Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.     

Effect of carrageenan on non-specific resistance to LPS-induced endotoxemia in mice

The study showed that kappa/lamda-carrageenan increase non-specific resistance to impact of Escherichia coli lypopolysaccharide (LPS)-induced endotoxinemia in mice. Carrageenan was administered intragastrically in dose 100 mg/kg/day during 5 days followed by intraperitoneal injection of LPS in dose 1 mg/kg. Carrageenan hampered the involution of thymus, hypertrophy of adrenal glands, the changes on level of thyroid hormones and corticosterone in serum, the activation of glycogenolysis, glycolysis, and peroxidation of lipids in liver.     

The effect of hydra peptide morphogen on the levels of beta-endorphin and some blood and adrenal hormones in albino rats]

The influence of PMH on the level of beta-endorphin and some hormones of blood and adrenal glands was studied. The dose A (10 mkg/kg) and dose W (100 mkg/kg) of PMH were used in our experiments. Earlier it has been discovered, that PMH in such doses stimulated the processes of cell division in 24 hours since the moment of injection. The stimulation was dose-dependent. Within 24 hours PMH in A dose decreased the concentration of beta-endorphin in the blood 2.7-fold, ad in dose W increased it 2 times. The level of corticosterone in blood and adrenal glands after the injection of PMH in dose A exceeded the control data trustworthy in 4 and 24 hours since the moment of injection. In dose B in 4 hours 1.5-fold reduction of corticosterone concentration took place in the blood. Increase in epinephrine level in adrenal glands was observed after PMH administration in two doses. Content of T3 increased in 4 hours after PMH injection in dose B. The role of hormonal changes in stimulating cell division accompanied by PMH injection is discussed. The data received show that PMH influences directly proliferative processes.     

Involvement of GABAB receptors in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) axis in rats

Previous experiments have shown that the GABA_B receptor agonist -baclofen given subcutaneously to male rats significantly enhanced plasma concentrations of adrenocorticotropic hormone (ACTH) and the adrenocortical hormones corticosterone and aldosterone. The goal of the present study was to investigate whether the stimulatory effects on adrenocortical steroids elicited by -baclofen in vivo could be reversed by the selective GABA_B antagonist CGP 35 348. One hour before subcutaneous administration of 3 mg/kg -baclofen, a dose of 600 mg/kg CGP 35 348 or saline was administered intraperitoneally. The stimulatory effect of -baclofen on ACTH, corticosterone and aldosterone was significantly reduced by 60% after pretreatment with CGP 35 348. The GABA_B antagonist CGP 35 348 by itself had no effect on ACTH or the adrenocortical hormones. These results indicate that GABA_B receptors are involved in the -baclofen-induced activation of the HPA axis in rats. In vitro, however, neither -baclofen nor CGP 35 348 had any effects on corticosterone and aldosterone release from perifused adrenal cells. These results suggest that the participation of GABA_B receptors in the activation of the HPA axis induced by -baclofen in vivo does not occur at the level of the adrenal gland, and therefore must occur at the level of the pituitary or the brain.     

Hormones of hypothalamic-pituitary-thyroid axis are significant regulators of synthesis and secretion of vitamin K-dependent plasma coagulation factors

