Fulltext search in archive

The prophylaxis against microbial airway infections of cystic fibrosis (CF) patients is an emerging application of chicken yolk antibody (IgY), however, no data on the effect of inhaled IgY have been published yet. Rats were daily (for 28 days) exposed to an aerosol of IgY, ovalbumin (OVA), Fab fragment of IgY, or PBS and their serum, bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation signs. There were no marked changes in lung parenchyma, except for an elevated number of alveolar macrophages in the OVA-exposed group. While the administration of OVA or IgY aerosols slightly increased levels of cytokine TNF-α and GRO/KC in BAL fluid, a marked elevation of GM-CSF in serum was observed after the OVA inhalation. The administration of Fab induced expression of IL-1β > IL-18 in serum, in contrast no effect exerted by IgY. Our results suggest that the aerosolized IgY did not cause any deleterious effects in rat lungs.

Leptin down-regulates orexigenic and up-regulates anorexigenic neuropeptide gene expression in hypothalamus. Surgical removal of adipose tissue leads to decrease in circulating leptin concentrations in rats. In the present study, we tested: (a) regulation of neuropeptide gene expression in hypothalamus, (b) food intake, and (c) standard growth rate after removal of adipose tissue in rats. Partial lipectomy caused an approximately 10-fold reduction of subcutaneous, retroperitoneal and epididymal adipose tissue weight (at the end of experiments adipose tissue weight was 1.5 ± 0.9 in lipectomy and 15 ± 3.9 g in control rats; statistically significant). Compared to control rats, the animals subjected to lipectomy presented increased food intake, standard growth rate, and decreased serum leptin concentrations (2.6 ± 0.8 vs. 3.7 ± 1.2 ng/mL in the controls, statistically significant). These changes were associated with approximately twofold increase in neuropeptide Y, threefold increase in agouti-related peptide (orexigenic neuropeptides) and about 50% decrease in pro-opiomelanocortin and cocaine-amphetamine-regulated transcript peptide (anorexigenic neuropeptides) mRNA levels in the hypothalamus. These results suggest that partial lipectomy, leading to a decrease in circulating leptin concentrations, may exert an effect on hypothalamic orexigenic and anorexigenic neuropeptide gene expression, and consequently modulate food intake and standard growth rate in rats.

Natural products with antidiabetic activities provide important sources for the development of new drugs in the treatment of diabetes mellitus. This present work focuses on the antidiabetic activity of a hydro-methanolic (2:3) extract of the sepals of Salmalia malabarica on the blood glucose, the carbohydrade metabolic enzyme, oxidative stress, glycated haemoglobin and transaminase activity in streptozotocin (STZ) induced diabetic rats. Diabetic rats show a significant diminution in the activities of hexokinase, glucose-6-phosphate dehydrogenase and an elevation in the activity of glucose-6-phosphatase in the liver and skeletal muscle. Administration of hydro-methanolic extract of the sepals of Salmalia malabarica to diabetic rats resulted in a significant recovery in the parameters concerned. In the liver and kidney, the activities of catalase (CAT) and peroxidase (Px) were decreased significantly and levels of conjugated diene (CD) and thio-barbituric acid reactive substance (TBARS) were increased significantly in diabetic rats which recovered significantly after administration of hydro-methanolic extract of S. malabarica. Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities which are increased in diabetes were restored by the extract. Glycated haemoglobin (HbA_1C) levels were resettled significantly in the extract treated group compared to the diabetic group. The antidiabetic activity of the extract was supported after a comparison with glibenclamide, a standard antidiabetic drug.

