Mutagenic, cancerogenic and teratogenic effects of alcohol.

Alcohol is mutagenic, cancerogenic and teratogenic in man. Ethanol is mutagenic via its first metabolite, acetaldehyde. This is substantiated by the findings that acetaldehyde induces chromosomal aberrations, sister-chromatid exchanges and cross-links between DNA strands. Methanol, a contaminant of many alcoholic beverages, is also mutagenic via its metabolite, formaldehyde. In addition, different indirect pathways may lead to mutations by alcohol. The cancerogenic activity of alcohol remains unverified by modern standard carcinogenicity tests. Ethanol and other alcohols, as well as aldehydes, inhibit RNA synthesis in cells and in cell-free transcriptional systems. A reduction of cellular RNA synthesis may play an important role in the mutagenic, carcinogenic and teratogenic activity of alcohol.


Mutagenicity of nitrosodiethanolamine on Salmonella typhimurium.

Nitrosodiethanolamine was examined in the Ames assay for bacterial mutagens. In absence of S9 activation a mutagenic effect was found.


A negative test for mutagenic action of microwave radiation in Drosophila melanogaster.

Microwave radiation (2450 MHz CW) was tested for mutagenicity in Drosophila melanogaster. Embryos in water were exposed to the electromagnetic field with a mean specific absorption rate of 100 W/kg. A sensitive somatic test system was used, in which mutagenicity was measured as the frequency of somatic mutations for eye pigmentation. With the test system used, microwaves did not show any mutagenic activity.


Mutagenicity tests with griseofulvin.

Griseofulvin was studied for its ability to induce structural chromosomal aberrations in germ and somatic cells of the male mouse. It was also tested for its capacity to produce his+ revertants in Salmonella typhimurium. All tests yielded negative results, whereas highly significant effects were recorded in control assays with thio-TEPA.


Effects of cancer chemotherapeutic agents on testicular DNA synthesis in the rat. Evaluation of a short-term test for studies of the genetic toxicity of chemicals and drugs in vivo.

Changes in the rate of testicular DNA synthesis in the rat were studied at various times after single doses of 12 cancer chemotherapeutic agents. The animals were given intravenous injections of [14C]thymidine and [3H]thymidine 24 and 3 h, resp., before they were killed. By combining measurements of the free serum radioactivity and the testicular incorporation of the differentially labelled precursor, different response patterns were obtained for agents with different modes of action. The DNA-damaging agents cyclophosphamide, chlorambucil, thio-TEPA, busulphan, CCNU and procarbacine, after some delay, caused  a decrease of testicular thymidine incorporation and a corresponding increase of free serum radioactivity. The non-DNA-damaging agents 5-fluorouracil, methotrexate, hydroxyurea and cytosine arabinoside had a rapid effect on testicular thymidine incorporation and produced diverse response patterns different from that of the DNA-damaging agents. Actinomycin D and also vinblastine caused changes in testicular thymidine incorporation and showed response patterns different from those of the other agents. These results show that simple measurements of testicular DNA synthesis may provide useful information for the evaluation of genotoxic effects of chemical compounds and may help one to distinguish between DNA-damaging agents and metabolic inhibitors of DNA synthesis.


Medical technology -- a different view of the contentious debate over costs.

There is a growing conviction that medical technologies are major contributors to escalating costs, and regulating them is generally viewed as the least contentious way to control expenses in the 1980's. Five forms of technology control are being discussed or developed. All aim to reduce costs by controlling big, expensive technologies in the class of computed tomographic (CT) scanning. We present evidence that technologies such as the CT scanner account for far less of the growth in medical expenditures than do the collective expenses of thousands of small tests and procedures. Furthermore, we suggest that each strategy for controlling large technology involves substantial practical and conceptual problems that would severely limit its effectiveness. We thus suggest a shift away from attempts to harness the big technologies, and toward incentives to encourage the more discerning use of all technologies. To this end, we propose changes in physician reimbursement and education and expanded insurance incentives to encourage physicians and hospitals to be more selective in the use of technology.


[Effect of multivalent cations on the enzymatic determination of glucose with glucose oxidase].

Iron and copper ions, in a concentration greater than 10(-4) M, inhibit the indicator reaction of a glucose oxidase-peroxidase reagent for the enzymatic determination of glucose, when weakly complexing buffers or buffer-free reaction media are used. The addition of EDTA and other complexing agents or, time-dependently, the buffer ions themselves reverse the inhibition to a great extent. The discussed mechanism of inhibition is based on the assumption that the metal ions share in the re-oxidation of the co-enzyme of glucose oxidase.


Controlled smoking.

The health risks of smoking are related to the interaction of what is smoked, smoking rate, and the topography of consumption. Assessment and treatment efforts should take all three of these factors into account. A working model of smoking behavior is proposed which involves the consideration of antecedents, concomitants, and consequences of smoking on cognitive, behavioral, situational and physiological levels. Further, the relative importance of these factors is not assumed to be the same across individuals. An approach to smoking risk reduction, called controlled smoking, is proposed which includes the elements of: (1) comprehensive assessment, (2) individualized goals, (3) emphasis on regulation, and (4) a skill development approach to treatment. Finally, some possible commonalities among behavioral approaches to substance abuse are presented.


[Reactions of limbic cortex neurons to stimulation of the splanchnic and sciatic nerves and mammillary region of the hypothalamus].

The background and evoked activities of the limbic cortex neurons to electrical stimulation of the splanchnic and ischiatic nerves and the mammillary body of the hypothalamus were investigated in anesthetized cats. In the presence of effective convergence of sensory visceral and somatic volleys on the limbic cortex neurons low convergence of volleys from the central hypothalamic and peripheral sources was observed. Orthodromic and antidromic responses to the stimulation of the mammillary body were detected testifying to the existence of direct bilateral connections between the anterior limbic cortex and the mammillary body.


Dopamine inhibition of action potentials in a prolactin secreting cell line is modulated by oestrogen.

Secretory activity of the anterior pituitary gland is regulated by the brain through stimulatory and inhibitory substances released from nerve endings in the median eminence of the hypothalamus and carried by the adenohypophysial portal blood system to their respective target cells. These hypothalamic influences are modulated by the feedback action of peripheral hormones. Prolactin (PRL) secreting cells are, at least partially, under the stimulatory influence of thyrotropin releasing hromone (TRH) and of oestrogens. However, they are mainly controlled by inhibitory substances among which dopamine (DA) is one of the most potent in vivo as well as in vitro. The inhibitory effect of DA is reversed by oestrogen in vitro. The mechanism by which these factors interact on their target cells is poorly understood. The recent discovery that anterior pituitary cells are excitable and that they are able to generate Ca2+-dependent action potentials has led to the suggestion that these effects are involved in a stimulus-secretion coupling at the membrane level. In this paper, we report that DA inhibits both the spontaneous and TRH-induced action potentials in clonal PRL pituitary cells. In addition, oestradiol-17 beta is able to reverse the inhibitory effect of DA.


[Morphofunctional interrelationships between the hippocampus and hypothalamus in rats].

Evoked reactions of the hypothalamic arcuate and medial preoptic nuclei neurons were recorded when the hippocampus was stimulated by single stimuli in anaesthetized rats. In the arcuate nucleus phasic responses and primary inhibition were found to be dominant and in the medial preoptic nucleus--both phasic and nonspecifical responses. After injection of the horseradish peroxidase into the stimulated hippocampal region stained cells were found in the nuclei of the mammillary complex, mediobasal hypothalamus and in the medial preoptic nucleus. Groups of stained neurons were observed in the periphery of ventro- and dorsomedial, lateral and mammillary nuclei of the hypothalamus. In all the studied structures, except the medial mammillary nucleus, reticular-like cells were found alongside with spindle-like and triangle neurons. The data obtained are discussed in connection with the problem of hypothalamo-hippocampal interaction.


Brain TRF immunoreactivity during various physiological and stress conditions in the rat.

Methanol extracts of several rat tissues (hypothalamus, amygdala, the rest of the forebrain, brain stem and pancreas) were partially purified in SP-cation exchange chromatography and measured in TRF radioimmunoassay. It was found that hypothalamic and amygdaloid TRF contents were highest during the light period of the day, but brain stem TRF had an opposite rhythm. Hypothalamic TRF content rose after 10 min by 14% (p less than 0.05) when the rats were exposed to transfer stress. During short-time immobilization stress tests, hypothalamic TRF rose by 41% (p less than 0.05) after a 10-sec immobilization. Cold exposure did not produce any changes in hypothalamic TRF contents within 45 min. Handling stress and time of day appear to be the most important factors influencing the hypothalamic TRF content and have to be taken into account when measuring TRF.


Immobilization stress and prolactin secretion in male rats. Possible roles of dopamine and TRH.

Immoblization stress had a biphasic effect on serum prolactin levels: the early short stimulatory phase followed by a long inhibitory phase in male rats. Stress induced the rise in serum prolactin without concomitant increase in serum TSH levels which declined during the immoblization for 300 min. Other stressors, ether inhalation or formalin s.c. injection, or TSH i.v. injection, which were effective in controls failed to elevate serum prolactin after the 300-min immobilization. Serum TSH responded to TRH after the stress as well. Pimozide, dopamine receptor blocker, was effective in increase of serum prolactin in the stressed rats as well as in controls. In pimozide pretreated rats, elevated serum prolactin levels decrease in 10 min by the immobilization and returned to the preimmobilization levels thereafter which were higher than those in stressed animals without pimozide treatment. It is suggested that TRH is not a physiological PRF in the stress-induced prolactin release and that the dopaminergic system may be activated by the immunoblization stress, resulting in decrease of the prolactin-releasing activity of the pituitary.


Occlusion of the cerebral arteries in Recklinghausen's disease.

Two children, aged 18 months and 6 years, who had Recklinghausen's disease, had occlusion of cerebral arteries. One child had no motor deficit but the other had right hemiparesis and partial occlusion of the left posterior cerebral artery, a fact not found in the literature.


[Cannulation of the subclavian vein using the subclavicular route: technic of choice for fluid therapy and prolonged total parenteral feeding].

The various routes to the large veins and the technique for placing a long-term plastic catheter for fluid therapy and prolonged total parenteral feeding, are described with respective limitations and contraindications. It is considered that cannulation of the subclavian vein by the subclavicular route using Cavafix instrumentation is preferable because it is comparatively easy to carry out complications are limited, and scrupulous asepsis is possible. It can also be applied in any patient even in the most serious of conditions without having to make him take up a special position.


[Plasma hyperosmolarity aspects in intensive care and its treatment with potassium canreonate].

Intravenous administration of 400-600 mg/day potassium canrenoate normalised plasma osmolarity and permitted rapid re-establishment of the metabolic picture in 9/12 patients with hyperosmolarity admitted to a resuscitation department for complex physiopathological pictures. The soundness of the drug in this sense is affirmed, as well as its permission of the recommencement of parenteral nutrition.


[Treatment of acute renal insufficiency in intensive care. Current perspectives with TPA and proxazole].

A critical assessment is made of cases of ARF observed in a resuscitation department over the last three years. Reference is made to the physiopathological and pharmacological premises underlying the employment of a different therapeutic protocol, based on the maintenance of high diuresis with proxazol and the use of TPA to establish a nitrogen balance with a high cal/N ratio, coupled with the administration of histidine.


[Total parenteral nutrition in surgery].

Following a number of general remarks regarding the metabolic physiopathology of the surgical patient, the indications and biochemical premises for total parenteral nutrition are examined. Stress is also labor, on problems of administration routes and modalities and on the chemico-clinical controls needed to weigh up the technique. Finally, the results of personal experience in the treatment of 16 patients whose prevalent pathology consist of necrotico-haemorrhagic A.P. and its sequelae are reported. The usefulness of the technique is confirmed because it offers interesting results in difficult and often dramatic surgical situations.


Cortical projection to hand-arm motor area from post-arcuate area in macaque monkeys: a histological study of retrograde transport of horseradish peroxidase.

In four macaque monkeys horseradish peroxidase (HRP) was injected into physiologically defined hand-arm motor area. Ipsilaterally, HRP labeled neurons were found in both upper and lower limbs of the posterior bank of the arcuate sulcus and in an area surrounding the arcuate spur. Contralaterally, labeled neurons were found in the same areas, though less dense in concentration. Labeled neurons were found mostly in layer III of the cortex.


Assessment of the cost/effectiveness of chemotherapy for skin and urinary tract infections using in vitro sensitivity testing.

Results of skin and urine cultures performed by a Wellington laboratory over a selected period, were used to estimate the prevalence of common organisms and their in vitro sensitivity to chemotherapeutic agents, to determine the most efficacious and economical, anti-infective therapy. For streptococcal or mixed gram positive infections penicillin is the antibiotic of choice. For mild to moderate staphylococcal infections, erythromycin is indicated. A single dose of cotrimoxazole is economical for uncomplicated urinary tract infections, however urine culture seems warranted. Reservations are expressed regarding the assessment of in vitro sensitivity to cotrimoxazole and possible development of resistance to this agent. Ampicillin/amoxycillin is indicated for organisms resistant to sulphonamides. The need to supply doctors with information on changing sensitivity patterns of micro-organisms in the community is emphasised.


Prolactin response to thyrotropin-releasing hormone in normal and complicated late pregnancies.

Maternal serum prolactin level (PRL) was determined with radioimmunoassay in normal and complicated late pregnancy. The mean basal PRL levels were not statistically different among normal (179.3 ng/ml), preeclamptic (169.7 ng/ml), hypertensive (171.4 ng/ml), twin (194.8 ng/ml), or diabetic pregnancies (134.4 ng/ml), although 3 of 17 diabetic women had abnormally low PRL levels. The PRL response to 200 micrograms of intravenously administered thyrotropin-releasing hormone (TRH) was investigated and found similar in normal, preeclamptic, hypertensive, and twin pregnancies. There was no response to TRH in 2 of 3 diabetics with a low basal PRL level. One of these diabetic patients experienced an unexplained intrauterine death 4 weeks later; the others delivered term infants, 1 of whom died of respiratory distress syndrome (RDS). These preliminary results suggest that low basal PRL levels and unresponsiveness to TRH may be related to a poor fetal or neonatal prognosis in diabetic pregnancies.


Fetal movements in human pregnancies in the third trimester.

Fetal movements (FM) were measured using a real-time B-scan method in 50 women in the third trimester. One hundred ninety-five observations were made. The number of FM per 20-minute observation period was similar in normal, diabetic, and hypertensive pregnancies and in patients with placenta previa, but was significantly lower in patients with Rh isoimmunization and an affected fetus. The number of FM did not vary with gestational age, mode of delivery, or birth weight and was significantly increased in patients either with a reactive nonstress test (NST) or in the presence of fetal breathing movements (FBM). Fetal movements were absent before delivery in 4 patients: In 3, the fetus died in utero and in the other a positive contraction stress test (CST) was observed. Conversely, in 2 other fetuses who died in utero, FM were observed during the last examination before death. In both, the cause of fetal death was related to an acute change. No relationship between FM and neonatal death was observed. These data suggest FM monitoring may be helpful in evaluating antepartum fetal condition.


The in vitro and in vivo effects of a surgical lubricant on the recovery of gonococci from the endocervical canal.

A surgical lubricant containing phenylmercuric borate, tested in vitro, was shown to alter the recovery of the gonococcus. In vivo studies of 150 patients, 60 (40%) of whom were infected with Neisseria gonorrhoeae, were performed to determine if examination with the surgical lubricant, as compared to tap water, altered the ability to recover N. gonorrhoeae from the cervix. Results indicated that although the surgical lubricant containing phenylmercuric borate was bacteriostatic in vitro, it did not alter the recovery of N. gonorrhoese from infected patients.


Distribution of ligandin in normal and azocarcinogen-treated rat liver and azocarcinogen-induced liver tumors.

Antibodies were raised in rabbits against pure ligandin. Employing the fluorescent antibody procedure, an antigen identical to ligandin was shown to be uniformly distributed in the hepatic cells of both normal rat liver and in early and late 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB)-treated liver. Ligandin was absent in liver carcinomas induced by this azocarcinogen. The results obtained with fluorescent antibody procedure were confirmed by the immunoquantitation of ligandin in the cytosols prepared from normal rat liver, early and late 3'-Me-DAB-treated liver, mixtures of both late 3'-Me-DAB-treated liver and liver carcinomas and liver carcinomas. Riboflavin-deficient diets lowered significantly the hepatic ligandin content.


Study of the anti-tumor effect of polypeptide pineal extract.

Bovine pineal polypeptide extract (PPE) exerted an anti-tumor effect on mouse-transplantable tumors: mammary cancer (RSM), squamous cell cervical carcinoma (SCC), hepatoma-22a and lympholeukemia LIO-1, and had no effect on Harding-Passey melanoma and leukemia L-1210. It was shown that PPE possessed the ability to decrease the incidence of DMBA-induced mammary adenocarcinomas in rats. The daily administration of 0.5 mg PPE prolonged the life span of rats by 25% and failed to influence spontaneous tumor development. The arguments in favor of a possible mechanism of anti-tumor action of the pineal gland are submitted. It is suggested that the anti-tumor effect of PPE may occur when the syndrome of cancrophilia is induced by tumor transplantation or chemical carcinogens.


A case of neurofibromatosis with severe osseous disease of the thoracic spine.

A case of neurofibromatosis in a 7-year-old boy from Greenland is presented. The patient suddenly developed a severe thoracic scoliosis because of a total luxation of the upper thoracic vertebrae caused by erosion from soft tissue tumours in the region. Tomography revealed the bone changes, and CT whole-body scanning showed the extent of the soft tissue tumours and also the destruction of the vertebrae. The diagnosis was verified by biopsy.


Effects of levamisole on the immune responses of experimentally malnourished rats.

Levamisole (Ketrax), and anthelmintic drug commonly used in the tropics, has been found to restore the impaired spontaneous rosette-forming lymphocytes and delayed cutaneous hypersensitivity reactions in experimentally malnourished rats. It, however, has no effects on plaque-forming cells. The drug was also found to reconstitute the histologic integrity of the thymus in malnutrition.


A circulating inhibitor of platelet aggregation in Bartter's syndrome.

Aggregation studies were performed on platelets from five patients with Bartter's syndrome. Epinephrine failed to induce aggregation in all five patients. Adenosine 5'-diphosphate (ADP) produced a single reversible phase of aggregation, and there was depressed sensitivity to collagen. Response to ristocetin was normal. There was a dose-related inhibition of ADP-induced platelet aggregation when plasma from the patients was addeded to normal platelet-rich plasma. This inhibition was diminished or absent when patients were receiving aspirin. Washed platelets from two patients who were no longer undergoing aspirin therapy, showed a normal response to epinephrine in normal platelet-poor plasma. Bleeding time was reduced from 23 minutes to 12 minutes in one patient while on aspirin therapy. These studies suggest that a circulating inhibitor of platelet aggregation, probably of prostaglandin origin, is present in the plasma  of patients with Bartter's syndrome.


Organochlorine residues in six species of estuarine birds, South Carolina, 1971-75.

In South Carolina between 1971 and 1975, authors evaluated the occurrence of organochlorine residues in the laughing gull (Larus atricilla), white ibis (Eudocimus albus), glossy ibis (Plegadis falcinellus), American oystercatcher (Haematopus palliatus), willet (Catoptrophorus semipalmatus), and ruddy turnstone (Arenaria interpres). Tissues of birds found dead and eggs were analyzed, eggshell thicknesses were measured, and incidental observations were made of reproductive success and population status. Eggshell thickness of the white bis, American oystercatcher, and laughing gull were not significantly different (P less than 0.05) from the pre-1947 norms. DDE and polychlorinated biphenyls (PCBs) were found most frequently and at the highest concentration in eggs. DDE residues declined significantly in oystercatcher eggs, and declined slightly in laughing gull eggs; no change was noted in white ibis eggs. No consistent trends were found for dieldrin and PCBs. Authors found no obvious problems with reproductive success of any species. Populations of the five species breeding in South Carolina appear stable. The white ibis and laughing gull in South Carolina have experienced population explosions over the past 50 years; the glossy ibis has increased substantially since the first documented breeding records in 1947.


Shell thinning and residues of organochlorines and mercury in seabird eggs, Eastern Canada, 1970-76.

Organochlorine and mercury concentrations are reported for 252 eggs of Leach's storm-petrel (Oceanodroma leucorhoa), double-crested cormorant (Phalarocorax auritus), common eider (Somateria mollissima), common tern (Sterna hirundo), razorbill (Alca torda), common murre (Uria aalge) black guillemot (Cepphus grylle), and Atlantic puffin (Fratercula arctica) from the Bay of Fundy, the Gulf of St. Lawrence, and the open Atlantic shore of Canada during 1970-76. Concentrations of all organochlorines except DDE and polychlorinated biphenyls (PCBs) were low. DDE, PCBs, and mercury residues were highest in cormorant and petrel, intermediated in alcids, and lowest in eider and tern. Temporal and spatial aspects of contamination patterns are discussed. Authors conclude that only in cormorants were DDE residues high enough to cause, through eggshell thinning, local population declines.


