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.     

Lack of effect of cortisone,thyroxine and insulin on the developmental pattern of mouse intestinal glucose-6-phosphatase activity

Summary Daily administration for 3 days of cortisone (25 g/g b.wt), thyroxine (1 g/g b.wt) or insulin (12.5 mU/g b.wt) to 8-day-old suckling mice does not induce a premature decrease of the phosphohydrolase activity of intestinal glucose-6-phosphatase.Supported by grant MA-5969 from the Medical Research Council of Canada (D.M.). C.M. is a recipient of a studentship from MRC of Canada. D.M. is a chercheur-boursier du Conseil de la recherche en santé du Québec.     

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.     

Uptake of D-glucose anomers by rat retina

Summary Uptake ofd-glucose anomers by isolated rat retina was studied. After 3 min incubation at 37°C in the presence of or anomer (750 g/ml), a significantly greater uptake (1.32 mg/g wet tissue) of -anomer was observed compared with that of -d-glucose (1.11 mg/g wet tissue). This result and other data suggest that the carrier ford-glucose transport in the retina prefers the -anomer stereospecifically.Acknowledgment. The authors are grateful to Mr S. Suzuki for his technical assistance.     

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.     

Erythrocyte 2,3-diphosphoglycerate in anaemic sheep

Summary Experimental anaemia resulted in an increase of red cell 2,3-DPG from 0.11 M/gHb to 0.99 M in haemoglobin A sheep and from 0.21 M to 1.5 M in haemoglobin B sheep. Production of haemoglobin C as a result of anaemia was confined to haemoglobin A only. The results, therefore, appear to suggest that the rise in 2,3-DPG in the red blood cells of different haemoglobin types is independent of haemoglobin C.This work was supported by grants from the National Health and Medical Research Council, The Clive and Vera Ramaciotti New South Wales Foundations and Helena Rubinstein Foundation, Inc. We wish to thank Mr J. Sheedy for his expert technical assistance, and Professor G. J. Brewer for his constructive criticism.     

Physicochemical studies of indocyanine green (ICG): absorbance/concentration relationship,pH tolerance and assay precision in various solvents

Summary Indocyanine green (ICG) obeyed the Beer-Lambert law within the concentration range 1.25 g/ml–10.0g/ml in distilled water, methanol, dimethylformamide (DMF), 1.2-propanediol and aqueous buffers (pH 9.0), but only up to 7.5 g/ml in human bile and 0.5% human albumin, and only to 5.0 g/ml in human duodenal fluid. ICG was rapidly (<1 h) decomposed to a colorless derivative at pH<5 and >11, but remained relatively stable for 48 h at pH 8–10. ICG is an indicator and a weak acid with a pKa of 3.27. In bile stabilized with 25% methanol, the precision of the method (CV) is 5% and the accuracy is 106–127%.     

Effects of cortisone and thyroxine on intestinal trehalase activity in infant mouse

Summary Cortisone acetate (25 g/g b.wt/day) administration to 8-day-old suckling mice induces a premature increase of trehalase activity along the entire small intestine. On the other hand, thyroxine (1 g/g b.wt/day) is unable to provoke a precocious increase of trehalase activity. Trehalase appears to be the only brush border membrane disaccharidase controlled solely by glucocorticoid hormones during the postnatal maturation of the intestine.Supported by grant MA-5969 from the Medical Research Council of Canada to D.M. C.M. is a recipient of a studentship from MRC of Canada.     

Phenytoin-induced DNA synthesis and inositol 1,4,5-triphosphate formation in L-929 fibroblasts

Summary Culture of L-929 fibroblasts in the presence of phenytoin (2.5–5.0 g/ml) increased DNA synthesis, as indicated by increased [³H]thymidine uptake, while a higher dose (20 g/ml) inhibited DNA synthesis. In like manner, a low dose of phenytoin (5.0 g/ml) was effective in increasing inositol 1,4,5-trisphosphate formation while a higher dose (10 g/ml) tended to inhibit this activity. These data suggest that the formation of inositol phosphate second messengers may play a role in phenytoin-induced fibroblast proliferation and connective tissue growth.     

Platelet aggregation is inhibited by phycolectins

Lectins from four marine algal species were examined for interaction with human platelets. The lectin designated hypnin A, from the red algaHypnea japonica, inhibited adenosine diphosphate (ADP)-or collagen-induced human platelet aggregation in a dose-dependent manner. Complete inhibition was observed at concentrations of 100 and 5 g/ml of the lectin with, ADP (2 M) and collagen (0.2 g/ml)-induced platelet aggregation, respectively. At the inhibitory concentration of 0.5 to 100 g/ml, the lectin did not induce aggregation of resting platelets. Lectins from the other three algal species also inhibited ADP-induced human platelet aggregation. These results indicate that the algal lectins are a new group of inhibitors and may be useful to study glycoconjugates on platelet membranes and to design novel platelet aggregation inhibitors.     