Ocimum sanctum L. (OS) leaves have been shown to have a potential for lipid-lowering action. The present study was conducted to evaluate the anti-hyperlipidaemic ability of the EO extracted from OS leaves in rats fed with a high cholesterol (HC) diet. EO of OS leaves was extracted using the hydrodistillation method and its chemical composition was further determined by GC-MS. The results showed that phenylpropanoid compounds (eugenol and methyl eugenol) were the major components of the EO. There were no significant differences in body weight gain, food intake, and heart weight in all groups of rats. The HC diet apparently raised the serum total cholesterol, LDL-C and atherogenic index without significant effect on serum triglyceride, whereas it decreased the HDL-C level. The EO significantly decreased serum total cholesterol, LDL-C, triglyceride and atherogenic index whereas no significant effect on HDL-C was observed. EO depressed a high level of liver total cholesterol and triglyceride whereas no significant effect on both lipids excreted in faeces was found. It can be concluded that the EO extracted from OS leaves contributes to a lipid-lowering action in HC rats. Its anti-hyperlipidaemic action is predominantly due to the suppression of liver lipid synthesis. Phenylpropanoid compounds, the main composition of EO are possibly responsible for the lipid-lowering effect.

The present study was carried out to investigate the hypoglycaemic effect of S-allyl cysteine (SAC), a garlic component, on some biochemical parameters of STZ induced diabetic rats. STZ induced diabetic rats were treated with SAC at two different doses (100 mg/kg b.w. and 150 mg/kg b.w.) for 45 days. Treatment with SAC significantly decreased the levels of blood glucose, glycosylated hemoglobin, blood urea, serum uric acid, serum creatinine, and diminished activities of pathophysiological enzymes such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). The antihyperglycaemic nature of SAC is also evidenced from the improvement in the levels of plasma insulin and haemoglobin. Further, the results are comparable with glyclazide, an oral standard drug. A 150 mg/kg b.w. dose produced a better effect than a 100 mg dose. Thus, the present findings suggest that SAC may be considered as an effective therapeutic agent for the treatment of diabetes mellitus.

The present study was designed to investigate the antihyperglycaemic effect of ethanolic extract of Cardiospermum halicacabum Linn. (Sapindaceae) leaves on normal and streptozotocin (STZ) diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitonial administration of STZ. The Cardiospermum halicacabum leaf extract (CHE) was administered orally at three different doses to normal and STZ-diabetic rats for 45 days. The diabetic rats showed an increase in levels of blood glucose and glycosylated haemoglobin (HbA_1c) and a decrease in the levels of insulin and haemoglobin (Hb). In addition, diabetic rats showed a significant reduction in the activity of glucokinase and an elevation in the activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1, 6-bisphosphatase. Treatment with CHE significantly decreased plasma glucose and HbA_1c, and increased the levels of insulin and Hb. CHE administration to diabetic rats reversed these enzyme activities in a significant manner. Thus, the results show that CHE possesses an antihyperglycaemic activity and provide evidence for its traditional usage in the control of diabetes. The 200 mg dose of the extract produced a better effect than 50 or 100 mg doses.

The present study investigated the effect of the aqueous extract of Helicteres isora L. (Sterculiaceae) bark on oxidative stress in the heart of rats during diabetes. The aqueous extract of Helicteres isora bark (100 mg, 200 mg/kg body weight, b.w.) was screened for its antioxidant effect in streptozotocin (STZ) induced diabetic rats. An appreciable decrease in peroxidation products, thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and hydroperoxides (HP) was observed in the heart tissues of Helicteres isora (HI) treated diabetic rats. The decreased activities of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-tranferase (GST) and glutathione (GSH) in diabetic rats were brought back to near normal range upon HI treatment. Tolbutamide was used as the standard reference drug. These results suggest that HI possesses promising antioxidative activity in STZ diabetic rats.

This study was designed to evaluate the effect of Terminalia chebula fruit extract on the levels of plasma and tissue glycoprotein components in streptozotocin-induced-diabetic rats. Oral administration of T. chebula fruit extract at a concentration of 200 mg/kg body weight for 30 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as fucose, hexose, hexosamine and sialic acid in the diabetic rats treated with the fruit extract. The observed decrease in the levels of plasma insulin and C-peptide in the diabetic rats was elevated to near normal by T. chebula fruit extract treatment. Histological observations made on the pancreatic tissue of control and experimental groups also revealed the beneficial effect of T. chebula fruit extract. The efficacy of the fruit extract was comparable with glibenclamide, a known hypoglycaemic drug.

