Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

Central nicotinic receptor blockade inhibits emotionally conditioned pressor responses in rats

A conditioned stimulus previously paired with electric footshock produced an increase in blood pressure in conscious, freely moving rats. The conditioned pressor response was reproducible. Intracerebroventricular injection of the nicotinic receptor antagonists hexamethonium (1–10 g) or pentolinium (10 g) but not the muscarinic receptor antagonist methylatropine (3 g) produced an inhibition of the conditioned pressor response, whereas intraarterial injection of hexamethonium (10 g) did not affect the response. Intraventricular injection of the cholinesterase inhibitor physostigmine (3–10 g) produced an enhancement of the conditioned pressor response. These results are consistent with the possibility that central nicotinic receptors play a role in the expression of the emotionally conditioned pressor response in rats.     

Antidiuretic effects of oxytocin in the Brattleboro rat

Summary The antidiuretic activity of oxytocin (OT) was measured in Brattleboro rats with congenital diabetes insipidus. A dose dependent antidiuretic response was found in animals receiving chronic infusions of 0.1 g/h, 1.0 g/h, and 5 g/h of OT. OT infused at the rate of 5 g/h over a 7-day period completely reversed the symptoms of diabetes insipidus. The results support the concept that OT serves as a weak agonist of vasopressin at the level of the kidney and at pharmacological levels exhibits antidiuretic activity.     

Repercussions de l'hyperthyroïdie sur le contenu total en ADN du cervelet de rat âgé de 6 et 35 jours. Effets comparés de la LT3 et de la DLT4

Summary The total cerebellar proteins RNA and DNA contents from DLT4- and LT3-treated rats was studied at 6 and 35 days of age. The effect of injections of 5 g/j of DLT4 is comparable to that of 25 g of LT3 at birth, followed by 0.5 g every 2 days. On the other hand, injection of 0.5 g of LT3 every 2 days does not induce any significant modification of the total DNA contents in the cerebellum.     

Storage of irradiated human blood; a source of error in quantitative chromosome analysis

Summary Human whole blood was irradiated with 2.5 Gy of 220 kVp X-rays and stored before culture with 9.7 M BrdU and 19.4 or 38.7 M BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 M BrdU. In 66 h cultures at 19.4 M BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 M BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2–3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells.     

The length-tension diagram of single muscle fibres of the crayfish

Zusammenfassung An isolierten Muskelfasern vonAstacus fluviatilis wurde mittels Kaliumkontraktur die Spannung-Sarkomerlängenrelation untersucht. Maximale Faserspannung wird bei einer Sarkomerlänge von 10,5 entwickelt. Werden Fasern zu einer Sarkomerlänge von 16,5 gedehnt, so ist die Spannung nicht mehr messbar. Diese Sarkomerlänge ist etwas grösser als diejenige (14.45), die aus der Länge der dicken Filamente (3.95) und der optimalen Länge hervorgeht.     

Exogenous fibronectin modifies the aggregation of collagen-stimulated human platelets

Summary Fibronectins (FN) are adhesive glycoproteins whose role in platelet aggregation is unclear. Addition of 3, 6 and 12 g/ml of human plasma FN in vitro to isolated human platelets, which had been freed from plasma FN by gel filtration and subsequently stimulated with collagen, inhibited the last stage of platelet aggregation. With 3 and 6g/ml of FN a shortening of the lag-time was also observed. These data showed that FN may play a role in platelet-collagen interaction as well as in platelet-platelet interaction.     

Failure of somatostatin to influence experimental tumor cell growth in vivo and in vitro

Summary The influence of somatostatin on tumor cell growth was studied in vivo in mice (sarcoma 180 ascites tumor and Lewis lung tumor) and in vitro on nontransformed and polyoma-transformed cell lines. 4 or 20 g/100 g of cyclic somatostatin and 4 g/100 g of linear protamin Zn-bound somatostatin were injected s.c. twice daily in the in vivo study. Cyclic somatostatin (1, 4 or 10 g/ml) was added twice daily to the cell cultures. Somatostatin administration influenced neither the survival of animals nor the growth rate of cultured cell lines. *** DIRECT SUPPORT *** A2025117 00011     

Disruption of mitochondrial function as the basis of the trypanocidal effect of trifluoperazine onTrypanosoma cruzi

Summary The tricyclic anti-calmodulin drug trifluoperazine (TFP) inhibited growth and motility of epimastigotes ofTrypanosoma cruzi, at concentrations lower than 100 M, and motility and infectivity of the bloodstream trypomastigote form at 200 M. Electron microscopy of TFP-treated epimastigotes showed that the major effect was at the mitochondrial level, with gross swelling and disorganization. The oligomycin-sensitive, mitochondrial ATPase was completely inhibited by 20 M TFP, and the same drug concentration caused a 60% decrease in intracellular ATP content. The results suggest that the trypanocidal effect of TFP may be related more to mitochondrial damage than to the well-known anticalmodulin effect of the drug.     

