Effects of obesity and diabesity on heart rhythm in the Zucker rat.

Obesity and type 2 diabetes mellitus are risk factors for hypertension, coronary heart disease, cardiac arrhythmias including atrial fibrillation, heart failure and sudden cardiac death. The effects of obesity and diabesity on heart rhythm were investigated in the Zucker diabetic fatty (ZDF) and Zucker fatty (ZF) compared to the Zucker lean (ZL) control rat. In vivo biotelemetry techniques were used to assess the electrocardiogram and other cardiac and metabolic parameters.

Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist in mice.

The imidazole-based H3R antagonist with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES)-induced convulsions in mice having valproic acid (VPA) as a reference antiepileptic drug (AED). Additionally, H3R antagonist was evaluated for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.

Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide.

Anticonvulsant and procognitive properties of the non-imidazole histamine H3 receptor antagonist DL77 in male adult rats.

It has become clear that histamine H3 receptors (H3Rs) are implicated in modulating epilepsy and memory in laboratory animals. The new non-imidazole H3R antagonist DL77 has excellent selectivity profile and shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 values of 2.1 ± 0.

Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists.

To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic drugs (AEDs), aromatic ether, and diether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in the maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in rats. The anticonvulsive effects of a systemic injection of 1-12 on MES-induced and PTZ-kindled seizures were evaluated against the reference AED phenytoin (PHT) and the structurally related H3R antagonist/inverse agonist pitolisant (PIT). Among the most promising ligands 2, 4, 5, and 11, there was a significant and dose-dependent reduction in the duration of tonic hind limb extension (THLE) in MES-induced seizure subsequent to administration of 4 and 5 [(5, 10, and 15 mg/kg, intraperitoneally (i.

Thromboembolic injury and systemic toxicity induced by nicotine in mice.

Nicotine is involved in the pathogenesis of hematological and cardiopulmonary diseases. The understanding of the pathophysiological mechanisms underlying these undesirable effects is however unclear. Cigarette smoking, nicotine gums and patches are common sources for nicotine ingestion.

Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol.

Ligands targeting central histamine H3 receptors (H3Rs) for epilepsy might be a promising therapeutic approach. Therefore, the previously described and structurally strongly related imidazole-based derivatives belonging to carbamate class with high H3R in vitro affinity, in-vivo antagonist potency, and H3R selectivity profile were investigated on their anticonvulsant activity in maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in Wistar rats. The effects of systemic injection of H3R ligands 1-13 on MES-induced and PTZ-kindled seizures were screened and evaluated against the reference antiepileptic drug (AED) Phenytoin (PHT) and the standard histamine H3R inverse agonist/antagonist Thioperamide (THP) to determine their potential as new antiepileptic drugs.

Acetylcholinesterase inhibitors as pretreatment before acute exposure to organophosphates: assessment using methyl-paraoxon.

Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of organophosphorus compounds (OPCs). The usefulness of pyridostigmine, the only compound approved by the Food and Drug Administration (FDA) for such pretreatment, has been questioned. In search for more efficacious alternatives, we have examined in vivo the efficacy of a group of ten compounds with known anti-AChE activity (pyridostigmine, metoclopramide, tiapride, ranitidine, physostigmine, tacrine, amiloride, methylene blue, 7- methoxytacrine and K-27) to reduce mortality induced by the OPC methyl-paraoxon.

Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined.

Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death.

Heart rhythm disturbances in the neonatal alloxan-induced diabetic rat.

Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. Their electrocardiograms may show several alterations from normal patterns, many of them related to the QT. Various diastolic and systolic abnormalities are frequently reported in diabetic patients, and the severity of the abnormalities depend on the patients' age and the duration of diabetes.

Pretreatment for acute exposure to diisopropylfluorophosphate: in vivo efficacy of various acetylcholinesterase inhibitors.

Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors before exposure to organophosphorus compounds (OPCs) can reduce OPC-induced mortality. Pyridostigmine is the only FDA-approved substance for such use. The AChE-inhibitory activity of known AChE inhibitors was quantified in vitro and their in vivo mortality-reducing efficacy was compared, when given prophylactically before the exposure to the OPC diisopropylfluorophosphate (DFP).

Toxicokinetics of aflatoxin in pregnant mice.

Our objective was to study the toxicokinetics of aflatoxin (AF) in pregnant mice. Aflatoxin B1 (AFB1) was administered intraperitoneally (IP) to groups of pregnant mice in single doses of 20 mg/kg on gestation day (GD) 13 and orally at the same gestational age. Controls received (IP and oral) a proportionate volume of solvent only.

