Physiology and Pharmacology
Volume:14 Issue: 3, 2010

Electrophysiological studies have demonstrated a relationship between aging and atrioventricular (AV) nodal conduction and refractoriness. The aim of the present study was to determine the effects of nodal aging on dynamic AV nodal field potential recording during atrial fibrillation (AF) in rabbit. Two groups of male New Zealand rabbits (neonatal 2-week-olds and adult 12-week-olds, n=14 each group) were used in this study. Field potential recordings were executed by silver electrodes with a diameter of 100 M. Pre-defined stimulation protocols of AF, zone of concealment (ZOC) and concealed conduction for determination of the electrophysiological properties of the AV-node were separately applied in each group. Results of the study showed that mean ventricular rate (HH) during atrial fibrillation was smaller in the neonatal compared to the adult group (229.1 ± 8.3 versus 198.6 ± 13.1 msec, respectively). Also ventricular distribution conduction pattern showed two peaks in the adult and one peak in the neonatal group. Analyzing the zone of concealment in different rates and after concealed beat indicated that the zone of concealment in neonates were significantly smaller compared with adult rabbits and increasing zone of concealment, which is accompanied with increasing ventricular rate is abrogated in the neonatal group (5 ± 3.3, 12.2 ± 6.3 msec). The results of this study showed that the electrophysiological protective dynamic behavior of the AV node during atrial fibrillation is smaller in neonates compared to adults. Narrower zone of concealment, abrogation rate dependent trend of the zone of concealment and shorter nodal refractoriness can account for the specific nodal electrophysiological properties of neonatal rabbits.

Evidence suggests that neuronal apoptosis in neurodegenerative diseases is correlated with inflammatory reactions. The beneficial or detrimental role of apoptosis in neuroinflammation is unclear. Elucidating this question may be helpful in management of neurodegenerative diseases. Since TNF-α is able to induce apoptosis as well as increased viability of the cells by activation of caspases or NF-kB, respectively, the question is what will happen if the balance between the two pathways is disturbed by inhibition of apoptosis. In this study, we used β–amyloid peptide (soluble Aβ monomer) injection into the Wistar male rat prefrontal cortex for induction of neuroinflammation in the hippocampus. Levels of TNF-α and caspase-3 were determined via western blot analysis. Using chronic intracerebroventricular administration of caspase inhibitors, z-VAD –fmk and z-DEVD-fmk, we inhibited apoptosis. Exploring consequences of apoptosis inhibition, activity of NF-kB was evaluated via western blotting. After β–amyloid peptide injection we observed an increase in TNF-α and caspase3 as an inflammatory cytokine and apoptotic marker, respectively (P<0.001 and P<0.0001, respectively). As a consequences of apoptosis inhibition, nuclear NF-κB was decreased and cytosolic NF-κB was increased and these changes were significant compared to Aβ-injected group (P<0.001 and P<0.05, respectively). Caspase inhibition as an initiator of apoptosis, probably by attenuation of NF-kB activity, protect cells from abnormal survival and proliferation.

Following a traumatic brain injury (TBI), the excessive release of proinflammatory cytokines is major cause of cerebral edema that can cause permanent neuronal loss. This study examined the changes in brain concentrations of proinflammatory cytokines IL-1, IL-6, TNF-α and TGF- after different doses of estrogen or progesterone treatment in brain-injured rats at 6 and 24 h post-injury. Adult female rats were divided into 14 groups, and underwent either bilateral ovariectomy (12 groups) or sham surgery (2 groups). The hormones or vehicle were given intraperitoneally 0.5 h after TBI. Moderate TBI was induced by Marmarou method in TBI or treatment groups and brain levels of proinflammatory cytokines were measured 6 and 24 h post-injury. The results indicated that high dose of estrogen (E2) and low dose of progesterone (P1) increase brain levels of IL-1 6 h post-injury by 52.8% and 79.2%, respectively compared to the vehicle. By the 24th h post-injury brain IL-1 level was reduced 27.5% and 27%, respectively compared to vehicle, when estrogen low dose (E1) and E2 were administered. Progesterone high dose treatment reduced brain level of IL-6 by 45.9% at 6 h post-injury and P1 treatment reduced IL-6 level by 20.5% at 24 h post-injury when compared to the vehicle. The brain TNF-α level was reduced by 72.5% by P2 at 6 h and 48.5% by E2 at 24 h post-injury, when compared to the vehicle. In addition, TGF- level seem to be increased by E1 up to 3.37 times at 24 h post-injury compared to the vehicle. Both doses of hormones showed increased levels of TGF- at 6 h post-injury, when compared to the vehicle. We conclude that progesterone and estrogen may change the levels of proinflammatory cytokines in the acute or delayed phases after TBI and this may be one of the mechanisms by which hormones reduce cerebral edema.