Residues of polychlorinated biphenyls and DDT in water and sediment of the St. Lucie Estuary, Florida, 1977.

sigma DDT residues in the St. Lucie River bottom sediments increased after Lake Okeechobee water was discharged through the St. Lucie Canal into the area. sigma DDT levels were highest in sediment samples from the Palm City area, ranging from 1.8 ppb to 6.15 ppb. Sediment samples from the A1A Highway Bridge area contained 1.6-6.8 ppb Aroclor 1254. Levels of polychlorinated biphenyls (PCBs) and sigma DDT in sediment samples from the junction of the St. Lucie and Indian Rivers were not detectable. Surface water samples from the estuary did not show any detectable DDT or PCB residues.


Ultrastructural observations on mast cell degranulation and its prevention.

The surface alterations of rat peritoneal mast cells during degranulation induced by calcium chloride (CaCl2) and its prevention by salbutamol sulfate (Sal. Sulf.), chlorpheniramine maleate (CM), and disodium cromoglycate (DSCG) were followed with a scanning electron microscope. CaCl2 caused a protuberation of the cytoplasmic granules already after 30 s, an advanced degranulation after 60-75 s, and a complete destruction of the cells after 180 s of incubation. The degranulation process was prevented by Sal. Sulf., CM, and DSCG. A comparison of the surface changes induced by these agents with the ultrastructural findings observed with a transmission electron microscope showed that neither Sal. Sulf. nor CM prevented the alterations of the internal structure of the cells, suggesting that these substances act mainly on the cytoplasmic membrane. The best prevention for both the surface and the internal structure of the cells was obtained by DSCG, indicating that this substance is a stabilizer of both membrane and internal organelles of the mast cells.


Comparison of nucleotide sequences of large T1 ribonuclease fragments of 18S ribosomal RNA of rat and chicken.

Nucleotide sequences of large T1 ribonuclease fragments of 18S ribosomal RNA of Novikoff rat ascites hepatoma cells and chicken lymphoblastoid cells were determined and compared. Among the 19 large T1 ribonuclease fragments examined of rat 18S ribosomal RNA, 12 fragments were found to be the same in chicken 18S ribosomal RNA. Three fragments of rat 18S ribosomal RNA were not found among large T1 ribonuclease fragments of chicken 18S ribosomal RNA. Four fragments of rat 18S ribosomal RNA were found to be changed in chicken 18S ribosomal RNA. All the changes were point mutations except the change in the largest T1 ribonuclease fragment 1 which is 21 nucleotides long. 2'-0-methylation at the center of the fragment was lost in chicken 18S ribosomal RNA; all the other nucleotides were the same.


Further characterization of a cell-free system for measuring replicative and repair DNA synthesis with cultured human fibroblasts and evidence for the involvement of DNA polymerase alpha in DNA repair.

DNA repair synthesis can be specifically measured in osmotically opened, confluent cultured human fibroblasts after exposure to DNA damaging agents such that both induction and mediation of DNA repair synthesis can take place in this cell-free system. Alternatively, by utilizing osmotically shocked, log phase cells and altering the DNA precursors, pH and ionic strength, replicative DNA synthesis can be specifically monitored. Autoradiographic studies show that virtually all of the nuclei from the lysates of the confluent, UV-iradiated cells are lightly labeled in the fashion characteristic of DNA repair. By contrast, only a fraction of nuclei is labeled in a population of unperturbed, opened log phase cells and the labeling is heavy and characteristic of replicative synthesis. Furthermore, equilibrium density gradient sedimentation shows that DNA synthesis in lysates of log-phase cells is semiconservative, whereas that with UV-irradiated cells is repair synthesis. This open cell system has been used to study the enzymology of DNA repair. Thus, dideoxythymidine triphosphate, a specific inhibitor of DNA polymerases beta and gamma, does not inhibit either replicative or repair synthesis. By contrast, aphidicolin, a specific inhibitor of DNA polymerase alpha, inhibits DNA repair and replicative synthesis in both intact and permeabilized cells. Finally, phage T4 UV-exonuclease stimulates repair synthesis, but only when phage T4 UV-endonuclease is also added to the UV-irradiated nuclei.


Pre-operative intravenous feeding--a controlled trial.

Seventy-four patients with a pre-operative diagnosis of stomach or oesophageal cancer were entered into a randomized, controlled clinical trial to assess the value of a short course of pre-operative intravenous nutrition. The effectiveness of this treatment was assessed by the clinical course and monitored by means of immune and biochemical profiles. Pre-operative parenteral nutrition given over a 7-10-day period resulted in a significant reduction in the incidence of postoperative wound infections. Clinical benefit was confined to those patients who had a low serum albumin on admission to hospital. It is doubtful whether this limited benefit justifies the routine use of intravenous feeding, with its attendant hazards, in the pre-operative preparation of patients with upper gastrointestinal cancer.


[Regularities in the synthesis of neutral protease from Bacillus subtilis].

Experiments were carried out to study the formation of extracellular protease by the suspension from Bacillus subtilis str. 103 washed cells selected at the growth stages characterized by the highest rate of the enzyme synthesis (after 12 and 35 hours). In relation to the protein and RNA synthesis as measured by 14C-valine and 14C-uracyl the cells of that age showed a high metabolic activity. The enzyme synthesis by the cells of the log-phase was inhibited completely with chloramphenicol and by the cells of the stationary phase--almost completely. The experiments demonstrated the protease synthesis insensitive to riphampycin for a long time. This may be indicative of a certain pool of long-lived mRNA responsible for the biosynthesis.


[Synthesis of L-aspartic acid by Escherichia coli and Pseudomonas fluorescens as related to the cultivation conditions].

The capacity of the cultures Escherichia coli str. 85, 113, BC, C and K-12 and Pseudomonas fluorescens str. 1 to synthesize L-aspartic acid from fumarate and ammonium ions was studied. E. coli str. 85 was shown to synthesize the largest amounts of aspartic acid. The cultivation conditions which helped to increase the activity several times were selected. The product of fumarate amination by ammonium ions was identified and found to be L-isomer of aspartic acid with an angle of rotation of [alpha] 20/D = +25,5 degrees in 6 N HCl.


[Products of bacterial destruction of sodium dodecyl sulphate].

The products of Na dodecyl sulphate destruction by the three bacterial cultures--Pseudomonas aeruginosa, Flavobacterium devorans, Achromobacter guttatus--were examined. The cultures were shown to decompose Na dodecyl sulphate in a similar way. The primary mechanism of destruction was found to be hydrolysis of the sulpho-ester bond in the molecule, leading to the separation of sulphate-ion and formation of dodecanol. Products of bacterial destruction of alkyl sulphates did not show foam forming capacity.


[Stabilization of proteases from Bacillus subtilis in solution].

Experiments were carried out to study the effect of the styrene and maleinic acid copolymer on the activity of proteases produced by Bacillus subtilis--protosubtilin G15x. Unlike the hydrophilic ethylene--maleinic acid copolymer, styrenated maleinic acid produced a stabilizing effect on proteases via hydrophobic interaction. It is suggested that at least two forms of the enzyme differing in their activity and stability are involved in the process of inactivation. On the basis of the data obtained a scheme of protease inactivation is proposed.


[Dynamics of B1 aflatoxin and Aspergillus flavus spore formation on rye and wheat grain].

Rye and wheat grain was infected with Aspergillus flavus spores. The dynamics of B1 aflatoxin and spore formation was studied. The synthesis of B1 aflatoxin in the mold-affected grain started simultaneously with the emergence of fungal spores; its further accumulation in the grain correlated with an increase in the spore number till the stage of maximum spore formation. The highest level of aflatoxin synthesis was inversely proportional to the number of Aspergillus flavus spores which infected the grain before its molding.


Absorbed dose from secondary electrons in high energy photon beams.

The absorbed dose in high energy photon beams due to scattered electrons from the irradiated air volume and from beam-shaping platforms has been calculated using the Fermi-Eyges theory of multiple scattering. The results are presented as lateral surface absorbed dose distributions across the field for three different radiation qualities, namely 60Co, 6 MV and 21 MV X-rays. For 60Co the relative absorbed dose due to electrons expelled in air reaches a value as high as 30% of the absorbed dose at dose maximum at a field size 40 X 40 cm2 and an SSD of 100 cm. The absorbed dose from electrons emanating from beam-shaping platforms contribute significantly to the absorbed dose at the surface when the platform is placed closer than 20--40 cm from the surface for field sizes greater than 10 X 10 cm2 to 40 X 40 cm2 respectively.


Cross immunological reactions between three haptens of the "para" group and 4-aminoantipyrine.

Cross passive hemagglutination reactions between sulfanilic acid (SA), para-aminobenzoic acid (PABA), p-phenethidine (PT) and 4-aminoantipyrine (4-AA) haptens have been investigated using conjugates of diazo derivaties of these compounds with homologous serum proteins. Intense cross passive hemagglutination reactions were found between PABA, SA and 4-AA haptens. Although anti-PT sera cross reacted intensely with PABA, SA as well as with 4-AA haptens, antibodies cross reacting with PT were not detected in any of the anti-PABA, anti-SA and anti-4-AA antisera. The conjugates containing a heterologous hapten de not substantially alter the titer of the hemagglutination reactions performed with erythrocytes coated with the homologous hapten, but completely suppress the hemagglutination reactions performed with erythrocytes coated with this hapten as well as with other, but not all, heterologous, haptens. The results support the conclusion that the apparent polysensitization to drugs may actually rely upon cross reactions with haptens chemically related to the immunizing one.


Physical activity in modern industry.

The research carried out in order to estimate the physical effort under the present circumstances of the industrial technological development have pointed out that most of the activities in the heavy industry branches are now carried on within the frame of medium load. An evident trend was found of extending the activities implying light work in mechanized mining, automatic glass-processing, thermo-power stations, but tasks requiring high energy cost are still in forestry, mining, building. Significant differences in the physical capacity related to the level of occupational physical load have been revealed. Experimental working regimens as well as programmes of gynmastics during the breaks of the shift in activities of lower physical effort proved to have a beneficial effect on performance, on work capacity and fatigue prevention. Maximum permissible duration of loads carried by women and factors of stress were also assessed in occupational activities where women are employed in increasing number. The present problems of physical activity in industry require further research into: more detailed aspects connected with the increase of static effort, effect of physically active recreation, methods for improving physical capacity. Further studies are also expected to assess and evaluate physical effort in new occupations.


