Alpha-tocopherol ameliorates nephrotoxicity associated with the use of colistin in rabbits

The alarming rise in the rate of multi drug resistant, life threatening gram negative infections has brought renaissance in the use of Colistin for last two decades. The major constraint in its utilization is its nephrotoxicity. Therefore it is being underused which is favoring the development of resistance. This study assesses the prevention of nephrotoxicity associated with high and low toxic doses of Colistin by alpha-tocopherol. Thirty rabbits were randomly divided into five groups. Baseline serum urea, creatinine and electrolytes were estimated. A loading dose of colistin was given in the form of infusion followed by I.M injections for six days. In the preventive groups alpha-tocopherol was additionally given orally for two weeks. Rabbits were sacrificed 24 hours after the last dose. The kidney slides graded and statistically analyzed using [chi square]. The results of serum analysis were compared using one way analysis of variance followed by post hoc tukey test. There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident. Alpha-tocopherol attenuated the renal insult in both the toxic groups. As damage induced by colistin is oxidative in nature, thus it was concluded that the protection offered by alpha- tocopherol is due to its antioxidant activity

Potentiating effect of rifampicin on methimazole induced hepatotoxicity in mice

Methimazole [MMI] is a widely used drug for hyperthyroidism. However, its clinical use is associated with hepatotoxicity. Though the precise mechanism of hepatic damage is still far from clear, role of metabolic activation and reactive metabolites have been implicated. The present study was designed to investigate the role of enzyme induction in bio activation based hepatotoxicity of methimazole in mice. Thirty male mice were randomly divided into five groups. Hepatotoxicity was induced by single intraperitoneal injection of methimazole [1000mg/kg]. Pretreatment with rifampicin which is a potent enzyme inducer was carried out for 6 days prior to administration of methimazole. The extent of hepatic damage was determined by measuring serum alanine aminotransferase [ALT] and alkaline phosphatase [ALP] along with histopathological grading of liver samples. The elevated levels of biochemical markers by methimazole were potentiated by pretreatment with rifampicin. This potentiation of hepatic injury was also observed in liver histopathological examination. These findings suggest induction of microsomal enzymes as a potentiating factor of methimazole induced hepatotoxicity

Effect of Dicloefnac Sodium on Aspirin's Antithrombotic role

Objective: To assess whether diclofenac sodium interferes with the anti-platelet effect of low dose aspirin

Study Design: Quasi-experimental study

Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College and Armed Forces Institute of Pathology Rawalpindi

Material and Methods: Eighteen healthy volunteers, divided into three groups, between the ages of 22-50 years, after written informed consent were selected according to a set criterion. They were given aspirin [150mg] once a day and diclofenac sodium 50mg three times a day for six consecutive days while use of any other drug was prohibited. Blood samples were taken from the study subjects on two occasions, before starting drugs and then on the seventh day. Blood samples were analyzed for platelet aggregation [ADP and collagen induced] and serum thromboxane B2 levels

Results: When a single daily dose of 150mg aspirin is taken with three daily doses of diclofenac sodium [50mg], results show that the anti-platelet effect of aspirin still remains. The mean platelet aggregation with ADP was reduced to 55.83 +/-- 5.38 percent from a baseline value of 71.67 +/-- 5.27 percent. Similarly if collagen was used as a reagent the aggregation of platelets was markedly reduced to 40.83 +/-- 6.63 from a baseline of 66.67 +/-- 6.54 percent. Results showed a prominent inhibition of aggregation of 22.10 percent for ADP and 38.75 percent for collagen. Also, mean thromboxane B2 levels reduced markedly from 971.11 +/-- 128.91 pg/ml to 702.99 +/-- 101.59 pg/ml

Conclusion: It is safe to use diclofenac sodium with aspirin, as the anti-platelet effect of the latter is not attenuated

Study of preventive effect of Melatonin on high dose Vancomycin induced Nephrotoxicity in rabbits

Objective: To explore the nephropreventive effects of melatonin on vancomycin-induced nephrotoxicity in rabbits