Application of low-frequency stimulation (LFS) is a new method for treatment of drug resistant epileptic patients. Previous studies demonstrated that activation of receptors coupled to Gi proteins is one of the mechanisms of the anticonvulsant effect of LFS. Thus, in this study, alterations in the expression of RGS4 and RGS10 proteins, as negative regulators of Gi proteins, were investigated.

Animals were kindled by perforant path stimulation in a rapid kindling manner (12 stimulation per day, 1 ms pulse duration at 50 Hz). LFS (8 stimulation per day, 0.1 ms pulse duration at 1 Hz, 200 pulses) was applied to the perforant path 5 minute after the termination of kindling stimulations. After electrophysiological recordings for 6 days, the dentate gyrus of the animals was removed and RGS4 and RGS10 protein expression was studied by western blotting technique.

Application of LFS significantly retarded kindling acquisition and increased the number of stimulations to achieve different stages of seizure. LFS also significantly reduced after discharge duration. In addition, application of LFS after kindling stimulation reduced the expression of RGS4 and RGS10 proteins.

Results of the present study showed that LFS has anticonvulsant effects on the perforant path kindling. Application of LFS following kindling stimulation reduced the expression of RGS4 and RGS10 proteins. Reduction of the expression of these proteins results in the longer activation of signaling pathways of Gi proteins, which may be responsible for LFS anticonvulsant effects.

Impaired wound healing in diabetic patients is a major clinical problem, which is associated with significant morbidity and mortality. Estrogen has positive effects on neoangiogenesis, reepithelialization and cell proliferation. In this research, effect of estrogen on wound healing in diabetic male rats was investigated. This study was performed on male Wistar rats (body weight 200±20 g), which were divided into 2 groups of normal and diabetic rats. Each group was divided into 3 subgroups of control, sham and test. A circular full-thickness wound with a diameter of 1.5 cm was created on the back of streptozotocin(stz)-induced diabetic as well as nondiabetic rats. Estradiol benzoate (10 μg/sc) was daily administered to test subgroups for 28 days, while the sham subgroups received injections of placebo. The control subgroup did not receive anything. Size measurement and pathological evaluation of the wound was performed on days 3, 5, 7, 14, 21, 28. In the macroscopic study, there was a delay in the wound healing of diabetic group in comparison with normal group. From day 7, wound healing had considerable change in estradiol subgroups in both normal and diabetic rats (p<0.05). In the microscopic study, coating tissue reorganization, granulation tissue and neoangiogenesis formation were surveyed as semi-quantitative parameters. In all cases, estradiol receiving subgroups showed impressive improvement compared to the sham subgroup. This research finds that estrogen can improve the impaired wound healing of diabetic rats and this effect is related with the rate of wound healing and wound structure.

Estradiol is a neuroactive steroid, which is found in several brain areas such as locus coeruleus (LC). Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membranebound receptors like glutamate and GABAA receptors. LC is involved in noradrenergic descending pain modulation.

In order to study the effect of 17β-estradiol on both acute and persistent pain modulation and its mechanisms, formalin was injected into the hind paw of male rats. Formalin-induced responses including licking and flexing duration and paw jerking frequency were recorded for 60 min after injection of 50 μl of 2% formalin. Also, the expression of α2 and γ1 subunits of GABAA receptor genes were examined by RT-PCR technique.

The results of the current study showed that intra-locus coeruleus injection of 17β-estradiol attenuated the second phase, but not the acute phase of formalin induced pain (P< 0.05). GABAA receptor antagonist (bicuculline) reversed the antinociceptive effect of 17β-estradiol, but the expression level of α2 and γ1 subunits of GABAA receptor genes were not significantly changed.