Intrauterine growth restriction and skeletal variations in mouse fetuses induced by vigabatrin administered at preimplantation stages of development.

Epileptic women do not withdraw antiepileptic drug (AED) therapy during pregnancy, therefore, exposure to AED during preimplantation stages might result in considerable embryonic concentrations endangering development. Neither clinical nor experimental research has addressed this important issue adequately. Vigabatrin (VGB), a second generation AED, is both effective and well tolerated as an add-on therapy in epilepsy with partial seizures.

Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat.

The protective effect of Tribulus terrestris in diabetes.

Tribulus terrestris L (TT) is used in the Arabic folk medicine to treat various diseases. The aim of this article was to investigate the protective effects of TT in diabetes mellitus (DM). Diabetes is known to increase reactive oxygen species (ROS) level that subsequently contributes to the pathogenesis of diabetes.

Beneficial effect of supplemental lipoic acid on diabetes-induced pregnancy loss in the mouse.

Uncontrolled diabetes mellitus (DM) is an etiological factor for recurrent pregnancy loss, fetal growth disorders, and major congenital malformations in the offspring. Antioxidant therapy has been advocated to overcome the oxidant-antioxidant disequilibrium inherent in diabetes. The objective of this article was to evaluate the beneficial effects of alpha-lipoic acid (LA) on fetal outcome in a mouse model of streptozotocin (STZ)-induced DM.

Ranitidine in acute high-dose organophosphate exposure in rats: effect of the time-point of administration and comparison with pyridostigmine.

Weak and reversible inhibitors of cholinesterase, when co-administered in large doses, can act in a protective manner against more potent inhibitors such as organophosphates. The clinically widely used histamine type 2 (H2) receptor blocker ranitidine is among H2 blockers the most potent inhibitor of acetylcholinesterase but roughly three to four orders of magnitude less potent than paraoxon (an irreversible organophosphate esterase inhibitor) or pyridostigmine (a reversible carbamate esterase inhibitor). We have previously shown that in vitro ranitidine confers some protection against inhibition of cholinesterases by paraoxon and that in vivo it both increases the number of rats surviving an acute paraoxon exposure and also protects to some degree the cholinesterases from organophosphate inhibition.

Mitochondrial dysmorphology in the neuroepithelium of rat embryos following a single dose of maternal hyperthermia during gestation.

Hyperthermia is teratogenic to human and animal embryos and induces mainly anomalies of the nervous system. However, the teratogenic mechanism is poorly understood. Mammalian embryos are known to switch from anaerobic to aerobic metabolism around the time of neural tube closure.

Estrogen and ghrelin increase number of submucosal urethral and anal canal blood vessels in ovariectomized rats.

Objectives: Urinary and fecal control deteriorates after menopause, but it is not clear whether this is age or hormone related. This study investigates whether administration of estrogen and/or the anti-aging growth hormone-releasing peptide, ghrelin, improves the adverse effects of menopause/aging on urethral and anal canal submucosal blood vessel counts in middle-age rats.

Methods: Female Wistar rats (13 months old) underwent ovariectomy, followed 1 month later by intraperitoneal once-daily administration of 17-beta estradiol (10 microg/kg), ghrelin (2 microg/kg), both hormones, or vehicle (n = 6 in each of four groups) for 42 days.

Ultra-structural morphological abnormalities of the urinary bladder in streptozotocin-induced diabetic female rats.

The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium.

Amelioration of sodium valproate-induced neural tube defects in mouse fetuses by maternal folic acid supplementation during gestation.

Infants of epileptic women treated with valproic acid (VPA) during pregnancy have a higher risk of developing spina bifida than those of the general population. VPA induces exencephaly in experimental animal embryos. But the pathogenetic mechanism remains rather elusive.

Effects of ovariectomy and hormone replacement on collagen and blood vessels of the urethral submucosa of rats.

Collagen and blood vessels of the urethral submucosa of ovariectomized rats were studied following 28 daily subcutaneous injections of 17-beta estradiol (n=6, group 1), medroxy-progesterone acetate (n=6, group 2), both drugs (n=6, group 3) or vehicle (n= 6, control) and after sham surgery without castration or injection (n=6). Investigations included the immunohistochemistry of estrogen and progesterone receptors and collagen fibres, Western blot analysis of collagen types I and III and counting periurethral vessels by light microscopy. Our results showed positive immunostaining with estrogen, progesterone and collagen types I and III in all samples.