Effects of administration of co-trimoxazole and folic acid on sperm quality and histological changes of testes in male rats

Background: Male infertility has been reported following long-term sulfasalazine, however, the precise effects of co-trimoxazole on sperm quality is controversial

Objective: In this study, we evaluated the effects of co-trimoxazole and its co-administration with folic acid on sperm quality and histological changes of testes in male rats

Materials and Methods: In this experimental study, 136 male Wistar rats were divided into 9 groups: I [control], II [vehicle] received saline, III: received folic acid [1 mg/kg /daily i.p., and IV- IX received co-trimoxazole [30, 60, and 120 mg/kg/daily; i.p.]+folic acid [1 mg/kg/daily; i.p.] for 14 or 28 days. Sperm samples were obtained from each group at the end of 14[th] and 28[th] days. Sperm numbers, motility, and viability were evaluated on a hemocytometer. Hematoxylin and Eosin stained testes were done for evaluation of the number of Leydig cells, vascularity, spermatids, spermatocytes, and means of seminiferous tubules diameter under light microscopy

Results: Co-trimoxazole treatment for either 14 or 28 days caused a significant decrease in the percentage of sperm number, motility, and viability [p<0.001] compared to the control group. Also, high doses of co-trimoxazole caused a significant decrease in testes structural abnormalities means of seminiferous tubules diameter, spermatids, and spermatogonia] compared to the vehicle group [p<0.001]. Folic acid co-administration with co-trimoxazole partially reversed the decrease in sperm quality and structural abnormalities of high doses of co-trimoxazole [60 and 120 mg/kg/daily] [p<0.001]

Conclusion: The data showed the adverse effects of co-trimoxazole on sperm quality and testes morphology which was protected partially by folic acid co-administration in rats. The underlying mechanism [s] needs further investigations

Patterns of psychotropic medication prescriptions by psychiatrists for private clinic outpatients in Kerman province, Iran

The aim of this study was to assess the pattern and utilisation of psychotropic drug prescriptions by psychiatrists in Kerman Province, Iran. The prescriptions of 27 psychiatrists were randomly selected from two Iranian public insurance organisations and were analysed for the mean number of drugs/prescriptions, drug category and the most frequently prescribed drug in each category as well as overall. A total of 6,414 prescriptions were analysed. The mean number of drugs per prescription was 2.9. Antidepressants [61.0%] were the most frequently prescribed category of psychotropic medications, followed by antipsychotics [29.5%], sedative/hypnotics or anti-anxiety drugs [27.5%] and mood stabilisers [18.5%]. The combination of antidepressants with antipsychotics was the most commonly prescribed combination [18.8%]. Fluoxetine [16.5%] and trifluoperazine [13.5%] were among the most frequently prescribed antidepressants and antipsychotics, respectively. Clonazepam [10.5%] was the most commonly prescribed benzodiazepine agent, followed by alprazolam [8.5%]. In terms of total drug utilisation, sertraline [12.4%] was the most commonly used psychotropic medication followed by fluoxetine [9.7%], trifluoperazine [6.6%], propranolol [4.5%] and clonazepam [3.7%]. A high proportion of psychotropic prescriptions in Kerman Province were for antidepressants, followed by antipsychotics and the benzodiazepines. Further research is needed to determine the underlying correlation between prescription practice and the diagnosis and patient characteristics, as well as to investigate the use of different psychotropic medications

Efficacy of Melissa officinalis in suppressing ventricular arrhythmias following ischemia-reperfusion of the heart: a comparison with amiodarone

We aimed to assess the influence of Melissa officinalis [lemon balm], a well-known herbal drug with numerous applications in traditional and modern medicine, on cardiac conduction and susceptibility to lethal ventricular arrhythmia. Forty-two male Wistar rats were divided into a control group [CTL], an M. officinalis group that received the aqueous extract of M. officinalis L. intraperitoneally [i.p.] at dosages of 50, 100, 200 and 400 mg/ml/kg, respectively, and an amiodarone group [Amio group] that received 30 mg/ml/kg i.p. of amiodarone. Heart ischemia/reperfusion was induced by the ligation and release of the left anterior descending branch of the left coronary artery. There were no statistical differences between the groups in the basal heart rate and blood pressure. PR, corrected QT [QTc] and QRS intervals increased in the M. officinalis and Amio groups. PR and QTc were statistically significant only in the Amio group and QRS was significant only in the group receiving 400 mg of M. officinalis [M400 group] in comparison with the CTL group. During the reperfusion period, the decrease in ventricular fibrillations was statistically significant in all groups [except the M400 group] when compared with the CTL group. The score of arrhythmia severity also decreased, but was statistically significant only in the Amio group [p < 0.05 vs. CTL group].Conclusions: Our findings suggest that M. offcinalis extract has a mild protective effect against reperfusion-induced lethal ventricular arrhythmias in rats