Present data about hormonal regulation of haemostasis are often contradictory and are mostly based on clinical observations. The aim of the current research is to study the effects of the hormones of hypothalamic-pituitary-thyroid (HPT) axis on plasma levels (i.e. on the synthesis and secretion) of vitamin K-dependent coagulation factors in rats. The study was carried out on 65 male Wistar rats, divided into five groups. The animals were injected subcutaneously (s.c.) once daily for three consecutive days as follows: the first group was injected with Thyrotropin releasing hormone (TRH), in a dose of 0.06 mg/kg b.w.; the second group by Thyroid stimulating hormone (TSH), with a dose of 1 MU/kg b.w., the third and the fourth group respectively with Liothyroninum (Triiodothyronin ? T3) and Levothyroxinum (Thyroxin ? T4) with a dose of 0.08 mg/kg b.w. each. The control group rats were injected with saline (the solvent of the hormones), following the same schedule and volume per kg b.w. The necessary quantity of blood was acquired by a cardiac puncture under ether narcosis, and antigen levels of plasma factors II, VII, IX and X (FII:Ag, FVII:Ag, FIX:Ag and FX:Ag) were determined by ELISA kits (Diagnostica Stago, France). TRH, TSH, T3 and T4 significantly decreased the plasma antigen levels of FII and FVII (p<0.001). TRH, T3 and TSH reduced significantly FIX:Ag level( p<0.001 for TRH and T3 and p<0.05 for TSH) while T4 did not exert significant changes ( p>0.05). FX:Ag level was also significantly reduced by TRH, T3 (p<0.001), TSH and T4 (p<0.01). Plasma levels of vitamin K-dependent coagulation factors F??:Ag, FV??:Ag, F?Х:Ag and FХ:Ag are significantly reduced under the influence of the hormones of hypothalamic-pituitary-thyroid axis which signifies their decreased synthesis and secretion. T4 does not induce substantial changes in FIX:Ag plasma level.     

Effect of lithium chloride on the thyroid gland of white rats]

The morphological and functional changes in the thyroid tissue of white rats injected lithium chloride at doses 0.5 mekv/kg and 1.0 mekv/kg (groups 1 and 2, respectively) during three weeks were studied by the radiometric, histological and biochemical methods. The radiometric, histological and biochemical methods. The inhibitory action of lithium chloride on hormonogenesis in the thyroid gland and secretion of thyroid hormones into the blood was proved to be directly related to the lithium dose and concentration in the blood. The data of intravital radiometric and morphological analysis of the organs of the 1st group animals suggest some activization of the gland function, with the secretion of the hormones into the blood being suppressed. Increased concentration of the drug inhibits hormonogenesis and secretion of thyroid hormones into the blood.     

The effect of adrenal cortical hormones on the calcium content of rat aorta.

The administration of prednisone in a dose of 10 mg/kg b.w. per os and of deoxycorticosterone in a dose of 10 mg/kg i.p. to rats weighing 200--220 g 24 hours before the experiment did not affect significantly the calcium content of the aortic vascular tissue. Metopiron, which influences biosynthesis of the adrenal hormones, likewise did not affect the calcium content when administered i.p. in a dose of 500 mg/kg b.w. and did not inhibit reserpine-induced calcium depletion. The results thus failed to confirm the hypothesis that reserpine influences the calcium content of the vascular wall via stimulation of corticold release.     

Selenium altered the levels of lipids, lipid peroxidation, and sulfhydryl groups in straitum and thalamus of rat

The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) on the lipid levels (total lipids, phospholipids, cholesterol, gangliosides), thiobarbituric acid reactive substance (TBARS), and sulfhydryl group (-SH) in the straitum and thalamus of a male Wistar rat was studied after 7 d of treatment. The level of total lipids and cholesterol was significantly and dose-dependently elevated in the straitum and thalamus with 0.1 and 0.2 mg/kg of sodium selenite. However, the cholesterol level was significantly increased only with 0.2 mg/kg of sodium selenite in the thalamus. The level of phospholipids and gangliosides was more significant with 0.1 mg/kg of sodium selenite as compared to 0.2 mg. No significant alteration on the gangliosides level was observed in the thalamus with various doses of sodium selenite although the elevation with 0.2 mg dose was 25.9%. The content of TBARS was elevated dose dependently in straitum, but its level was depleted significantly with 0.1-mg/kg dose of sodium selenite in the thalamus. The level of the -SH group was significantly depleted in the straitum with 0.1-mg/kg dose of sodium selenite; conversely, this dose has significantly elevated the levels of-SH group in the thalamus.     