Study Design: Laboratory based randomized controlled trial

Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College, Rawalpindi, from May 2017 to June 2017

Material and Methods: Seventy rabbits were divided into three groups. Group A served as a control group [n=10], group B [n=30] received I/P vancomycin 200mg/kg twice a day for seven days while group C [n=30] received I/P melatonin 10mg/kg 30 minutes prior to vancomycin administration for seven days. Animals were sacrificed on the eighth day. Biochemical analysis was done for serum urea, creatinine, sodium and potassium on day 0 and day 8. Kidneys were sent for histopathology. Statistical analysis was carried out by using Microsoft Office Excel 2010 and SPSS version 21. One way ANOVA, followed by 'Post Hoc Tukey' test was used for biochemical parameters

Results: Vancomycin induced massive renal damage [grade III] and led to elevation in biochemical parameters, while melatonin pretreatment prevented the renal damage and the biochemical parameters were also significantly reduced with a p-value of <0.001 for serum urea, creatinine and potassium but had insignificant p-value for serum sodium levels

Conclusion: The study outcome indicates the potential of melatonin to prevent Vancomycin induced nephrotoxicity by virtue of its antioxidant property

Analysis of Artemether and Dihydroartemisinin by high performance high liquid chromatography in biological fluids-issues and solutions

Artemether-Lumefantrine is the most widely recommended antimalarial combination used to treat millions of patients suffering from malaria. Artemether undergoes rapid metabolism and gets converted to its active metabolite dihydroartemisisn. Drug analysis is a vital aspect to evaluate drugs in research. There are a number of methods available for the determination of artemether in biological fluids. These methods include HPLC based UV detection, GS-MS, HPLC-ECD and HPLC-MS/MS. This article reviews different methods for the determination of artemether in the biological fluids. Among the available methods HPLC-MS/MS proves to be the most accurate and reliable one for analysis. This has the advantage of improved sensitivity and selectivity with smaller sample volume

Protective effect of pioglitazone on gentamicin induced nephrotoxicity in rabbits

Objective: To evaluate potential role of pioglitazone in protecting kidneys from nephrotoxic insult produced by Gentamicin

Study design: Comparative study on animal model

Place and Duration of Study: Department of Pharmacology Army Medical College, duration of study was six months

Material and Methods: Twenty four rabbits were randomly divided into four groups [n=6]. Group [Gp]-1 received 1 milliliter [ml] isotonic saline intraperitoneally [IP] daily for 13 days. Gp-2 received gentamicin 40 miligram/kilogram/day [mg/kg/day] IP daily for 13 days. Gp-3 received pioglitazone salt 10 mg/kg/day dissolved in drinking water via feeding tube for 13 days. Gp-4 received pioglitazone salt 10 mg/kg/day via feeding tube plus gentamicin 40 mg/kg/day IP for 13 days. Blood was collected on days 0 and 14 for estimation of serum urea and creatinine. All animals were sacrificed and kidneys were removed for renal histological examination

Results: Pioglitazone did not show any nephroprotective effect against gentamicin induced nephrotoxicity

Conclusion: Pioglitazone fails to exhibit nephroprotective potential when administered along with nephrotoxic dose of gentamicin

IS CO Q10 really valuable in shielding statin induced myopathy-an exploration

Objective: This study was designed to scrutinize the shielding effects of Co enzyme Q10 [Co Q10] supplementation in statin associated muscular adverse effects in rabbits

Study Design: Randomized controlled trial

Place and Duration of Study: Pharmacology dept Army Medical College Rawalpindi from Jan 2012 to Jun 2012

Material and Methods: Twenty two healthy rabbits were taken and divided into four equal groups randomly with six in each batch. The two groups [Gl and G2] were given toxic doses of simvastatin [60mg/kg/day] with and without Co Q10 [5mg/kg/day] orally for 14 days and rest of two groups [G3 and G4] were kept on therapeutic doses [Img/kg/day] of simvastatin with and without Co Q10 [5mg/kg/day] orally for 90 days. Blood samples were drawn and serum creatinine kinase [CK] and lactate dehydrogenase [LDH] were assessed before and after the drug therapy. Histopathological examination was done to observe the inflammatory changes under light microscope. The results were analyzed by applying paired [t] test, independent [t] test and ANOVA test for biochemical markers and 'Chi-Square test' for histopathologcal findings. The p-value < 0.05 was considered significant