It may be concluded that the analgesic effect of 17β-estradiol in formalin induced inflammatory pain is possibly mediated through the interaction with membrane-bound GABAA receptors, however this effect is not exerted at the gene expression level.

Ketoprofen is an NSAID and selective COX-1 inhibitor. In our previous study the role of flunixin meglumine, a nonselective COX inhibitor was studied on seizure and its anticonvulsant effects were confirmed. Therefore this research is performed to assess the role of a selective COX-1 inhibitor, ketoprofen in treatment of seizures induced by PTZ. In this research, male Wistar rats (200±20 g) were given intracerebroventricular injections (1μl volume in each), of saline or ketoprofen (25 μg, 50 μg and 100 μg) before intraperitoneal administration of PTZ (80 mg/kg) for induction of seizure. Then, seizure score and times of onset of every stage of seizure were recorded during 20 minutes after PTZ administration. The data was analyzed by one-way analysis of variance (ANOVA) and nonparametric tests. Result of this research indicated that the injection of 50 μg of ketoprofen significantly increased the time of onset of partial seizure compared to the control group. Also ketoprofen with doses of 50 and 100 μg significantly increased the time of onset of generalized (tonic-clonic) seizures compared to the control group. On the other hand, 25 μg of ketoprofen did not have a significant effect in comparison with the control group. Fifty μg of ketoprofen decreased the seizure score compared to the control, but this decrease did not reach significance (P>0.05). We conclude that ketoprofen has anticonvulsive properties.

Ulcerative colitis is a chronic inflammation of the large intestine (colon). In patients with ulcerative colitis, ulcers and inflammation of the inner lining of the colon lead to symptoms such as; abdominal pain, diarrhea, and rectal bleeding. Previous studies have shown that Matricaria recutita L. have a series of physiological effects; for example spasmolytic, carminative, antioxidant and anti-inflammatory. In the present study, the effect of this herbal aqueous extract on a model of acute experimental colitis was evaluated.

Experiments were performed on 5 groups (N=7) of male NMRI rats (230-280g). Three groups were administered orally different doses of extract (10, 20 and 30 mg/kg), fourth group received vehicle and the last considered as control group. For induction of colitis the rats were fasted for 36 hours and then anaesthetized with ether, at the last stage 2 ml of acetic acid 4% was instilled via the anus. After 24 hours the macroscopic study showed the colitis indices.

The aqueous extract of M. recutita with doses of (20 and 30 mg/kg) significantly reduced colon weight/length ratio. Extract with the highest dose (30 mg/kg) was effective to decrease as well as inflammation severity and extent. The histopathological studies of colon section showed that, curing or treating effects of extract 10, 20, and 30 mg/kg is mild, moderate and completely, respectively.

It is concluded that Matricaria recutita L. aqueous extract was effective in treatment against experimental acute colitis. It can decrease inflammatory indices of ulcerative colitis.

Previously, we demonstrated that i.p. injection of aqueous extract prepared from aerial parts of Drosera Spatulata (Droseraceae) can induced remarkable analgesia in both phases of formalin test in rats. Because, analgesia induced in acute phase of formalin test mainly mediated by activation of central analgesic mechanisms and also paragigantocellularis (PGi) nucleus is part of brain descending pain control systems; the role of this nucleus in analgesic action of the extract on acute pain studied by its effect on PGi neural activity that augmented by injection of formalin to contralateral hind paw of anesthetized rats. Firing rate of PGi neurons by extracellular single unit recording technique were recorded in 20 urethane anesthetized (1.2- 1.5 g/kg, i.p.) male rats in control, Drosera extract (0.05 mg/kg, i.p.) treated and sodium salicylate (300 mg/kg, i.p.) receiving groups. Formalin (50µl, 2%, s.c.) injected 30 min after each of the above treatments to intraplantar surface of hind paw of rats and change in response of opposite PGi neurons was recorded. Data was analyzed by Wilcoxon ranking test. Extract injection increased firing rates in 66.6% of PGi neurons and decreased 16.6% of neurons (p<0.001), but had no effect on 16.6% of neurons in formalin injected rats. Sodium salicylate treatment decreased significantly firing rates in 50% PGi neurons in formalin pretreated rats (p<0.001). The relation between PGi neuronal augmentation and analgesia was reported previously. Thus, the augmentations of firing rates in high percent of PGi neurons after the extract injection provide a document about the role of PGi nucleus in reduction of pain in acute phase of formalin test.