The most physiological processes that take place in the body have a circadian rhythm which is controlled by an internal biological clock located in the suprachiasmatic nucleus. The indole melatonin synthesized in the pineal gland, acts to synchronize these biological rhythms, and also it is synthesized and released following a circadian rhythm. The present study analyzed the levels of melatonin over a 24-hour period in Wistar rats in both basal and control conditions and after the oral administration of 125 mg/kg tryptophan, the amino acid that is the precursor of this indole, for 7 days. The levels of melatonin in the plasma and the pineal gland were measured by radioimmunoassay every hour during the night, and every 4 hours during the day. The results indicated that the tryptophan administration provoked raised levels of melatonin at all hours studied in both plasma and pineal. Of the chronobiological parameters studied, there were also increases in the values of the melatonin MESOR with respect to the values obtained in the basal and control groups (the respective increases being 45% and 52% in plasma, and 46% and 47% in the pineal), as well as an advanced acrophase with respect to the basal and control groups. In summary, our findings confirm that tryptophan intake one hour before lights-off increases melatonin levels in plasma and pineal over a 24-hour period, as well as advancing the peak of its synthesis.

Phytochemicals in fruits, vegetables, spices and traditional herbal medicinal plants have been found to play a protective role against many human chronic diseases including cancer and cardiovascular diseases. These diseases are associated with oxidative stress caused by excess of free radicals and other reactive oxygen species. Fractions rich in flavonoids obtained from S. hispida seeds were orally administered at three different doses of 20, 40 and 80 mg/kg BW to HFD fed rats. The antioxidant activity of a flavonoid-rich fraction was measured both in vitro and in vivo. The flavonoid-rich fraction effectively scavenged DPPH^* and ABTS^*+ radicals in vitro. Further, the results showed elevated activities of free radical-scavenging enzymes (SOD, CAT and GPx) and increased levels of non-enzymic antioxidants (GSH, vitamins C and E). TBARS and lipid hydroperoxides decreased significantly in flavonoid-rich fraction treated rats compared to HFD control. Among the doses used, 40 mg/kg BW dose showed maximum effect. Thus, the results indicate that a S. hispida seed flavonoid-rich fraction possesses free radical scavenging and antioxidant activity both in vitro and in vivo.

This study aimed to examine the effects of short and long term exposures to 81 mG EMF intensity. It focused on the roles of ROS, Ca²⁺ and calcium channel blocker (CCB) on the rat brain. Rats were exposed to 81 mG EMF intensity at the mobile phone base station for one and four weeks (2 hr/day, EMF exposed group). Another group of rats was pretreated with CCB (amlodipine 20 mg/kg) for four weeks and similarly exposed to EMF (EMF + amlodipine group). Sham exposed and amlodipine control groups were used. At the end of the study, Ca²⁺ as well as pro-inflammatory and oxidative stress markers were measured. Immunohistochemical staining for Bax in brain samples was carried out. Short term exposure evoked a cellular adaptation response. This was evident by a transient increase in brain levels of Ca²⁺, glutathione (GSH) and serum tumor necrosis factor alpha (TNFα). Long term exposure to EMF was lethal; progressive oxidative damage, and a prolonged increase in the Ca²⁺ level accompanied by a marked pro-inflammatory reaction (TNFα and CRP) were demonstrated. These alterations were ameliorated by pre- and con-comitant treatment with amlodipine. Furthermore, it restored the EMF induced apoptosis in brain to near normal. In conclusion, EMF is a stressor agent that induces an imbalance between ROS generation and antioxidant defense response. Calcium ions may play a pivotal role in enhancing oxidative stress, pro-inflammatory reactions and apoptosis associated with EMF exposure. Therefore calcium channel blockade seems to play a role in brain protection.

