In Vivo Study on Laxative Effect of Prunus amygdalus Oil

Objective: In this study, we assessed the laxative effects of Prunus amygdalus oil (PAO) in constipation model of mice. Method: The animals were divided into 6 groups and Prunus amygdalus oil was orally administered in two dose-strengths (3.0 ml/kg/day and 6.0 ml/kg/day) in mice. Group one was administered with Lactulose (30 ml/kg/day) as standard. Understandings of the possible mechanism of laxative action 2 groups of animals were pretreated with atropine (10 ml/kg/day) that moderately inhibit the laxative activity of Prunus amygdalus oil. Results: Results of our study revealed that treatment of PAO was effective in increasing the fecal number and fecal weight and this increase was very close to standard drug Lactulose, which indicate the laxative activity of oil. Those groups of animals which were previously administered with atropine partially inhibit the laxative activity of Prunus amygdalus oil, specifying that laxative action is mainly facilitated through muscarinic receptors activation and indicated the occurrence of Acetylcholine like component. Conclusion: Our study results revealed the laxative activity of PAO mediated mainly with the cholinergic pathway. This study provides a basis for beneficial use of Prunus amygdalus oil in constipation.

Methylphenidate-induced hepatotoxicity in rats and its reduction by buspirone

Methylphenidate is commonly use for the treatment of attention deficit hyperactivity disorder [ADHD], but its long term use was found to produce hepatic necrosis in mice. Purpose of this study was to investigate that coadministration of buspirone [drug which attenuates methylphenidate induced sensitization] may attenuate methylphenidate-induced hepatotoxic effects and to determine the effect of challenge dose of haloperidol [D2 antagonist that blocks the effects of methylphenidate in case of intoxication] on SGPT and SGOT levels in methylphenidate treated rats. Estimation of SGPT and SGOT were performed using kit method. Prolong oral administration of methylphenidate at a dose of 2.0 mg/kg/day, buspirone at a dose of 10 mg/kg/day, their co-administration and challenge dose of haloperidol [1 mg/kg i.p.] in rats increased SGPT concentration and decreased SGOT concentration, effect is more pronounced in methylphenidate treated rats and potentiate with administration of haloperidol challenge dose. In conclusion our analysis showed that methylphenidate and challenge dose of haloperidol is associated with elevation of SGPT in rats, which is attenuate in co-administration of methylphenidate buspirone treated rats. To quantify the risk of methylphenidate-induced hepatic injury and role of buspirone to reduce the injury further pharmacoepidemiological investigations are required

Effect of haloperidol on behavioral sensitization and cognition in methylphenidate and buspirone-methylphenidate co-administered rats

Attenuation of methylphenidate-induced behavioral sensitization and cognitive tolerance by buspirone coadministration has been reported previously. Dopamine D2-receptors are considered to be important in methylphenidateinduced sensitization. This study was designed to monitor the responsiveness of D2 receptors following long-term methylphenidate, buspirone and their co-administration in rats by the challenge dose of haloperidol. Effects of haloperidol challenge dose [1 mg/kg i.p.] were monitored after 6 weeks [till the behavioral sensitization produced] from oral repeated [twice a day for 6 week] administration of methylphenidate [2mg/kg/day], buspirone [10mg/kg/day] and their co-dministration. Motor activity was compared by using familiar environment of home cage and novel environment of open field and cognitive activity was compared by using water maze were monitored 30, 60, and 90 minutes post injection respectively. We found that haloperidol reduced motor activity in familiar as well as in novel environment and showed impaired cognitive performance in water maze. The effects were more pronounced in methylphenidate treated rats as compared to buspirone and methylphenidate co-administration treated rats. Increased response of haloperidol in methylphenidate treated rats can be explained in terms of super-sensitization of D2 receptors, which results in behavioral sensitization that is not observed in co-administration treated rats. Buspirone prevents D2 receptor's super-sensitization by increasing serotonergic inhibitory influence on dopamine neuron

Prevalence of mecA: Genotyping screening of community acquired- MRSA isolates in Karachi, Pakistan

Among resistant nosocomial and community pathogens, MRSA has become the most serious pathogen, causing life threatening infections worldwide. In S.aureus, quick and exact recognition of methicillin [cefoxitin] resistance has become essential. The benchmark for MRSA identification among S.aureus is the detection of the mecA gene that causes the expression of protein [PBP2a] culpable for classic â-lactam resistance. However, the utter reliance on amplification of mecA gene as a hallmark in confirmation of methicillin [cefoxitin] resistant S. aureus is the matter of distrust by some investigators. The current investigation designed to analyse the prevalence of mecA gene among phenotypically positive MRSA isolates using molecular method and to correlate its prevalence to conventional techniques. Furthermore, antimicrobial sensitivity of mecA positive staphylococci was determined by Kirby Baeuer method. For this purpose, 201 clinical staphylococcal specimens were recovered from various diagnostic laboratories in Karachi City, Pakistan. Phenotypic existence of methicillin resistance in S. aureus was observed to be 51.7%. In contrast, when organisms were subjected for amplification of mecA gene by PCR, mecA positive isolates were 36/104 [35%] MRSA isolates. Current work raise question towards the usefulness of molecular identification of mecA gene in confirmation of methicillin resistance without correlating with conventional methods. Therefore, it is essential to consider the other possible resistance mechanisms for Beta-lactams that may interact with mecA gene in the development of methicillin resistance mechanism in Staphylococcus