Learning and memory deficits in some diseases are new subjects of research. Bupropion, as dopamine and noradrenaline reuptake inhibitor and an antidepressant agent, has been previously shown to affect learning and memory processes. This study was designed to test the effect of intra-hippocompal bupropion injection on active avoidance learning task in rats. Adult male Wistar rats (obtained from Pasteur Institute of Iran, weighing 200-250 g) were tested for learning behavior in a two-way active avoidance shuttle-box. The animals were divided into control, sham operated, vehicle and 3 treatment groups treated with different doses of intra-hippocampal bupropion (0.25 mg/1 μL, 1.25 mg/5 μL and 2.5 mg/10 μL, injected during 1-2, 5 and 10 min, respectively). Drug was injected by a stereotaxic implanted guide cannulae. Briefly, 10 days after the stereotaxic surgery, rats were trained (20 trails, 2 times each day) in a twoway active avoidance task shuttle box. Sessions were started at the same time of the day and an interval of 5 hours was between the 2 sessions. Tests were repeated on 5 consecutive days. Rats received bupropion or vehicle 30 min before each test and the learning process was assessed. Analysis of the data showed significant differences in the number of avoidance reactions in the early sessions of trials of the learning tasks between vehicle and bupropion treated animals (p<0.05). Bupropion can decrease the number of avoidance reactions and increase the reaction latency. Although bupropion is a dopamine reuptake blocker, but it is concluded that bupropion can bind to other receptors such as acetylcholine receptors and interfere with the learning and memory processes. Key words: Bupropion, Shuttle-box, Active avoidance learning, Hippocampus, Antidepressant

Angiogenesis, the process of new blood vessel formation from pre-existing vessels, has important physiological roles in embryonic development, female reproduction cycle, and wound healing. It is also crucial for pathological processes in several diseases especially tumor growth and metastasis. Thereby, inhibition of angiogenesis as an addition to the conventional therapies such as chemotherapy and radiotherapy has attracted the attention of scientists.

Different studies have shown that botanical derivatives specifically antagonize new vessel formation in tumors without significant toxicity to normal tissues and without major adverse reactions. Furthermore, many studies have revealed that the active ingredients of these natural products inhibit tumor cell proliferation through interference with other physiological pathways such as intracellular signaling pathways. A number of studies have also demonstrated that many traditional foods especially plant derived foods have preventive potential against around one third of cancers. Therefore, plant rich diet can inhibit the progression of many chronic diseases such as malignant solid tumors which are related to angiogenesis.

The use of exercise along with herbal supplements is one of the recommended methods for controlling obesity and its complications, but its effects have been controversial due to the diversity of training programs and also herbal supplements. Hence, the objective of this study was to investigate the effects of 10 week ginger and progressive resistance training on C-reactive protein (CRP) and other cardiovascular risk factors in obese men. In a double-blind design, 32 obese men (BMI≥ 30) were selected and randomized to four groups (each group comprised of 8 subjects): 1- ginger (GI) 2- resistance training plus placebo (PLRT) 3- resistance training plus ginger (RTPL) and 4- placebo (PL). Subjects of groups 1 and 3 consumed 1 gr ginger/d for 10 weeks, while subjects of groups 2 and 3 performed progressive resistance training at the same time. To evaluate lipid profiles, insulin resistance and CRP, blood samples were collected at the beginning of the first week and after the last week. Moreover, body composition and anthropometric indices were measured simultaneously. After 10 weeks of interventions, both GRT and PLRT groups showed a significant decrease in WC, WHR, body fat percent, body fat mass, total cholesterol and insulin resistance, while these remained unchanged in two PL and GI groups (P>0.05). Moreover, significant decreases in the mean values of CRP were observed in all groups except the placebo group (P<0.05). According to our results, resistance training was a preventive approach to reduce the cardiovascular risk in obese men. Moreover, ginger supplementation did not have any influence on the lipid profile and insulin resistance at a dose of 1 gr/day, however, it exerted favorable effects on CRP in obese men.