Results: The biochemical markers went up sharply [Gl. CK=28899.5 +/- 874.09 IU/L and LDH = 4694.33 +/- 352 IU/L] and [G2. CK = 29191.33 +/- 3019.79 IU/L and LDH = 4334.83 +/- 143.44 IU/L] as compared to baseline values

They were given toxic doses of simvastatin with and without Co Q10. Histopathological examination of muscular tissue also revealed gross inflammatory changes in these groups. However histopathological examination of groups who were given therapeutic doses of simvastatin with and without Co Q10 for 90 days showed mild to moderate inflammatory changes but serum CK and LDH remained in the normal ranges in these groups

Conclusion: Our results suggest that Co Q10 supplementation could not produce any beneficial effects on the statin induced muscular adverse effects

Establishment and comparison of nephrotoxicity associated with the use of various doses of colistin in rabbits

Objective: This study was designed to assess the nephrotoxicity associated with various doses of Colistin sulfate in rabbits

Study Design: Laboratory based randomized controlled trials, Place and Duration of Study: This study was held at Army Medical College, Rawalpindi. Study period was from 15[th] April till 30[th] April 2012

Material and Methods: Rabbits were divided into three groups of six rabbits each. Baseline serum urea, serum creatinine and serum electrolytes were estimated. A loading dose of colistin infusion was given followed by I.M injections for six days. Rabbits were sacrificed 24 hours after the last dose and both kidneys were sent for histopathology

Results: There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident

Conclusion: It was established that we may safely escalate dose of colistin up to four times the currently recommended schedule to combat the threat of resistance when using it for one to two weeks

Manual vacuum aspiration [MVA]: a safe and effective alternative for the surgical management of early pregnancy loss

Objective: To assess and document safety, efficacy and patient acceptability of Manual vacuum aspiration [MVA] in the management of early pregnancy loss [EPL], performed in the treatment room setting

Study Design: Quasi-experimental, [clinical trial]

Place and Duration of Study: Treatment Room, OBGYN department, PNS Shifa from Nov 2010 to 31[st] Mar 2013

Material and Methods: Single centre prospective study conducted at Obstetric and Gynecology department, PNS Shifa from Nov 2010 to Mar 2013. A total of 414 women with EPL consented for MVA in the treatment room under local anesthesia, out of which 400 women underwent MVA

Results: Overall MVA was 94.5% effective in treating pregnancies through 13 weeks of gestation. There were no major complications. Minor complications: retained products of conception and endometeritis were treated easily

Conclusion: MVA is safe, effective and economical alternative to conventional dilatation and curettage for the treatment of EPL. Treatment in the outpatient setting allows better post-procedure physical and emotional quality of life; avoids general anesthesia, has immense potential in primary health care setting

Polymorphisms of the ABCB1 gene in the pakistani population

To investigate the frequency of the single nucleotide polymorphism C1236T in exon 12 of the ABCB1 gene in Pakistani population and to compare it with published data on Asian and Caucasian populations. A cross-sectional observational study. Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering [IBGE], Islamabad, from August 2012 to May 2013. C1236T polymorphism was investigated in 426 Pakistani subjects. The frequency was compared with the published data on other Asian and Caucasian populations. The frequencies of ABCB1 C1236T were 16.4% for CC, 44.1% for CT and 39.4% for TT. Pakistanis differed significantly from all the European populations compared in the distribution of the TT genotype of C1236T ABCB1 [p < 0.05]. The Pakistani population also differed significantly from some of the European populations in the distribution of CC and CT genotype [p < 0.05]. There was significant difference in the genotype frequency of the ABCB1 gene compared to other populations. This study has provided a framework for future pharmacogenetic and pharmacokinetic studies on this polymorphic variant of ABCB1 gene in the Pakistani population