Physical fitness in different groups of industrial workers.

Maximum oxygen consumption was determined by the indirect method (with submaximal effort) in 155 forestry workers, 120 miners, 240 tool manufacturers (turners, planers etc.), 75 control-board operators. Differences were found according both to age and occupation. Variance analysis showed that age had a greater impact (F = 68) than occupation (F = 20). The highest values were recorded in foresters (57 -- 39 ml/kg/min depending on age). In miners the average values were 49 -- 35 ml/kg/min, while toolmakers and pannel operators showed maximum oxygen consumption of 45 -- 32 ml/kg/min, VO2 being nearly the same in both groups of occupation for the respective groups of age. Values of 50 ml/kg/min or above were found in 88% of 20 -- 29 year -old foresters and in 54% of the miners, while in toolmakers and in pannel operators such vales of VO2 were found only in 37% and 27% respectively, of the cases.


Physical work load in modern mining.

Following our Institute's involvement in the physiology of mining work (since 1953), this paper deals with underground work load investigated in terms of time, energy expenditure and heart rate in coal miners working with various types and degrees of mechanization. Results showed that a chamber coal face and at heading (coal or sterile rock) mechanization of haulage and loading (conveyor belt and loading machine) led to 50 -- 100 kcal reduction of energy expenditure/hour. At longwall faces, mechanization of haulage (by conveyor) or hewing and loading (with drum-combine) shortened shoveling time, while there was an increase of manual work in the tasks of supporting which was conducive to metabolic rates of 300 kcal/hour. In the case of fully mechanized coal working, including supporting, there was a significant decrease of energy expenditure.


[Manipulation box to measure the motor performance involving the distal musculature of the arm in primates (author's transl)].

For studies of motor performance in the baboon, regarding precise finger movements, a new latch-box was developed. The device was designed so as to involve mainly the distal musculature of the arm. Handling the different knobs or latches which open the compartments of the box had to be performed in a given motor sequence. Monkeys were trained to use two fingers of the hand: thumb and index. Data are presented which show that, after exclusion of a central nervous structure, it is possible to differentiate the performance obtained with the device described above that obtained in a pointing task, mainly involving the proximal musculature.


Motion sickness-induced food aversions in the squirrel monkey.

Conditioned aversions to colored, flavored water were established in Squirrel monkeys (Saimiri sciureus) by following consumption with 90 min of simultaneous rotational and vertical stimulation. The experimental group (N = 13) drank significantly less of the green, almond-flavored test solution than did the control group (N = 14) during three post-treatment preference testing days. Individual differences were noted in that two experimental monkeys readily drank the test solution after rotational stimulation. Only two of the experimental monkeys showed emesis during rotation, yet 10 monkeys in this group developed an aversion. These results that (1) motion sickness can be readily induced in Squirrel monkeys with simultaneous rotational and vertical stimulation and (2) that conditioned food aversions are achieved in the absence of emesis in this species.


The Ranvier node as a chemo-electric pulsatory unit: a study of its structure-functions relations.

The Ranvier node of (Rana temporaria) frog nerve fibres is investigated by electron microscopy, Particular attention is given to the paranodal septate structures and to the extranodal junction of two Schwann cells. An interpretation of the functional meaning of these structures along with a quantitative analysis of the Schwann extranodal junction as regards the diffusion from/to the node is attempted. A 73 per cent reduction of the diffusion coefficient is obtained if the extranodal Schwann cell processes are considered impermeable to the diffusing vectors which indicates a protective role. Only 1 per cent reduction is obtained in the case of excitation-involved cations to which the Schwann cell membrane is considered to be permeable. This indicates the active role of the Schwann cell in the extranodal area ion diffusion, by minimizing the variations in ion concentration near the nodal membrane. Thus the nervous fibre-Schwann cell assembly may be regarded as a balanced pulsatory chemo-electric unit.


Vascular considerations in the use of a latissimus dorsi myocutaneous flap after a mastectomy with an axillary dissection.

Is an intact thoracodorsal vascular pedicle necessary for clinical rotation of a latissimus dorsi myocutaneous flap? Our laboratory and clinical experiences indicate that it is not necessary. These are described herein.


Seizures abolished by excision of a cavernous hemangioma of the scalp and skull.

A large vascular malformation of the supraorbital and scalp areas was present in an adolescent girl who had seizures and headaches. Removal of the malformation included the outer table of the skull. The patient has had no seizures during a two-year follow-up.


Noradrenergic agonists and antagonists: effects on conditioned fear as measured by the potentiated startle paradigm.

Clonidine (10-40 microgram/kg) produced a dose-dependent reduction of fear as measured by the potentiated startle effect (increased acoustic startle in the presence of a cue which had been previously paired with shock). The reduction of potential startle could not be accounted for entirely by a general depressant effect of clonidine on startle nor by an acceleration of extinction. Piperoxane and yohimbine, which are associated with anxiety in humans, increased potentiated startle, whereas propranolol and WB-4101 did not. These results provide further evidence that the potentiated startle paradigm in the rat is sensitive to drug that alter anxiety in humans. Moreover, they support the hypothesis that norepinephrine transmission is important for the expression of fear or anxiety.


Effects of trifluoperazine, chlorpromazine, and haloperidol upon temporal information processing by schizophrenic patients.

Healthy controls, unmedicated, actively symptomatic schizophrenics, and similar patients undergoing treatment with either trifluoperazine, chlorpromazine, or haloperidol were studied with tests of temporal discrimination and measures of transmitted information shown previously to be sensitive to various kinds of brain dysfunction, including haloperidol effects in a nonpsychotic population. Variations in psychophysical method, cognitive load, discrimination complexity, and sense-mode conditions permitted representative sampling of the temporal processing. Untreated, actively psychotic patients showed no impairment of temporal processing while all three antipsychotic medications were associated with significant deficit; trifluoperazine and haloperidol produced the most deficit, with chlorpromazine in the middle between the higher potency drugs on the one hand and unmedicated patients and healthy controls on the other.


Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons.

Responding maintained under progressive ratio (PR) and fixed ratio (FR 160) schedules of IV saline or cocaine (0.01-4.0 mg/kg) injections was studied in baboons. Each injection was followed by a time-out period which was 3-h with the PR schedule and was either 3 or 12 with the FR schedule. On the PR schedule the ratio requirement was systematically increased each day until reaching the 'breaking point' at which self-injection performance fell below a criterion level (one or zero injections per day). Overall response rates on the PR schedule increased with progressive increases in the ratio until a maximum at which an abrupt reduction in responding occurred. With the 3-h time-out the dose-breaking point function on the PR schedule was similar to the dose-response rate function on the FR schedule. These dose-effect functions were inverted U-shaped curves characterized by a graded ascending limb (0.01-0.32 mg/kg) and a downturn at the highest doses (3.0-4.0 mg/kg). On the FR schedule the downturn in the dose-response rate function was attributable to a cumulative drug effect as revealed by manipulation of time-out duration and analysis of sequential interresponse time distributions and cumulative response records. PR and FR schedules provide similar information about the relative reinforcing efficacy of different cocaine doses.


Prolongation of the ejaculation latency in the male rat by thioridazine and chlorimipramine.

Thioridazine (3 mg/kg) and chlorimipramine (1.5-6.0 mg/kg) prolonged the ejaculation latency and increased the number of mounts but did not change the number of intromissions preceding ejaculation. Blockade of peripheral and central noradrenaline receptors by phentolamine and phenoxybenzamine respectively resulted in a suppression of all aspects of the sexual behavior with increasing doses. DL-5-HTP (25-100 mg/kg) in combination with an inhibitory of peripheral 5-HTP decarboxylase (benserazide, 25 mg/kg) produced, like chlorimipramine and thioridazine, a prolongation of ejactulation latency and an increase in the number of mounts preceding ejaculation. Selective inhibition of 5-HT reuptake however, by zimelidine (0-20 mg/kg) or alaproclate (0-20 mg/kg) did not affect the mating behavior. At higher doses of these drugs some animals failed to initiate sexual activities. There was an increase in the postejaculatory interval but not change in the ejaculatory latency. It is concluded tha the prolonged ejaculation latencies observed following treatment with thioridazine or chlorimipramine is not due to a blockade of central or peripheral adrenergic alpha-receptors.


Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression.

5-Hydroxytryptamine (5-HT) uptake was studied by using blood platelets from 13 patients with endogenous depression (Hamilton rating scale 33 +/- 7) and 13 healthy volunteers. An improved method with a short incubation time and low substrate concentration was used, and the incubation was performed in Krebs-Henseleit buffer (pH 7.4) at 37 degrees C. A clear difference in 5-HT uptake by blood platelets was noted: The Vmax of the reaction in patients was 39, and in controls 71 pmol per 2 x 10(7) platelets in 5 min. There was no significant difference in the Km. After a 4-week treatment with imipramine, a competitive inhibition of 5-HT uptake with an increased Km was seen; after a similar treatment with amoxapine there was little change in 5-HT uptake. Amoxapine was inferior to imipramine as an inhibitor of 5-HT uptake, also in vitro. There was no difference in clinical recovery in these treatment groups. These results may be of importance so as to understand the potential biological differences between depressed patients and normal persons.


Facilitation of self-stimulation of the prefrontal cortex in rats following chronic administration of spiroperidol or amphetamine.

The effect of chronic administration of spiroperidol, a dopaminergic antagonist, on self-stimulation of the prefrontal cortex was investigated. When spiroperidol was administered either before or after daily self-stimulation tests for 9 days, self-stimulation rates were significantly elevated for several weeks following withdrawal of the drug. Self-stimulation of the nucleus accumbens, supracallosal bundle, and other forebrain sites was not altered, suggesting that the increased self-stimulation of the prefrontal cortex was not due to increased motor activity. Self-stimulation of the prefrontal cortex was also facilitated by chronic administration of d-amphetamine whereas self-stimulation of the supracallosal bundle was suppressed and self stimulation of the nucleus accumbens was unchanged. The results suggest that dopamine modulates self-stimulation of the prefrontal cortex. Additionally, the effects of chronic spiroperidol on self-stimulation of this structure may model the therapeutic effects of neuroleptics in humans.


The involvement of serotonergic neurons in the central nervous system as the possible mechanism for slow head-shaking behavior induced by methamphetamine in rats.

