Physiology and Pharmacology
Year:2004 | Volume:8 | Issue:1|Papers Count:15

Middle cerebral artery occlusion (MCAO) is the most common cause of focal cerebral ischemia (FCI) in mankind. Experimental induction of MCAO in animals can elucidate the role of neural substances released from damaged cells of the infarct region and to evaluate drug interactions for reducing the infarct volume. For this purpose, focal cerebral ischemia was produced in 21 male rats weighing 300-400 g. The rats were anesthetized using chloral hydrate (400 mg/kg, i.p.). After performing a general surgical operation, right common carotid artery was exposed up to its bifurcation to external and internal arteries. Then, a 90-min MCAO was achieved by advancing a nylon thread via internal carotid artery up to the level of middle cerebral artery, followed by reperfusion. After 24 h, standard neurological examinations (NS) were performed. Finally, the animals were decapitated to remove the brains and prepare them for the measurement of infarct volume using histological techniques and microscopic evaluation. The results of this study indicated that MCAO intraluminal technique induces a consistent focal cerebral ischemia in the rat, and hence, can be used as a reliable technique to investigate the neurotoxic and neuroprotective actions of chemical substances released from damaged cells from the ischemic regions of damaged brains, and to analyze the involved pathophysiological mechanisms after reperfusion.

Several non-sexual behaviors depend on the gender and phases of the estrous cycle of the rat. In this research study, the effect of different phases of the estrous cycle, ovariectomy, and estradiol treatment on the passive avoidance learning was evaluated in female nits. For this purpose, virgin female Wistar rats weighing 180-230 g were used. The experiments were performed on two groups of rats. With normal estrous cycles and/or ovariectomized ones. For assessment of learning and memory, passive avoidance learning (PAL) paradigm was used.The results indicated that although conditioned avoidance response is facilitated at diestrous and diminished at proestrous phases, but the observed difference was not significant (p>0.05). Meanwhile, ovariectomy significantly enhanced step-through latency (STL) in retention step as compared to the sham-operated female rats (p<0.001), and daily treatment with estradiol benzoate (EB, 10 µg) for 3 consecutive days decreased the response as compared to ovariectomized rats (p<0.001).In conclusion, these findings indicated that ovariectomy could enhance passive avoidance conditioning response and this is abolished by daily injection of estradiol to ovariectomized animals. Therefore, it seems that the effect of endogenous estradiol on passive avoidance learning may be inhibitory, rather than facilitatory, as it has been postulated by other investigators.

It has been shown that swimming stress and glucocorticoid injection significantly decrease the withdrawal syndrome signs of opioids in mice. In the current study, the effect of restraint stress on withdrawal syndrome signs was investigated in morphine-dependent mice. The experimental strategy of this study was performed on four groups of randomly divided rats;i.e., group A, which received normal saline (negative control), group B receiving morphine (positive control), group C, which received morphine after stress, and group D, which received morphine and stress at the same time. Animals in groups C and D were kept in restrainer for 7 consecutive days (4h/day). Data were subjected to the t test and one-way ANOVA and followed by Tukey test for multiple comparisons. The results showed that a significant reduction in stool weight occur in group D (0.48 ± 0.12 g) in comparison with group B (1.14 ±.0.23 g) respectively (p<0.05). However, no significant change in stool weight was observed comparing groups B and C. In addition, no significant change was observed in the number of jumping among groups B, C, and D.It can be concluded that restraint stress exerts short-term inhibitory effect on morphine action in gastrointestinal tract. The mechanism (s) underling this phenomenon remains to be elucidated.

Considering the widespread application of medicinal plants for the treatment of human illnesses with lower side effects in comparison with currently used medicines, this filed has been the subject of many research studies around the world. This study was conducted to evaluate the possible effect of Humulus lupulus L. hydroalcoholic extract on the hormonal system of hypophyseal-gonadal axis of adult male Balb/C mice (250 g). After extract preparation, its lethal dose was determined as 1800 mg/Kg. Thereafter the effective doses 80, 180, 280, 380, and 480 mg/Kg were used in this study. The extract was administered intraperitoneally once a day for one month. The control group received no treatment. After the last injection of the extract, serum samples were obtained for hormone assay of hypophyseal-gonadal axis.The results showed that only the levels of LH and testosterone in this axis significantly decrease with no significant change for FSH. This reduction can be attributed to the presence of some phytoestrogenic compounds in the extract including 8-prenylnaringenine. In this respect, it may be claimed that long-term administration of the extract increases the plasma level of. estrogen and in this way affect the performance of hypophyseal-gonadal axis. In addition, the extract could reduce the release of LH from adenohypophysis through a negative feedback mechanism, and in this way may lead to reduced release of testosterone from testis.

Nerve growth factor (NGF) plays an essential role in survival and differentiation of somatic motor and sensory, and sympathetic neurons. NGF is synthesized and released from the central nervous system and with a lower amount from peripheral cells. After discovering neurotrophins and, especially NGF, it has been tried to treat neuronal damages using exogenous neurotrophins. The non-amine catechol compound 4-methylcatechol (4-MC) is one of the potent stimulators of nerve growth factor synthesis in fibroblasts and astrocytes in the rat. In addition, administration of 4-MC after sciatic nerve injury enhances regeneration of non-myelinated and myelinated axons in rats.In this research study, 24 adult male rats weighing 200-250 g in three groups were used.First group left untreated and second group received daily injection of 4-MC (150 µg/Kg) intraperitoneally for 8 weeks after ligation. The third (control) group received daily intraperitoneal injection of PBS. Behavioral tests including evaluation of spontaneous behavior, responses to pressure and thermal (warm water at a temperature of 42 ˚C) stimulation, acetone test, and grasping and placing reflexes were examined. All behavioral tests were carried out on days 7, 14, 21, 28, 42, and 56.It is concluded that administration of 4-MC could attenuate the mechanical and thermal allodynia and thermal hyperalgesia and lead to recovery of motor reflex in this peripheral neuropathic model.

Diagonal band of Broca (DBB) is part of the limbic system with involvement in cardiovascular regulation. It has recently been shown that microinjection of L-glutamate into horizontal limb of this region (hDB) elicits cardiovascular depressive responses. This area also contains a large population of GABAergic neurons. In this research study, the cardiovascular responses elicited by glutamate and GABA (GABAA receptor) systems of hDB were evaluated. Experiments were performed on 36 anesthetized and artificially ventilated rats. Drugs were microinjected into hDB at a volume of 50 nl. Blood pressure and heart rate were recorded before and at different time points after each experiment. The average changes in the mean arterial pressure and heart rate at different intervals were compared using Repeated Measures ANOVA.The results showed that microinjection of 50 nl of L-glutamate (0.25 M) into hDB decrease mean arterial pressure (24.4±3.7 mmHg) and heart rate (25.2±3.8 bpm). In addition, injection of AP5 (1 and 5 mM) as an antagonist of glutamate NMDA receptors and CNQX (0.5 and ImM) as an antagonist of glutamate AMPA receptors had no significant effect on the mean arterial pressure and heart rate. On the other hand, microinjection of GABAA receptor antagonist bicuculline (1 nmM) increased both the mean arterial pressure and heart rate (p<0.01), and musimol as a GABAA agonist (500 pM) significantly decreased both mean arterial pressure and heart rate (p<0.01).These results demonstrated that stimulation of the glutamatergic system leads to a reduction in blood pressure and heart rate, which was similar to previous findings, while inhibition of NMDA and AMPA receptors has no significant effect on these parameters.Furthermore, stimulation of GABAA receptors could reduce blood pressure and heart rate and their inhibition is accompanied with a rise in these parameters.

Reestablishment of blood perfusion to ischemic tissues paradoxically results in further tissue injury, which is called ischemic-reperfusion (IR) injury. Injurious factors are reactive oxygen species (ROS) and among them hydroxyl radical (OH) is the most dangerous. Aromatic cycle trapping of hydroxyl radical and detection of hydroxylated metabolites. With high performance liquid chromatography and electrochemical detectors (HPLC-ECD) has been known to be the most sensitive method of ROS detection. Efficacy assessment of intravenous injection of aromatic cycles via this method and estimation of the effect of metabolic pathways in production of these metabolites were the most important goals of this research study. Since redox active metals including Fe and Cu and non-redox active metals like Zn have important roles in production or inhibition of ROS production, therefore, assessment of plasma changes of Cu and Zn concentration during reperfusion was another purpose of this research. For this purpose, bilateral IR of rat kidney pedicles was conducted. Rate of salicylate trapping of OH and production of dihydroxy benzoic acids (DHBA) as indices of OH production was measured. Therefore, plasma concentration of Cu and Zn were measured using atomic absorption spectrophotometer 30 and 90 minutes after reperfusion. Renal injury was confirmed by measurements of plasma creatinine concentration before and 24 hours after reperfusion. Data analysis using ANOVA test indicated that renal IR significantly increased OH production after reperfusion and OH causes renal nephrotubular injury.This research showed that intravenous injection of sodium salicylate and measurement of its hydroxylated metabolite can be considered as a reliable method for measurement of hydroxyl radical production during reperfusion. The time-dependent pattern as observed in this research together with estimation of metabolic production rate of 2,5 DHBA may induce the idea for using it for the measurement of hydroxyl radical production. Also, this study implied that reperfusion after 1 hour bilateral renal ischemia does not change plasma Zn and Cu concentration.

Approximately 200 million people worldwide and about 200,000 people in Iran are infected with HCY virus. Hepatitis C is one of the leading causes of liver failure and cancer and is the single most common indication for liver transplantation.A quasi-experimental study was conducted on 54 patients with chronic hepatitis C. The patients were treated with a combination of PD feron-B (3 MID, three times per week) plus ribavirin (600-1000 mg per day) for one year. CBC and platelet counts and liver and thyroid function tests were performed at 3rd, 6th, 9th and 12th months. In addition, HCY-RNA was measured using RT-PCR method at 3rd and 12th months. For statistical analysis, t test, chi-square, repeated measures ANOYA and regression analysis tests were used.The results showed that the therapy continued in 52 patients (96.3%) and 47 (90.4%) out of them were male. In addition, the reduction in liver enzymes was significant (p<0.001).HCY-RNA was negative in 77.8% of the patients at the end of 3rd month and in 85.4% at the end of treatment (p>0.001). Meanwhile, in 18.9% of the patients, no complication was noted and in the other 81.9%, there was no serious side effect. Finally, valuable models for prediction of HCY-RNA and the level of aminotransferases at the end of therapy were obtained (P>0.001). Since no serious side effect was. observed during therapy period and considering its compatibility with other drug regiments, accessibility and cost-effectiveness of PD feron-B, therefore, this combination therapy can be recommend in patients with chronic hepatitis C.

Sensory experience during critical period has a profound effect on maturation of visual cortical wiring. The critical period, itself, is affected by the environmental signals and known to be prolonged as a result of sensory deprivation. Electrophysiological evidence is indicating a substantial effect of visual deprivation on the visual conical response properties. In this study, the effect of light deprivation on short term spatial working memory of rats was evaluated in: 1. the period of life in which the critical period is normally going away, and 2. adult rats. Normal light (LR)- and dark (DR)-reared rats at ages of 40 (P40) and 60 (P60) days were trained in an eight arm radial maze. Number of the trials needed for two consecutive successful navigations to reach the criterion, number of the errors within each session and the elapsed steering time were assessed. The P40DR rats revealed an obvious better task performance on all of the trials as compared to their relative LR controls. Also, the results indicated that DR rats rely less on the brightness level in the testing room than do LR ones. In addition, no marked difference was observed between the groups at P60, however, as compared to those at P40, they required fewer trials to attain the criterion and made fewer errors in the navigations but almost the same performances among themselves.It is concluded that on the spatial working memory performance, the dark rearing leaves the visual cortex more plastic, confirming the electrophysiological reports that indicate a higher cortical plasticity following the visual deprivation.

Gentamicin (GM) is an effective antibiotic against severe Gram-negative bacteria.However it can produce nephrotoxicity in human. Reactive oxygen species have been proposed as the causative factors of its renal side effects. This study was performed on the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney.For this purpose, male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: Group 1 (control) was tyrode-perfused kidneys. Group 2 (GM), in which 200 µg/ml of gentamicin was added to the perfusate. Group 3 (GM + Vit C), the same as group 2 but vitamin C (200 mg/L) was added to the drinking water for 3 days and 100 mg/L to the perfusate. Group 4 (GM + Vit E), the same as group 2 but vitamin E (100 mg/100 g BW, i.p.) was injected 12 h before experiment. Group 5 (GM + Vit C + Vit E) the same as group 2 but vitamins E and C were co-administered (the same as Groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N-acetyl-B-D-glucoseaminidase (NAG), alkaline phosphates (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) contents were measured. The results showed that gentamicin causes a significant nephrotoxicity as demonstrated by an increase in urinary LDH, NAG, and ALP. In addition, a decline in GSH and a marked decrease in GFR were observed as compared to controls. On the other hand, vitamin C inhibited the gentamicin-induced increase in urinary enzymes, but did not show a significant effect on the GSH and GFR. In. this respect, vitamin E not only inhibited gentamicin-induced increase in urinary enzymes, but also prevented the gentamicin-induced GSH decline without a significant improvement regarding GFR. Furthermore, co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity as demonstrated by preservation of GFR and GSP levels and prevention of an increase in urinary enzyme activities. Therefore, it is concluded that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation and protection in gentainicin-induced nephrotoxicity.

Estrogen as a female sex hormone involved in reproductive system has also many important metabolic effects. This hormone could exert beneficial protective effect on the cardiovascular system of women. This protective effect is due to its effects on liver and plasma lipids and lipoproteins. In this study, the effect of two different doses of estradiol and ethinyl estradiol valerate on concentrations of serum lipids and lipoproteins in female rats (n = 30) were investigated. For this purpose, two concentrations (0.1 and 1 mg/ml) of hormones were prepared. Thereafter, 4 different test groups were daily injected with 0.2 ml of one concentration. The control group received only 0.2 ml of sesame oil. Estradiol was injected subcutaneously daily for two months. During all experiments, rats received normal standard pelleted food. Finally, blood samples were taken and the concentrations of total cholesterol, triglyceride, VLDL, HDL and LDL were measured using autoanalyzer. The results suggested that ethinyl estradiol and estradiol valerate may decrease concentrations of the serum total cholesterol and LDL. It was also indicated that ethinyl estradiol increases the concentrations of serum triglyceride and VLDL, but none of them have any effect on serum HDL concentration.