Search

Stress is associated with high risk of psychological disorders and cognitive impairment. Psychostimulants are known to enhanced cognition but prolong use causes behavioural sensitization. The locomotor response to psychostimulant potentiated after repeated exposure to stressful stimulus & dopamine play a major role in sensitization-like phenomena. The present study is conducted to visualize responsiveness of dopamine D2 receptors by challenge dose of haloperidol following long term psychostimulant administration in restrained & unrestrained rats. Behavioural Effects of oral methylphenidate (10mg/kg/day 2 times daily) & modafinil (75mg/kg/day once daily) administration in restrained (exposed to immobilization stress for 2 hours daily) and unrestrained rats were monitored for 35 days till the behavioral sensitization produced by using home cage (performed after every two days), open field, Head Dip Test and passive avoidance test (PAT) weekly. The effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 35 days of treatment using Home Cage, Open Field, Head Dip and PAT, 30-, 60-, 90- & 120-minutes post injection. The result shows that restrained stress potentiate stimulant-induced behavioural sensitization, produced cognitive deficits and decrease exploratory activity but both stimulants improved cognitive performance and exploratory activity in PAT and head dip test respectively effect was more pronounced in modafinil treated rats. Challenge dose of haloperidol ameliorated motor activity in Home Cage and Open Field, impaired cognition in PAT and decreased activity in head dip test, effect was significant in psychostimulant treated rats but more pronounced in saline treated restrained and psychostimulant treated restrained rats which could be due to supersensitization of D2 receptors that leads to increased sensitivity of stress on stimulant induced behavioural sensitization. This study will help to investigate drugs that could prevent psychostimulant induced behavioural sensitization in stressful environment by understanding of neurobiological basis of the effect of psychostimulants on stress induced motor and cognitive deficits.

Stress is associated with high risk of psychological disorders and cognitive impairment. Psychostimulants are also known to potentiate cognition & ameliorate depression, but their long-term use causes behavioural sensitization. The locomotor response to psychostimulant potentiated after repeated exposure to stressful stimulus & dopamine is thought to play a major role in sensitization-like phenomena. The present study is conducted to visualize responsiveness of dopamine D2 receptors by challenge dose of haloperidol following long term psychostimulant administration in restrained & unrestrained rats. Behavioural Effects of oral repeated administration of methylphenidate (10mg/kg/day 2 times daily) & modafinil (75mg/kg/day once daily) in restrained (exposed to immobilization stress for 2 hours daily) and unrestrained rats were monitored to observe locomotor sensitization, by using familiar environment of home cage (performed after every two days) and novel environment of open field (weekly) however, exploratory activity in Head Dip Test and cognitive activity in passive avoidance test (PAT) were carried out weekly for 35 days (till the behavioral sensitization produced). Effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 35 days of treatment using Home Cage, Open Field, Head Dip and PAT, 30-, 60-, 90- & 120-minutes post injection. The result shows increase in locomotor activity in drug treated rats potentiated by restrained stress and sensitization effect was significant in 3rd week of psychostimulant administration and was more pronounced in modafinil treated rats. Exploratory activity in Head dip test reduced by restrained stress whereas potentiated by MOD & MPH in unrestrained rats. In restrained rats only MOD prevents stress-induced effect on exploratory behaviour. Restrained stress produced cognitive deficits but MOD and MPH improved cognitive performance in PAT. Challenge dose of haloperidol ameliorated motor activity in familiar and novel environment, impaired cognition in PAT and decreased activity in head dip test, effect was more pronounced in psychostimulant treated restrained mice. This study will be beneficial for the understanding of neurobiological basis of the effect of psychostimulants on stress induced motor and cognitive deficits so helpful to investigate drugs that could prevent psychostimulant induced behavioural sensitization in stressful environment

Methylphenidate (MPH) is a psychostimulant, beneficial in attention deficit hyperactivity disorder (ADHD). Previously it has been shown that MPH-induced locomotor sensitization could be attenuate by buspirone co administration however the effect of chronic MPH and co-administration of MPH-buspirone on biochemical and hematological parameters are unknown. This study is designed to investigate these parameters after long term administration of MPH, Buspirone and their combination in rats. 40 male Wister rats were divided in to 4 groups, and treated with saline, MPH (2mg/kg/day), Buspirone (10mg/kg/day) and MPH-Buspirone co-administration (2mg/kg/day ±10mg/kg/day; respectively) up to six weeks. Administration of MPH significantly increase blood glucose level in saline treated control rats, however co-administration of MPH-buspirone exhibited less effect on blood glucose levels. Serum creatinine levels significantly decreased in all treated groups as compared to control but highly significant results were seen with combination treatment. Co-administration of MPH-buspirone and buspirone treated rats exhibited increased cholesterol and hemoglobin values. All treated groups showed increased values of hematocrit, MCV, MCH and MCHC compared to control group. RBCs and WBC's count were decreased in all treated groups. The platelet count rose significantly by Buspirone and MPH-buspirone administration, while MPH showed decreased platelet count. Thus, results suggested that prolong co-administration of MPH-buspirone is safe and effective for ADHD patients by preventing adverse effects not only on behavioral but also on biochemical and hematological parameter.