Oxime K203 is a new compound designed to be used as an acetylcholinesterase reactivator for the treatment of intoxication following exposure to tabun and certain pesticides. After intramuscular administration of a therapeutic (23 mg/kg) dose, the time-course of plasma concentrations of K203 in rats was determined by HPLC. Maximum concentrations were reached between 40 and 60 min (16.5±2.1 μg/ml in 40 min and 16.6±2.0 in 60 min, respectively) with the concentration being relatively constant during this period. There was no significant effect on the plasma concentration of thiobarbituric acid reactive substances (TBARS) during the administration of K203, indicating an absence of oxidative stress. Indeed, administration of K203 led to a significant increase in low molecular weight antioxidants which could tentatively be interpreted as representing a beneficial effect.

The purpose of our study was to examine the early expression of p21 and activated transcription factors ATF-2, CREB, Elk-1, p53 after soman and VX poisoning, to throw light on the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman (60 μg.kg^-1 - 70% LD₅₀) or VX (8 μg.kg^-1 - 70% LD₅₀). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-ATF-2^Thr-69/71, phospho-CREB^Ser-133, phospho-Elk-1^Ser-383, phospho-p53^Ser-15, and protein p21 expressions were measured using computer Image analysis in apical and cryptal enterocytes of the colon transversum. After soman poisoning, we observed an increased phospho-CREB in cryptal enterocytes 4, 24, and 72 h after poisoning, while apical enterocytes expressed increased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and 24 h after soman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were not changed 4, 24, and 72 h after soman poisoning. VX poisoning did not change any of measured parameters. Soman and VX showed a different effect on cellular signalling. Soman seems to cause additional effects, which are not related to the basic mechanism of nerve agent-induced toxicity and which temporarily suppress promitotic pathways of proliferating cells and persist in cells during the differentiation process.

Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than curcumin. The aim of this study was to evaluate the effect of THC on the blood glucose, plasma insulin and fatty acid composition of the total lipids in the liver, kidney and brain of control and streptozotocin (STZ)-nicotinamide diabetic rats. The analysis of fatty acids showed that there was a significant increase in the concentrations of palmitic acid (16:1), stearic acid (18:0) and oleic acid (18:1) in the liver, kidney and brain, whereas the concentrations of linolenic acid (18:3) and arachidonic acid (20:4) were significantly decreased. Oral administration of the THC (80 mg/kg body weight) for 45 days to diabetic rats decreased the concentrations of fatty acids, viz., palmitic, stearic, and oleic acid, whereas linolenic and arachidonic acid were elevated. These results suggest that THC exhibits antidiabetic and antihyperlipidemic effects in STZ-nicotinamide induced diabetic rats. It also prevents the fatty acid changes produced during diabetes. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose. The results of the present study indicate that THC showed an antihyperlipidemic effect in addition to its antidiabetic effect in type 2 diabetic rats.

The present investigation shows the antihyperglycaemic activity of aqueous extract of bark of Helicteres isora L. (100, 200 mg/kg b.w./p.o.) in streptozotocin (STZ) induced diabetic rats. Blood glucose levels, body weight, food and liquid intake were measured on every 5^th day over a period of 14 days. A single injection of STZ at a dose of 60 mg/kg b.w./i.p. elevated the glucose levels >240mg/dl after 5 days. Administration of H. isora at a dose of 100, 200 mg/kg/p.o. resulted in a significant (p