Evaluation of antinociceptive effect of pregabalin in mice and its combination with tramadol using tail flick test

The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin [1 to 400 mg/Kg], tramadol [10 to 80 mg/Kg] or their combination intraperitoneally. Then latency time, maximum possible effect [%MPE] and area under curve [AUC] were calculated in tail flick test. The antinociceptive indexes were significantly increased in10, 100 and 200 mg/kg of pregabalin while tramadol showed dose-dependent antinociception [effective dose 50% was 54 to 79 mg/Kg]. The antinociceptive effect of 100 mg/Kg of pregabalin [%MPE = 35 +/- 4%] was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses [10 mg/Kg] of tramadol and pregabalin did not increase%MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin [10 mg/Kg] increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism[s] and statement of interaction are needed to expand these findings to clinical applications

Antinociceptive effect of aqueous extract of Origanum vulgare L. in male rats: possible involvement of the GABAergic system

The objective of the present investigation was to assess the possible involvement of GABAergic mechanism in analgesic effect of aqueous extract of Origanum Vulgare [ORG] in a rat model of acute pain test. Sixty-three anaesthetized male Wistar rats [200-250 g] were cannulated into the left ventricle. Five to seven days after the recovery from surgery, ORG extract was intraventricularly injected at dose of 3 ?g/rat i.c.v. Then, baclofen [10 mg/Kg, IP], CGP35348 [100 nmol/Kg, i.c.v], muscimol [1 mg/Kg IP] and bicuculline [5 mg/Kg IP] were separately injected 20 min before the injection of ORG. The experimental groups were compared with intact [control] group [n = 7]. The response latency of rats to thermal stimulation was recorded using Tail-Flick test. Injection of ORG extract resulted in a significant and dose-dependent increase in the response latency. There was also a significant increase in the response latency after co-administration of ORG extract with baclofen when compared with control group. However, following co-administration of ORG extract/bicuculline, a significant decrease in the response latency was observed compared to control group. In conclusion, the results of the present study suggest that aqueous extract of Origanum vulgare L. ssp. viridis possesses antinociceptive activity in a dose-dependent manner and ORG-induced antinociception might be mediated, at least in part, by both GABA receptors

[Effects of different phases of estrous cycle on brain edema and neurological outcomes after severe traumatic brain injury in female rats]

Sex is one of the main recovery parameters after traumatic brain injury [TBI]. During estrus cycle phase, plasma estrogen and progesterone levels are very different. So in this study, we have assessed different effects of these phases in brain edema and neurological outcomes. Adult female Albino-N-MARI rats were divided into 6 groups [14 per group] including metestrus, diestrus, proestrus, estrus, ovarictomized [OVX] rats, and sham group [without TBI and ovary]. In all groups, brain water content for the measurement of brain edema, evans blue content for the measurement of brain vascular permeability, neurological scores, plasma estrogen and progesterone levels were assessed after severe TBI. Brain water content in diestrus, proestrus and estrus groups showed a significant decrease as compared with OVX group [P<0.001] but it was not significant in metestrus group. Evans blue content in proestrus group was lower than estrus and OVX groups [P<0.001]. Also, in diestrus group it was lower than OVX group [P<0.01].Neurological scores showed significant increases in proestrus group 4 hours after severe TBI as compared with metestrus, diestrus and OVX groups [P<0.01]. 24 hours after severe TBI, neurological scores in all groups were higher than OVX [P<0.001]. Brain water content and brain vascular permeability in sham group was lower than OVX, besides neurological scores in sham group were higher than OVX [P<0.001]. This study showed that brain edema, evans blue content and neurological scores after severe TBI are related to estrus cycle different phases. This could be related to differences in female sex hormones in different phases of estrus cycle

Evaluation of Origanum vulgare L. ssp. viridis leaves extract effect on discrimination learning and LTP induction in the CA1 region of the rat hippocampus

