Physiology and Pharmacology
Year:2006 | Volume:9 | Issue:2|Papers Count:32

Amygdala and piriform cortex have critical role in temporal lobe seizures and determination of their precise role in these kinds of seizures is very important. In this study the effect of electrical lesion of amygdale basolateral-laeral nuclei on the piriform cortex kindled seizures was investigated.Rats were kindled by daily electrical stimulation of piriform cortex. In the first experiment fully kindled animals received intra-amygdala 2% lidocaine (for reversal neuronal inhibition) bilaterally. Five min later, animals were stimulated and seizure parameters were measured. In second experiment, the amygdala of kindled animals was lesioned by electrical DC current bilaterally and animals were stimulated 24 h later. Daily stimulations of these animals continued for 5 days after lesion. Intra-amygdala lidocaine reduced the kindled seizures severity. There were significant increase in stage 4 latency and decrease in stage 5 duration. Amygdala lesion reduced the seizures severity more dramatically and all seizure parameters with except to seizure stage were reduced significantly. The significant reduction in seizure parameters was observed for 4 days after amygdala lesion.The basolateral-lateral amygdala neuronal activity has a critical role in propagation of epileptic seizures from piriform cortex. Elimination of this activity decreases the severity of piriform cortex kindled seizures. However, this decrease is temporally and several days later (probably because of other brain regions activation) the seizure parameters return to their control values.

The cerebellum is responsible for coordination of movement and maintenance of balance. Purkinje cells (PCs) are principle neurons of anatomically well defined cerebellar modules and it is proposed that coordination of movement is achieved by encoding timing signals in the rate of firing and pattern of activity these cells. Understanding of cerebellar timing requires an appreciation of the intrinsic firing behavior of PCs.In order to determine how changes in membrane biophysics including Ca2+ and K+ channels activity influence the electrical activity of Purkinje neurons, intracellular recording from acutely prepared cerebellar slices was performed. PCs fired spontaneously bursts of calcium or sodium-calcium spikes which were separated by quiescent- interburst periods. They also showed long lasting bursts and long silence periods. Cadmium, a wild range of Ca2+ channels blocker, resulted in an elimination of calcium spikes while left the sodium aetion potential intact. Blockade potassium channels by 4-AP and TEA improved the spontaneous activity and limited silence period. 4-AP also prolongedthe burst and interburst period and decreased the firing frequency. On the other hand, apamin, a neurotoxin from bee venom, known to selectively block small conductance of calcium activated potassium channels (SK), and a-dendrotoxin (DTX), specific blocker of Kv1 channels, shortened the burst and interburst duration. DTX and apamin also increased the frequency of burst occurrence and DTX decreases intraburst frequency.In conclusion, with the data presented it is fair to state that intrinsic membrane properties including K+ channels activity, seem to play important roles in the formation of firing patterns in Purkinje neurons.

There are controversial reports about the sex differences in pain perception and morphine withdrawal signs following acute and chronic morphine administration. Therefore, the difference in withdrawal signs during time-courses of induction of morphine addiction is still of interest. In the present study the sex difference in the perception of acute, chronic and interphase pain of formalin test following chronic morphine administration for 10, 15, 20, and 26 days has been investigated. Also the severity of morphine dependence was assessed by observing withdrawal signs induced by naloxone hydrochloride in different days of addiction process.The addicted and control animals (n=8 per group) received morphine sulfate and sucrose, respectively, in their drinking water.Our results showed that acute and interphase pain was higher in female rats receiving morphine for 10,20, 26 days, in comparison with similar treated male rats but there were not differences in chronic pain perception between two sexes. Some morphine withdrawal signs like abdominal contractions and writhing were significantly higher in female rats but other withdrawal sighs including diarrhea, teeth chattering, ptosis, restlessness and weight loss were not different.It may be concluded that the acute and interphase pain of formalin test and some withdrawal signs of addicted female rats are higher than addicted male rats. This might be due to differences of central nervous system sensitivities with respect to morphine consumption in both sexes.

