few mitochondria are noticed. The tracheal brances and the cytoplasm of the respiratory epithelium come in contact with the epicuticle. The distribution of tracheoles, with surplus of tracheoles in a surface outside the hypodermis are close to the sub-cuticular area is found. The gills of Zygoptera appear to be merely respiratory organs having respiratory epithelium and the ions and water are resorbed from the modified rectal epithelium.


[Histopathogenetic aspects in a case of Fahr's disease (non arteriosclerotic calcinosis of the brain) (author's transl)]. The study of one case of non arteriosclerotic calcinosis of the brain (Fahr's Disease) gives an opportunity for a discussion on the main pathogenetic aspects of this syndrome. Some features of hypertrophy and hyperplasia of astrocytes contrast with the fair preservation of neurons. It is suggested that such condition should be considered as an "astroglial syndrome" in Seitelberg's terminology.


Studies on the toxic effect of cadmium in the rat. I. Testicular changes induced by a single subcutaneous injection of cadmium chloride. Adult male rats of Wistar strain were subcutaneously injected with a single dose of 0.025 mM CdCl2/kg body weight. The autopsies were performed 2 and 12 weeks post cadmium injection. Experimental animals showed a normal gain of body weight while a marked lowering of the testes weight was observed. The lowering of testes weight of cadmium treated rats occured mainly due to the necrosis of seminiferous tubules, volume of which is markedly lower if compared to intact control rats. After 2 weeks of experiment a marked enlargement of the interstitial gland of the testis occured while after 12 weeks the gland is markedly lower if compared to control rats and to rats studied 2 weeks post cadmium injection. Histochemical reactions for lactic, succinic, alpha-glycerophosphate and 3beta-hydroxy steroid dehydrogenases, NADH tetrazolium reductase, acid phosphatase and nonspecific esterases showed for irreversible necrotic changes of seminiferous tubules of cadmium treated rats while the damage to interstitial gland is only temporary.


[Sleep disturbances in a case of Morvan's chorea (author's transl)]. Six nocturnal polygraphic recordings were carried out in a young man with fibrillary chorea of Morvan, during the acute period of the disease. Sleep was remarkably fragmented by numerous and brief awakenings but the total sleep time fluctuated between 157 and 312 mins.; the sleep structure was altered by the almost total absence of stages 3,4 and REM. During the day, the subject had one or two periods of sleep (1-2 hours) and complained of being tired. The nocturnal awakenings were correlated by the patient with pain and burning dysaesthesiae of distal distribution that were more severe than those occurring during the day. The patient improved gradually, and five month later both sleep disturbances and other signs of disease had disappeared.


[Peculiar capillary convolution of the parietal pleura. III. Electron microscopy studies]. By means of electron microscopy and ultrahistochemical research it has been attempted to detail the structure and explain the function of the pleural tufts of the parietal pleura present in the ventral mediastinum of dogs. This led to the discovery that the varions forms present for the surface-enlarging pleura protusions in actuality exhibit corresponding morphological characteristics. As a special formation of the serous lamina of parietal pleura, they are covered by an occasionally incomplete mesothel unit. The parenchyma of these organs is compinsed of a macrophage-rich outer border zone and of a vessel-canying central zone. The experimental in vivo application of cationized ferritin in the pleura-space clearly indicated a high resorptive metabolism of the mesothel and of the pluripotential mesenchym cells. The higher incidence of lymphoplasmatic cell-forms in the proximity of the central vessels along with leucocytic cell infiltrations fulfill an immunocellular and phagocytic function. The structure of the cell population of the pleural tufts partaking on the resorption of matter out of the pleural space has been discussed in detail. The in vivo application of a cationized ferritin solution for the purpose of studying these resorptive processes has been critically judged.


[Alzheimer's disease. Histopathological and ultrastructural study of 6 cases (author's transl)]. Histologically Alzheimer's disease is chiefly characterized by senile plaques and neurofibrillary degenerations. Electron microscopy has clarified the basic morphological changes and has shed some light on the pathogenesis of the lesions. The senile plaque includes three components: neurites in various stages of degeneration, amyloid, and glial cells or processes. Degeneration of neurites is considered to represent the major change since it occurs before amyloid deposition, therefore playing a primary role in the development of the plaque: therefore the senile or neuritic plaque is the result of a neuronal disease, even though there is no evidence of perikarion injury. Neurofibrillary tangles are due to the accumulation in the neuronal cytoplasm of large clusters of abnormal neurotubules about 200 A diameter with periodic narrowings every 800 A (Twisted tubules). The nature and significance of the pathological material observed within the neurons are discussed.


Ultrastructure of cells of proper gastric glands and their stroma in hemorrhagic shock in the rat. Ultrastructural changes in the cells of the proper gastric glands and their stroma are biphasic in the hemorrhagic shock. First phase: "paralysis" of the capillary vessels with an oedema of their stroma, an intracellular oedema with hydropic degeneration of the parietal cells and a degranulation of the argentaffin and argentaffin-like cells. Second phase: ischemia of the gastric mucosa with ultrastructural features of: a) the increased secretion of the parietal cells, b) the degranulation of the chief gastric cells, c) the increased secretion processes in the mucous neck cells. These findings suggest that at last 2 factors coincide in the pathogenesis of so-called stress gastric ulcerations: biphasic disturbances of blood circulation initially damage the gastric mucosa and are followed the digestive hyperactivity of the gastric juice finally resulting stress ulceration.


Investigations on the ultrastructure of spermatozoa in chronic alcoholics. The semen of 25 chronic alcoholics aged between 28 to 52 years was examined. The period of alcoholism amounted to 15 years the average being 12.3 years. In each person the semen was twice morphologically studied and the ultrastructure of spermatozoa was evaluated. Submicroscopic changes consisted mainly in the abnormal electron density of nuclear chromatin, altered structure of the acrosome and mitochondrial spiral, as well as in more rarely observed disturbed arrangement of fibrils of the axial filament complex. The hitherto non observed structure in human spermatozoon ön the form of single, annular, "whorls" were described. The interdependance between ultrastructural changes of spermatozoa and fertility was discussed.


Histomorphological and ultrastructural studies of a rat myocardium in experimental conditions. A histomorphological and ultrastructural analysis of the adaptation reaction of the rat heart muscle during an early experimental alloxan diabetes has been carried out. Changes were observed in the orthomorphology of the ultrastructure which appeared as vesicular intercalated discs within the fasciae adherentes regions, as changes in the mitochondria, cell nucleus, myofibrills and in the sarcoplasmic reticulum with a simultaneous increase in the number of lipid bodies. The described alterations are dependent on the duration time of the experiment and on the disturbances in the entire and local system cellular metabolism.


[Submicroscopic structure of collagen--a basis for the interpretation of corresponding polarization-optical and histochemical findings]. In view of new possibilities of acquiring relatively quantitative information about the molecular structure of collagenous fibres in histological section with the help of polarization and histochemical methods a survey is given of the most important aspects of the molecular structure of collagen in connection with the formation of "cross-links", giving due attention to the role of functional groups. These create the basis for interpreting morphological findings covering free amino-groups of lysin and hydroxylysin, guanidine groups of arginine and carboxyl groups of glutamic acid and asparaginic acid, gained by adding phenol or toluidine blue to collagenous fibres and by performing path difference measurements. References made to the applicability of this polarization-histochemical method in clinical research and diagnostics, in gathering reproducible data on processes of development or growth and aging and pathological changes in collagen are intended to encourage wide use of this examination technique in practice.


A morphological study of antibody transport in the transparent fluid flowing form the lymph-folds of the copulatory organ into the cloacal lumen of the cock (Gallus domesticus). The lymph of the copulatory organ of the cock is produced mainly in the lymphobulbus phalli. The lymph fluid passes the secretory duct with its branching lymph capillaries and discharges into the lymph-fold. From here, it is released into the interstitial tissue through gaps of the lymph capillaries but also through the intercellular spaces between the endothelial cells of the lymph capillaries. A minor portion of the lymph is produced also in the lymph-fold from where it is transported in the interstitial tissue either by transfer vesicles of the circulatory blood capillaries or by pores and fenestrae of the transudatory blood capillaries. During the erection of the copulatory organ the lymph is pressed through the intercellular spaces of the epithelial covering the lymph-fold which is cylindrical and multistratified in shape. From here, it reaches the cloacal lumen in the form of transparent fluid (TF). TF was collected by different methods. It contains immunoglobulins which arise from plasma cells of the lymph-fold. Juxtaluminally, the lymph passage takes place via zonulae pseudooccludentes. The epithelial covering secretes a mucoid substance which is added to the TF prior to its following the spermatic phase as the final fraction of the ejaculate. Plasma cells and lymphocytes migrate along the lymph flow in the intercellular spaces of the epithelial covering of the lymph-fold. After an experimental application of antigen the sub- and intraepithelial cells and lymphocytes increase in number with their portion of active cells exceeding the less active ones. The increase coincides with the increase in antibodies detected in the TF where they may cause a local immunisation.


Early signs of leprosy in children.

Early signs of leprosy in children. Leprosy in children is more frequent than generally thought. Diagnosis is not easily made because early signs of the diseases are overlooked. Statistic data from the Dermatologic Clinic Pascua of Mexico City reveal that early signs are cutaneous in 67%  of cases: hypochromic and anesthetic infiltration, nodules, and alopecia of eyebrows and eyelashes. Neurological symptoms such as anesthesis, facial paralysis, thickening of nerves and trophic problems are present in 19.3% of cases. The nose mucosae are congested in 9.2% of cases. Systemic manifestations may be present in 4% of cases. Examination of contacts living with lepromatous patients is stressed as the best way to discover the early signs of the disease. Dermatological consultation in  general and pediatric hospitals is also recommended. If diagnosis is delayed, leprosy can induce physical, psychological and social disabilitation of the patient.


Collodion baby.

Collodion baby. The study of 198 collodion babies, 29 personal cases and 169 from the literature was undertaken. The collodion membrane with spontaneously desquamate between the 15th day and 3rd month of life. During the neonatal period one third of the infants die due to pulmonary complications or infection. The collodion membrane seems to have an increased permeability. The desquamation is followed by a relapse which leads to different keratinization disorders, most frequently nonbullous congenital ichthyosiform erythroderma.


Lymphomatoid papulosis. A model of immunoblastic reaction of the skin. In 3 cases of lymphomatoid papulosis with few ulceronecrotic lesions and 5 with the classic features of pytiriasis lichenoides acuta with necrotic lesions, a considerable part of the cellular component of the infiltrate of the lesions showed the morphologic and cytochemical characteristics of the cells described as immunoblasts. The authors consider that the lymphomatoid papulosis could represent an immunoblastic response to an unknown antigen.


Congenital and non-congenital depigmentation. The hypofunction of melanocytes results in congenital and noncongenital depigmentation. Congenital depigmentation can be further divided into two groups; the first is depigmentation caused by loss of melanization in premelanosomes represented by oculocutaneous albinism; the second group is congenital decrease of melanocytes represented by nevus dipigmentosus. In contrast, acquired progressive depigmentation represented by vitiligo vulgaris and Sutton's leukoderma is characterized by the loss of premelanosome synthesis. The pathogenesis of these three major types of melanogenic defects has been further discussed with the current clinical, biological and immunological view of melanogenesis.


HLA antigens in atopic diseases.

HLA antigens in atopic diseases. The immunogenetical relationship among atopic diseases was investigated from the point of human major histocompatibility antigen. The relationship between IgE level and HLA antigen was also discussed. (1) Atopic dermatitis had no high frequency in HLA antigens. HLA-B12 in bronchial asthma and HLA-BW40 in allergic rhinitis were frequently found in the population study. (2) No HLA-BW15 was observed in these three diseases. The term called 'disease-resistant antigen' was proposed in this paper. (3) We considered that IgE level is not controled by HLA antigen.


Organoid nevus.

Organoid nevus. The organoid nevus is a malformation of most of the normal tissue components in a strictly localized, smaller or larger area of skin, most commonly the scalp. It undergoes more or less predictable developmental changes in puberty and then remains stable, but is subject to secondary development of benign or semimalignant adnexal tumors in a significant percentage of cases. It may present clinically and histologically in a variety of forms, the most common ones being nevus sebaceus and nevus verrucosus. It may be associated with neurologic and skeletal abnormalities in the organoid nevus syndrome (Schimmelpenning-Feuerstein-Mims). Total excision before adolescence is the treatment of choice.


Studies with a new cardioselective beta-blocker, metoprolol. These studies indicate that the cardioselective beta-adrenergic blocking drug metoprolol might be expected to be at least as effective for the treatment of arterial hypertension as propranolol. The difference in effect on the peripheral vascular bed may be of importance when acute increase of the blood adrenaline level occur, as in severe anxiety states. Experience in long-term studies in all kinds of patients with raised arterial pressure has confirmed that metoprolol is an active antihypertensive agent of similar potency to other beta-blocking agents.


Dissociation of the renin lowering and antihypertensive actions of propranolol. Suppression of renin release by beta-adrenoceptor blocking drugs has been advocated as the prime blood pressure lowering mechanism of these agents. The present report casts doubt on this proposition in three ways. In the first study, involving 22 patients with borderline hypertension, patients with elevated plasma renin levels showed normalization of the blood pressure after pharmacological autonomic blockade with intravenous atropine, propranolol and phentolamine, the time course of the pressure fall being such as to exclude suppression of renin release as the antihypertensive mechanism. It is clear that in patients with mild hypertension and high plasma renin levels, the elevation of blood pressure is maintained by a neurogenic mechanism, the elevated plasma renin having no direct role in sustaining the higher blood pressure. In two additional studies involving 21 patients in all with mild to moderately severe essential hypertension, to whom propranolol was administereed by mouth for 1--3 months, two findings were of interest:1) patients with low-renin essential hypertension showed a good antihypertensive response to propranolol, and 2) in some patients a dosedependent dissociation of the renin and blood pressure lowering action of propranolol could be demonstrated. These findings militate against the assumption that propranolol selectively lowers the blood pressure in "renin-dependent" hypertension, and strongly suggest that the antihypertensive action of this drug is not mediated by depression of plasma renin activity.