Following the IV administration of d-methamphetamine (MA), rats showed slow head shaking (SHS) and stereotyped gnawing (SG) behaviors in a dose-dependent manner. Methysergide, cyrpoheptadine, and p-chlorophenylalanine given intracerebroventricularly (ICV) or systemically significantly blocked SHS behavior induced by 10 mg/kg MA. Combined administration of L-5-hydroxytryptophan and peripheral decarboxylase inhibitor (Ro 4-4602) enhanced SHS behavior. Tyrosine hydroxylase inhibitor (H44/68) blocked SG behaviors, but dopamine-beta-hydroxylase inhibitors (FLA 63 and U-14, 624) and combined administration of L-3,4-dihydroxyphenylalanine and Ro-4-4602 enhanced it. These drugs did not affect SHS behavior. Phentolamine, phenoxybenzamine, clonidine, isoproterenol, and propranolol given ICV or systemically showed no effect on either SHS or SG behaviors. These results suggest that SHS behavior is produced by the activation of seronergic neurons in the central nervous system and are consistent with the view that SG behaviors are mediated through the release of dopamine. Some neuroleptics inhibited SHS as well as SG behaviors, but the older of inhibitory activity of neuroleptics onSHS behavior was quite different from their effects on SG behaviors induced by MA or apomorphine.


Dopaminergic factors in human prolactin regulation: a pituitary model for the study of a neuroendocrine system in man.

This study in normal male subjects further investigates the effects of dopaminergic-antidopaminergic interactions as manifested by the prolactin response to dopamine and neuroleptic drugs. Incremental doses of dopamine hydrochloride (4 microgram/min, 15 microgram/min, 60 microgram/min, 300 microgram/min) were infused at a constant rate over 90-120 min after a fixed dose of a neuroleptic drug (sufficient for about half of the maximal prolactin response) had been given IV. A dose of dopamine in the order of 15-60 microgram/min appeared to match the "loss" of endogenous dopaminergic inhibition due to the antidopaminergic effect of the neuroleptic drug. The lactotrophic cells of the pituitary gland are suggested to serve as a model in man for the study of some basic neurohormonal mechanisms.


Dose and physical dependence as factors in the self-administration of morphine by rats.

Groups of naive rats were offered morphine sulfate for self-admininstration in doses of 0.0032-10 mg/kg for 6 days. On day 7 saline was substituted for morphine. Loss of weight was taken as physiological evidence of dependence. Rats that did not lose weight formed a single population whose mean injection rate did not differ from control rats receiving only saline injections. Injection rates for rats losing weight were log-normally distributed, and the mean of the logarithms of the injection rates was linearly related to the logarithm of the dose. Mean daily injection rates averaged 12 for controls, 23 at 10 mg/kg, and 411 at 0.01 mg/kg. A transient increase in morphine intake after an injection of nalorphine was taken as behavioral evidence of dependence. Nalorphine increased morphine intake when rats were self-injecting 0.32 and 1.0 mg/kg of morphine, but not 0.032 or 0.1 mg/kg. The reinforcing property of morphine may occur without behavioral evidence of dependence.


Water intake and time course of drinking after single or repeated chlordiazepoxide injections.

Chlordiazepoxide (5.0, 10.0 or 15.0 mg/kg) was given to rats either acutely or for 9 consecutive days. Its effects were examined in a 15-min drinking test in which latency to drink, volume of water consumption and the time-course of drinking were measured. Chlordiazepoxide (10.0 mg/kg) produced the strongest stimulant effect on drinking and enhanced the frequency of occurrence of drinking both at the beginning and at the end of the test period. Chlordiazepoxide (15.0 mg/kg) delayed the onset of drinking and its peak effect was observed later than for other injection conditions. Single and repeated administration of chlordiazepoxide had the same effects on the measures taken in the test. Initial sedation to the drug treatment and subsequent tolerance to this effect were not, therefore, factors influencing the drug effects observed in this experiment. Possible mechanisms underlying the stimulation of drinking by chlordiazepoxide are considered.


Morphine abstinence and serotonin supersensitivity in man: analogies with the mechanism of migraine?

Supersensitivity to serotonin during migraine attack has been previously observed. Since the attack has been attributed to a critical lowering of morphine-like factors, we can expect serotonin supersensitivity during morphine abstinence. Slight signs of morphine abstinence have also been induced in volunteers after mild (10-24 mg/day) and limited (3 days) treatment. To evaluate the sensitivity to serotonin, dopamine, noradrenaline, and tyramine in the smooth muscle of the hand dorsal vein, in vivo, the computerized venotest was applied before, during, and 24 h after withdrawal of morphine. Venous sensitivity to serotonin and dopamine (but not to noradrenaline and tyramine) increased 10- to 20-fold after morphine withdrawal. Venous monoamine supersensitivity in morphine abstinence, similar to that observed during migraine attacks, could be indirect evidence of an analogous mechanism in both conditions.


Involvement of central cholinoceptors in Metrazol-induced convulsions.

Atropine sulphate (10 mg/kg IP) afforded 90% protection against clonic convulsions induced by standard doses of metrazol (80 mg/kg SC) in mice, whereas atropine methonitrate (10 mg/kg IP) did not offer any protection. Furthermore, physostigmine (1 mg/kg IP) caused recurrence of convulsions in atropinzed metrazol-treated mice and converted the subconvulsive dose of metrazol (40 mg/kg SC) into a 100% convulsive dose. However, neostigmine (1 mg/kg IP) did not antagonize the protection afforded by atropine sulphate against metrazol. The results of the study suggest an involvement of central cholinergic mechanisms in metrazol-induced convulsions.


Ineffectiveness of deanol in tardive dyskinesia: a placebo controlled study.

In a double-blind placebo-controlled study, deanol acetamidobenzoate, administered in doses up to 1.5 g q.d. for three weeks to chronic schizophrenic patients presenting moderate to severe tardive dyskinesia, failed to alleviate the dyskinetic movements. However, there was a tendency for a significant increase in the schizophrenic symptoms of the deanol-treated group relative to the control group. The ineffectiveness of deanol in alleviating tardive dyskinesia is consistent with its inability to enhance brain acetylcholine synthesis. The worsening of the schizophrenic symptoms may possibly result from an interference by deanol with central cholinergic function.


Interactions between personal expectations and naloxone: effects on tolerance to ischemic pain.

Sixteen healthy subjects participated in an investigation of the interactive effects of naloxone and personal expectations of control, stress, and anxiety, on time tolerance to ischemic pain. Control and anxiety levels provided no significant naloxone-saline discriminations, but there was a significant interaction between stress levels and naloxone-induced reduction in tolerance to ischemia. This finding suggests that activity in the opiate system may be a function of the modifying influences of variable attitudes to environmental stress. A primary analgesic role for the endorphins is challenged, however, by the findings that tolerance levels failed to reveal naloxone reactors and stress levels were not significantly associated with differences in tolerance. The latter, on the other hand, correlated significantly with control and anxiety levels, indicating that further research is needed to clarify the complex relationship between these three variables and their effects on the modulation of pain perception.


Effects of abrupt and gradual withdrawal from long-term haloperidol treatment on open field behavior of rats.

The effects of abrupt and gradual withdrawal from long-term haloperidol treatment on rat open field behavior was studied. Abrupt withdrawal induced a significant increase in all parameters of activity observed except defecation, this increase being higher 72 h after the last haloperidol injection. Results were considered to be a consequence of supersensitivity of central dopaminergic receptors. These differences were almost unobservable in animals gradually withdrawn, thus suggesting that the phenomenon is reversible.


Alcohol consumption in male social drinkers as a function of situationally induced depressive affect and anxiety.

Forty male subjects were randomly assigned to one of two conditions designed to induce either positive (Incentive Gain Condition) or negative (Incentive Loss Condition) affective states. This procedure was validated by an analysis of pre and post manipulation scores on the Multiple Affect Adjective Check List. Following the incentive manipulation subjects participated in an ad-lib drinking situation (Alcohol Taste Rating Rask) believing that the experiment was concerned with the relationship between intelligence, taste sensitivity and alcohol preferences. Contrary to expectation the analysis revealed that more alcohol was consumed by subjects in the incentive gain condition, this effect being most pronounced in heavy social drinkers in the incentive loss and gain conditions. A second analysis demonstrated that significantly less alcohol was consumed by subjects who, prior to ad lib drinking, evinced greater degrees of depressive affect and anxiety. The discussion focuses on the implications of these findings for tension reduction models of alcoholism.


The in vivo distribution of an antidepressant drug (DMI) in male and female rats.

The accumulation of IP injected 3H-desipramine (DMI) in the brain and in the liver has been studied in both male and female rats. The total amount of DMI in the brains of females is 2 to 4 times that found in the brains of males. In females the amount of DMI is highest on the day of estrus and lowest on proestrus. This sex difference was not found following the injections of another psychoactive drug, 3H-chlorpromazine. In both males and females the level of DMI in the cortex and caudate is slightyl higher than in the hippocampus, septum and hypothalamus. The pharmaco-kinetics and dose dependence of the accumulation of DMI are also similar in males and females. Maximal levels are reached in the liver in less than 15 min, whereas in the brain it takes 30 min. The decline of radioactivity in the liver is faster than in brain. There is no saturation in the amount of DMI taken in brain. There is no saturation in the amount of DMI taken up in brain or liver in the dose range up to 40 mg/kg. The sex difference in the amount of 3H-DMI in brain, which may be the result of sex-dependent metabolism in liver microsomes, may explain the male-female differences in reaction to antidepressants.


Platelet monoamine oxidase activity in first-degree relatives of schizophrenic patients.

Platelet monoamine oxidase (MAO) is under genetic control. A lower MAO activity in chronic schizophrenia has repeatedly been reported, and it has been suggested that reduced activity of this enzyme reflects an increased vulnerability to schizophrenia. To test this hypothesis platelet MAO was determined in 65 first-degree relatives of 22 schizophrenic index patients and in matched healthy controls. No difference in mean activity between the two samples could be detected, suggesting that reduced MAO activity in schizophrenia is more likely to be a phenomenon secondary to the disease. A significant parent-offspring correlation of MAO activities was obtained.


Benzodiazepine receptors in the brain as affected by different experimental stresses: the changes are small and not undirectional.