Urethan inhibits basal and histamille-stimulated gastric acid secretion (GAS). Also, ether induces similar effect on the basal and stimulated acid output. Anesthetized animals are often used in studies of regulatory mechanisms of GAS. Therefore, considering the effect of anesthetic drugs on the acid secretion is very important. The aim of this study is to compare the effects of anesthetic drugs, ketamille-rompane and urethan, on basal and stimulated gastric acid secretion. For all gastric sampling, animals were anesthetized and a polyethylene tube was introduced into the stomach through esophagus and a cannula was inserted into the pyloroduodenal junction and passed up into the stomach for saline injection and aspiration of gastric secretion, respectively. Our experiments revealed that basal acid output significantly reduced in rats given urethan compared to ketamine-rompane treated rats (P<0.001). Also, intravenous infusion of histamine (0.5 mg/100 g/hr) and pentagastrin (2 microgram/100 g/hr) induced marked increase in acid secretion with a peak response that was started from min 30 and continued up to the end of experiments (min 90). Intravenous infusion of carbachol (1 microgram/100 g/ hr) induces marked increase in acid secretion with a peak response that was started from min 10 and continued up to min 90. In all groups, urethane compared with ketamine-rompane significantly reduced the stimulated gastric acid secretion.

The effect of morphine dependency on learning and memory is controversial. In the present study, the male rats were used to evaluate the effects of morphine dependency on spatial learning and memory. Dependent animals received morphine sulfate in drinking water for 20-30 days. Experiments were performed in two parts using Morris Water Maze (MWM). In part one, the effect of morphine dependency in normal and cold water was considered. In this part, animals were divided into four groups in simple randomized manner. The first two groups (control and dependent), were studied in normal water (20±2˚C), and two another groups, were studied in cold water (10-12˚C). Animals were studied in MWM from day 21. In part two, rats were divided into two groups (withdrawal-normal and withdrawal-cold) to evaluate the effect of withdrawal of morphine. The condition was similar to the first part of experiments, but application of morphine was stopped from day 21. 48 h later, experiments in MWM was begun. In each group of animals, the parameters of spatial learning and memory were analyzed. Data were subjected to t-test and ANOVA.The results showed: 1- Morphine dependency facilitated spatial learning and memory in MWM. 2- Cold water reduced swim speed but facilitated the formation of spatial memory. 3-Cold water abolished the effect of morphine on spatial learning but facilitated the effect on formation of spatial memory. 4- Withdrawal syndrome reversed the effects of morphine dependency. The mechanism(s) underling the phenomenon remains to be elucidated.

Primary dysmenorrhea has relatively high incidence which can influence the well being and activities of the sufferers. An clinical trial cross-over study was designed to compare the effectiveness of Vitamin E and Ibuprofen on on reducing the severity of dysmenorrhea symptoms. Seventy five female students, aged between 18-22 (X+SE) who were suffering from primary dysmenorrhea were recruited. After having written consent they were divided in two groups of 40 and 35 and were received 500 units of Vit E (2 tablets of 400 and 100 units) and 1200 mg Ibuprofen (400 mg TDS) per day respectively. Treatment with Vit. E was started 2 days before the beginning of menstruation and continued until the first day of bleeding (3 days in total) and Ibuprofen was administered only during the first 24 hours of mence (only one day. Monitoring was carried out fore 2 consecutive cycles in both groups, crossover was carried out and observation was continued for another 2 cycles. The result of this study indicate that both vitamin E and Ibuprofen could reduce the severity of the pain similarly, nevertheless but Vit E consumption, complications such as digestive disorders and fatigue were significantly less compared to Ibuprofen. It appears that Ibuprofen could be replaced by Vit. E in reducing complications of dysmenorrhea.