Experimental immunity against trypanosomiasis

Summary 9 groups of 6 female rats were used in an experiment using fraction 3 ofTrypanosoma rhodesiense. 500 g gave 100% immunoprotection and 1000 and 1500 g gave 66% immunoprotection when challenged with 5×10² T. brucei. 2 groups of 10 female rats were tested for a short period inoculation immune response. In this, 750 g of fraction 3 ofT. rhodesiense gave 70% immunoprotection when challenged withT. brucei.I thank the University of Zambia for support; Dr M. A. Q. Awan, Mazabuka, Zambia, forT. rhodesiense andT. brucei; Prof. J. W. Kibukamusoke, Dr O. Okong'o and Dr W. W. Anokbonggo for advice; Mr L. Nyaliti for technical help.     

Different effects of D-glucose anomers for respiration of bacterial germinated spores

Summary Effects of - or -D-glucose on the respiration of germinated spores (only germinated spores not including swollen spores and elongated spores) ofBacillus subtilis andB. megaterium were studied. In our conditions, net amount of oxygen consumed by 10¹⁰ germinated spores ofB. subtilis per min after addition of - or -D-glucose was 1.6 g or 6.6 g (/=4.13), while that byB. megaterium was 4.5 g or 6.8 g (/=1.51), respectively. However, the net amounts of oxygen consumed by 10¹⁰ vegetative cells per min after addition of - or -D-glucose were identical, forB. subtilis in both cases 443.0 g and forB. megaterium in both cases 604.4 g.     

Nitric oxide-related pancreatic endocrine responses to hyperglycaemia in the conscious calf

Mean plasma insulin concentration was reduced and mean plasma glucose concentration increased following the administration of N-nitro-L-arginine methyl ester (L-NAME; 100 mol kg^–1 i.a.) in conscious calves given continuous infusions of exogenous glucose (30–60 mol min^–1 kg^–1 i.v.). It is concluded that the rise in plasma insulin concentration which occurs in these animals in response to glucose is mediated, at least in part, by a nitric oxide-related factor (NOx).     

Inhibition of hepatic Na+, K+-adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat

Summary Na⁺, K⁺-adenosinetriphosphatase (Na⁺, K⁺-ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 moles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10–1300 M) caused significant and dose dependent reductions of Na⁺, K⁺-ATPase activity at taurolithocholate concentrations above 100 M. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na⁺, K⁺-ATPase activity.This work was supported by the Swiss National Science Foundation.The authors thank Mr H. Sägesser and Miss B. Schütz for technical assistance.     

Effects of 18-hydroxydeoxycorticosterone on central nervous system excitability

Summary The effects of 18-hydroxydeoxycorticosterone (18-OH-DOC) on central nervous system excitability were studied in adrenalectomized rats. Sixty-four evoked potentials (EP) recorded from the pontine reticular formation were averaged before and after the injection of vehicle and hormone. 750 g of 18-OH-DOC dissolved in 0.5 ml of a 41 saline Cremophor-EL solution were injected i.v. A decrease of 55.7±6.1% in the amplitude of the EPs was observed with the hormone 16.3 min±2.7 (SE) after injection. Amplitude values returned to baseline levels 38 min±6.8 (SE) after injection. The secretion of 18-OH-DOC is greatly increased by ACTH and might modulate central nervous system function.     

Deciduogenic effects of mediators of the polyphosphatidylinositol pathway in pseudopregnant mice

Intraluminal injections (15 l) of either concanavalin A (125 g) or ionophore A 23187 (0.01 mol) induced a decidual cell reaction (DCR) in the uterus of day 4.5 pseudopregnant mice. However, when these agents were administered in different combinations with each other or with CaCl₂ (15 mol) and phorbol-12-myristate-13-acetate (1.6 nmol), interacting effects occurred to either enhance or inhibit each of the others' independent deciduogenic capacities. The results suggest that the polyphosphatidylinositol pathway and Ca²⁺ are involved in the induction of the DCR in mice with complex interactions occurring between the active components of the pathway to modulate the outcome of the transformation process.     