Effect of selenium on lipids, lipid peroxidation, and sulfhydryl group in neuroendocrine centers of rats

The effects of various doses of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) were studied on the content of phospholipids, cholesterol, esterified fatty acids (EFA), gangliosides, thiobarbituric acid reactive substance (TBARS), and sulfhydryl group in neuroendocrine centers of male Wistar rats for 7 d. The lowest dose of Se (0.05 mg/kg) did not alter the above parameters significantly in neuroendocrine centers. The content of phospholipids was depleted significantly in the pituitary and depletion in the pineal was 80.22% with a 0.1-mg/kg dose of Se, but this dose elevated its level significantly in the hypothalamus. Conversely, a 0.2-mg/kg dose of selenium elevated the level of phospholipids significantly in the pituitary and hypothalamus, the elevation in the pineal was 70%. Selenium, 0.1 mg/kg, elevated the level of cholesterol in the pituitary but depleted its level in the pineal (56.8%) and hypothalamus (13.60%). Selenium, 0.2 mg/kg, elevated the level of cholesterol significantly in the hypothalamus but its level was not significant in the pituitary and pineal. The depletion of esterified fatty acid in the pituitary and pineal with doses of 0.1 and 0.2 mg/kg was significant in the pituitary, whereas its depletion in the pineal was 85.4% and 69.26%, respectively. Selenium, 0.1 and 0.2 mg/kg, depleted the level of gangliosides significantly and dose dependently in the pituitary but has elevated its level significantly and dose dependently in the hypothalamus. Its depletion in the pineal was 87.1% and 67.8% with the 0.1- and 0.2-mg/kg dose of selenium, respectively. Selenium, 0.1 mg/kg, increased the content of TBARS significantly in neuroendocrine centers and its elevation in the pineal was 703.8%. Selenium, 0.2 mg/kg, elevated its level in the pituitary and it was 126.9% in the pineal, but this dose depleted its level significantly in the hypothalamus. The content of the sulfhydryl group with a 0.1-mg/kg dose of selenite was depleted significantly in neuroendocrine centers and it was 55.9% in the pineal. Selenium, 0.2 mg/kg, depleted the level of the sulfhydryl group more significantly in the pituitary and pineal, but its elevation in hypothalamus was significant.     

Secretin, VIP, and PHI stimulate rat proximal duodenal surface epithelial bicarbonate secretion in vivo

The surface epithelial cells of the stomach and duodenum secrete bicarbonate at rest and in response to a number of agonists including the gastrointestinal hormones, glucagon, and GIP. Since those hormones with structural homology may have similar effects, the purpose of the present study was to examine the effect of graded doses (6, 24, and 96 nmol/kg) of pure porcine secretin, VIP, and PHI on bicarbonate secretion by the proximal duodenum containing Brunner's glands. Experiments were performed in vivo on unanesthetized Sprague-Dawley rats with chronic Thiry-Vella type loops of the proximal 2 cm of duodenum. The order of testing was random and only one hormone was tested on a single day. Compared to the saline control, each dose of VIP produced a significant increase in duodenal bicarbonate secretion in a dose-response manner. The two higher doses of secretin and only the 96 nmol/kg dose of PHI significantly increased bicarbonate output. The responses to 96 nmol/kg dose of secretin and VIP were similar, and each was significantly greater than observed with PHI. It is concluded that secretin and VIP stimulate proximal duodenal bicarbonate secretion and are more potent than PHI.     

Somatostatin effect on the level of adenyl nucleotides in the blood and tissues of rats during short-lasting hypothermia

Short-lasting hypothermia during thiobutabarbital general anaesthesia causes no decrease of the absolute ATP level in the blood and liver of rats. The adenylate energy charge in the tissues is relatively high - 0.86 in the liver and 0.85 in the muscles, which might be an evidence of a significant "energy sparing" during moderate hypothermia (26 +/- 1 degree C). Somatostatin in a dose of 20 micrograms/kg of body weight given to the rats during hypothermia decreased the ATP level, the ATP/ADP ratio and the adenylate energy charge in the studied tissues, especially in the liver, evidencing increased intensity of catabolic processes caused by the inhibitory action of somatostatin on the release of insulin and glucagon, among other hormones, and on the change of the insulin/glucagon ratio.     

