Comparative study of telmisartan with pioglitazone on insulin resistance in type 2 diabetic mice

Objective: To evaluate and compare the effects of telmisartan and pioglitazone on peripheral insulin resistance in diabetic mice

Study Design: Randomized control trail

Place and Duration of Study: National Institute of Health, Islamabad and pharmacology dept, Army Medical College, from 17th March to 17th June 2014

Material and Methods: Twenty four BALB/c mice, both male and female, of 35 to 40 grams were used for this study. Animals were randomly divided into four groups. Two were taken as control groups, one was normal control and the other was diabetic control. Two were taken as interventional groups and received either pioglitazone or telmisartanfor four weeks after induction of diabetes

Results: After treatment, pioglitazone reduced all the biochemical parameters significantly when compared with diabetic control. Negative correlation between glucose and insulin was changed into positive correlation [r-value, 0.92] with significant p-value [0.015] in pioglitazone treated group, while telmisartan only managed to convert a negative correlation between insulin and glucose into statistically non-significant positive

Conclusion: Telmisartan although reduces glucose levels and improves beta cell mass but the effect is statistically non-significant as compared to pioglitazone. In hypertensive type 2 diabetics a combination of these two drugs may help in reducing the dose of pioglitazone and consequently the cardiovascular adverse effects of pioglitazone

Ondansetron: a newer aspect of dose response relationship on ileal smooth muscles of rabbit

There are several life threatening deadly diseases in our world but 'Cancer' out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting [CINV]. Ondansetron, a 5-HT[3] receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups [n=6] and ileal smooth muscles activity was recorded on power lab [USA]. The effects of increasing concentrations of acetylcholine, serotonin and ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration [1ml] of ondansetron [10 Omega M] were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10 PSI M it was 28.8%, whereas with 10XI M the amplitude decreased to 16.87%, it reached to plateau at 10 Omega M. Response of acetylcholine and serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron [10 Omega M]. Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist

Ranitidine potentiates the effect of metoclopramide on gastro-intestinal motility in rabbits

Objective: To explore the synergistic potential of ranitidine on prokinetic activity of metoclopramide on isolated duodenal model of rabbit

Study Design: Laboratory based randomized controlled trial

Place and Duration of Study: Multi-disciplinary Laboratory, Army Medical College, Rawalpindi with study duration of 12 months

Material and Methods: Dose response curve of ranitidine and metoclopramide were constructed by adding cumulatively increasing concentrations of the two drugs on isolated duodenum of rabbits separately. A fixed dose of ranitidine was then selected for studying its potentiating effect on increasing concentrations of metoclopramide on isolated duodenum of rabbits utilizing iWorx Data acquisition unit AHK/214

Results: Ranitidine enhances the prokinetic effect of metoclopramide

Conclusion: Ranitidine enhances the contractile effect of the gut in vitro and potentiates the prokinetic effect of metoclopramide. So we conclude that ranitidine is a better choice for patients suffering from gastroesophageal reflux disease [GERD] along with gastroparesis as it enhances the prokinetic effect of metoclopramide

Early detection of doxorubicin-induced cardiotoxicity and its prevention by carvedilol.

Background: The objective was to detect doxorubicin (Dox) - induced myocardial injury at early stage by quantitative estimation of cardio specific protein, cardiac troponin I (cTnI) and to explore the cardioprotective effects of carvedilol. Methods: The study design was lab-based randomized controlled in-vivo in rabbits conducted from January to August 2012. Cardiotoxicity was produced by single intravenous injection of 12 mg/kg body weight (BW) of Dox in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pre-treated with carvedilol 30 mg/kg of BW for 10 days before injecting Dox. Results: Dox induced cardiotoxicity was depicted by markedly raised serum levels of cTnI, creatine kinase-MB, lactate dehydrogenase, and Grade 3 necrosis of the heart tissue in rabbits. The pre-treatment with carvedilol resulted in improved serum levels of these biomarkers and the histological picture of heart tissue. Conclusions: Quantitative serum estimation of cTnI detects the presence of cardiotoxicity much before cardiac dysfunctions can be revealed by any other diagnostic technique. It can lead to significant economic impact in the management of cancer patients because the troponin-negative subjects can be excluded from long-term cardiac monitoring programs that involve high costs imaging techniques. The outcome of Dox chemotherapy can be made successful with the concurrent use of carvedilol.

comparative study of the beneficial effects of ipratropium and beclomethasone against insulin-induced tracheal tissue contraction in a guinea pig model