Impaired daily rhythms in vertebrate physiology occur with age. Particularly, age-related changes in melatonin and serotonin rhythms and hypercortisolemia have been reported to be linked to age-related disorders. This study was aimed at assessing the effect of a Jerte Valley cherry-based nutraceutical product (patent no ES 2342141 B1), which contains high levels of tryptophan, serotonin, and melatonin, on the serum melatonin, serotonin, corticosterone, and total antioxidant capacity (TAC) levels in young and old ring doves (Streptopelia risoria) and rats (Rattus norvegicus) as representatives of animals with diurnal and nocturnal habits, respectively. The animals consumed the cherry product for 10 days. Serum melatonin, serotonin, corticosterone, and TAC were measured with commercial ELISA kits. The consumption of the cherry product induced a significant increase in the circulating levels of melatonin and serotonin, as well as in the serum TAC and a significant decrease in the circulating levels of corticosterone in both species and groups of age as compared to their respective values in the control groups. The consumption of a Jerte Valley cherry-based nutraceutical product may help to counteract the decrease in melatonin and serotonin and the increase in oxidative stress, suggesting a potential health benefit especially in aged populations where these parameters have been found to be altered.

In the present investigation, we studied the effect of aqueous green tea extract (GTE), alcoholic turmeric extract (ATE), and water-soluble Chitosan (WSC), individually/or in mixture, on the testicular tissue content of total cholesterol (TC), triglycerides (TG), phospholipids (PL), and thiobarbituric acid reactive substance (TBARS), in addition to nitric oxide (NO) in obese rats.
The testicular weight of the obese rats was increased more significantly than control; TC, TG, PL, TBARS and NO were significantly higher in the obese group. GTE reduced testicular weight and significantly reduced other estimated parameter. ATE significantly increased testicular weight, with apparent peritesticular vascular congestion. It significantly decreased all other studied parameters. WSC significantly increased testicular weight, with significant reduction of all other parameters. The mixture of the three drugs non-significantly decreased testicular weight, and significantly decreased other parameters, except NO, which was significantly more elevated than the obese control. We concluded that obesity induced a significant increase in testicular weight, in addition to TC, TG, PL, TBARS and NO, in comparison to the normal control subjects. An efficient protection against obesity-induced changes was achieved by each individual drug, while the mixture of GTE, ATE and WSC showed less protective potential than each individual drug.We here recommend the use of GTE, ATE in treating obesity-related testicular dysfunction and suggest that attention should be paid to the possible effect of WSC on the bioavailability of other concomitantly-used drugs and suggest a pertinent clinical benefit of both GTE and ATE.

Oxidative stress may cause free radical reactions to produce deleterious modifications in membranes, proteins, enzymes and DNA. Valproic acid is a major anti-epileptic drug with a broad spectrum of anti-epileptic activity. Chronic treatment with valproic acid can lead to elevated serum ammonia levels and specific oxidative metabolites of valproic acid have been associated with the drug's toxicity. The influence of sodium valproate treatment on lipid peroxidation and lipid profiles and the detoxifying effects of α-ketoglutarate on sodium valproate induced toxicity were studied in rats. The levels of thiobarbituric acid reactive substances, hydroperoxides and lipid profile variables (cholesterol, phospholipids, triglycerides and free fatty acids) were significantly increased in sodium valproate treated rats. Further, non-enzymic antioxidants (reduced glutathione) and the activities of the enzymic (superoxide dismutase, catalase, glutathione peroxidase) antioxidants were significantly decreased in sodium valproate treated rats. The levels were observed to be normal in α-KG + sodium valproate treated rats. These biochemical alterations during α-KG treatment could be due to (i) its ubiquitous collection of amino groups in body tissues, (ii) the participation of α-KG in non-enzymatic oxidative decarboxylation of the hydrogen peroxide decomposition process and (iii) its role in the metabolism of fats which could suppress oxygen radical generation and thus prevent lipid peroxidative damage.

Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) is one of the highly toxic organophosphorus compounds misused as chemical warfare agents for military as well as terroristic purposes. It differs from other highly toxic organophosphates in its chemical structure and by the fact that the commonly used antidotes (atropine in combination with an oxime) are not able to sufficiently eliminate its acute toxic effects.
The neuroprotective effects of the newly developed oximes (K027, K048) or trimedoxime in combination with atropine (atropine, K027/atropine, K048/atropine and trimedoxime/atropine mixtures) on rats poisoned with tabun at a lethal dose (270 mg/kg i.m.; 120% of LD₅₀ value) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automaticmeasurement of motor activity. The neurotoxicity of tabun was monitored at 24 hours and 7 days following tabun challenge. The results indicate that atropine alone is not able to protect rats from the lethal effects of tabun. Five non-treated tabun-poisoned rats and five tabun-poisoned rat treated with atropine alone died within 24 hours. On the other hand, atropine combined with all tested oximes allows most tabun-poisoned rats to survive within 7 days following tabun challenge. All three oximes tested combined with atropine seem to be sufficiently effective antidotes for a decrease in tabun-induced neurotoxicity in the case of lethal poisonings, although they are not able to eliminate tabun-induced neurotoxicity completely. Due to their neuroprotective effects, all the tested oximes appear to be more suitable oximes for the antidotal treatment of acute tabun exposure than the currently used oximes (pralidoxime, obidoxime, HI-6).

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. The present study investigated the effect of EMS and Metformin on dearrangement in glycoprotein levels in the streptozotocin-nicotinamide induced type 2 diabeteic model. Succinic acid monoethyl ester was administered intraperitoneally for 30 days to normal and diabetic rats. The effect of EMS on glucose, insulin, and plasma and tissue glycoproteins were studied. The effect of EMS was compared with Metformin, a reference drug. The levels of glucose, glycosylated haemoglobin and plasma glycoproteins containing hexose, hexosamine and fucose were increased significantly whereas the level of plasma insulin and haemoglobin were decreased significantly in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats was followed by a decreased level of glucose, glycosylated haemoglobin and plasma glycoproteins. The levels of plasma insulin, haemoglobin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that the EMS possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect.

Standard haematological procedures in preclinical subchronic and chronic toxicity studies are carried out on dogs, rats and other mammals. In vitro clonic assays CFU-GM, BFU-E, CFU-E, CFU-Mgkr and pluripotent stem cells are used in screening candidate compounds to predict acute cytopenias, but they are not able to reveal the risk of suppression which can develop after repeated administration. No in silico studies have yet been published in haematotoxicology. More recent haematotoxicological in vivo models represent invertebrates: they can be used in both ecotoxicology and in the screening of myelotoxicity.

We studied the influence of physical activity stress on the circadian rhythms of melatonin and corticosterone in 3-month old male Wistar rats. Every two hours for 24 h around the clock, an animal from the stressed group was first made to swim for two hours, and was then subjected to a further ten minutes of forced swimming using a modification of the apparatus employed in the Porsolt test. The capacity to resume swimming after the exhausting 2-hour swim was measured by the number of swimming movements that were made by the animal in the additional 10-min swimming period. Blood was collected immediately after the trial, and the plasma melatonin and corticosterone levels determined by RIA. Control group blood was collected at 1-h intervals in the periods from 22:00 to 06:00 and from 16:00 to 18:00, and at 2-h intervals during the remaining periods. The control rats presented plasma melatonin and corticosterone circadian rhythms with nocturnal (02:00) and diurnal (17:00) maxima, respectively. The pattern of these rhythms in the stressed rats was flatter, and the animals tested during hours of the night presented greater endurance than those tested during daytime hours. This suggests that, in evaluating an animal's response to stress, it is important to take into account the co-ordination between the time of day when the physical stressing test is applied and the natural sleep/activity periods of the study species.

The radioprotective substances amifostine (WR-2721) and cystamine were tested in rats following their parenteral administration (i.p., i.m., and i.v.). Cystamine is more toxic than amifostine in mice as well as in rats. Amifostine was less toxic after intravenous injection. The radioprotective effects of WR-2721 (160 mg.kg^-1) and cystamine (40 mg.kg^-1) were not significant when they were administered parenterally 15 - 20 mins before lethal doses of whole body fission neutron irradiation in the thermal column of reactor VVR-S and 30-days lethality served as an integral criterion of postradiation injury to the rat body. The fission neutrons spectrum was characterized by mean energy 0.9-1.0 MeV with 30-40% fluency participation of moderate (E=0.1 MeV) neutrons. The contamination with gamma rays was 22-30 %; the dose rate of whole irradiation was within 0.3 to 0.8 Gy.min^-1.