Zur Umwandlung von β-Pyridylcarbinol in Nicotinsäure im tierischen Organismus

Summary By way of the perfusion technique, it is shown that the liver of the rat readily converts-pyridyl-carbinol to nicotinic acid. The turnover attains a rate of 0.5M/g/min.     

Unusual antimicrobial compounds fromAeollanthus buchnerianus

Using bioassay guided isolation, three novel 12 carbon polyoxygenated fatty acids and a novel abietane diterpene have been isolated from the the chloroform extract of aerial parts ofAeollanthus buchnerianus (Lamiaceae). Rigorous spectroscopic methods were used for compound identification. (Z,Z)-8-acetoxy-5-hydroxydodeca-2,6-dienoic acid and (Z,Z)-5,8-dihydroxydodeca-2,6-dienoic acid inhibited the spore germination ofCladosporium cucumerinum (both with Minimum Inhibitory Dose (MID) values of 1 g) andAspergillus niger (MID 5 and 25 g respectively). Further, they also reduced the hyphal growth ofPythium ultimum. (Z)-5-hydroxy-6,7,8-triacetoxydodeca-2-dienoic acid exhibited short term inhibition of the growth ofCladosporium cucumerinum. The novel abietane diterpenoid, (rel)-14-acetoxyabiet-7-en-18-oic acid inhibited the growth of the gram positive bacteriaBacillus subtilis, staphylococcus aureus andStreptomyces scabies (MIC values 80, 20 and 20 g ml^–1 respectively).     

Somatic growth in hypophysectomized pituitary-homografted rats is promoted by prolactin

Summary Hypophysectomized male rats bearing a homograft of two adenopituitaries under the kidney capsule showed a significant increase in b.wt as compared to hypophysectomized non-homografted animals. Radiommunoassay of growth hormone (GH), ACTH, -MSH,-endorphin and prolactin (PRL) revealed that only the latter was highly increased in the plasma of hypophysectomized homografted rats. These animals showed also increased levels of plasma corticosterone. However, daily injection of corticosterone failed to promote somatic growth in hypophysectomized non-homografted rats. These results suggest that PRL, and not other hormonal factors, promotes somatic growth in hypophysectomized homografted rats, and stress the concept that only PRL is secreted in significant amounts by pituitary homografts.     

Effect of cadmium on polyribosome structure and function in mouse liver

Summary Cadmium chloride injected to mice (20 moles/kg) provokes in the livers a degradation of polyribosomes and diminishes their protein synthetic ability measured in vitro. CdCl₂ added in a final concentrations between 30 and 100 M to the protein synthetic cell-free system derived from livers of control mice inhibits its activity.Acknowledgments. We are grateful to Prof. P. Sokoli for helpful discussion. The work was supported by Wellcome Trust grant and by a gift of chemicals from Kemika, Zagreb. We are grateful to both these organizations.     

The use of 5-fluorocytosine and ketoconazole in the culture of the erythrocytic stages ofPlasmodium falciparum and some tumor cell lines

Summary In vitro culture systems are often contaminated by bacteria and fungi. It is therefore often necessary to supplement culture media with agents such as penicillin/streptomycin, gentamycin or amphotericin B. The latter cannot be used in the in vitro culture of erythrocytic stages ofP. falciparum, and thus anti-fungal agents have not been regularly used in this system. We describe the prophylactic use of 5-fluorocytosine (5-FC) and ketoconazole (KTZ) in tissue cultures at concentrations up to 300 and 10 g/ml respectively which have no effect on the growth ofP. falciparum (FCR-3 strain). A melanoma cell line (C32) and a line of uterine carcinoma (C41) were also unaffected by similar concentrations of 5-FC and KTZ. When dissolved in complete culture medium (RPMI 1640) with 10% human plasma, the minimum inhibitory concentration of 5-FC for a susceptible strain ofCandida remained below 2 g/ml. These experiments suggest that 5-FC (at 50 g/ml) alone or in combination with KTZ (at 1 g/ml) is a useful addition to the armamentarium of antimicrobials available to the tissue culture biologist for a variety of cell culture systems.