Association of anti-emetic efficacy of ondansetron with G2677T polymorphism in a drug transporter gene ABCB1 in Pakistani population

To determine the association of ABCB1polymorphism G2677T with anti-emetic efficacy in patients treated with ondansetron for preventing postoperative nausea and vomiting. A clinical trial. Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering, Islamabad, from 2012 to 2013. Four mg ondansetron was administered intravenously 30 minutes before the end of surgery. A total of 246 patients with the complaints of nausea and vomiting and 244 patients without nausea and vomiting were analyzed for G2677T polymorphism using PCR-RFLP method. Results were described as frequency percentages and chi-square test with significance at p < 0.05. The patients with TT genotype had significantly lower incidence of postoperative nausea and vomiting during the first 2 hours [p < 0.001] and between 2 - 24 hours after surgery as compared to other genotypes [p < 0.001]. The patients with GG genotypes had significantly higher incidence of this complaint [p=0.014]. Polymorphism of ABCB1 has an association with responsiveness for ondansetron. There is a role for genetics in the management of PONV

Prevalence of cyp2d6*4 genotype and its association with tamoxifen induced hot flashes in Pakistani female breast cancer patients

To investigate the frequency of CYP2D6*4 in Pakistani breast cancer patients for the first time and also investigate its association with tamoxifen induced hot flashes. A retrospective study carried out in Nuclear Medicine, Oncology and Radiotherapy Institute [NORI] Islamabad and Combined Military Hospital Rawalpindi [CMH]. Pre and postmenopausal breast cancer women who were advised 20mg/day of tamoxifen as adjuvant therapy were recruited for the study. The data from January 2000 to September 2013 was collected from the medical records of the outpatient breast cancer clinics. 232 women who fulfilled the eligibility criteria were initially recruited and their peripheral whole blood samples were taken. CYP2D6*4 was determined by using PCR-RFLP, allele*4 was not identified in 9 women and study was conducted on 223 women. None of the women died during the study period. Data of 223 women was analysed and the allele frequency of CYP2D6*1 was 86% and that of CYP2D6*4 was 14%. Women with CYP2D6*4/*4 did not experience mild to moderate or severe hot flashes as compared to women heterozygous or homozygous for wild type allele *1. The frequency of CYP2D6*4 allele in Pakistani breast cancer women is 14% which is comparable to the Caucasians moreover CYP2D6*4/*4 genotypes have lower incidence of hot flashes, but the results are not statistically significant

Hepatotoxicity; preventive and therapeutic role of dexamethasone in LPS/Endotoxin induced

Background of Study: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria being one of it. Mortality remains very high in septic patients despite the advanced treatments rendered in intensive care units due to multiple organ damage including hepatotoxicity

Study Design: Randomized controlled laboratory trial

Period: 04 months from March 2014-June 2014. Setting: Department of Pharmacology and Therapeutics, Army Medical College, NUST, Rawalpindi

Aim of the Study: The present study was undertaken to learn dexamethasone's competence in prevention and treatment of LPS/ endotoxin induced hepatotoxicity in mice

Material and Methods: Endotoxin induced hepatotoxicity was reproduced via LPS of serotype E.Coli O111:B4 administrationintraperitoneally at a dose of 10mg/kg and all mice were sacrificed 17 hours latters. Dexamethasone [3mg/kg of b.w. i.p] was given 30 minutes before LPS in separate set of animals to determine its preventive role. Whereas therapeutic efficacy was adjudged by giving dexamethasone 2 hour after LPS administration. Hepatotoxicity was determined by estimation of serum ALT and AST and histopathological analysis of liver sections

Results: LPS administration was associated by statistically elevated serum ALT and AST and marked hepatic inflammation. Dexamethasone was efficacious in a version of LPS induced hepatic dystrophy both when given as pre and post-treatment. Serum ALT and AST were statistically lower when compared to LPS group. Also hepatic inflammation was statistically lessened by dexamethasone