Studies have shown that S-nitrosothiols (RSNOs) are able to affect glucose metabolism and blood pressure in animal models. This paper describes an investigation into the effect of two RSNOs, S-nitrosocaptopril (CapSNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) on fasting and postprandial blood glucose concentration, and systolic and diastolic blood pressures. Rats administered intravenously with CapSNO and SNAP, using dosages of 2.0, 5.0 and 12.5 mg/kg BW, showed a dose-dependent hyperglycaemic effect. Intravenous administration of 12.5 mg/kg BW of CapSNO and SNAP caused a statistically significant increase in fasting blood glucose concentration compared to rats treated with the same dosage of captopril. SNAP-treated rats showed a significantly greater elevation of fasting (F2) blood glucose concentration (5.91 ± 0.27 mmol/l) compared to CapSNO-treated rats (5.11 ± 0.08 mmol/l. However there was no significant difference in postprandial blood glucose concentrations. SNAP, CapSNO and captopril significantly reduced both systolic and diastolic blood pressures. This was accompanied by an increase in heart rate. The anti-hypertensive property of CapSNO and SNAP was more significant than that of captopril. CapSNO was more potent than SNAP in reducing blood pressure, suggesting that CapSNO may act via a combined mechanism that involves ACE inhibition and NO release.

We studied the influence of four methods of euthanasia (decapitation, exsanguination via cardiocentesis following ether anaesthesia, Nembutal anaesthesia, or immersion in a CO₂ atmosphere) on the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the brain and in the blood of mature female rats. A significant decrease was observed in the activity of AChE in the whole blood in the group treated with Nembutal. There were no significant changes in the activity of BChE with any method of euthanasia. Euthanasia in a CO₂ atmosphere was the best technique with respect to the results indicating lack of affect on the activity of AChE and BChE in the periphery and the brain, as well as from the point of view of the welfare of the animals.

The protective and anticonvulsive efficacy of two prophylactic mixtures (PANPAL consisting of pyridostigmine, benactyzine, and trihexyphenidyle and pyridostigmine plus biperiden) administered prior to the administration of soman in a lethal dose (1.5 LD₅₀) with or without antidotal treatment (atropine + HI-6) was evaluated using rats as experimental animals. The pretreatment was applied 30 and 60 min before intoxication and the antidotal therapy was administered 1 min after soman poisoning. The anticonvulsive efficacy of both prophylactic combinations was determined using a seven degree scale. Non-treated soman-poisoned rats died within 10 min after soman challenge showing severe tremor, subconvulsions and generalized convulsions. More than 90% of pretreated animals survived for 24 hrs following soman poisoning and they were observed to be free from soman-induced toxic signs 24 hrs after soman administration. Our findings confirm that both prophylactic mixtures are able not only to protect experimental animals from the lethal effects of soman but also to eliminate most soman-induced toxic signs. Our results confirm that both prophylactic mixtures should be considered as a pretreatment for nerve agent poisoning, especially in the case of the threat of exposure to soman.

Our research group has previously studied the role of melatonin in the immune system of birds and mice, finding that incubation with both pharmacological and physiological doses of melatonin augmented the activity of phagocytes from these animals, and that this activity was lowered in pinealectomized animals. Since melatonin is synthesized from the amino acid tryptophan, the aim of the present work was to determine whether the administration of tryptophan might affect the plasma levels of melatonin and the phagocytic activity of peritoneal macrophages over the course of a circadian cycle. The study animals were 14-week-old male Wistar rats. They were administered tryptophan orally in a daily single dose of 125 mg/kg at 19:00 h for 21 days. Prior to beginning this treatment, the circadian rhythms of plasma melatonin and phagocytic activity were evaluated under basal conditions over a 24-h period, taking blood and cell suspension samples each 2 hours during the light period (08:00-20:00) and each hour during the dark period (20:00-08:00), since it is during this latter period that the secretion of melatonin is maximum. The results showed that, under basal conditions, the rats' plasma melatonin levels and phagocytic activity peaked at 02:00. After the tryptophan administration, there were increases in plasma melatonin levels with respect to basal and control-group values, with a peak at 21:00, and in the phagocytic activity of the peritoneal macrophages, which peaked at 02:00. This suggests that the tryptophan administration stimulated melatonin synthesis, leading to increased and earlier peaking plasma levels of this hormone, and augmented the innate immune response carried out by the peritoneal macrophages as a result of the immunoregulatory action of melatonin.