Ameltolide. I: Developmental toxicology studies of a novel anticonvulsant

Ameltolide, a novel anticonvulsant agent, has been shown in animal models to be effective in controlling seizures. The developmental toxicity of ameltolide was evaluated in two species. Naturally mated rats and rabbits were dosed once daily by gavage on gestation days (GD) 6-17 and 6-18, respectively. Rats were given doses of 0, 10, 25, or 50 mg/kg; rabbits were given 0, 25, 50, or 100 mg/kg. Laparotomy was performed on rats on GD 20 and on rabbits on GD 28. In rats, maternal toxicity was indicated at the 25- and 50-mg/kg dose levels by depressed body weight gain. Fetal body weight was depressed at the 50-mg/kg dose level. Fetal viability and morphology were not affected. The no-observed effect levels (NOEL) for adult and developmental toxicity in the rat were 10 and 25 mg/kg, respectively. In rabbits, maternal toxicity was indicated by a net loss in body weight at the 50- and 100-mg/kg dose levels. Fetal viability and body weight were depressed at the 100 mg/kg dose level. Shortened digits occurred on the right forepaw of one fetus at the 50-mg/kg dose level (in conjunction with severe maternal toxicity) and on the hindpaws of two fetuses from separate litters at the 100-mg/kg dose level. Incomplete ossification of the phalanges occurred on the forepaws of nine fetuses from four litters at the 100-mg/kg dose level. Ameltolide was weakly teratogenic in the rabbit. The NOEL for adult and developmental toxicity in the rabbit was 25 mg/kg.     

Administration of low doses of TSH result in a rapid increase in the metabolic rate of young lambs

A low dose of TSH (Thyroid Stimulating Hormone) can induce a rapid increase in VO2 and the response is dose dependent. Lambs aged 36 to 289 h were used. 5.0 i.u./kg TSH, the highest dose used, caused an initial inhibition of response but during the second and third post injection hours VO2 increased to control level. The intermediate TSH dose, 1.0 i.u./kg TSH resulted in a clear increase in VO2 even in the first post-injection hour, which further increased in the second and third hours. This change was significantly greater than in controls. Animals treated with the lowest dose, 0.5 i.u./kg TSH divided themselves into 2 distinct populations: responders, where an immediate and significant increase in VO2 occurred and non responders, where a small inhibition of metabolism was evident. The responder group had a significantly lower pre-injection VO2 and a significantly lower mean body weight, than the non responders. In the responders, the stimulation of metabolism was greater than at either of the higher TSH doses. These results indicate that low, but not high doses of TSH induce a rapid metabolic response. The argument in favour of a short-term role for thyroid hormones is thus strengthened.     

Short-term influence of 3,5,3'-triiodothyronine infusion on resting metabolic rate of the young pig

The influence of 3,5,3'-triiodothyronine (T3) on resting metabolic rate (RMR) has been examined in the young pig. A dose of 10, 20 or 40 nmol T3/kg body weight was infused intravenously for periods of between one and 4 h and oxygen consumption and activity were measured over the following 20 h. There was no change in RMR during the period of T3 infusion. Results 12-20 h after infusion were influenced neither by the time at which the animal was fed nor by the length of infusion. Immediately after infusion there was a marked increase in plasma T3 concentration, followed by a rapid decline. Levels were much higher than those recorded previously after feeding. Only after 40 nmol T3/kg was there a significant 12% increase in RMR during the period 12-20 h after infusion (P less than 0.02). The significance of these results in relation to the source of the postprandial increase in plasma T3 and the action of thyroid hormones at the cellular level is discussed.     