Conclusion: Low dose dexamethasone has beneficial role in reduction of LPS/endotoxin induced hepatic injury in experimental model of sepsis

Determination of the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits: a comparative study

To determine the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits. Comparative experimental study. The animal house of Army Medical College, Rawalpindi, and the pathology department of Army Medical College, Rawalpindi, from July 2009 to January 2010. The effects of levofloxacin on gentamicin-induced nephrotoxicity were evaluated in rabbits. Twenty four rabbits were used in this study which were randomly divided into four groups [n= 6 in each group]. Six animals were injected for 15 days with saline [NaCl; 0.9%], six with gentamicin alone at doses of 20 mg/kg of body weight/12 h [intramuscularly], six with combination of gentamicin [20 mg/kg/12 h] with low therapeutic doses of levofloxacin [30 mg/kg/24 h] and the last six were treated with gentamicin and high therapeutic doses of levofloxacin [50 mg/kg/24 h]. Levofloxacin was given by intraperitoneal route. Gentamicin induced nephrotoxicity was evaluated by histopathological and serum analysis. The extent of nephrotoxicity was significantly increased when gentamicin was given in combination with levofloxacin both in low and high doses. Levofloxacin enhances gentamicin induced nephrotoxicity and extent of this nephrotoxicity increased with increasing dose of levofloxacin

case control study of risk factors associated with female breast cancer

To find the association of various risk factors with breast cancer. It was a case-control study. The study was carried out in NORI Hospital Islamabad and Combined Military Hospital Rawalpindi between August, 2013 and February, 2014. Two hundred breast cancer patients and 200 control subjects were inducted. A short approved and planned questionnaire was used to collect data regarding basic demographic, menstrual and reproductive characteristics of participating females. Cases and controls were then interviewed after taking written consent. Breast cancer patients and control subjects did not differ regarding age [p = 0.15], early menarche [OR for menarche at <13 years vs. >/=13=1.3, 95% CI = 0.84 - 2.02], and history of breast cancer in 1st degree relatives did not increase breast cancer risk [OR = 1.0, 95% CI = 0.57- 1.74]. Nulliparous women had significantly higher risk than parous women [OR = 2.43, 95% CI = 1.22 - 4.84] and women with late menopause compared to women with early onset of menopause were also at higher risk for breast cancer [OR for menopause at >/= 50 vs. < 50 = 5.16, 95% CI = 2.59 - 10.29]. Nulliparity and menopausal age of more than 50 years was associated with increased breast cancer risk. Breastfeeding and age less than 25 years at first live birth was not protective against breast cancer

Effect of smoking on nausea, vomiting and pain in the post-operative period

Objective: To determine the effect of smoking on the post-operative nausea and vomiting [PONV] as well as severity of pain in the post-operative period

Methodology: A total of 147 patients undergoing elective laparoscopic cholecystectomy under general anesthesia were divided into 2 groups of non-smokers [n=75] and smokers [n=72]. In the first 24 hours after surgery the frequency of PONV and the severity of pain on Visual Analogue Score were assessed

Results: The group of non-smokers had statistically more nausea and vomiting [n=59, 78.6%] as compared to that of smokers [n=20, 27.7%] [p<0.05]. However there was no significant difference in the maximum pain scores in both the groups [p>0.05]

Conclusion: We conclude that frequency of PONV is less in smokers as compared to non-smokers

Protective effect of metformin against gentamicin induced nephrotoxicity in rabbits