Hyperlipidaemia is one of the major risk factors of cardiovascular complication in diabetes. A study was undertaken to evaluate the antihyperlipidaemic activity of pterostilbene. Oral administration of pterostilbene (40mg/kg bodyweight) to streptozotocin-nicotinamide induced diabetic rats for 6 weeks significantly reduced the elevated serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL)-cholesterol levels and significantly increased the serum high-density lipoprotein (HDL)-cholesterol level. In addition, pterostilbene also significantly lowered the levels of triglycerides, phospholipids, free fatty acids and total cholesterol in the serum, liver and kidney of diabetic rats.

A significant aspermatogenic activity, ascertained by microscopic studies of seminiferous tubules and interstitial tissue, and by the observation of the entrance of immunity and fibrocytic cells in mice injected with polyspermine (PS) or polyspermine conjugated to monomeric or dimeric RNase A (PS-RNase A or PS-dimeric RNase A, respectively), was found either in mice injected or in non-injected testes. Polyspermine and its complexes with RNase A destroyed all spermatogenic and intertestitial tissue, including Leydic cells, as well as their ability to secrete testosterone. The total loss of spermatogenic activity in injected testes is irreversible because spermatogonia cells also were destroyed. The injection of PS into both mice testes determined the total degeneration of testicle tissue in 50% of injected testes. The second half of testes was also partly degenerated, and if they were re-injected, almost all testes were fully destroyed. PS-dimeric RNase A injected once into both testicles produced a stronger degeneration and also the interruption of testosterone secretion in comparison with the effects due to injection of mice with PS or PS-RNase A. In all mice treated with these substances, as well as in rats in which PS was injected twice into their testes, we detected polymorfonucleates, monocytes, plasma cells, lymphocytes and fibrocytic cells. Antibodies against PS, PS-RNase A or PS-dimeric RNase A did not influence the aspermatogenic activity. Animals in which a repeated intra-peritoneal injection was carried out did not lose body mass and remained in good condition, with the exception of mice injected with spermine.

Hibiscus sabdariffa (Linn) (family Malvaceae), is an annual dicotyledonous herbaceous shrub plant popularly known as 'Gongura' in Hindi or 'Pulicha keerai' in Tamil, which is an indigenous edible medicinal plant used in Ayurvedic Medicine in India, China and Thailand. We have investigated the influence of Hibiscus sabdariffa leaf extract (HSEt) on the levels of circulatory ammonia, urea, lipid peroxidation products such as TBARS (thiobarbituric acid and reactive substances), HP (hydroperoxides) and liver marker enzymes such as AST (aspartate transaminase), ALT (alanine transaminase) and ALP (alkaline phosphatase), for its hepatoprotective effect in ammonium chloride induced hyperammonemia. Ammonium chloride treated rats showed a significant increase in the levels of circulatory ammonia, urea, AST, ALT, ALP, TBARS and HP. These changes were significantly decreased in rats treated with HSEt and ammonium chloride. Our results indicate that HSEt offers hepatoprotection by influencing the levels of lipid peroxidation products and liver markers in experimental hyperammonemia and this could be due to its free radical scavenging property and the presence of natural antioxidants. The exact mechanism has to be still investigated and the isolation of active constituents is required.