The objective of this study was to determine the effect of aqueous extract of Origanum vulgare L. ssp. Viridis [ORG] on discrimination learning and long term potentiation [LTP] in CA1 region of the rat hippocampus. A group of adult male Wistar rats weighing 275 +/- 25 g received aqueous extract of ORG [150, 300, 450 mg/kg/day] by intraperitoenal injection for one week, and the other group received saline [n=6]. A wooden T-maze was used to evaluate the discrimination learning. In electrophysiological experiments, the effects of ORG leaves extract on induction and maintenance long term potentiation [LTP] in CA1 hippocampus area was determined. LTP was evaluated in CA1 region after high-frequency stimulation [200 Hz] of the Schaffer collaterals. Also, serum antioxidant levels were analyzed in the two groups [n=4]. Statistical analysis showed significant decreases in the number of total [significantly at the dose of 300 and 450 mg/kg] and wrong [significantly at the dose of 300 mg/kg] entrance into opposite box of T-maze procedure in ORG-treated animals [P<0.05]. In electrophysiological study, the rats which had received ORG [150, 300, and 450 mg/kg] showed an increase in both population spike amplitude [59.7 +/- 14.1%, 85 +/- 14.7% and 49.3 +/- 8.7% respectively, compared to 39 +/- 9.2% increase in saline group] and maintenance of LTP in hippocampus CA1 after high frequency stimulation in Schaffer collateral pathway. In serum antioxidant assay, level of antioxidants in ORG groups [300 and 450 mg/kg] remarkably increased in comparison to saline group [P< 0.05 and P<0.001, in turn]. Our result suggest that Origanum aqueous extract can improve the learning criteria in rats

intracerebroventricular [ICV] administration of w-7, a calmodulin inhibitor, attenuates the development of morphine tolerance in rats

The present study was performed to determine the effect of intracerebroventricular [ICV] administration of W- 7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. This study was carried out on male wistar rats, weighing 200-250 g. Morphine was administered daily [15 mg/kg for 8 days]. The threshold to thermal nociceptive stimuli was measured by tail-flick test. W-7 [0.25, 0.5 and 1 micro mol/rat] was injected through ICV. Maximal possible effect percentage [MPE%] was considered as analgesia index. Our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of W-7 [0.5 and 1 micro mol/rat] decreased the development of tolerance to it. In conclusion these data showed that chronic injection of W-7 inhibited the development of morphine tolerance which indicates that calmodulin and its dependent pathways may play a role in the morphine tolerance processes

[Differences of intensities regarding withdrawal signs in experimental methods for inducing morphine dependency]

In the present study, we compared the intensity of physical dependency, mortality rate and weight changes in some common methods for inducing morphine dependency. Six common different methods for morphine dependency were chosen in wistar rats. In all methods, morphine dependency was induced by repeated morphine injection. Precipitation of morphine withdrawal signs were performed on the last day in each method, 4 hours after the last morphine injection for 20 minutes. The withdrawal signs included: vertical jumping, wet dog shakes, diarrhea, teeth chattering, ptosis, head shakes and rearing. Our results demonstrated that all groups of treated rats showed withdrawal signs following naloxone challenge. However, the intensities of withdrawal signs [vertical jumping, wet dog shakes, diarrhea, teeth chattering, head shakes and rearing] were significantly different among these methods. Also, mortality rate and amount of weight loss were significantly different among the different methods. This study demonstrates that different experimental methods of morphine dependency can induce different intensities of withdrawal signs, mortality rate and weight loss

Effect of cuneiformis nucleus inactivation by lidocaine microinjection on the analgestic response of morphine in rats

The present study was performed to evaluate the analgesic effect of morphine microinjection into the cuneiformis nucleus [CnF] and the effect of inactivation of this area by lidocaine on pain modulation. Rats were anaesthetized by thiopental [45-60 mg/kg/i.p.] and placed in a stereotaxic instrument, and then a guide cannula was implanted just one mm above the CnF. Following surgery and recovery period, various doses of morphine [10, 20 and 40 micro g/0.5 micro l saline] and lidocaine 5% [0.5 micro l] were microinjected into the CnF. Antinociceptive response was measured by tail flick latency [TFL] and maximal possible effect [% MPE] for 25 min at 5-min intervals, before and after any injection in control and experimental groups. The results of this study showed that morphine microinjection into the CnF increased TFL in a dose-dependent manner. TFL was also increased significantly after lidocaine microinjection. However, co-microinjection of morphine and lidocaine increased TFL which was less than morphine microinjection alone. The intravenous morphine injection with lidocaine microinjection increased TFL significantly, as compared to morphine microinjection. These effects were reversed by naloxone administration. In summary, the results of this study showed that morphine microinjection into the CnF caused a significant analgesic response which indicates that CnF may be involved in pain modulation