[Effect of pindolol (Visken) on blood pressure and plasma renin activity in various forms of hypertension]. 1. In 20 of 20 patients (100%) with borderline hypertension Visken normalized the labile blood pressure. The high renin values after stimulation due to orthostasis and saluresis decreased significantly (p less than 0,01). 2. In 3 of 12 patients (25%) with hyporeninemic essential hypertension Visken alone normalized the blood pressure. The low renin values increased to the normal range. 3. In 4 of 18 patients (22%) with normoreninemic essential hypertension Visken normalized the blood pressure. The normal renin values showed a decreasing tendency within the normal range. 4. In 4 of 10 patients (40%) with hyperreninemic essential hypertension Visken normalized the high blood pressure. In 3 of these patients renin decreased distinctly. 5. In 4 of 20 patients (20%) with renal hypertension a therapy with Visken alone normalized the blood pressure. In 3 patients the high renin values decreased to the normal range. 6. In the most other patients of the groups II to V the additional therapy with diuretics and reserpine normalized the blood pressure. In these cases the renin values showed different reactions corresponding to the different effects of betablocking agents, saluretics or reserpine on the plasma renin activity [7]. 7. It is interesting, that Visken not only suppresses high renin values (borderline hypertension [6], hyperreninemic essential hypertension), but also increases low renin values to the normal range in patients with hyporeninemic essential hypertension. Because in essential hypertension the high blood pressure per se may be responsible for the renin suppression [3,4], this increase of renin activity is possibly the consequence of blood pressure reduction, while the decrease of renin activity after Visken may be the cause of blood pressure reduction.


The effect of prindolol on plasma noradrenaline, plasma renin and sodium-potassium metabolism in patients with essential hypertension. The chronic administration of prindolol in patients with essential hypertension resulted in the following: 1) a significant decrease in blood pressure and heart rate (with only the exception of the unchanged diastolic blood pressure after the stimulus of the seven-minute standing period), 2) a significant decrease of plasma noradrenaline concentrativn at rest and under orthostatic conditions, 3) a significant decrease of PRC at rest and an even more pronounced suppression of PRA after the stimulus of upright posture, 4)a significant decrease in total exchangeable sodium and 5) a concomitant significant increase in total body potassium even with an increase in body weight. These findings are not subject to easy interpretation. In particular, we cannot conclude which of the changed parameters plays the initial role in lowering blood pressure. A working hypothesis might presume that beta blocking agents inhibit central and/or peripheral sympathetic nervous activity. The results reduction in plasma renin concentration would in turn lead to a drop in aldosterone secretion rate indicated by the increase in potassium and decrease in sodiummour data would support such a sequence of events.


[Hemodynamic long-term effects of a beta-receptor blockader (Pindolol) in primary essential hypertension]. 1. Pindolol lowers blood pressure both, immediately after administration by a reduction of cardiac output and heart rate and after long-term administration by reducing peripheral resistance. Cardiac index, initially decreased, reached the control value after 8 weeks of treatment. 2. The persistent reduction in heart rate and increase of the cardiac index during exercise after prolonged treatment together with the increase of right and left heart filling pressures seems to be due to augmentation of the Starling mechanism. The increase of the stroke volume at rest and during exercise diminished the blood-pressure lowering effect of the drug. 4. The exercise-induced increase of noradrenalin was abolished by acute administration of pindolol. After long-term treatment, however, we found a consistent and significant elevation of the plasma-catecholamines. This may reflect the development of heart failure [1], a tyramin- or cocain-like action of pindolol [2] or an indirect sympathicomimetic effect of this drug at low doses (10--15 mg/day orally ) [3]. 5. The elevation of plasma-noradrenalin reflects increased sympathetic tone and may be responsible for the increase in stroke volume and plasma renin activity observed by several authors. 6. Since there was no evidence for a hemodynamic mode of action, the lowering of blood rpessure by pindolol may be a central effect.


[Clinicopharmacological studies with pindolol following intravenous and oral administration]. The beta-adrenoceptor blocking potency of pindolol after intravenous and after oral administration was compared in clinical pharmacological experiments in healthy volunteers. Equal doses of pindolol were aequiactive 75 min after intravenous and 2 h after oral administration on tachycardia due to isoprenaline infusions as well as on tachycardia due to exercise on the cycle ergometer. The results of this comparison of pharmacodynamic effects confirm the good enteral absorption reported in pharmacokinetic studies.


A new method for rapid identification of influenza virus isolates. With the use of bacteria sensitized by influenza virus strain-specific antisera, virus isolates can be identified rapidly. One drop of virus suspension is mixed with one drop of sensitized bacteria on a slide that is then agitated; reaction occurs within 10 minutes. The test is subtype-specific. The mehod is based on the fact that the cell wall of the Cowan type 1 strain of Staphylococcus aureus contains abundant quantities of an antigen, known as protein A, that reacts with the IgG molecule by binding it in such a manner that the antibody-combining sites remain free. If an antigen homologous to the antibody coated on the surface of the bacteria is added to the suspension of sensitized staphylococci, agglutination occurs.


Management of maple syrup urine disease in Canada. Committee for improvement of Hereditary Disease Management. Nine patients with classic maple syrup urine disease (MSUD) and four with variant forms are under care at five treatment centres in the network affiliated with the National Food Distribution Centre for the Treatment of Hereditary Metabolic Diseases (the "Food Bank"). Diagnosis was made by clinicians and not from mass screening programs. MSUD requires complex emergency treatment to prevent severe neurologic damage, but effective management is compatible with normal growth and development. Long-term treatment requires continuous monitoring of the response to diets restricted in branched-chain amino acids; semisynthetic diet products free of branched-chain amino acids, provided by the Food Bank, are essential. Centralized treatment programs reduce the cost of treatment and maximize the potential benefits. The leucine requirement for adequate somatic growth during infancy in MSUD was found to be 200 to 600 mg/d; this range is lower than that estimated for infants with an intact leucine catabolic outflow pathway. The requirements for isoleucine and valine in infancy were also found to be lower than published values for normal infants.


Failure of acetylmethadol in treatment of narcotic addicts due to nonpharmacologic factors. Acetylmethadol, a new narcotic substitute, has a longer duration of action than methadone. Seventeen subjects, former heroin users currently under methadone treatment, entered a study of the toxicity and efficacy of this drug. Only nine subjects completed the assessment phase of the study and began the acetylmethadol phase, and only one completed the 8-week study phase. Hence, no conclusions can be drawn about acetylmethadol's efficacy. The high attrition rate was unrelated to pharmacologic factors; the subjects were concerned that if this drug was effective there would be no methadone to take home and hence no opportunity to trade, sell or "play with" (that is, combine with other drugs) the latter. This study emphasizes the difficulty in determining the efficacy of specific drug treatments for opiate-dependent patients.