N-(5′-Phosphopyridoxyl)-4-aminobutyric acid: a stable bisubstrate adduct inhibitor of rat brain 4-aminobutyric acid aminotransferase

Summary N-(5-Phosphopyridoxyl)-4-aminobutyric acid, a stable adduct of pyridoxal phosphate and 4-aminobutyric acid, has been shown to be a potent inhibitor of rat brain 4-aminobutyric acid aminotransferase (GABA-T) with a K_i of 1.4 M.Acknowledgments. This work was supported in part by the United Parkinson Foundation, l'Association Canadienne l'Ataxie de Friedreich, and the Medical Research Council of Canada.     

Relevance of specific activity in experimental erythrocytocide by55Fe

Summary Iron loads between 0.20 g and 26 g, added to 5Ci⁵⁹Fe, were followed for up to 150 days in mice. Relative organ uptake increased as a function of iron load in liver and kidneys while it decreased in bone marrow and blood. Several weeks after injection, all load-related differences disappeared.Research carried out under the auspices of the US Department of Energy and by NIH GRANT HL-15685-02.     

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.     

Promotion of epithelial keratinization by N-methyl-N′-nitro-N-nitrosoguanidine in rat forestomach in organ culture

Summary The effect of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) on epithelial differentiation of fetal rat forestomach was investigated in organ culture. When forestomach tissues removed from 16.5-day fetuses were treated with 5 g and 3 g of MNNG per ml for 1 h, epithelial keratinization was observed after 4 and 5 days, respectively, whereas it occurred after 6 days in control cultures. A clear dose-response relationship was found in the promotion of epithelial keratinization by MNNG.This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.Acknowledgment. The authors wish to express their gratitude to Prof. T. Mizuno of the University of Tokyo for valuable suggestions.     

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.     

Artificial spawning effected in the fresh water teleost,Cyprinus carpio by clomiphene citrate

Summary Triweekly i.m. injections of clomiphene citrate (group 1, 25 g/0.5 ml and group II, 50 g/1.0 ml) were administered for a period of 3 months during the preparatory period to female fresh water teleosts exhibiting ovarian recrudescence, while a control group received 0.5 ml of physiological saline throughout the period of experimentation i.e., from February through April. 50 g clomiphene citrate treatment brought about a steady increase in ovarian size, and oocytes began to enlarge and mature and finally ovulation took place in April. This is 4 months ahead of their normal occurrence.The authors wish to express their gratitude to Richardson Merrel Co. for supplying the sample of clomiphene citrate, and Dr K.N. Udupa, Institute of Medical Sciences, Banaras Hindu University, Varanasi for facilities.     

High and low affinity transport ofL-arginine in rat brain synaptosomes

The uptake ofL-arginine into purified rat brain synaptosomes was investigated with respect to time and various concentrations ofL-[³H] arginine. Specific uptake was found to be linear with time for up to 5 min of incubation at 37°C. Electrolytes, including sodium chloride, potassium chloride, magnesium chloride and calcium chloride, inhibited uptake of 3 ML-arginine, and the inhibitory effect increased with increased electrolyte concentration under constant osmolarity. It was found thatL-arginine was transported into synaptosomes by two uptake components — a high affinity component (3.5 M) and a low affinity component (100 M). These two components were similar to the Ly⁺ system because of their extreme sensitivity to inhibition byL-lysine andL-ornithine but were distinguishable from each other by kinetic analysis of the uptake data and by their relative sensitivity to inhibition by several amino acids.     

The effect of insulin on the electrophoretic mobility of rat hepatocytes

Summary The addition of insulin (10 U) to a suspension of isolated hepatocytes in Krebs-Ringer bicarbonate solution. causes an increase in the negative electrophoretic mobility of the cells from –1.68 m sec^–1 V^–1 cm to 2.26 m sec^–1 V^–1 cm. This observation supports the findings by other workers that the binding of insulin to its receptor leads to a marked change in the membrane.Acknowledgment. We wish to thank the Medical Research Council for the provision of the microelectrophoresis apparatus and initial running costs of the project.     

Critical period and ecdysone titers in the pupae ofPieris brassicae

Summary The ecdysone titer in the haemolymph of pupae of Pieris brassicae shows a sharp peak (1.90 g/ml) on days 5 and 6 of the pupal stage. Isolated abdomens were able to form adult abdomens at 72 h, this being 2 or 3 days before maximum ecdysone levels and at a time when the concentration of hormone in the abdominal haemolymph was only 0.23 g/ml.     

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