Natural oils are rich in polyunsaturated fatty acids (PUFs) like omega 3, omega 6 and other nutrients that boost physical and mental health. Traditionally these oils have been used to treat joint pain associated with several inflammatory conditions. In this study, we investigated the antioxidant and analgesic properties of the sesame oil (SO), fish oil (FO) and combination of these two oils (SO+FO). Different concentrations of the SO, FO and SO+FO combination 0.02-4mg/ml were used for assessing the free radical scavenging activity by DPPH method and the IC50 value was calculated. Acetic acid-induced abdominal writhing test, tail immersion and hot plate models were used to determined analgesic effect. Results showed that both oils were well tolerated as no signs of toxicity or death were noticed during the observational study period. SO+FO combination showed the best antioxidant properties as shown by DPPH assay. Similarly in analgesic models, SO and FO significantly reduced the number of abdominal contractions (p0.05) however, SO+FO (1:1) exhibited highly significant results (p0.001) in writhing reflex test. Furthermore, SO and FO both increased the reaction time on a hot plate as well as in tail flick test (p0.05) whereas, SO+FO significantly increased reaction time (p0.001) in hot plate and in tail flick test as compared to SO and FO single treatments. Conclusively, our results suggest that the combination of both oils (SO+FO) exhibited significant antioxidant and analgesic potential that it could be considered as one of the active combinations for relieving pain in adjunctive treatment for joint pain associated with rheumatoid arthritis.

Drug utilization evaluation (DUE) is an arrangement of continuous, orderly, criteria-based assessment of medication utilizes to guarantee that medicines are utilized suitably. In the event that treatment is regarded to be improper, provider and patient intervention may be important to optimize therapeutic efficacy. In the present study drug utilization evaluation of Piperacillin/Tazobactam was carried out in prospective manner. A well structured data collection form was constructed to collect the related information regarding demographic, clinical use, indication, culture sensitivity criteria, outcomes of therapy, renal impairment cases of dose adjustments and appropriate use. Results of chi square indicated insignificant relationship between gender and as p value was found to be p=0.446 and 0.111 for use of drug alone and in combination. Similarly insignificant relationship between gender and use of drug in combination with other antibiotics as p value was found to be p=0.111. It was found that from 61-70 years (Therapeutic Effectiveness; n=12, 9.37%), (Therapeutic Failure; n=10, 45.45%) and mortality (n=1, 50%) were quite higher. The prescription pattern was in accordance with standard guidelines. Study indicated need to elevate prescribers to pursue generic prescribing and rationally utilize antibiotics to avert advancement of resistance at the level of hospital and community. These sorts of studies are valuable for acquiring data about medication utilize designs and for recognizing inconceivable expense of medicines.

Stress increases the susceptibility of drug abuse and drugs of abuse impair behavioral tolerance. It has been shown that stress exposure enhances the sensitivity to the reinforcing properties of drugs, augments locomotor sensitization effects of drugs of abuse and impairs behavioral tolerance. Previously, it has been shown that long-term administration of psychostimulants (Methylphenidate and Modafinil) induced locomotor sensitization effect that was more pronounced after 13 days of drug administration and was greater at high dose. The present study is designed to investigate the relationship between restraint stress and psychostimulants (Methylphenidate and Modafinil) that induced sensitization. Methylphenidate (10 mg/kg/day twice a day), modafinil (75 mg/kg/day once daily), and saline (0.9% NaCl; 1 ml/kg/day) were administered orally to treated and control animals. Rats were exposed to immobilization stress for 30 days (until locomotor sensitization produced) to monitor any change in drug-induced behavioral sensitization. The motor activity was compared daily by using familiar environment of home cage and weekly by novel environment of open field. The results show that the methylphenidate and modafinil-induced locomotor sensitization is enhanced and impaired behavioral tolerance in repeated restrained rats. It shows that the psychostimulants like methylphenidate and modafinil produce greater locomotor sensitization in stressful environment, suggesting addictive effects of stress and psychostimulants (methylphenidate/modafinil) on dopaminergic neurotransmission. These finding may be helpful to develop potential pharmacotherapies for the patients with co-occurring depression and substance abuse/dependence disorder.