Selenium-induced alteration of lipids,lipid peroxidation,and thiol group in circadian rhythm centers of rat

The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, ip) on the contents of lipids (phospholipids, cholesterol, esterified fatty acids, gangliosides), thiobarbituric acid reactive substance (TBARS), and thiol group in circadian rhythm centers (preoptic area, brainstem, and posterior hypothalamus) of male Wistar rats was studied after 7 d of treatment. The content of phospholipids was elevated significantly with a dose of 0.1 mg/kg of selenite in the preoptic area and brainstem, but a 0.2-mg/kg dose has depleted its level significantly in these regions. The alteration of phospholipids in posterior hypothalamus was not significant with three doses of sodium selenite. The level of cholesterol in the preoptic area was inhibited significantly with a dose of 0.05 mg/kg sodium selenite, but its level was elevated significantly with a dose of 0.2 mg/kg selenite in the preoptic area and brainstem. Alteration with three doses of sodium selenite in the posterior hypothalamus was not significant. The ganglioside level in the preoptic area and brainstem was elevated significantly with a 0.1-mg dose of sodium selenite; conversely, a 0.2 mg dose of sodium selenite caused a significant depletion on its content in these areas. In the posterior hypothalamus, the ganglioside level was depleted significantly with a dose of 0.1 mg, but elevated significantly with a dose of 0.2 mg of sodium selenite. The level of esterified fatty acids was decreased significantly in the preoptic area and brainstem with a dose of 0.1 mg/kg sodium selenite, but in these regions, its level was elevated with a dose of 0.2 mg/kg sodium selenite and its elevation was significant in the preoptic area. In the posterior hypothalamus, the alteration of esterified fatty acids with three doses of sodium selenite was not significant. The effect of 0.1 and 0.2 mg/kg sodium selenite on the TBARS level and thiol group in sleep centers was significantly opposite to the wakefulness center. A sodium selenite dose of 0.1 mg/kg had depleted the content of TBARS in the preoptic area and brainstem but elevated the content of the thiol group significantly in the posterior hypothalamus. On the other hand, a 0.2-mg/kg dose of sodium selenite has significantly elevated the content of TBARS but depleted the content of the thiol group significantly in the posterior hypothalamus. No dose-dependent alteration was observed on the content of lipids, TBARS, and thiol group in the circadian rhythm centers of rats.     

Influence of yohimbine on release of anterior pituitary hormones

We used a double-blind crossover design to study the effects of alpha 2 adrenoreceptor blockade with yohimbine on levels of anterior pituitary hormones. A dose of yohimbine was used which raised plasma norepinephrine from 379 +/- 74 (S.E.) to 730 +/- 143 pg/ml and mean arterial pressure from 83 +/- 4 to 92 +/- 5 torr (p less than 0.025). This dose (125 micrograms/kg, then 1 microgram/kg/min) also altered mood when compared to saline infusion. In spite of these changes, when prolactin, cortisol, ACTH, beta-endorphin, TSH and growth hormone were measured after 45 minutes of yohimbine infusion, no changes from baseline were noted. These data suggest that in normal man, at rest, alpha 2 adrenoreceptors in the hypothalamus, adenohypophysis or other brain areas do not tonically modulate release of these hormones into the blood.     

An Evaluation of Diazacon as a Potential Contraceptive in Non-Native Rose-Ringed Parakeets

ABSTRACT Rose-ringed parakeets (Psittacula krameri) have become widely established outside their native range through accidental or deliberate release. Potential economic impacts on agriculture, conservation concerns, and mixed public opinion regarding the species have highlighted the need to develop effective but humane management options. Fertility control might provide such a solution if a safe and environmentally benign contraceptive was available. The chemical 20,25-diazacholesterol dihydrochloride (diazacon) has previously been used to reduce reproductive output in avian species through reduction of blood cholesterol and cholesterol-dependent reproductive hormones. We orally dosed captive rose-ringed parakeets with a solution of either 9 mg/kg or 18 mg/kg of diazacon for up to 10 days and found that a dose of 18 mg/kg for 10 days temporarily reduced blood cholesterol levels with no adverse side effects. We evaluated this dose level in a captive population in semi-natural conditions during the 2008 breeding season and found a significant decrease in fertility. We concluded that diazacon has potential for fertility control in this species if a suitable formulation and delivery system is developed for free-living populations.     