Echocardiographic features of an unusual case of aortic valve endocarditis. In a patient with aortic valve endocarditis a myocardial abscess, complete heart block and acute aortic regurgitation developed. Echocardiography gave evidence of large aortic valve vegetations, and at operation vegetations were found to have destroyed the right coronary cusp and part of the noncoronary cusp. Following surgery the patient recovered. Echocardiography may prove to be a useful noninvasive technique to aid in the timing of surgical therapy in patients with valvular vegetations.


Practical guidelines for assessing patients positive for hepatitis B surface antigen. In assessing the patient the hepatitis B surface antigen (HBsAg) the physician must decide on the basis of physical findings, results of laboratory tests and biopsy, when indicated, whether the patient is an asymptomatic carrier or has acute or chronic hepatitis. Asymptomatic carriers of HBsAg must be educated in personal hygiene and the possibility of transmission, should not be allowed to donate blood or breast-feed and should not work with blood products for human use or pharmaceutical products designated for intravenous use. However, it is otherwise not necessary to advise these individuals to change their profession.


Feasibility of routine testing for hepatitis B surface antigen in hospital employees and restriction of carriers. In 1972-73, 48 hospital staff members were tested selectively for hepatitis B surface antigen (HBsAg); 4 (8.3%) were found to be HBsAg-positive. In 1974-75, 1415 staff members were tested routinely before employment and at periodic health examination; 25 (1.8%) were found to be HBsAg-positive. Of the HBsAg-positive staff members 55.2% were Asians, this proportion being significantly (P less than 0.05) greater than that of any other ethnic group, and 31.0% were southern Europeans. Nurses and laboratory technologists were the largest professional groups among the HBsAg-positive staff, each accounting for 20.7%. Our results indicate that it is impractical to carry out routine testing of hospital staff for HBsAg. Selective testing and restriction from work in their units is proposed for staff of the renal and peritoneal dialysis units, the emergency department and the intravenous team and dietary staff who handle food directly.


Detection of core antibody in hepatitis B infection. Hepatitis B core antigen (HBcAg) is found on the decoated Dane particle and on a morphologically similar particle detected mainly in the nucleus of hepatocytes of patients with hepatitis B. HBcAg prepared from the liver of a chimpanzee infected with hepatitis B virus was used to test human serum for core antibody (anti-HBc) by complement fixation. Anti-HBc was found in serum collected from patients with hepatitis B in both the acute and convalescent stages, from carriers of hepatitis B surface antigen (HBsAg) and from patients with chronic liver or renal disease who were carriers of HBsAg. It was not found in patients with hepatitis A or infectious mononucleosis, or in healthy persons who were not carriers of HBsAg.


[The urinary excretion of pregnanediol during pregnancy determined by gas-liquid chromatography. I. Its evolution throughout the normal and pathological pregnancy (author's transl)]. Employing the technique described by Van Kampen and Anker, modified by Macarulla et al., 180 pregnant women have been studied (66 normals and 114 with different pathology: infertility, toxemia, diabetes, Rh isoinmunization, gemelar pregnancy and abortions), taking 319 determinations of pregnanediol in 24 hours urine samples. The analysis of the results show in normal pregnancy a progressive increase of the urinary pregnanediol from the beginning of gestation, this increase being more intense from the 20th week, reaching the maximum value in the 37th week and from this point descending slowly. In patients with toxemia, the values of pregnanediol (in the majority of the cases) are decreased, while in pregnant women with antecedents of infertility are increased from the 36th week of pregnancy, although they had protective treatment from first months of pregnancy. No manifest deviations of urinary pregnanediol from the normal values exist in diabetic pregnant women, Rb isoinmunization or gemelar pregnancies. In aborted pregnancies the pregnanediol values are markedly decreased without a tendency to increase, contrary to the threats of abortion in full-term pregnancies.


[The urinary excretion of pregnanediol during pregnancy determined by gas-liquid chromatography. II. Its relation with other parameters controling pregnancy (author's transl)]. The relation between the urinary pregnanediol determined by gas-liquid chromatography during pregnancy, with ultrasonic findings (biparietal diameter, thickness and echorrefringency of the placenta and the appreciated quantity of amniotic fluid), with biochemical parameters of control of pregnancy (beta-glucoronidase, total and thermostable alkaline phosphatase), with amnioscopic findings, and with several studied parameters of the amniotic fluid by amniocentesis, were studied. A good relation exists with the parameters which denote placentary insufficiency and fetal risk (irregularity in the homogeneity of the placenta, elevation of the total and thermostable alkaline phosphatase, positive amnioscopy) and also with those that are related with fetal maturity (biparietal diameter, shake test, organge cells, creatinine in amniotic fluid, etc.). These results indicate that the determination of urinary pregnanediol can be one of the tests controlling the normal and pathological pregnancies, being useful in the detection of fetal risk and the diagnosis of the intrauterine fetal maturity.


[BAME-Esterase activity in plasmas from blood of human placental interveillous space and umbilical cord vessels (author's transl)]. The authors studied an enzymatic activity (BAME-esterase) from human plasma, intimately related with the bradykinin release mechanisms. The optimal conditions of evaluation of the different plasmas were determined. Lately, the authors showed the results obtained with plasma from maternal peripheral blood, umbilical vessels blood and human placental intervillous space blood. It was concluded: 1. The study of enzymatic kinetics allows to establish a reaction time of 30 minutes, and the enzymatic concentration contained within 0.5 ml. of plasma, as ideal parameters to determine the enzymatic activities into the different compartments. 2. In the cases studied, considered clinically normals, the enzymatic activity in plasma from the interveillous space, before and after the detachment of the placenta, was greater than in peripheral maternal and umbilical vessels bloods. The activity in umbilical artery plasma was greater than in umbilical vein and practically the same as in maternal plasma. 3. The esterase activity values into the compartments studied in pre-eclamptics, were similar to that found in the cases considered clinically normal.


[The urinary excretion of pregnanediol during pregnancy determined by gas-liquid chromatography. III. Its relation with the obstetric results (author's transl)]. 269 determinations of urinary pregnanediol by gas-liquid chromatography were made in 140 patients during pregnancy. A relation between the pregnandioluria and the fetal results (adequacy of the weight to gestational age, Apgar score at one and five minutes of birth, umbilical artery blood PH and perinatal mortality) as well as the global evaluation of the placenta (macroscopic aspect, vascular index of Kawai et al. and Scott and Jordan index) was studied. The results show that in the cases with fetal pathology (small for date, depression, acidosis, perinatal death) as well as in the cases with placental pathology, the values of pregnanediol were significantly decreased from the first months of pregnancy, which indicate that the placental insufficiency is a very precoz chronic process and on the other hand, that the determination of urinary pregnanediol is a good method for its detection.