Curcuma longa (turmeric) powder is used abundantly as spice. Turmeric has also been traditionally applied to treat some diseases such as skin inflammation and trauma, bile disorders, diabetes and cancer, especially through Asia and India. Antioxidant properties and therapeutic effects of turmeric have been reported in several literatures. Curcumin as theTurmeric effective substance is used frequently in the investigations but since people are usually using the turmeric powder, this study was performed by administration of its powder. Wistar male rats were used as experimental animals (n=6) in this study. Plasma Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT) levels were measured before and 24 h, one week and two weeks after i.p. injection of CCL4 (0.005 cc/kg), dissolved in liquid paraffin (0.5 cc/kg). In sham control group, animals were treated only by the vehicle. To investigate the therapeutic effects of the turmeric, in post treatment group, animals were orally treated with turmeric rhizome powder (4 g/kg/day) after CCL4 injection. To investigate both the protective and therapeutic effects of the turmeric in pre and post-treatment group, 15 days oral pretreatment of Curcuma longa powder was applied to the animals, and it was followed by post treatment of the powder after CCL4 injection for several days. To investigate the protective effects of the turmeric in pre-treatment group, treatment was as same as the previous group, except the post treatment.In comparison to sham control, AST and ALT levels in the control group significantly increased 24 hrs after CCL4 treatment and remained high until the last measurement (p<0.001), but there were no significant differences between sham control and other three groups. In the histophysiological study, vacuolar state, hepatocyte lipofication and necrosis were chosen as hepatocytotoxicity criterions, in comparison to sham control group, hepatocytotoxicity was obvious, but there were no hepatocytotoxicity in the pre- and pre+post-treated groups, 24 and 48 h after CCL4 injection.The results showed possible therapeutic and protective effects of Curcuma longa powder on the hepatocyte damage induced by CCL4.

Opioid addiction is one of the main problems for the health services. In the present study, the effects of water-alcohol extract of Papaver rhoeas on the expression and acquisition of morphine-induced behavioral sensitization were investigated.Mice became sensitized (5 mg/kg, once daily, for three consecutive days; s.c.) or tolerate (50 mg/kg, twice daily for three consecutive days; s.c.) to morphine and the extract before the morphine injection (acquisition) or on the test day (expression) was administrated to them. In a pilot study, different doses of morphine and the extract were administered to the animals in order to evaluate if the drugs can produce any locomotion effects.Results showed that: subcutaneous (s.c.) administration of morphine (0.5-50 mg/kg) increased locomotor activity in the animals. The response was more significant in dose 50 mg/kg of morphine. On the other hand, intraperitoneal (i.p.) administration of the plant extract (25, 50 and 100 mg/kg) did not show any effect. Daily injection of morphine (5 mg/kg; s.c.) for three consecutive days and then five days resting induced sensitization in the animals, so that the morphine sensitized animals showed an extra ordinary response to the ineffective dose of morphine (5 mg/kg; s.c.). Injection of extract (25, 50 and 100 mg/kg, i.p.) 30 min before the morphine administration decreased the acquisition of morphine-induced behavioral sensitization. Administration of the plant extract (25, 50 and 100 mg/kg, i.p.) 30 min before the test, also decreased the expression of morphine-induced behavioral sensitization. Injection of morphine (50 mg/kg; twice daily) for three consecutive days induced tolerance in the animals, so that the morphine tolerated animals did not show any response to the effective dose of morphine (50 mg/kg; s.c.). Injection of extract (25, 50 and 100 mg/kg, i.p.) 30 min before the morphine administration decreased the acquisition of morphine-induced tolerance. Administration of the plant extract (25, 50 and 100 mg/kg, i.p.) 30 min before the test, increased the expression of morphine-induced behavioral tolerance.It could be concluded that the extract of Papaver rhoeas can reduced both the acquisition and expression of morphine-induced behavioral sensitization -and also the acquisition of morphine tolerance but enhances the expression of morphine tolerance in mice which may be true in the human.

Tolerance and dependence are two main problems which have limited morphine administration as an analgesic drug. Following acute and chronic administration of morphine changes in the level of sex steroids and the activity of calcium channels are reported. The enzyme 5 a-reductase plays a pivotal role in the conversion of testosterone to dehydrotestosterone and therefore reduces the testosterone levels. In this investigation, we tried to study the effects of acute and chronic administration of finastride (inhibitor of 5 a-reductase) on morphine dependence in the male rats. Morphine dependency was induced by the intraperitoneal (i.p.) injection of morphine for 4 days (20, 30, 40 and 40 mg/kg respectively at days 1-4). Physical dependence to morphine was observed following administration of naloxone (2 mg/kg-i.p., day 5).Acute administration of finastride at 5th day (5 mg/kg-i.p., twice with 2 hours interval), decreased all withdrawal signs significantly, while the administration the vehicle, caster oil, did not. Chronic administration of finastride prior to daily administration of morphine during days 1-4 significantly decreased all withdrawal signs at the day 5. This finding indicates that inhibition of testosterone metabolism in the CNS using finastride may be able to modulate the withdrawal sings expression and prevents the development of physical dependence.