Efficacy of Ginkgo biloba on Vaginal Estrous and Ovarian Histological Alterations for Evaluating Anti‐Implantation and Abortifacient Potentials in Albino Female Mice

Ginkgo extract, EGb 761 is known as a vasoregulatory variable for the conventional reproduction therapy. EGb 761 was orally administered in 0 (control), 3.7, 7.4, and 14.8 mg/kg bw/day for 28 days (thereafter mated with normal fertile male), from day 1 to day 7 of pregnancy or from the 10th to 18th day of pregnancy, respectively. Vaginal smears were performed daily. On 20th day of pregnancy, the females were killed by cervical dislocation and their kidneys, liver, brain, placenta, spleen and ovaries were removed and weighed. The ovaries were prepared for histological examinations, and then ovarian follicles were counted. Maternal toxicity, estrous cycle, reproductive hormones, ovarian follicle counts, resorption index, implantation index, fetal viability and fetuses, and placenta mean weights were evaluated. There was a dose‐dependent ovarian toxic effect of EGb 761. Ovarian follicle counts, resorption index, implantation index, fetal viability were significantly reduced in 14.8 mg/kg bw/day dose. Treatment with 14.8 mg/kg bw/day EGb 761 induced disruption of estrous cycle and caused maternal toxicity, in addition to fetal toxicity. Therefore, the data obtained indicate that Ginkgo biloba extract at 14.8 mg/kg bw/day dose level exhibit toxic effect on reproductive cyclicity and could have anti‐implantation and abotifacient properties in female mice.     

Results of an experimental study of the pharmacokinetics of polymyxin B sulfate]

Pharmacokinetics of polymyxin B sulfate of Soviet production was studied in various species of animals with the use of different administration routes and dosage. After a single intramuscular administration of the drug to dogs in doses of 1.1 and 2.2 mg/kg the antibiotic was detected within 5 hours at the maximum level during the 1st hour. A two-fold increase of the dose was accompanied by 1.5 times increase in the antibiotic level. Repeated administrations of polymyxin B sulfate in a dose of 4.5 mg/kg did not result in an increase in the blood level as compared to a single use of the drug. When polymyxin B sulfate was administered intravenously, the concentration peak was observed in 15 minutes independent of the dosage. Later the antibiotic level decreased. The maximum level of the drug in the mice was observed 1 hour after its intramuscular administration in a dose of 8 mg/kg, the highest levels being registered in the kidney tissues and urine.     

Pathophysiological changes in experimental polycystic ovary syndrome in female albino rats: Using either hemin or L-arginine

Polycystic ovary syndrome (PCOS), one of the important endocrine disorders affecting females in the reproductive age, is caused mainly by an abnormal oxidation status that subsequently causes inflammatory conditions. Thus, this study aims to examine the possible individual prophylactic effects of gasotransmitters, hemin, or L-arginine in letrozole-induced PCOS. Fifty adult female albino rats were used and separated into a control group, which received the vehicle; a letrozole-induced PCOS group (L), which received letrozole orally at a dose level of 1 mg/kg for 21 days; a letrozole+hemin (L+H) group, which received letrozole plus hemin at a dose level of 25 mg/kg injected IP twice per week for 21 days; and a letrozole+L-arginine (L+A) group, which received letrozole plus L-arginine at a dose level of 200 mg/kg orally for 21 days. During PCO induction, the body weight and Lee index were measured. Serum glucose, insulin, lipid profile, gonadotrophic hormones, testosterone, estrogen, and tumor necrosis factor alpha were assayed, while ovarian tissues were analyzed to measure the oxidative state and histopathological changes. Our results proved that either hemin or L-arginine administration could improve the oxidative state, the inflammatory reaction, the hormonal imbalance, and the metabolic disturbances in PCO rats, which was confirmed by a histopathological examination of the rats’ ovaries. In conclusion, either hemin or L-arginine had protective effects against PCOS with better pathophysiological changes with hemin.