Oxidative and glicolytic metabolism of the frontal cortex (latero-frontal) and of the posterior cortex (latero-occipital) in relation with the sexual activity of the rat. The authors of this paper have ascertained the glycolytic metabolism and the oxidative metabolism (intake of QO2), of the frontal and posterior cortex in female rats at different stages of the sexual cycle, as also in ovariectomized animals, by the intake of glucose and the production of lactates. The results indicate a statistically significant increase of the oxidative metabolism of the posterior cortex (latero-occipital) in the estrual and proestrual phases, in comparisons with the diestral phase. The frontal cortex (latero-frontal) did not show any significant difference; moreover, the glycolitic metabolism did not alter in any of the tissues under observation. These findings, seem to suggest possible participation of the posterior cortex (latero-occipital) on the regulation of sexual cycle of the rat. The activation of this cortex occurs through the preponderant imbricantion of the tri-carboxylic acid cycle.


[Hystereoscopy with CO2. Technique, indications and contraindications (author's transl)]. The Hysteroscopy occupies again at the present time an important place among the gynecological explorations, since Lindeman introduced the use of controlled carbonic anhydride for the distensión of the uterine cavity. This work studies the technique, indications and contra-indications as well as the value of the hysteroscopy in the first 80 explorations performed in the Gynecological Endoscopy Unit of the Centro de Estudios sobre Repoducción Humana, from Barcelone (Spain). The results are commented and the reach of such endoscopic exploration is analised as routine technique of exploration in comparison to other exploratory techniques used in the study of uterine cavity.


Serum luteinizing hormone follicle-stimulating hormone and prolactin in neonatal-androgenized rats. Serum levels of LH, FSH, Prolactin and Testosterone of 90 days old male rats androgenized soon after birth were determined by specific radioimmunoassay and were compared to untreated rats. LH and FSH levels were also determined in 90 days old female rats neo-natally treated with testosterone and compared with normal diestrus rats. Androgenization of male rats significantly increased serum FSH and Prolactin levels without producing changes in plasma LH and testosterone concentrations. Similar increase in the FSH levels were found in androgenized female rats although plasma FSH concentrations were lower than in the male groups. These results obtained in male rats give an additional evidence that androgens acting in the first days of life are responsible of the higher levels of FSH and Prolactin that characterize the male or tonic pattern of gonadotrophin secretion.


[The effect of androgens upon the differentiation of Cowper and Bartholin glands in rat fetuses (author's transl)]. In the present paper, a study is made of the normal structure shown in Bartholin and Cowper glands of 100 female fetuses and 100 male fetuses of Wistar rats at the end of gestation, with the structure of bulbouretral glands that formed in 70 female fetuses of the same species and period of gestation masculinized by androgens. In relation to the Bartholin glands, whose bilateral sketch is constant in the fetuses, we can affirm that it shows significant differences of structure with regards to the sketch of the Cowper gland. On the opposite, the histologycal details of the latter, are entirely identical to those shown by the bulbouretral glands of the masculinized female fetuses, a fact which permits us to affirm that these are authentic Cowper glands, not only because of their position, but also because of their structure. This morphological data corresponds to a masculinization phenomenon and demonstrates that the Bartholin and Cowper glands are very sensitive to the effect of androgens during gestation.


Human chorionic somatommamotropin (HCS) and pregnancy. Its relation with insulin. Plasma HCS levels have been measured in normal and pathological pregnant women. In the normal group HCS levels increased from 6--8 weeks till 33-34 weeks and then felt significantly. HCS pattern in prediabetic and chemical diabetic pregnant women was similar to the normal group. However HCS levels in chemical diabetics were significantly higher during the first two trimesters. HCS levels increased in twin pregnancy, diminished in cases of eclampsia, hypertension, fetal growth retardation, mole and blighted ovum, and disappeared after intrauterine death. Nothing could be deduced from the obese and Rh-isoimmunization groups. It is confirmed the value of HCS determination as an index of placental maturation. Also, insulin/HCS ratio may be of some aid in the study of carbohydrate intolerance in pregnancy.


[Metabolism of nucleic acids in testicles of adult rats deficient in vitamin A]. Avitaminosis A, applied on deficient rats receiving retinoic acid leads to an important decrease of thymidine incorporation in testicular DNA in vivo as well as in vitro. On the contrary uridine incorporation in RNA is considerably increased in vitro as well as in vivo. The function of ribosomes, as measured by the aggregation ability in the polysomes, is not altered by vitamin A deficiency. From these results one can say that the degenerescence of rat testicle is accompagnied by a decrease of DNA anabolism and a stimulation of RNA anabolism due to an increase of its catabolism (compensatory synthesis).


Thiamine absorption in the rat. IV. Effects of caffeic acid (3,4-dihydroxycinnamic acid) upon absorption and active transport of thiamine. The effects upon thiamine absorption in-vitro and in-vivo by caffeic acid (a thiamine antagonist isolated from bracken) was studied, partly using 14C-thiamine. It was again shown that caffeic acid reduced the quantity of thiochrome positive thiamine, dependant upon the concentration ratio caffeic acid/thiamine. Caffeic acid was able to pass across the intestinal wall and to exert its antithiamine effect in the serosal incubation fluid. When caffeic acid was present in the mucosal fluid the amount of thiochrome positive thiamine passed to the serosal side was diminished according to the mucosal caffeic acid concentration. In-vitro studies with 14C-thiamine revealed, however, that thiamine modified and turned into a thiochrome negative form by caffeic acid was absorbed similarly to unaffected thiamine. Active transport in-vitro of thiamine was significantly inhibited by the presence of caffeic acid.


Isolation, partial characterisation of antithiamine factor present in rice-bran and its effect on TPP-transketolase system and Staphylococcus aureus. 1. A light yellow viscous oily antithiamine compound designated as Compound X was isolated from rice-bran and it was composed of three components--glucose, a yellow viscous oily substance (Fraction A) and a reddish brown amorphous substance (Fraction B). 2. 1 mg of Compound X inactivated 3.5 microgram of thiamine hydrochloride whereas 1 mg of Fraction A inactivated 26.5 microgram of thiamine hydrochloride. Fraction B had no antithiamine activity. 3. Fraction A was partially characterised as benzene nucleus with ortho dihydroxyl groups, one methyl group and a side chain containing hydroxyl and carboxylic acid groups. 4. Compound X as well as Fraction A inhibited the utilisation of ribose-5-phosphate by TPP-TK system of human erythrocyte hemolysate and the growth of Staphylococcus aureus was retarded by these compounds.


Enzymatic microassay of pyridoxal-5'-phosphate using L-tyrosine apodecarboxylase and L-(1-14C) tyrosine. A microassay for pyridoxal-5'-phosphate (PLP) is described, which incorporates both the enzymatic and radioisotopic techniques. The method is based upon the stoichiometric decarboxylation of L-(1-14C) tyrosine by L-tyrosine apodecarboxylase and PLP. This method is an extensive modification of the ones reported by us previously, the main features of this present method being the ease of preparation of the enzyme extract and the substrate, elimination of the preincubation period and shortening of the 14CO2-trapping step. The assay as described here is rapid, highly sensitive and specific.


Erythrocyte glutathione metabolism in cobalt-deficient goats. Cobalt deficiency was produced in goats by feeding them rhode grass hay. The deficient animals excreted increased amounts of methyl malonic acid in their urine, indicating a lack of vitamin B12. Erythrocyte reduced glutathione levels increased with the onset of anemia. There was a concomitant increase in the levels of erythrocyte glutathione reductase (GSSG NADPH Reductase) and glutathione peroxidase (GSH:H2O2 peroxidase)during deficiency. These results are compared with similar observations reported for vitamin B12 deficiency in humans.


Ascorbic acid synthesis in certain guinea pigs. Three guinea pigs fed a vitamin C-free diet manifested no symptoms of scurvy even after 4-8 months, normally increased in body weight and excreted quantities of ascorbic acid in urine far exceeding the total body pool of ascorbic acid. The course of healing subsequent to experimental trauma in one of these animals proved to be entirely normal and vitamin C concentration in its liver after 8 months of a scorbutogenic regimen was found to be more than twice that in guinea pigs with a daily intake of 10 mg ascorbic acid. It is evident that certain guinea pigs are capable to synthesize ascorbic acid that fully covers the needs of the organism. However, the freqency of occurence of such guinea pigs appears to be extremely small.


In vivo acylation of triglycerides and phosphoglycerides of liver subcellular fractions with palmitate-1-14C in rats fed vitamin A. Incorporation of palmitate-1-14C into liver and its mitochondrial, and microsomal triglycerides and phosphoglycerides of rats fed 100000 I.U. of vitamin A for two days has been studied. Feeding of vitamin A significantly increased triglycerides in liver and its mitochondrial, microsomal and supernatant fractions as compared to the controls. A significant increase in total phospholipids and phosphatidyl choline was noted in liver mitochondrial and microsomal fractions of vitamin A fed rats. The incorporation of palmitate-1-14C (counts/min/liver) into triglycerides of liver mitochondrial, microsomal and supernatant fractions of vitamin A fed rats was significantly higher, whereas in phosphatidyl ethanolamine and phosphatidyl choline it was not significantly different from the controls.


Effect of vitamin E deficiency on the level of superoxide dismutase, glutathione peroxidase, catalase and lipid peroxide in rat liver. The activities of superoxide dismutase, glutathione peroxidase, catalase and xanthine oxidase were simultaneously studied in vitamin-E deficient and -supplemented rat liver and also measured the lipid peroxide content in liver. The lipid peroxide content of vitamin E-deficient rat liver, estimated by thiobarbituric acid, increased as compared with that of vitamin E-supplemented rat liver. No marked changes of activities of superoxide dismutase, glutathione peroxidase and catalase were observed, but the activity of xanthine oxidase which is strong superoxide generator increased in vitamin E-deficient rat liver. These results suggest that vitamin E prevents the accumulation of lipid peroxide, but not controls the level of peroxide scavenging system such as superoxide dismutase, glutathione peroxidase and catalase.


The relation of impaired vitamin A and E tolerance to fat absorption in biliary diversion. Eleven patients have been studied after cholecystectomy with exploration of the common bile duct (CBD) and insertion of a T tube for free biliary drainage. Prior to clamping the T tube no significant rise was seen above fasting serum vitamin A and E, or serum triglyceride levels after 6 of the patients had been given these substances in a liquid test meal. In addition no rise in fasting vitamin E levels was seen after 3 subjects had been loaded for 4 days with 0.5 g DL alpha-tocopherol acetate/day. Faecal fat collections performed on 9 subjects indicated that over 70% of the ingested fat was absorbed. All these findings returned to normal when the T tube was clamped and the intraluminal flow of bile re-established. We conclude that deficiency of bile may allow the absorption of fat in the absence of fat soluble vitamins.


Lipoperoxides in organs of vitamin E deficient rats fed large amounts of highly unsaturated fats. Rats were fed diets containing 10% cod liver oil with and without a supplement of tocopherol acetate for 32 weeks. The determination of peroxides in lipid extracts of adipose tissue, liver, heart and skeletal muscle by different methods was attempted. High amounts of peroxides were found only in adipose tissue of vitamin E deficient animals. Small values were found in other tissues of both groups. The problem whether the organs contain true lipoperoxides, or some other substances are responsible for the peroxide estimates, is discussed.


Effect of micellization on rate of cupric-ion-promoted hydrolysis of dicarboxylic acid hemiesters. The effect of micellar sodium lauryl sulfate on the rate of cupric-ion-promoted hydrolysis of some dicarboxylic acid hemiesters was investigated at pH 5, ionic strength 0.1 M, and 40, 45, and 50 degrees. The rate of cupric-ion-promoted hydrolysis of sodium n-decyloxalate in the micellar phase is about 50 times as fast as that in the bulk solution. The formation constant of the intermediate chelate complex, cupric decyl oxalate, was decreased in the micellar phase, while the rate of attack of hydroxide ion upon the chelate complex was increased. The overall rate increase is attributed to the increase in the entropy of activation for the reaction in the micellar phase. The rates of hydrolysis of sodium hydrocortisone 21-hemisuccinate and sodium hydrocortisone 21-hemi-(3,3-dimethylglutarate) were unaffected by copper ion.


Subnanogram assay for pilocarpine in biological fluids. A method for the determination of pilocarpine was developed in which the imidazole ring of pilocarpine was acylated with heptafluorobutyric anhydride, using triethylamine as a catalyst. After cleanup, the pilocarpine derivative was analyzed using GLC with electron-capture detection. The limit of sensitivity was 25-50 pg of pilocarpine, which had been subjected to the derivatization and cleanup procedures. The method was specific for pilocarpine, with the isopilocarpine derivative eluting prior to the pilocarpine derivative.


Circular dichroism spectra of tetracycline complexes with Mg+2 and Ca+2. The study of Ca+2 and Mg+2 complexes of tetracycline in buffered solution was undertaken to determine their stoichiometry and the chelation sites. Circular dichroism was used to follow complex formation. Modified tetracyclines, in which potential complexation sites were blocked, were used to determine the participation of particular sites in complexation. Calcium formed a 2:1 metal-ion to ligand complex, while the magnesium complex formed at a 1:1 ratio. Formation of the calcium complex involved addition of one metal ion to the C-10, C-11 site with subsequent addition of a second metal ion at the C-12, C-1 site. The magnesium chelate occurred at the C-11, C-12 beta-diketone site.


N-Halo derivatives IV: Synthesis of low chlorine potential soft N-chloramine systems. A number of low chlorine potential, soft N-chloramines containing nitrogen-chlorine bonds of different polarity were prepared. These novel N-chloramine systems were based on derivatization of 2-amino-2-methyl-1-propanol.


N-Halo derivatives VI: Microbiological and chemical evaluations of 3-chloro-2-oxazolidinones. Comparative antimicrobial activity of 3-chloro-2-oxazolidinone (I), 3-chloro-4-methyl-2-oxazolidinone (II), 3-chloro-4,4-dimethyl-2-oxazolidinone (III), and N-chlorosuccinimide (IV) was evaluated in aqueous buffers in the absence and presence of 5% horse serum. All four compounds had similar bactericidal activity in the absence of horse serum, but I and III had superior activity relative to IV when serum was present. Compound III was considerably more stable with respect ot loss of positive chlorine and bactericidal activity than I and II when stored in 0.1 M sodium dihydrogen phosphate buffered to pH 7.0 at 40 degrees. Thus, III is potentially the most useful bactericidal agent of those evaluated. The chlorine potentials of I, II, and III, the rate constants for transfer of positive chlorine from I and III to morpholine in aqueous solutions, and the hydrolytic stabilities of I and III with respect to loss of positive chlorine were evaluated. These data, together with previously calculated data for IV, are used to rationalize the observed bactericidal activities.


Effect of storage at specified temperature and humidity on properties of three directly compressible tablet formulations. Direct compression tablets containing sodium starch glycolate, an alginate derivative, or povidone as a disintegrant, magnesium stearate as a lubricant, amaranth as a tracer, and dibasic calcium phosphate dihydrate as the matrix were stored for 30 days at 23 degrees and 75% relative humidity (R.H.), 45 degrees and 75% R.H., and 65 degrees and 40% R.H. Samples were evaluated after 0, 10, 20, and 30 days for size, hardness, and dissolution characteristics. Although no significant changes in the dimensions or hardness of the three tablet formulations, prepared at three different compaction pressures, were observed, the dissolution efficiency of the systems showed significant changes, some systems dissolving more rapidly and some more slowly after storage. In some cases, the changes were so substantial as to indicate the possibility of significant changes of the bioavailability of drugs formulated in such systems. The relevance of this work to the problem of evaluating aging effects on the physical properties of tablets is discussed.


Disaggregation of compressed tablets.

Disaggregation of compressed tablets. Tablets of dibasic calcium phosphate containing varying proportions of intra- to extragranular maize starch were prepared at three compaction pressures. The surface area generated per tablet after 10 and 30 min of disintegration was measured with an automated counter by a new technique. The optimum starch combination that produced the maximum surface area in a tablet formulation was either 2.5% intra-12.5% extragranular or 15% intragranular starch alone. The distribution of starch did not affect the resultant strength of the tablets, and maximum generation of surface area was achieved by compacting the tablets at as low a pressure as practical.


Dissolution characteristics and oral absorption of digitoxin and digoxin coprecipitates. A marked increase in the dissolution rates od digitoxin and digoxin was attained by dispersing the drugs in two inert solid carriers, poloxamer 188 and deoxycholic acid. The 1 and 10% (w/w) drug-carrier solid dispersions were prepared by the solvent method. The former dissolved significantly faster than the latter. The oral administration of 10% (w/w) digitoxin-carrier coprecipitates to mice significantly increased toxicity. This observed increase is attributed to an increase in the rate and, possibly, the extent of oral absorption of the drug. Although a 10% coprecipitate of digoxin in both carriers showed an increase in the dissolution rate, no increase in oral toxicity was observed. X-ray diffraction patterns indicated that both digitoxin and deoxycholic acid undergo crystalline modifications due to treatment by the solvent, but the exact nature of the drug-carrier solid dispersions was not revealed.


Electrochemical evidence for interaction between chlorpromazine hydrochloride and trifluoperazine hydrochloride and the flavin coenzymes. Polarographic and chronopotentiometric methods were applied to study the effects of the phenothiazine tranquilizers chlorpromazine hydrochloride and trifluoperazine hydrochloride on the electrochemical behavior of the flavin coenzymes flavin mononucleotide and flavin adenine dinucleotide. The effects of the drugs were measured mainly by decreases in the diffusion currents, id, developed in the polarographic experiments and by a similar decrease in the chronopotentiometric constant, ior1/2, in the chronopotentiometric experiments when the coenzymes were reduced in the presence of the added drugs. The observed interference with the redox properties of the coenzymes could conceivably be related to the reported ability of the drugs to inhibit respiration and produce their tranquilizing effect.


Fluorometric determination of trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles in biological materials. Interest in the 5-, 6-, and 7-trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles as potent, orally active anti-inflammatory agents required a method for their determination in serum, urine, and feces to permit studies of their absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific procedure was developed based on an ethyl acetate extraction of alkaline specimens and subsequent fluorometric analysis of ethanolic solutions of the extract residues. The method is sensitive to 0.1 microgram/ml, 0.5 microgram/ml, and 0.7 microgram/100 mg of these compounds in serum, urine, and feces, respectively. Overall mean recoveries and standard deviations of the 5-, 6-, and 7-trifluoromethyl-substituted compounds from biological samples were 102.2 +/- 3.0, 102.2 +/- 5.4, and 100.5 +/- 5.7%, respectively. The procedure was applied successfully to absorption studies with 2,3-bis(4-methoxyphenyl)-7-(trifluoromethyl)indole in the dog.


Effect of nonionic surfactants on percutaneous absorption of salicylic acid and sodium salicylate in the presence of dimethyl sulfoxide. Fifteen nonionic surfactants, 10% (w/w), were each incorporated into white petrolatum USP ointment base containing 10% (w/w) salicylic acid or 11.6% (w/w) sodium salicylate with 10% (w/w) dimethyl sulfoxide. Percutaneous absorption was determined from blood salicylate levels in New Zealand white rabbits at regular intervals for 8 hr following application of the ointment. Percutaneous absorption of salicylic acid was increased significantly when sorbitan monopalmitate, sorbitan trioleate, poloxamer 231, poloxamer 182, polyoxyethylene 4 lauryl ether, polyoxyethylene 2 oleyl ether, or polyoxyl 8 stearate was added to the ointment containing dimethyl sulfoxide, salicylic acid, and white petrolatum. Percutaneous absorption of sodium salicylate was increased significantly when sorbitan monolaurate, sorbitan monopalmitate, or poloxamer 182 was added to the ointment containing dimethyl sulfoxide, sodium salicylate, and white petrolatum.


Dissolution of two-component solids.

Dissolution of two-component solids. The dissolution rates of compressed two-component mixtures were investigated. A good correlation between the composition of the solid and its observed dissolution rate was demonstrated by regression analysis. A model for dissolution was applied to compressed mixtures of aspirin-salicylic acid, aspirin-phenacetin, phenacetin-caffeine, and aspirin and caffeine (the last mixture complexes in solution).


Pharmacology of Quercus infectoria.

Pharmacology of Quercus infectoria. The galls of Quercus infectoria (Fagaceae), a commonly available plant in Iran, were studied pharmacologically. Two fractions were employed, a dried acetone-treated methanol extract dissolved in water (Fraction A) and a subfraction prepared by chloroform-methanol extraction (Fraction B). Fraction A was active as an analgesic in rats and significantly reduced blood sugar levels in rabbits. Fraction B had CNS depressant activity. Data obtained with a treadmill indicated a decreased activity ratio by Fraction B, suggesting a possible interference in motor coordination. It potentiated the barbiturate sleeping time significantly without changing the onset time or the loss of the righting reflex. In addition, Fraction B exhibited a moderate antitremorine activity by causing a delay in the onset and a decrease in the severity of tremorine-induced tremors. The local anesthetic action of Fraction B was evident due to the complete blockade of the isolated frog sciatic nerve conduction.


Potentiometric and spectral investigations of anhydrotetracycline and its metal-ion complexes. The interaction of various metal ions with anhydrotetracycline was investigated. A comparison of the UV-visible and fluorescence spectral characteristics of anhydrotetracycline and its metal-ion complexes with a number of modified anhydrotetracyclines in the presence of metal ions suggested that the C-11 oxygen was involved in metal-ion binding. Secondary binding was observed in the A-ring by circular dichroism when the primary site was blocked.


Lipid-protein interactions: enhancement of enzyme activity of L-glutamic acid dehydrogenase by nonionic detergents. Five nonionic detergents enhanced the activity of L-glutamic acid dehydrogenase [L-glutamate:nicotinamide adenine dinucleotide phosphate oxidoreductase (deaminating) (EC 1.4.1.3)]. These detergents activated the enzyme toward alpha-ketoglutaric acid reduction, causing a decrease in the sensitivity of the enzyme to allosteric regulation by guanosine 5-triphosphate. There was also a diminution of the enhancing effect of the modifier adenosine 5-diphosphate on the enzyme's L-glutamic acid dehydrogenase activity. These detergents may cause a conformational change in the enzyme, and this change could lead to an increase in the binding of the substrates for the alpha-ketoglutaric acid reduction. Accompanied with this conformational change would be a decrease in the binding of the modifier guanosine 5'-triphosphate, with no concomitant change in the binding of the adenosine 5'-diphosphate modifier.


High-pressure liquid chromatographic determination of chlorphenesin carbamate and the beta-isomeric carbamate. A high-pressure liquid chromatographic assay was developed for the determination of chlorphenesin carbamate and its beta-isomeric carbamate. A single 4-mm i.d. X 30-cm column, prepacked with 10 micrometer fully porous silica gel particles, is used with 3% methanol in 50% water-saturated butyl chloride as the mobile phase. The procedure separates chlorphenesin carbamate from several possible impurities in addition to the beta-isomeric carbamate. The assay was applied to bulk drug and compressed tablets. The relative standard deviations for the assays of chlorphenesin carbamate and the beta-isomer are approximately 1 and 2%, respectively.


Molecular connectivity VII: specific treatment of heteroatoms. The molecular connective index, chi, initially designed for hydrocarbons, has been formally extended to molecules containing heteroatoms. The sigma value of the heteroatom is modified to take account of its number of attached hydrogen atoma, sigmaiv = Zv - hi. These values were successfully tested on boiling points and molar refractions. A table of sigmav values is presented for nitrogen, oxygen, fluorine, chlorine, bromine, and iodine in various bonding situations.


Trace analysis of 2,4,5-trichlorophenoxyacetic acid, its glycineamide, and their alkaline hydrolyzable conjugates in mouse blood, urine, and feces. Chemical methods were developed for the trace analysis of the herbicide 2,4,5-trichlorophenoxyacetic acid, its glycineamide, and their alkaline hydrolyzable conjugates in mouse blood, urine, and feces. The salient elements of the methods are extraction of the free acids with benzene, methylation, cleanup on a silica gel column, and quantification via electron-capture GLC. Any unextracted conjugates remaining in the substrates are then subjected to alklaline hydrolysis, and the liberated 2,4,5-trichlorophenoxyacetic acid is assayed. Data are presented concerning recoveries of the compounds from the three spiked substrates. The utility of the procedures is illustrated by a preliminary pharmacolinetic study employing parallel electron-capture GLC and radioassays of the three substrates from mice injected with a single intravenous dose of 14C-2,4,5-trichlorophenoxyacetic acid. GLC characteristics and partition values of the the compounds and hydrolysis of the glycineamide under various conditions also are discussed.


Mechanistic studies on transcorneal permeation of pilocarpine. The mechanism of corneal pilocarpine penetration was studied in the albino rabbit using radiochemical techniques. The apparent rate and extent of pilocarpine accumulation in the aqueous humor and the various cell layers of the cornea were determined for both intact and abraded eyes. For the first time, drug levels were monitored in the epithelium and stroma-endothelium of the intact cornea using a tissue-scraping technique. In addition, a new postinstillation rinsing method was devised to evaluate the rate of corneal uptake. The results demonstrate a dual role for the corneal epithelium, both as a barrier to drug penetration and as a reservoir for drug in the intact cornea. The transcorneal pilocarpine flux is slower than the data appear to indicate, and previous overestimates of the apparent absorption rate constant are due to parallel elimination processes occurring at the absorption site. Pharmacokinetic parameters were determined for each tissue to generate an overall mechanism for corneal permeation.


Correlation of absorption of sulfamethazine boluses with dissolution using a new dissolution apparatus for veterinary tablets. A rotating-basket apparatus for dissolution testing of veterinary bolus tablets was designed and constructed. Sulfamethazine boluses containing different disintegrating agents were evaluated in vitro and by blood level data following administration to cattle. The dissolution t50 and various pharmacokinetic parameters showed directly compressible starch and carboxymethylstarch to be the most effective disintegrants in the concentrations employed while magnesium aluminum silicate and microcrystalline cellulose were about equal but less effective than the previous disintegrants. A bolus formulation containing no disintegrant gave even less satisfactory results. A correlation was established between the dissolution t50 and the time to peak plasma level and also between the t50 and the area under the plasma-time curve for the first 36 hr.


GLC determination of l-2-hydroxy-N-cyclopropylmethylmorphinan in plasma and urine. A specific method was developed for the determination of l-2-hydroxy-N-cyclopropylmethylmorphinan in plasma and urine by GLC, using flame-ionization detection. The method involves the extraction of the compound into ether from plasma or urine at pH 7.4, followed by back-extraction into 1 N HCl. The acid phase is ether washed and made alkaline, and the compound is reextracted into ether. The ether is evaporated to dryness, the residue is dissolved in methanol, and an aliquot is analyzed by GLC. The same method is applicalble to plasma and urine samples following deconjugation of the compound with glucuronidase-sulfatase. The overall recovery is 93.1 +/- 9.4% SD) in the concentration range of 0.020-2.0 microgram/ml. The method was successfully applied to plasma and urine specimens obtained after administering single 25-mg oral doses to humans.


Determination of cyanocobalamin by thermal decomposition of the cyano group using an ion-selective electrode. A method for the simultaneous determination of cyanocobalamin, cobinamide (Factor B), and hydroxocobalamin in the solid state is described. The method is based on heating at 120 degrees for cobinamide and at 140-145 degrees for cyanocobalamin (15-20 min). The cyano content in the sample is distilled as hydrocyanic acid, trapped in 0.1 M potassium nitrate at pH 12-13, and determined by means of the cyanide ion-selective electrode. The error of this method, statistically established, does not exceed +/-3%.