Gentamicin is used against gram negative infections, but major problem encountered is nephrotoxicity that occurs in 10-20% of therapeutic regimes. Gentamicin induced oxidative stress plays an important role in this nephrotoxicity. Recent data has shown metformin to possess antioxidant activity. Purpose of study was to evaluate potential role of metformin in protecting kidney from nephrotoxicant insult. Thirty-six rabbits were randomly divided into six groups [n=6]. G-1 received 1 ml isotonic saline intraperitoneally [IP] daily for 13 days. G-2 received gentamicin [150 mg/kg/day] IP for last 6 days of 13 days. G-3 received gentamicin [40 mg/kg/day] IP for 13 days. G-4 received metformin salt [100 mg/kg/day] dissolved in drinking water via feeding tube for 13 days. G-5 received metformin salt [100 mg/kg/day] via feeding tube for 13 days plus gentamicin [150 mg/kg/day] IP for last 6 days of 13 days. G-6 received gentamicin [40 mg/kg/day] IP plus metformin salt [100 mg/kg/day] via feeding tube for 13 days. Blood was collected on days 0 and 14 for serum urea and creatinine estimation. All animals were sacrificed and kidneys were removed for renal histological examination. Metformin showed nephroprotective effect. It blunted nephrotoxic insult at 150 mg/kg/day of gentamicin, whereas showed complete nephroprotection at 40 mg/kg/day of gentamicin. Metformin offers complete nephroprotection at low toxic dose ranges of gentamicin. This could offer an efficacious and cheaper treatment alternative in those diabetics who also suffer from gram-negative infections

Antidiabetic actions of powdered plant and aqueous extract of allium sativum [Garlic] bulbs in type-II diabetic patients

To study hypoglycemic properties ofpowdered plant and aqueous extract of Allium sativum [Garlic] bulbs in type-II diabetics. Experimental human study. This study was conducted at the Hamdard Institute of Pharmaceutical Sciences Islamabad and Army Medical College Rawalpindi from_. The study was performed on 45 humans, which were divided into 3 groups i.e. Group A, B and C. Group A comprises of 15 patients of type-II diabetes, taking no drugs for diabetes. Group B comprises of 15 patients of Type-II diabetes taking oral hypoglycemic agents with inadequate control of blood sugar levels. Group C was control group, containing 15 healthy volunteers. The study was divided into 2 phases. Initially, after baseline sampling for blood glucose and urinary glucose, all the subjects were given powdered bulbs of Allium sativum orally, at low [20 mg/kg/d], intermediate [30 mg/kg/d] and high [45 mg/kg/d] doses, for 14 days. At day 15, blood and urine sampling was done. After 1 week, all the subjects were administered aqueous extract of Allium sativumbulbs orally, at low [20 mg/kg/d], intermediate [30 mg/kg/d] and high [45 mg/kg/d] doses, for 14 days. At the end, sampling was done again. Both dry powdered plant and aqueous extract of bulbs of Allium sativum [Garlic] decrease blood and urine glucose levels in type-II diabetics, especially in the groups who were taking oral hypoglycemics and had inadequate control of blood glucose previously. Allium sativum has significant hypoglycemic activity, particularly in high dose, and can be combined with oral hypoglycemic agents in type-II diabetics

Effects of rocuronium pretreatment on muscle enzyme levels following succinylcholine

Succinylcholine revolutionized anaesthetic practice by providing intense neuromuscular blockade of very rapid onset and ultrashort duration, thereby greatly easing the maneuver of tracheal intubation. However the worth of succinylcholine is limited by the frequent occurrence of muscular side effects which manifest biochemically in the form of rise in serum creatine kinase [CK]. The administration of small doses of nondepolarizing muscle relaxants before the administration of succinylcholine has been shown to decrease the incidence and severity of muscular side effects experienced by the patients. This study was aimed at evaluating the efficacy of technique in reducing the muscular side effects of succinylcholine, biochemically manifested as rise in CK. Sixty healthy adults were enrolled in the study who were scheduled for minor muscle cutting surgeries under general anaesthesia. They were assigned at random to two groups of thirty patients each. They randomly received succinylcholine for intubation and a precurarization dose of rocuronium followed by succinylcholine for intubation. Blood samples were drawn for estimation of serum creatinine kinase. There was a significantly raised CK in the succinylcholine group. In the precurarization group the rise in CK was prevented and the levels were significantly less as compared to the group which received succinylcholine alone. Present study concluded that precurarization with rocuronium was effective in reducing the succinylcholine-induced rise in creatinine kinase