Rats and mice were exposed to several different stress situations to investigate whether brain benzodiazepine receptors were sensitive to altered external or internal environmental circumstances. All stresses were applied for several days. Electrical foot shock and post-natal isolation of newborn pups resulted in small (7--25%; P less than 0.05--0.001) decreases in benzodiazepine receptor binding in some cerebral cortex or hippocampal areas while immobilization stress resulted in a small (9%; P less than 0.05) increase in frontal cortex. Other brain areas (i.e., striatum, cerebellum, pons-medulla, and occipital cortex) and other stress forms (isolation of male mice, forced swimming in cold water, or chronic amphetamine intoxication) did not change receptor binding. The effect of prolonged stress on benzodiazepine receptors is complex and not very pronounced.


Antinociceptive effects of central and systemic administrations of nicotine in the rat.

Nicotine (0.16--0.50 mg/kg, SC) was found to exert a potent antinociceptive action on thermal stimuli as measured by the tail-flick test. This antinociceptive action of nicotine could be blocked by centrally active nicotinic or muscarinic blockers implicating both classes of cholinergic receptors in this effect. Quaternary blockers, however, failed to prevent nicotine-induced antinociception. This finding, together with the ability of small doses of nicotine (25 micrograms) to induce potent antinociceptive effects when administered centrally, suggests a central site of action for the antinociceptive action of nicotine. The present results also support the suggestion that nicotine may selectively reduce sensitivity to certain classes of pain stimuli, perhaps through a central releasing action on acetylcholine.


Effects of caffeine and various xanthines on hornets and bees.

The effect of caffeine was assessed on Vespa orientalis hornets maintained either in sealed breeding boxes or as entire colonies free to forage, and also on Apis mellifera bees within their hives. In a number of instances the hornets were also used to study the effect of various bodily extracts of queen hornets and of the following xanthines: Purine; hypoxanthine; uric acid; theophylline; and theobromine. The studied materials were found to exert an effect on three categories of activities: (1) Motor motility, flight, and construction; (2) sensory response to light (retinal and extraretinal), noise, irritability, orientation; and (3) physiological changes in appetite, copulation, oviposition, hibernation, resistance to cold, and longevity. Up to a point the produced effects were reversible. Throughout the period of experimentation the test insects did not show signs of tolerance or addiction towards caffeine.


Differential effects of methylphenidate and d-amphetamine on stereotyped behavior in the rat.

Different equimolar doses of d-amphetamine and methylphenidate were compared for their potency in eliciting stereotyped behavior in rats. Although at lower doses d-amphetamine appeared more effective in causing stereotyped gnawing, repetitive body movements, and sniffing, at higher doses methylphenidate at certain times caused a greater incidence of gnawing than did d-amphetamine. Understanding these differences and comparing related biochemical correlates may lead to a better definition of mechanisms underlying psychostimulant effects.


Stretching and yawning: a role of glutamate.

Systemic injection of GDEE (glutamate diethyl ester), an antagonist of glutamate and aspartate receptors, induces stretching and yawning in rats. This was not accompanied by excessive grooming. Coupled with previous work these findings give evidence that a glutamatergic mechanism is involved in stretching and yawning.


Disruption of drug-dependent learning (memory retrieval) using an ethanol drug state: a replication.

Eight groups (n = 8 per group) of rats were trained to escape foot shock by turning in the correct direction in a T-maze and 24 h after reaching criterion all groups were tested with no foot shock. The four experimental groups were given alternating drug and nondrug test days while the four control groups always experienced the same drug state in training and in testing. Two experimental groups (transfer) heard a 1 kHz tone that was simultaneously paired with foot shock during training, and the tone continued to be sounded on all test trials. These two groups responded significantly (P less than 0.05) above random level with low response latencies on all days of testing, regardless of drug state. The other two experimental groups (DDL) did not receive the tone, and these groups demonstrated dissociated performance. The present study, using 2400 mg/kg ethanol, replicated the DDL and memory retrieval results of our previous chlordiazepoxide studies.


[Criteria in evaluating the nutritional status of the child in Costa Rica].

The present discussion reveals the need to review and substitute certain criteria currently used in Costa Rica in regards to: a) nutritional recommendations; b) standards of weight; and c) classification and evaluation of the nutritional status. Such concepts will lead to the adoption of alternate criteria and standards for a better assessment of malnutrition in children. Computation of the adequacy of the diet should be made as a function of the child's weight and not of his age (Sukhatme approach). The adoption of the Weight for Height and Height for Age criteria are recommended as a substitute for Weight for Age. The normal curves of weight and height of the National Center for Health Statistics (NCHS, USA) would be more accurate criteria. Systematic collections of weights and heights at the national level should be made, and the data processed by simple and rapid programs to discover and assess growth deficiencies. The philosophy and orientation, scientific basis, definition of target population, infrastructure and logistics of the nutrition intervention programs of Costa Rica, should be critically revised in the light of the present report. This particularly applies to the Program of Social Development and Family Allowances.


[Admissions for protein-calorie malnutrition at the National Children's Hospital, Costa Rica, 1975].

The hospital records of 478 children with protein-calorie malnutrition (PCM) were reviewed. These represented all children diagnosed as malnourished during 1975 (3.6 per cent of all hospital admittances in the National Children's Hospital); 52% of the cases were infants less than 6 months of age; 28% had low birth weight, a rate much in excess of the prevalence of low birth weight in the general population of Costa Rica (7%). In general, malnourished children had been weaned early, 75% during the first month of life. A considerable number of children belonged to "malnourishing families" which have particular characteristics favorable to establishment of malnutrition in the family. Thus, 36% of their siblings had also been admitted with malnutrition at a previous date to that of this study.


[Food consumption of children under 5 in rural communities of Costa Rica, 1977].

Six Costa Rican communities of different ecological settings were selected for the study of food intake in children under 5 years of age. Intake was expressed as calorie and protein adequacy. Calorie deficiency was more prevalent than protein defficiency. Practically there were no differences in adequacy by age, although 4 year-olds had a slightly greater deficiency than observed in a relatively more advanced rural region 4 years earlier. Only 13 per cent of the children selected at random were covered by Social Development and Family Allowances programs which provide for two "hot meals" per day. Calorie deficiencies of children benefiting from this program were of similar magnitude as those of children not attending the food distribution centers. These observations point to the need to carry out further investigation of the actual effectiveness and drawbacks of such programs.


Changes of the thyroid gland and periodontal tissues of marmosets related to experimental hypothyroidism.

Adult marmosets of both sexes, weighing about 300 grams received intraperitoneal injections of 1.5 mCi of I131. Alterations in periodontal and thyroid gland tissues were determined 30, 45, 60 and 90 days after the administration, using the histological method. In the thyroid gland, degeneration and necrosis of the follicles and absence of the colloid substance with later substitution of the glandular tissue by a cicatricial fibrous tissue were observed. In the periodontium changes occurred in the alveolar bone, followed by degeneration of the periodontal ligament with areas of hyalinization from 30 days period up to the conclusion of the experiment. The cementum and the dentine were the last structures to present evidences of degeneration, showing areas of resorption only in the 60 and 90 days periods.


[Confirmation of the presence of uteroglobin in tubal secretions].

The acrylamide gel electrophoresis of rabbit serum, of rabbit tubal secretions at the oestrus stage (STO) and at the luteal stage (STL), followed by immunodiffusion with anti-serum, was done to detect any tubal proteins which were not found in the rabbit serum. The anti-rabbit STO goat anti-serum was absorbed with rabbit plasma in order to purify antibodies to proteins found specifically in tubal secretions. This technique revealed the presence of a protein (STx) in STO and STL but not in the rabbit serum. The electrophoretic migration (Rf = 0.72) of the tubal protein (STx) is similar to uteroglobin (Rf = 0.74). The tubal protein was detected immunologically only in tissues where uteroglobin had been found by other workers: lungs, semen, Fallopian tubes and uterine secretions (5 days post-ovulation); further more a complete identity for the precipitating line existed between these extracts. These results corroborate the presence of uteroglobin or of a very similar protein in oestrus of luteal tubal secretions and in some other rabbit tissues.


Pharmacokinetics of propranolol in the cat and comparisons with humans and three other species.

The aims of this study were to describe the pharmacokinetics of propranolol in the cat, to compare pharmacokinetic parameters for propranolol in the cat with those of four other species and to apply the two-step infusion method of Wagner (Clin. Pharmacol. Ther. 16, 691-700, 1974) in order to attain a rapid steady-state level for propranolol in plasma. Seven healthy adult cats received propranolol either as an I.V. bolus or by the two-step I.V. infusion method. The latter method was very effective in rapidly attaining and maintaining steady-state plasma propranolol levels. Pharmacokinetic parameters for propranolol in the cat are as follows: plasma clearance, 31.3 ml/(kg x min); volume of distribution, 1.57 L/kg; elimination half-life, 35 min. When compared with other species, the order of plasma clearances for propranolol were: rat greater than dog greater than cat greater than man greater than monkey. A plot of total area under the plasma propranolol concentration-time curve versus dose was not linear at the lower doses, but was linear at doses greater than 0.242 mg/kg.


Inactivation of creatine kinase in physiological saline solutions.

To determine the optimal conditions for measuring the activity of creatine kinase released from isolated skeletal muscle preparations, we investigated the stability of the enzyme during storage in saline solutions of varying composition. Parameters studied were temperature, presence of albumin or dithiothreitol, calcium concentration and anionic composition. It is concluded that maximal activity is retained when samples are kept at 4 degrees C and analyzed within 24 hours in the presence of a thiol-protective compound. If longer storage periods are anticipated, inactivation is significantly retarded by addition of albumin or by decreasing the free calcium concentration of the storage salines.


Theileria mutans in Nigeria.

Two strains of bovine Theileria from northern Nigeria were shown to be identical to Theileria mutans in the indirect immunofluorescent antibody test. One of the strains was transmitted by the tick Amblyomma variegatum; large macroschizonts, typical for T mutans, could be demonstrated in infected cattle. It is concluded from these experiments and from the literature that there is reliable evidence so far for the occurrence in Nigeria of only two bovine Tehileria species, T mutans and T velifera.


Serological comparison of British Theileria mutans and Japanese T sergenti.

A serological comparison between British Theileria mutans and Japanese T sergenti using the indirect fluorescent antibody test, showed that the two parasites were indistinguishable. On the basis of this and previous findings it is suggested that the British parasite is identical with the Japanese one and that its name should therefore be changed to T sergenti.


[Experimental trachoma].