Buspirone attenuates methylphenidate-induced growth inhibition

Methylphenidate is effective in the treatment of attention deficit hyperactivity disorder [ADHD] in children and adults, but its long term use can cause potential adverse effect on growth rate and variable effects on appetite. Previous studies have shown that long term administration of psychostimulant drugs increases the effectiveness of somatodendritic 5-hydroxytryptamine [5-HT][-1A] receptors. Repeated administration of buspirone attenuates the effectiveness of somatodendritic 5-HT1A receptors. The present study was designed to test the hypothesis that coadministration of buspirone may attenuate methylphenidate-induced effects on growth rate and food intake. Growth rate was calculated weekly in terms of change in body weight as percentage of preceding week's body weight and food intake was calculated weekly by subtracting the amount of food left in the hopper from the amount of food placed in the hopper as % in preceding week mg/gm of body weight after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0 mg/kg/day decrease growth rate, but co-administration of buspirone at a dose of 10 mg/kg/day attenuates effect of methylphenidate on growth rate however food intake was significantly greater in all treated groups after 3 weeks of treatment. It is suggested that buspirone may oppose methylphenidate-induced growth inhibition by decreasing the sensitivity of somatodendritic 5- HT1A receptors. These findings may help to extend future therapeutics in ADHD

Attenuation of methylphenidate-induced sensitization by co-administration of buspirone

Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD [attention deficit hyperactivity disorder], but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine [5-HT][-1A] somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT[1A] somatodendritic receptors. This study was designed to determine that buspirone coadministration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0mg/kg/day enhanced motor activity in home cage i.e activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13[th] day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT[1A] somatodendritic receptors. These findings may help extend future therapeutics in ADHD

Evaluate the effect of mirabilis jalapa linn. seeds on liver function tests of healthy rabbits

Objective: To observe the effect of Mirabilis Jalapa seeds on Liver function tests of Rabbit

Study Design: Experimental study

Place and Duration of Study: This study was carried out in the Department of Pharmacology and Therapeutics, Baqai Medical College/ University for a period of 2 months from 1.10.2011 to 30.11.2011

Materials and Methods: For this study twenty seven rabbits of either sex were selected and divided in three groups, control group, low dose group and high dose group, each group having nine rabbits. The dose of the drug was calculated according to weight of the animals

Results: The liver function tests [LFT] were done after 60 days administration of mirabilis jalapa seeds. Total serum bilirubin in control group was 0.69 +/- 0.03, in low dose group 0.71 +/- 0.03 and in high dose group 0.73 +/- 0.03 with P value 0.197. Direct serum bilirubin was 0.34 +/- 0.02; 0.34 +/- 0.03; 0.31 +/- 0.03 with P value 0.687 in control group, low dose group and in high dose group respectively. Indirect serum bilirubin was 0.35 +/- 0.01 [control group]; 0.37 +/- 0.03 [low dose group] but in high dose group it decreased to 0.32 +/- 0.02 with P value 0.409. SGPT in control group was 78.7 +/- 3.01; in low dose group it was 74.1 +/- 2.08 and in high dose it was 100.0 +/- 2.08 with P value 0.001. Serum alkaline phosphate [IU/ L] was 44.4 +/- 1.53 with low dose it was 26.1 +/- 1.14 with high dose it was 114.6 +/- 1.14 with P value 0.001

Conclusions: Mirabilis Jalapa seems to be useful drug and further studies regarding its use are recommended

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose [8mg/kg/day] and at low dose [2mg/kg/day] of methylphenidate in 1st and 2nd week whereas more decreased by the above doses in 3rd week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed

Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic5HT-[IA] receptors effectiveness. Repeated buspirone administration attenuates 5-HT[IA] soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD

Cognition-enhancing effect of oral therapeutic doses of methylphenidate in rats

To determine the effects of oral therapeutic doses of methylphenidate, on memory. It was thought that long term use of methylphenidate possibly may lead to tolerance in the ability of the drug elicit enhancement of learning and memory. A dose-dependent effect may therefore help to extend the therapeutic use of the drug for better clinical response. Experimental / Analytic study. This study was conducted in the Department of Pharmacology, Faculty of pharmacy, University of Karachi, Karachi for a period of period of 4 weeks. Twenty-four male Albino Wister rats [weighing 180-220g] were randomly assigned to four groups, one control and 3 test groups. The experimental protocol was designed to administer methylphenidate orally two times daily for 4 weeks. Four groups were: [i] Saline [1.0 ml/kg/ day], [ii] Methylphenidate [2mg/kg/day] [iii] Methylphenidate [5mg/kg/day] [iv] Methylphenidate [8mg/kg/day] treated groups. Behavioral activity of rats i.e. performance of rats in passive avoidance test was monitored weekly. The experiment was performed in a balanced design to avoid the order effect. In the present study methylphenidate treated rats exhibited an increased in Passive Avoidance learning as there was increased in the latency time to reach the punished compartment as compared to control rats. This memory improvement effect of methylphenidate on PA was dose dependent in 1[st] week as the rats treated with 8 mg/kg/day took greater time to reach the dark box than 5mg/kg/day and 2mg/kg/day, but in 2[nd], 3[rd] and 4[th] week it was seen that rats treated with fore mention doses took same time but greater than 1[st] week to enter the punishable compartment. It can be concluded that high dose produce greater cognitive effect in short term treatment than low and moderate doses, however in long-term treatment all the doses produce similar improvement in memory without tolerance in cognition

Comparison on hepatotoxicity profile of diclofenac sodium and diclofenac potassium on rabbits

Aim of this study was to determine the clinical hepatotoxicity of diclofertac sodium and of diclofenac potassium, further to evaluate whether these drugs could elicit liver cell destruction and anemia, and which drug is comparatively safer for prolong use. Experimental study. This study was conducted in the Department of Pharmacology; Faculty of Pharmacy, University of Karachi, Duration of study was 30 days. Male 50 rabbits were equally divided into 5 groups, group A was served as control and the group B and C were diclofenac sodium [0.8mg/kg/day and 1.5mg/kg/day], and group D and E were of diclofenac potaasium [0.8mg/kg/day and 1.5mg/kg/day], treated. All the animals were caged in pair in an iron caged with free access to grass and hay of standard diet and tap water for a period of 30 days. At the end of 30 days blood was collected through cardiac puncture from each rabbit and was analyzed to determine the levels of SCOT, SGPT, Bilirubin, ESR and Erythrocyte count. The experimental results suggest that SCOT and SGPT levels were significantly increased in diclofenac sodium treated rabbits after 10 and 30 days [P < 0.01], while diclofenac potassium treated rabbits showed significant result, [P < 0.05] only after 30 days of treatment. The level of bilirubin was significantly increased in diclofenac sodium treated rabbits after 10 days and 30 days [P < 0.01] and diclofenac potassium also showed significant result [P < 0.05] after 30 days treatment. Erythrocyte count decreased in both control and treated rabbits after 10 days but control results are not significant. After 30 days diclofenac sodium showed highly significant decreased count of erythrocytes [P < 0.01] but diclofenac potassium showed only significant results [P < 0.05]. E.S.R values significantly increased in diclofenac sodium and diclofenac potassium treated rabbits after 10 days and 30 days. Our study concluded that as compared to sodium, potassium salt of diclofenac is safer for prolong pain management as the incidence of adverse effects were comparably lower in potassium salt

Chamomile tea: Herbal hypoglycemic alternative for conventional medicine

Chamomile is considered as one of the oldest and also documented as medicinal plant. It has shown to be an anti-inflammatory, astringent and antioxidant especially in floral part since ancient times. Recent studies reported that chamomile has potential to lower blood sugar levels in hyperglycemia

In the present study we have investigated the pharmacological effects of chamomile tea on fasting and post prandial glucose levels and HbAlC in blood of diabetic rats [alloxan induced] and the results were compared with glibenclamide as standard. Statistical analysis was performed using SPSS. It has been observed in our study that it has reduced progressively the fasting and post prandial blood sugar levels, significantly in alloxan induced diabetic rats particularly on day 30and 60

It also reduced the level of HbAlC significantly at the end of the study and the effects were similar to that of the standard group

Chamomile tea administration has also controlled the reduction in weight in diabetic rats as compared to diabetic control and the results were not very much different from standard. Results from the present study indicate that chamomile tea have a glucose lowering effect in diabetic rats so its daily consumption can be potentially useful in hyperglycemia and it can be used as a substitute of conventional drug treatment. Further studies are necessary to elucidate the exact molecular mechanism involved in anti-diabetic action of chamomile

Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats treated with theophylline and caffeine

Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine [5-HT] acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine [m-CPP] at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine [a component of coffee and tea] or theophylline [a component of tea] as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may, attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed