Statin therapy and Vitamin D

Background: Statins are well-known drugs used in dyslipidemia and cardiac disorders since several years. Recently, it has been reported that long-term use of statins reduce serum vitamin D level. When statins are administered to patients with low vitamin D more muscular side effects have been reported. On the contrary, a few studies report that statins might increase vitamin D level competing with its metabolism. Hence, this study was conducted to evaluate the association between statins and vitamin D.Methods: 125 participants who fulfilled the selection criteria were enrolled in the study. 65 subjects belonged to control group and 60, statin group. The blood sample was collected for Vitamin D estimation. The results were correlated with a demographic profile, nature of statin and the muscular side effects and compared with control group.Results: The mean vitamin D level in statin group was 15.82 ng/ml±11.51 and 20.57 ng/ml±7.007 in the control group. The difference was found to be statistically significant.  13.85% in the control group and 10% in statin group had sufficient vitamin D level. 18.33% and 36.92 % had insufficient levels and 71.67% and 49.23% had a deficiency in the statin and control groups respectively.  Myalgia was reported by 30 among 60 subjects (50%) in statin group and 5 among 65 subjects (7.69%) in the control group.Conclusion: The present study has shown that statin therapy is associated with low vitamin D level and that this could contribute to the increased incidence of myalgia in the statin group

Effect of vitamin D on atorvastatin induced blood sugar changes in Wistar albino rats

Background: Statins are hypocholestrolemic agents used in atherosclerotic vascular disorders. They act by inhibiting hepatic hypoxanthine methyl glutaryl CoA reductase enzyme. They are reported to cause hyperglycemia as an important adverse event. This study was conducted to investigate atorvastatin induced blood sugar changes in Wistar, albino, male rats and the influence of vitamin D on the blood sugar changes. Methods: Forty, 12 weeks old male, Wistar albino rats, were selected and randomly allocated to 5 groups of 8 animals, each. Animals in Group 1 were administered normal saline orally and served as controls. Group 2 and 3 received atorvastatin 2 mg and 4 mg, respectively, orally. Group 4 and 5 received 200 IU of vitamin D along with 2 mg and 4 mg of atorvastatin respectively, orally. The drugs were administered once, every day for 3 months. Body weight and fasting blood sugar were estimated at baseline and at the end of every month for 3 months.Results: In control animals (Group 1) and animals treated with atorvastatin along with vitamin D (Group 4 and 5), fasting blood sugar levels did not change significantly and the body weight increased. In animals treated with only atorvastatin (Group 2 and 3), fasting blood sugar was significantly increased and body weight did not change.Conclusions: This study has demonstrated that chronic use of atorvastatin 2 and 4 mg may lead to fasting hyperglycemia and it could be prevented by co-administration of 200 IU of vitamin D, in male Wistar albino rats. Randomized control studies in humans are further required to recommend routine use of vitamin D in patients receiving atorvastatin

Pharmacokinetic interaction between alcohol and two of the commonly prescribed anti-hypertensive drugs-amlodipine and nebivolol

Background: Alcoholism is one of the leading causes of secondary hypertension. Many a times in clinical setting, many hypertensive patients also happen to be alcoholics, either social/moderate drinkers or suffer from alcohol dependence. For these patients, cessation of alcohol consumption is advocated and counselled as part of diet and lifestyle modifications. However, compliance rates have been found to be variable. Therefore, these patients consume alcohol and also take anti-hypertensive medications on a day-to-day basis. This study was initiated to explore influence of alcohol on the pharmacokinetics of anti-hypertensive drugs – Amlodipine and Nebivolol.Methods: 24 human volunteers were recruited for the study after obtaining informed consent. 12 volunteers each for Amlodipine, Nebivolol and alcohol’s effect on the drugs respectively were evaluated. Two standard drinks of alcohol were administered in respective period as per randomization. Clinical confinement and blood sampling was carried out as per ethics committee approved protocol in accordance with good clinical practice principles.Plasma samples were analyzed using validated LC-MS/MS bio-analytical method, for quantification of Nebivolol and Amlodipine in lines with good laboratory practice principles. Pharmacokinetic and statistical analysis of results was evaluated using WinNonlin Version 5.3.Results: The pharmacokinetic parameters were evaluated statistically and ANOVA results suggest that despite changes in individual parameters, the bioavailability was comparable, as both Cmax and AUC0-inf were well within the range of 80-125%.Conclusions: It is clearly observed that there are variations in all pharmacokinetic parameters when the drug is administered with alcohol. However, the same are well within acceptable limits and bioavailability of the drugs is comparable when administered with alcohol. Hence, two standard drinks of alcohol have limited effect on the pharmacokinetics of Amlodipine and Nebivolol. Further studies are required to evaluate influence of higher and frequent doses of alcohol on pharmacokinetics of Amlodipine and Nebivolol

BURDEN OF THERAPY IN PATIENTS SUFFERING FROM DIABETES MELLITUS AND HYPERTENSION

Objective: To estimate a) monthly expenditure for treatment of diabetes mellitus (DM), hypertension (HTN) and both (DM+HTN) and b) economic burden (EB) and psychological burden (PB) of therapy of DM, HTN and DM+HTN.Methods: An observational questionnaire-based study was conducted among 180 patients. The monthly cost of drug therapy was assessed based on the drugs they were taking and the cost of individual drugs. The EB and PB were assessed using a validated questionnaire and data analysed by ANOVA followed by post hoc test.Results: Among 216 patients who were interviewed, 180 fulfilled the selection criteria. Among 180, 75 had DM, 40 HTN and 65 had both. Prevalence of DM and DM+HTN was higher among females and of HTN equal among males and females. The average total monthly cost of therapy for DM was INR 2077, for HTN INR 1464 and for DM+HTN INR 2269.Significant correlation was found between income and percentage of expenditure (p<0.001) in all the groups. The PB was found to correlate with low income (p<0.001), poor education (p<0.05) occupation (p<0.01) in DM+HTN and number of tablets (p<0.01) in DM and DM+HTN groups.Conclusion: The cost of therapy was higher for DM+HTN and DM. The percentage of expenditure was higher in low-income group and burden of therapy was directly proportional to the number of tablets, poor educational and occupational status; and inversely proportional to income

Study to assess the prevalence of human leukocyte antigen-A*3101 allele among Indian epileptic patients and its influence on safety and efficacy of antiepileptic therapy

Background: The objective was to study the prevalence of human leukocyte antigen (HLA)-A*3101 allele among epileptic patients and to assess the safety and efficacy of antiepileptic therapy.Methods: 295 subjects were selected and divided into two groups, Group I had 192 epileptic patients and Group II had 103 normal healthy controls. After written informed consent, 30 ml of mouthwash sample was collected from each subject and DNA was extracted by standard salting-out technique and used for HLA-A*3101 genotyping by two-step nested allele-specific polymerase chain reaction amplification and agarose gel electrophoresis.Results: In Group I, 12 (6.25%) of the 192 patients were tested positive for HLA-A*3101 allele and all were taking carbamazepine (CBZ). Among them, 56 (30%) subjects had developed less severe adverse effects such as headache and giddiness, skin rashes and memory disturbances, and HLA-A*3101 was present in 8 of them while 136 had no adverse effects in which 4 of them were tested positive for the allele. In Group II, 3 (2.9%) of the 103 healthy controls were tested positive for the allele. No difference was found in response to antiepileptic therapy between allele positive and negative patients.Conclusion: The present study had shown that HLA-A*3101 is prevalent in 6.25% of the Indian epileptic population under study. The presence of this allele has a significant association with the development of mild cutaneous reactions like skin rashes. However, no difference was observed in allele positive patients in response to antiepileptic therapy in comparison with allele negative patients

High performance thin-layer chromatography and in vitro cytotoxic studies on ethanol extract of Matricaria chamomilla L (Asteraceae) flowers

Purpose: To develop a high performance thin-layer chromatography (HPTLC procedure for quantitation of apigenin in ethanol extract of Matricaria chamomilla (Babunaj) flowers, and to evaluate the extract for in vitro cytotoxic effect on MCF-7 cell lines. Methods: Quantification of apigenin was carried out using a CAMAG TLC system. A combination of toluene, ethyl acetate and formic acid (4.5:3.5:0.2 v/v/v) was used as mobile phase, with densitometry detection at 336 nm. The HPTLC procedure was subjected to validation as per ICH guidelines. The cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results: A sharp apigenin band at Rf of 0.51 was obtained, and the content of apigenin in the extract was 0.062 % w/w. The detection limit (LOD) and quantification limit (LOQ) were 0.19 and 0.57 ng/band, respectively. MTT assay results indicate that M. chamomilla was cytotoxic to Michigan Cancer Foundation-7 (MCF-7) cells, with half-maximal concentration (IC50) of 74 µg/mL. Conclusion: The developed HPTLC method is linear, precise, accurate and specific for the determination of apigenin. M. chamomilla exerts cytotoxic effect on MCF-7 cell line via induction of apoptosis

Evaluation of mosquitocidal activity of <i>Annona squamosa </i>leaves against <span style="font-size:14.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";color:black;mso-ansi-language:EN-IN; mso-fareast-language:EN-IN;mso-bidi-language:HI" lang="EN-IN">filarial vector mosquito, <i>Culex quinquefasciatus </i>Say</span>

363-365  Methanolic extract of leaves of A.squamosa was tested for mosquitocidal effect against C.quinquejasciatus. A liquid mosquito insecticide formulation was prepared with the extract (1, 3 and 5 %w/w) using deodorized kerosene as solvent and investigated for its knock-down and 24 hr mortality. The extract formulation produced dose dependent activity, exhibited significantly shorter knock down KD50 and KD90 values and produced significant mortality. The results suggest the potential mosquitocidal effect of A.squamosa on C.quinquefasciatus.</span

Elucidation of the lesions present in the transcription defectivefitA76 mutant ofEscherichia coli: Implication of phenylalanyl tRNA synthetase subunits as transcription factors

Earlier reports from our laboratory dealt with the identification, mapping and characterization of a temperature sensitive mutant (fitA76) with a primary transcription defect at 42‡C and two of its suppressors (fitA24 andfitB). We report here the cloning and molecular characterization of a 2-1 kb DNA fragment which complemented the Ts phenotype of thefitA76 andfitA24 mutants but not that due to thefitB mutant. Cloning of this fragment in the T7 expression vector pT7.5 revealed the synthesis of a 33 kDa protein. The fragment hybridized with the Kohara phages 322 and 323 whose overlapping regions includepheS,pheT andrplT genes. Nucleotide sequencing showed that the fragment contains the entirepheS gene and the N-terminal portion ofpheT. Although these results implied that thefitA andpheS genes could be one and the same, earlier data had ruled out such a possibility. In order to know whether thefitA76 mutation defines a novel allele ofpheS, thepheS region of thefitA76 mutant was also sequenced, revealing a G → A nucleotide transition at position 293 of the coding region. This lesion is the same as that reported for thepheS5 mutant. However, it is shown that thefitA76 mutant is primarily transcription-defective while thepheS5 mutant is primarily translation-defective. These results suggested that thefitA76 mutant might harbour another mutation, in addition topheS5. In this report, we present genetic evidence for a second mutation (namedfit95) in thefitA76 mutant. Thefit95 by itself confers a Ts phenotype on rich media devoid of sodium chloride. It is proposed that the subunits of phenylalanyl tRNA synthetase could act as transcription factors (Fit) also