To evaluate the acute effects of insulin on airway reactivity and the protective effects of beclomethasone and ipratropium against insulin-induced airway hyperresponsiveness on isolated tracheal smooth muscle in a guinea pig model. Materials and The trachea of each guinea pig was excised; one end of the tracheal strip was attached to the hook of the oxygen tube of a tissue bath and the other end was connected to a research-grade isometric force displacement transducer. The effects of varying concentrations of insulin [10[-7] to 10[-3]M] and insulin pretreated with a fixed concentration of beclomethasone [10[-6]M] and ipratropium [10[-6]M] on the isolated tracheal tissue were studied by constructing cumulative concentration-response curves. Changes in tracheal smooth muscle contractions were recorded on a 4-channel oscillograph. The means +/- standard error of the mean of the maximum amplitude of contraction with increasing concentrations of insulin and of insulin pretreated with fixed concentrations of beclomethasone and ipratropium were 35 +/- 1.13, 22 +/- 1.15 and 27.8 +/- 1.27 mm, respectively. The data showed that beclomethasone inhibited the contractile response of insulin to a greater extent than ipratropium. Thus we suggest that inhalational insulin pretreated with beclomethasone may be more efficacious than with ipratropium for the amelioration of potential respiratory adverse effects such as bronchoconstriction

Comparative study of protective effects of salbutamol and beclomethasone against insulin induced airway hyper-reactivity on isolated tracheal smooth muscle of guinea pig

Inhalational insulin was withdrawn from the market due to its potential to produce airway hyper-reactivity and bronchoconstriction. So the present study was designed to explore the acute effects of insulin on airway reactivity of guinea pigs and protective effects of salbutamol and beclomethasone against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Effects of varying concentrations of insulin [10[-7] to 10[-3] M], insulin pretreated with fixed concentration of salbutamol [10[-7] M] and beclomethasone [10[-6] M] were studied on isolated tracheal tissue of guinea pig by constructing cumulative concentration response curves. Changes in tracheal smooth muscle contractions were recorded on four channel oscillograph. The mean +/- SEM of maximum amplitudes of contraction with increasing concentrations of insulin, insulin pretreated with fixed concentration of salbutamol and beclomethasone were 35 +/- 1.13 mm, 14.55 +/- 0.62 mm and 22 +/- 1.154 mm respectively. Although salbutamol and beclomethasone both had a profound inhibitory effect on insulin induced airway hyper-reactivity, yet salbutamol is more efficacious than beclomethasone. So we suggest that pretreatment of inhaled insulin with salbutamol may be preferred over beclomethasone in amelioration of its potential respiratory adverse effects such as bronchoconstriction

Early detection of doxorubicin-induced cardiotoxocity and its prevention by d-tocopherol

To detect doxorubicin-induced myocardial injury by quantitative estimation of cardiospecific protein, Cardiac Troponin I [cTnl] at early stage and to evaluate the cardioprotective effects of a-Tocopherol. Lab based randomized controlled in-vivo study in rabbits. Department of Pharmacology in collaboration with Pathology department, Army Medical College Rawalpindi, Pakistan from Jan 2012 to Dec 2012. Eighteen healthy male adult rabbits were used. Cardiotoxicity was induced by single intravenous injection of 12 mg/kg of doxorubicin in a group of rabbits, control group was treated with normal saline only and the rabbits of third group were pretreated with a- Tocopherol 200 mg/kg of body weight for ten days before injection of doxorubicin 12 mg/kg. Doxorubicin produced severe cardiotoxicity confirmed by markedly raised serum levels of cTnl, CK-MB, LDH and grade 3 necrosis of the heart tissue in rabbits. The pre-treatment with a-Tocopherol resulted in improved serum levels of cTnl and the histological picture of heart tissue. The quantitative cTnl estimation for detection of cardiotoxicity at subclinical level can lead to significant economic impact in management of cancer patients because the troponin-negative subjects can be excluded from long term cardiac monitoring programs, which require high cost imaging techniques. Furthermore, the outcome of most potent and widely used doxorubicin chemotherapy can be made successful with the concurrent use of alpha-Tocopherol

Prevention of insulin induced airway hyper-reactivity with montelukast on isolated tracheal muscle of Guinea Pig

To explore the inhibitory effects of montelukast against insulin induced tracheal smooth muscle contraction of guinea pigs in vitro. Inhalational insulin was withdrawn from market in 2007 due to its potential to produce airway hyper-reactivity and bronchoconstriction. So we investigated the acute effects of insulin on airway reactivity and protective effects of montelukast against insulin induced airway hyper-responsiveness on isolated tracheal smooth muscle of guinea pig. Experimental study. This study was conducted in the Department of Pharmacology, Army Medical college Rawalpindi from December 2011 to June 2012. Effects of increasing concentrations of histamine [10[-8]- 10[-3] M], insulin [10[-8]- 10[-3] M] and insulin pretreated with fixed dose of montelukast [10[-5] M] were studied on isolated tracheal tissue of guinea pig. The tracheal smooth muscle contractions were recorded with Transducer on Four Channel Oscillograph.: Histamine and insulin produced a concentration dependent reversible contraction of isolated tracheal muscle of guinea pig. The mean +/- SEM of maximum amplitude of contraction with histamine was 92.5 +/- 1.20 mm as compared to 35 +/- 1.13 mm in insulin treated group. The maximum amplitude of contraction achieved with insulin in the presence of montelukast was 34.5 +/- 1.024 mm. Montelukast did not significantly inhibit the contractile response of insulin on isolated tracheal muscle of guinea pig, so pretreatment of inhaled insulin with montelukast has no clinical implication in amelioration of its respiratory adverse effects such as bronchoconstriction