This research was done to determine the effect of baclofen -GABAB receptor agonist - on milk production and its composition.Twelve Holstein cows were divided to four groups, and in each groups 25, 50, 75 and 100 [mg/ (kg/b.w.)] baclofen were daily injected for four days. Cows were daily milked once a day in sterile milking room for ten days; Milk compositions were measured and recorded by Milko-Scan machinery. This study indicated that this treatments increased milk yield 17, 14, 15 and 16percent, respectively (p<0.01). Protein, lactose and dry matter percent did not change significantly in any treatments. However, fat percent significantly increased (p<0.01). The results of this study suggest that baclofen increases milk production and fat percent; however, it does not have any effect on other milk compositions.

Opiate-induced addiction is one of the main problems of mankind societies and its treatment is one of the health priorities of community. Therefore, relative studies would be very crucial. The exact mechanism of dependence to opiates and their withdrawal syndrome remain unclear. It seems that dopaminergic system and locus coeruleus (LC) have an important role in the somatic signs expression of opioids withdrawal syndrome. In the present study, the effects of different Dl dopaminergic receptor agonist and antagonist administration into the LC on the expression of withdrawal signs of morphine dependence in rats were studied. Rats were divided into 8 groups (n=8). Two cannulae were stereotaxically implanted bilaterally into the LC. After 1 weak recovery, 7 groups rendered dependent to morphine (subcutaneously) during a 7 day period and nondependent animals were received saline with the same protocol. Animals received bilateral intra-LC injections of saline, SKF38393 (D1 agonist) or SCH23390 (D1 antagonist) before naloxone injection about 24 hours after the last dose of morphine or saline. Total withdrawal score as an index of withdrawal syndrome were decreased by SKF38393 (2,4 µg/site) but not by SCH23390. It is concluded that the D1 dopaminergic system in the LC may be involved in the morphine induced dependency in rats.

Sixteen healthy native dogs aged about 2 years with average body weight of 22.5±1.5 kg of both sexes were selected for this study. Dogs were divided randomly into four groups (4 dogs/group). Clinical signs were recorded and blood samples were collected for laboratory examination before injection of venom. The control group was injected with 1ml of saline solution and the groups 2-4 respectively received 0.1,0.5 and 1mg/kg of the venom powder of Vipera lebetina dissolved in 1ml saline solution, injected into the hind limb (biceps femoris) of each dog. Clinical signs were recorded and blood samples were collected at different time (10, 20, 30 and 60 minutes and 2, 4, 8 and 24 hours) after injection of venom examined for sedimentation rate, WBC count, number of neutrophils, RBC and platelet count, HCT, Hb concentration, MCV, MCH, MCHC, bleeding and clotting time, PT and PTT. The results were analyzed statistically.Results indicated that the main clinical signs were pain, pawing, weakness, whimpering, leash chewing, subcutaneous hemorrhage, hypotension and death in dogs in high doses. Heart and respiratory rate and body temperature in dogs of groups 2, 3 and 4 increased after injection of snake venom (P<0.05) which could be related to pain, stress and tissue damage at the site of venom injection. This resulted in an increase in body temperature due to release of pyrogenic substances especially in dogs of group 4. Number of white blood cells (WBC) decreased significantly (P<0.05) which could be related to stress and accumulation of white blood cells in the foci of exogenic factor and consumption of WBC and tissues damage. Comparison of means of platelets, indicated a significant difference in dogs of the group 3 (P<0.05). Primary decrease in the platelets of dogs is due to consumption of platelets in blood circulation at the site of venom injection and hemorrhage then increased due to body replacement. A significant increase (P<0.05) in coagulation, prothrombin and partial thromoplastin time in dogs of groups 3 and 4 was observed. This increase could be related to anticoagulant factor of the venom of this snake, which showed its effects in high doses. It is concluded that in addition to clinical signs and hematological changes, coagulopathy and hemolysis in high doses of Vipera lebetina venom were the main effects on hematological parameters in this respect.