During half a century, the agent of trachoma could be mainly demonstrated by inoculation to the conjunctiva of animals; by this mean the cycle of the agent could be revealed. There was a huge progress when T'ANG for these studies inoculated embryonated chicken eggs. However, experimentally infected animals are used at present time not only in trachome countries where do not exist laboratories: monkeys, guinea pigs, rabbits, rats and mice allow modern studies of chlamydial infection. Monkeys living in the countries where trachoma is endemic were selected because of their cheapness (orangoutan in Java, macaques in Northern Africa and in Taïwan, baboons in Africa). The monkeys selected by American workers are coming from South America. First pioneers (NICOLLE, CUENOD and NATAF, PAGES, JULIANELLE) have demonstrated the infectivity of animals and the place of the agent of trachoma on taxonomic point of view. As PAGES, we have demonstrated that infection could be regularly provoked when inoculating macaques; moreover a pannus could appear when adding hydrocortison drops or when infiltrating the cornea with tuberculin. Cultures of WEEKS bacilli were introduced in the eyes of trachomatous animals; we could observe an aggravation of the disease. If biology of trachoma is better known at present time, experimental trachoma is until now fundamentally important. It permits immunological studies especially for the purpose of vaccination; one can check terapeutical means for instance antibiotics; studies are performed to demonstrate cross immunizations or enhancement of defence (with levamisole). Experimental trachoma is hitherto and again for a long time commonly requested for the study of trachoma.


[Intralobal pulmonary sequestration and tuberculosis superinfection].

Among 16 pulmonary sequestrations observed in 23 years, 3 were associated with pulmonary tuberculosis. A detailed report is given on a 37-year-old man who was found by serendipity to have a right lower sequestration after 6 years treatment for tuberculosis; middle and upper lobe function had already been lost. Two and half years after pneumonectomy, the patient is in good health. Discussion centers on the diagnosis and potential complications of pulmonary sequestrations.


[Successful allotransplantation of an island of Langerhans].

Combined renal and pancreatic transplantation in patients with juvenile diabetes mellitus, diabetic nephropathy and renal insufficiency is designed to improve the poor prognosis observed with hemodialysis or renal transplantation alone. Interest has recently shifted from pancreatic organ to islet transplantation, in view of the absence of complications with the latter. However, no permanent success with islet transplants in diabetic patients has so far been reported. In the series presented, one patient with juvenile diabetes and subsequent renal failure was successfully treated with simultaneous kidney and intrasplenic pancreatic islet allotransplants. One year after the operation the patient has normal blood glucose levels without exogenous insulin, despite treatment with prednisone.


[Von Recklinghausen's neurofibromatosis and skeletal changes].

Two cases of von Recklinghausen's neurofibromatosis with osseous involvement are described and compared with cases in the literature. The most important skeletal lesions are dysplastic defects of the skull, macrocranium, deformities of the vertebral column with associated lesions of the vertebral bodies, congenital bowing, pseudarthrosis, length disparity and periostal dysplasias of the extremities, and congenital anomalies, erosions and cysts in the remaining skeleton.


[Is the use of large amounts of glucose in parenteral feeding a problem?].

Intravenous feeding with glucose as the sole carbohydrate was analyzed in a retrospective study of 30 patients. Very good assimilation of intravenous glucose without dangerous blood sugar variations could be demonstrated. As the administration of glucose was increased stepwise in the initial phase, the incidence of glucose intolerance was minimal. The good correlation of blood and urinary sugar shows that there is no problem in the control of carbohydrate metabolism during intravenous alimentation with glucose, and that urine samples provide adequate control after the initial phase.


[Scanning electron microscopic study of so-called carvable composite filling materials after over one-year functional period].

28 class-5 and 16 class-1 fillings were made from the composite material "Epoxydent" on a macaca speciosa monkey and examined with the electron microscope after a 15 months functional period. Statistically significant differences in the size of the marginal space were found to be larger than in comparable composites Adaptic, Concise, Compo-Cap and Cosmic. The spaces were frequently not located on the filling margin but inside, within the filling material. This is attributed to the "carving" technique during the gel phase of setting. The surface shows abrasions and porosities with loss of particles, sometimes fractures and discolored margins with secondary caries. It is not recommended to replace metal fillings by so-called carvable composits.


Structure of the constant and 3' untranslated regions of the murine gamma 2b heavy chain messenger RNA.

The complete coding sequence for the constant region of the mouse gamma 2b immunoglobulin heavy chain and the 3' untranslated region has been determined. The coding portion of the sequence is 1008 nucleotides long (amino acid residues 114 to 449), and the 3' noncoding region contains 102 nucleotides preceeding the polyadenylate. An extra carboxyl-terminal lysine residue which had not been observed in the gamma 2b or other gamma subclass protein sequences occurs in the nucleotide sequence and is probably processed posttranslationally. A 17-nucleotide sequence occurs with slight variation twice in CH1 and once in CH2 domains in the same relative location but with different translational phase. This sequence may be the site of crossover in a gamma 2b . gamma 2a heavy chain variant, an indication of possible recombinational activity of some kind.


Sequence of the cloned gene for the constant region of murine gamma 2b immunoglobulin heavy chain.

The complete nucleotide sequence of the gamma 2b constant region gene cloned from BALB/c liver DNA is reported. The sequence of approximately 1870 base pairs includes the 5' flanking, 3' untranslated, and 3' flanking regions and three introns. The C gamma 2b coding region is divided by these introns into four segments corresponding to the homology domains and hinge region of the protein. The introns separating the hinge from the CH2 domain and the CH2 from the CH3 domain are small (106 and 119 base pairs). A larger intervening sequence of 314 base pairs separates the CH1  and hinge regions. The stretch of DNA comprising this large intron plus the hinge shows a strong homology with the other CH domains.


Genetic mechanism accounting for precise immunoglobulin domain deletion in a variant of MPC 11 myeloma cells.

A variant of the MPC 11 cell line, M 311, produces a short immunoglobulin heavy chain. When compared with the parental gamma 2b heavy chain, M 311 was found to have a carboxyl terminal deletion comprising the CH3 domain. The COOH-terminal cyanogen bromide (CNBr) cleavage fragment of M 311 is identical to a corresponding segment ofa parental heavy chain CNBr fragment, with the exception of a substitution of asparagine for lysine at the COOH-terminal residue. This observation enabled prediction of both the parental DNA sequence in this region and the genetic mechanism which generated the variant, a frameshift followed by premature termination. This hypothesis is supported by studies of the DNA sequence of the MPC 11 gamma 2b constant region gene.


Problems encountered with hyperalimentation in critically ill patients.

An analysis of complications arising from hyperalimentation in 17 septic patients in an ICU is presented. All developed hypophyosphatemia. Hyperglycemia necessitated intravenous insulin in 16 patients. Hypoalbuminemia persisted in all patients despite 134 gm of protein a day. Abnormal liver function and azotemia were common. Catheter complications occurred in three of 90 catheter insertions. Mortality in this population was 70%. Guidelines for the use of Dextrostix for monitoring blood glucose levels and a protocol for hyperalimentation in patients with sepsis are suggested.


Lidocaine: a neglected anticonvulsant?

An elderly man had focal motor status epilepticus secondary to a frontal lobe hematoma. Phenytoin, phenobarbital, and diazepam did not stop the seizures. Intravenous lidocaine by bolus injection and continuous infusion rapidly controlled the seizures.


Recovery from Bacillus cereus sepsis.

A patient with acute leukemia developed two separate episodes of Bacillus cereus septicemia during one hospitalization. Leukopenia as a consequence of cytotoxic chemotherapy preceded both illnesses. The course of the infections was favorably influenced by the return of adequate numbers of circulating granulocytes and aminoglycoside therapy. Only one other compromised host is known to have recovered from this otherwise fatal disease.


Morphological changes in 49 chacma baboons after cardiac allografts.

The morhpological changes in 49 chacma baboons after cardiac transplantation were studied by light and electron microscopy. Non-immunosuppressed grafts were tolerated for an average of 10 days and immunosuppressed grafts for 18 days. Serial biopsy specimens of non-immunosuppressed grafts showed a progression in severity of rejection changes. Electron microscopy mirrored the light microscopic changes. Rejection changes in the baboon appear similar to those encountered in human and canine allografts. Heterotopic transplants showed more severe grades of rejection than would be compatible with life in orthotopic transplants.


Highlights of physiological research at the University of Cape Town, 1912-1978.

During the 68 years since it was founded, 548 publications have appeared from the Department of Physiology of the University of Cape Town, which has at different times included subdepartments of pharmacology and of medical biochemistry. The main fields of physiological research have been electrophysiology of the heart and of nerves, calcium metabolism (especially of teeth), endocrinology (especially of sex hormones), phonocardiography, bile secretion, exercise physiology (especially tests of physical fitness), measurement of obesity, renal physiology (especially membrane transport of sodium) and neurophysiology. Work continues in some of these fields.


Computed tomography in ossification of the posterior longitudinal ligament in the cervical spine.

Computed tomography of the cervical spine has been carried out on 21 patients with the ossification of the posterior longitudinal ligament. There was a correlation between the shape and the extent of ossification and the type of myelopathy. Computed tomography is important for operative intervention.


Effects of influenza, mumps, and western equine encephalitis viruses on fetal rhesus monkeys (Macaca mulatta).

Pregnant Rhesus monkeys were infected via instillation of influenza, mumps and western equine encephalomyelitis viruses respectively into the amniotic sacs at approximately 90 days gestation to determine if fetal infections would occur. Virus was recovered from fetal tissues after seven days in 100% of the exposed animals. Thus, the viruses are capable of causing fetal infection. Rhesus monkey fetuses were inoculated with influenza, mumps and WEE viruses by the direct intracerebral route at approximately 90 days gestation to determine possible teratogenicity of the viruses. influenza virus caused no malformations or measurable fetal effects. Mumps virus resulted in significant fetal mortality. WEE virus resulted in a 100% incidence of encephalitis and hydrocephalus. Thus, mumps and WEE viruses are teratogens in primates and are potential teratogens of man.


Fetal mortality and malformations associated with experimental infections of western equine encephalomyelitis vaccine virus in rhesus monkeys (Macaca mulatta).

Pregnant Rhesus monkeys were infected via installation of Western Equine Encephalomyelitis (WEE) vaccine virus into the amniotic sacs at 50 and 80 days gestation to determine if the resulting infections would produce fetal mortality or fetal malformations, particularly within the central nervous system. Of those receiving virus at 50 days gestation, 13 of 18 fetuses were aborted or dead in utero at time of Caesarean section; 2 of 18 were malformed (hydrocephalus and polyarthrosis); and 3 of 18 were anatomically normal. Of those receiving virus at 80 days gestation four of eight fetuses were aborted or dead in utero at time of Caesarean section, one of eight was malformed (hydrocephalus) and three of eight were anatomically normal. Three of three controls receiving neutralized virus at each gestational age were anatomically normal. Fetal WEE vaccine virus infection significantly increased fetal mortality and resulted in a significant incidence of fetal malformations.