Methylphenidate is a psychostimulant used for the treatment of (ADHD) attention deficit hyperactivity syndrome in children and adults. After chronic administration it is known to produce behavioral disorders including anxiety. Previous studies demonstrated that co-administration of buspirone can reduce behavioral and cognitive adverse effects produced by methylphenidate. The aim of the present study is to measure the levels vanillylmandelic acid (VMA) excretion in urine following prolong administration of methylphenidate, buspirone and their combination. Samples of urine for the estimation of the urinary VMA excretion were collected from treated and control male Wistar rats. We found significant (P0.01) raised urinary VMA excretion in methylphenidate group however significant (P0.01) reduction in VMA levels were seen after buspirone co-administration. Excretion of VMA in urine would allow the monitoring of sympatho-adrenomedullary system activity. This study could be helpful to increase the clinical use of methylphenidate in the treatment of different disoders.

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 β-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 β-lactams that may interact with mecA gene in the development of methicillin resistance mechanism in Staphylococcus.

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 co-administration 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.

Cognitive decline in Parkinson’s disease (PD) is defined as dementia which affects activities of daily living (ADL) function. Dementia is one of the recognized issues in the treatment of Parkinson’s disease patients (PDP) as it is becoming a major contributor to morbidity. The objective of our study was to evaluate the cognitive decline in Parkinson’s disease patients (PDP) and the influence of cognition on daily living function deterioration in cognitively impaired and cognitively unimpaired PDP. Cognitively impaired PDP (n = 24), and cognitively unimpaired PDP (n = 16) were administered MoCA and MMSE performance based tests for cognitive measurements and Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) to determine everyday functioning. The significances of MoCA and MMSE among cognitively impaired PDP and cognitively unimpaired PDP in univariant analysis were P < 0.001 and P < 0.05. In partial correlation, MoCA was strongly related to ADL function as compare to MMSE (r = 0.623, P = 0.001). Cognitively impaired PDP showed significantly lower score on visuo-construction and attention. Among all variables of MoCA domains, attention is strongly associated with instrumental activity daily living (IADL) scores (logistic regression coefficient = 0.672, P = 0.01). These results suggest that dementia affects daily living performances especially the IADL tasks like attention and execution. Therefore, the assessment of complex daily activities particularly IADL is probably useful for the diagnosis of early stage cognitive impairment in PDP. Further MMSE test is less sensitive than MoCA for detecting significant cognitive decline in PDP and impaired attention is an important determinant of ADL functions in cognitively impaired PDP.

Purpose: To assess the analgesic role of neuroleptics in hyperglycemic state.Methods: Amytryptiline and carbamazepine were selected for study. This study was carried out at Pharmacology lab, Institute of Research Pharmaceutical sciences, University of Karachi, and comprised of male and female mice, half of which were made diabetic by giving Alloxan. The objective of this study is to monitor the effects of neuroactive agents on analgesic activity in hyperglycemic mice.Results: It was observed that Amytryptiline exhibited highly significant analgesic effect in normal as compared to diabetic subjects. It was also observed that both amytryptiline and carbamazepine produce more rapid onset of action and longer duration of action in normal animals when compared with diabetic animals.Conclusion: The present work on normal and diabetic animals show that both Carbamazepine and Amytryptiline in normal animals produce rapid onset and longer duration of action when compared with diabetic animals.

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 co-administration 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.

Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D2-receptors are considered to be important in psychostimulant-induced sensitization. Study designed to compared the motor activity by using familiar and novel enviroments and cognitive effects by water maze and passive avoidance test after long term administration of methylphenidate(at the dose 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D2 receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13 days of drug administration were greater at high than low and medium doses.Challenge dose of haloperidol attenuate motor activity in familiar and novel environment and impaired cognition in water maze and passive avoidance test in all treated rats. The effect of Haloperidol in high dose treated rats were however somewhat greater than low and medium dose treated rats following methylphenidate and modafinil administration. Increased response of haloperidol in methylphenidate treated rats can be explained in term of supersensitization of D2 receptors which is greater in high dose treated rats. The results show that the role of D2 receptors to develop side effects such as behavioural sensitization and cognitive tolerance by the long term administration of psychostimulants is of sufficient importance and helpful in understanding the mechanisms underlying the undesirable effects of psychostimulants.

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-HT1A somatodendritic receptors. This study was designed to determine that buspirone co-administration 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 2.0 mg/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 13th 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 10 mg/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-HT1A somatodendritic receptors. These findings may help extend future therapeutics in ADHD.

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 somatodendritic 5HT-1A receptors effectiveness. Repeated buspirone administration attenuates 5-HT1A 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-HT 1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD.

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 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) 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.

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 HbA1C 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 30 and 60. It also reduced the level of HbA1C 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.

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.