The effects of electro-acupuncture on the canine muscle power were evaluated experimentally.The study was conducted on 10 adult breed dogs. Dogs were subsequently divided to two groups of (control and experimental) 5 dogs each. Anesthesia was induced and afterwards the right sciatic nerve was exposed in all dogs and crushed in full thickness, using artery forceps for 5 seconds. The experimental group was subjected to acupuncture therapeutic regimen, daily for ten minutes for two weeks. The electromyography (EMG) was done from semimembranosus (S 1) and semitendinosus (S2) Extensor (Ext) and Flexor (Flex) muscles before and after 14, 28 and 45 post-operative days. EMG recording showed significant differences in muscle force in S1 and S2 in the experimental group in comparison with the control.Finally, evaluation of electroacupuncture effects showed to be helpful to reduce muscle atrophy.

Carpal tunnel syndrome (CTS) is a clinical entity characterized with pain, paresthesias, and numbness in the distribution of the median nerve with weakness and atrophy of the thenar muscle in advanced cases. It is universally accepted that CTS is the clinical concordate of compression of the median nerve as it pass through the carpal channel. It is reported to be the most common of the entrapment neuropathies. Increasing evidence suggests that occupational factors, including forceful use of the hands repetitive use of wrist hands, and hand-arm vibration, are etio1ogic for CTS. When occurring as result of occupational exposure, the term "worked related carpal tunnel syndrome" is applied.In this study, we have randomly chosen and examined 100 university female students without any hard work and 100 women with various occupations (dentist, carpet- weaver, tailor, surgeon, housewife, etc) for having CTS with neurography.The neurography test showed that 3 female students and 29 working and housewife women were suffering from this syndrome (the ratio were about 1/10). Nerve conduction velocity have been decreased significantly and distal nerve latency have been increased significantly (p<0.001) in subjects with CTS. There was a direct relationship between having CTS and wrist activity (X2=25.1, p<0.001).The results showed that the rate of CTS increases in women with higher wrist activity.

It is known that ethnical and genetic factors influence the blood pressure (BP). Therefore, determination of high blood pressure is depending on normal blood pressure of different ethnics.In the present study BP of 704 randomly selected subjects aged 18 year and over including 336 male and 368 female were measured in the city of Mashhad.The results showed that in the studied population, systolic (S), diastolic (D), and mean (M) BP were 125.44±17.83, 82.67±12.05, and 96.93±12.72 mmHg respectively. SBP, DBP and MBP in female subjects were significantly lower than male subjects (p<0.001 for all cases). There were significant positive correlation between SBP, DBP, and MBP with both age and body mass index (BMI). However, there was not any correlation between blood pressure and degree of exercise habit among studied population. The distribution of hypertension in population of the city of Mashhad was different with those of rarely reported for some other cities of Iran and also some other countries. Some of these differences seemed to be statistically significant. 20.9% of the studied population had hypertension, which were divided into isolated systolic hypertension (5.8%), isolated diastolic hypertension (7.1%) and both (8%).The results of these studies showed the distribution of blood pressure and hypertension among a randomly selected population of the city of Mashhad.

In the present study the effects of two antiplasminogen monoclonal antibodies A2C8 and MC2B8 on the activation of the fibrinolytic system was studied.For this purpose, after separate steps like the culture of antibody producing hybridoma cells, their injection to mice, and purification of antibodies from ascites fluid, the effects of these antibodies was studied with various methods. Primary observation with pooled plasma showed that these antibodies in the presence of plasminogen activators (t-PA, u-PA and SK) can inhibit the activation of fibrinolytic system. According the results obtained from D-dimer assay, the inhibition effects of these antibodies is dose dependent. The other test that performed with S-2251 synthetic substrate showed that the activation of plasminogen in the presence of Urokinase and in the result, deterioration of this substrate was decreased in the presence of A2C8 and MC2B8 antibodies. In the present study we evaluated the effects and mechanism of two antiplasminogen monoclonal antibodies A2C8 and MC2B8 on the activation of the fibrinolytic system in the presence of plasminogen activators.