Toxicological studies on cefuroxime sodium.

The intravenous LD50 of cefuroxime sodium for mice was 10.4 g/kg. The maximum dosage administered in other acute toxicity tests was well tolerated by mice (10 g/kg, subcutaneous), by rats (4 g/kg, intravenous, 5 g/kg, subcutaneous) and by cats, dogs and monkeys (2 g/kg, intramuscularly). Cefuroxime sodium was administered subcutaneously (s.c.) or intramuscularly (i.m.) for 3 months to rats (100, 300 or 900 mg/kg/day) followed by a recovery period, and also for 6 months to rats and dogs (50, 150 or 450 mg/kg/day) and for 1 month to monkeys (150 or 450 mg/kg/day). In all these tests there were no serious toxic effects. Minor haematological changes were attributable in part if not entirely to haemorrhage and tissue reaction at the site of injection of large doses. In rats large doses caused some increase in urine volume and electrolyte excretion, and slightly aggravated an age related nephropathy. Administration to rats intravenously (i.v.) for1 month of up to 400 mg/kg/day had no toxic effects. In reproduction studies on mice and rabbits there were no adverse effects on fertility, organogenesis or the rearing of young.


Total body irradiation (T.B.I.). Preliminary results of a new technique in 30 patients with hematologic malignancy.

The authors present the preliminary results of a new technique of total body irradiation (T.B.I.) used in 30 patients with hematological malignancy. The schedule proposed is easy to use and reproducible. The clinical and hematologic tolerance is good even for patients having had previous cyclic polychemotherapy and/or large-field irradiation. Low-grade non-Hodgkin lymphomas previously nontreated appear to be the best indication. Further investigations have to be performed particularly to specify the interest of combining T.B.I. and chemotherapy or T.B.I. and radiotherapy in the treatment of non-Hodgkin lymphomas.


[Dose distribution of bone-seeking radiopharmaceuticals in the rat (author's transl)].

The biokinetics of 32P-P, 32P-PPi, 85Sr, 99mTc- and 113Sn-EHDP were evaluated in the young rat. The dose distribution of the beta-emitters 32P, 89Sr, 121Sn and 188Re was calculated from the measured biological half-lifes. The highest dose to soft tissues and therefore also to bone-marrow in relation to the bone dosis was found for 32P-P. The lowest dose was found for 89Sr. Favourable results were obtained in the diphosphonate compounds. The use of 32P-PPi instead of 32P-P appears to be advantageous, too. The dose relation between normal bone and the growth plate of the femur was significantly lower for 89Sr than for the other radiopharmaceuticals.


Testicular steroidogenesis in the rhesus monkey (Macaca mulatta.

Studies were undertaken to investigate testicular steroidogenesis in the Rhesus monkey Macaca mulatta. Testicular fragments (50 mg) were incubated for 3 hr with pregnenolone-7-3H or with progesterone-7-3H. The major metabolite of pregnenolone was progesterone (70.1%), with a lesser conversion to 17-hydroxyprogesterone (1.6%), androstenedione (3.3%), and testosterone (7.2%). The delta-5 intermediates 17-hydroxypregnenolone (4.6%) and dehydroepiandrosterone (8.6%) were also identified in the pregnenolone incubates. A majority of the progesterone substrate was not metabolized by the testicular fragments (80.1%), while some conversion to 17-hydroxyprogesterone (3.4%), androstenedione (4.8%), and testosterone (11.7%) occurred in the incubates. These results suggest that testicular fragments from the Rhesus monkey may convert pregnenolone to testosterone through both the delta-4 and the delta-5 pathways.


Accidental contamination of diagnostic cultures of mycobacteria and phage identification of the contaminating strain.

Phage typing of mycobacteria is a new technique not yet widely used for classification and intraspecies differentiation. Systematic long-term studies organized by the WHO have succeeded, using a battery of 11 different mycobacterial phages, in dividing M. tuberculosis into 3 different phage sub-groups, preliminarily labelled as A, B and C. A special case of phage-typing is presented which enabled identification of a virulent mycobacterial strain causing accidental contamination of diagnostic mycobacterial cultures. The strain was an old laboratory one, H37Rv, belonging to phage subgroup B.


[WR, a new strain of mice, highly sensitive to the cytogenetic effect of thiotepa].

Mice of the WR strain (genotype -aa, +WY) were selected for the appearance of black spots with normal pigmentation, presumably due to genetic recombination in the W gene region. The frequency of heterozigotes +WY with black spots was 25% in the 11th generation. The cytogenetic effect of thioTEPA (dose 5 mg/kg) was investigated in bone marrow cells of C57BL/10 NZW, 101/H and 129/Re mice. Mice of the WR strain were most sensitive to thioTEPA. It is suggested that the WR mice may be used as a sensitive object for the genetical screening of chemical compounds.


[Polyamine content in tissues of 7,12-dimethyl-benz(a)anthracene-induced sarcoma and liver of tumor-carrying rats].

Putrescine in determinable amounts is contained in the tumour tissue, in the liver tissue of normal animals it was not detected by the applied method. The spermidine content in the tumour is also considerably higher, it is 15.-3 times as high as that in the normal liver both per 1 g of fresh tissue and per 1 mg of RNA. The spermine content in the tumours is somewhat lower as compared to its content in the normal liver. The shifts in the contents of polyamines are of the same character both for the liver of rats with carcinogen-induced sarcomas and for tumours. Putrescine is determined in noticeable amounts in the liver of tumour-carrying rats. Thus, the carcinoven-induced sarcoma as well as the liver of rats with sarcomas are characterized by a high content of putrescine and spermidine as well as by a high value of the spermidine/spermine ratio.


[Changes in sperm ultrastructure of bulls with decreased sperm activity and freezability].

A decrease of sperm freezability occurred at the K. breeding station, and this situation lasted longer than a year. Out of the 2550 ejaculates taken from 42 breeding bulls within 12 months, 685, i.e. 26.7%, were unfit for use immediately after sperm collection, mostly owing to a low activity of spermatozoa and pathological forms of their motility, and another 469 ejaculates, i. e. 18.3%, were unfit for use after sperm freezing; on the whole, 1154 (i. e. 45.2%) ejaculates had to be excluded. It was revealed by the vital-lethal primuline test that the spermatozoa died quickly after collection. The findings obtained during an electron-microscopic examination of the spermatozoa at the beginning of the process included visible changes in the ultrastructure of the flagellum, particularly its middle piece (deformed shape, incomplete set of axial filaments, vacuolization of the flagellum, abnormal arrangement of the mitochondrial spiral), numerous abnormities of the external cytoplasmic membrane and invagination, vacuolization, and abnormal density of nucleoplasm. The primary changes on the flagella and in the nucleus give evidence that the testicular tissues were altered. The etiological factors behind these processes are believed to include a reduction in the resistance of bulls due to long-lasting consumption of feeds contaminated with the fungus Aspergillus fumigatus, insufficient movement and bad zoo-hygienic practices, all this combined with the secondary action of the infectious germs of Mycoplasma bovigenitalium, which were revealed by cultivation tests in 50% of the ejaculates of the bulls; a positive antibody titre was demonstrated in all bulls.


[The relationship between fermentation and the morphological structure of rumen epithelium in sheep fed pelleted feeds].

Wethers were fed complete granular feed rations including 41.81% of grass hay, 25.28% of barley, 15.37% of sawdust, 14.98% of molasses, 1.32% of urea, and 1.24% of mineral supplement in dry matter for 24 weeks. Samples of the dorsal rumen sac of these wethers were subjected to patho-anatomical, histological, histo-chemical, and electron-microscopical examination. Volatile fatty acids were also determined in the rumen fluid of slaughtered animals. The control group was given the same diet in the classical form with long hay. The rumen contents of the slaughtered animals of the experimental group had an increased level of total volatile fatty acids (125.93 mM) and butyric acid (17.8 M%). The acetate:propionate ratio was 3.66. No substantial differences were observed in enzymatic activity. Electronograms recorded an increase in the number of T cells and keratinizing cells -- this suggests an increased intensity of the process of keratinization.


[The occurrence of aflatoxins in some components and complete feed mixtures for pigs].

The feed components and complete feed mixtures used in pig breeding and fattening in June 1978 were examined qualitatively by the silica-gel thin-layer chromatographic method, and quantitatively by the method after Velasco. The object of the examination was the occurrence of aflatoxins. On the whole, 104 feed samples were taken and subjected to the laboratory examination; this total number included 77 samples (74.0%) coming from 24 farms and 27 samples (26.0%) from eight feed plants in the South Moravian region. The presence of aflatoxins was detected in 14 samples of the examined feeds, i. e. 13.4%. The highest content -- 1920 micrograms kg-1 -- was found in groundnut from India. As to the complete feed mixtures, aflatoxin was found in mixtures for pig fattening (A1 and SOL), in mixtures for pregnant sows (KPB), for lactating sows (KPK), and in the complete feed mixtunts ranged between 50 and 350 micrograms kg-1 of feed. The organoleptically altered feed samples, taken from metallic containers standing in front of the stables on the farms, contained aflatoxin almost in all cases. It will be necessary, on the basis of these findings, to take preventive measures during the harvesting, post-harvest treatment, and storage of grain and feed components, in order to avert the multiplication of the mould and deterioration of the feeds.


[Detection of chlamydia by the immunofluorescence method].

The possibility of detecting chlamydia by the direct immunofluorescence method was tested in the impression preparation of experimentally infected mice, chick embryos and naturally infected domestic mammals. In comparison with slight-microscope detection, this method was found to be sensitive and expedient. The greatest amount of antigen could be detected in the lungs of mice after intranasal infection already within 6 to 12 hours. In the other organs the findings were less ample; the visualization of the antigen had a good fluorescence brilliance if log 10 KEID50 was more than 3.0. In the tissues of chick embryos, the antigen could be detected in the impression preparations of the allanto-amnionic fluid, embryonal muscle, yolk sac, and chorio-allantoid membrane the fifth day after infection. After the intratracheal infection of ducklings with 1 000 000 infection doses, only individual specifically radiating cells with a low brilliance of fluorescence were detected in the organ preparations of ducklings killed 22 t0 57 days after infection. The method proved to be suitable for the detection of chlamydia in the organs of naturally infected domestic mammals in which a great amount of specifically fluorescing high-brilliance cells were found.