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   Table of Contents - Current issue
Coverpage
October-December 2016
Volume 7 | Issue 4
Page Nos. 155-198

Online since Friday, December 16, 2016

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Lesinurad: A significant advancement or just another addition to existing therapies of gout? p. 155
Ajay Gupta, Pramod Kumar Sharma, Arup Kumar Misra, Surjit Singh
DOI:10.4103/0976-500X.195897  
Gout is a metabolic disorder that usually presents as recurrent episodes of acute arthritis due to deposition of crystals in joints and cartilages. Despite the availability of several drugs for gout, its management is still less than adequate. There is always a search for newer, safer, and more potent urate-lowering therapies for treating patients inadequately controlled with available drugs. Lesinurad in combination with a xanthine oxidase inhibitor provides an effective mode of therapy in the management of hyperuricemia associated with gout. Lesinurad is a selective uric acid transporter 1 (URAT1) inhibitor. URAT1 is responsible for the majority of uric acid absorption from kidneys to the circulation. Lesinurad was granted marketing approval based on three randomized, double-blind, placebo-controlled; phase III clinical trials. It is devoid of interaction with organic anion transporters (OATs) such as OAT1 and 3, responsible for drug-drug interactions, an undesirable property associated with probenecid. On-going research is more focused on reducing inflammation consequent to deposition of crystals rather than production and excretion of urate. Various targets are being explored, and interleukin-1 beta inhibition seems to be one of the most promising approaches.
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RESEARCH PAPERS Top

Hypertension influences the exponential progression of inflammation and oxidative stress in streptozotocin-induced diabetic kidney p. 159
Rupadevi Muthaian, Rajaa Muthu Pakirisamy, Subramani Parasuraman, Ramasamy Raveendran
DOI:10.4103/0976-500X.195898  
Objective: To investigate the association of hypertension coexisting with diabetes mellitus with oxidative stress and inflammation in the kidneys of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Male Wistar rats were used for the experiments. Blood glucose (BG), urea, blood pressure (BP), and heart rate (HR) were analyzed before and 48 h after STZ injection. Further, these parameters were monitored up to 3 months of diabetes induction. Subsequently, the inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, and nitrate) and oxidative stress markers were estimated after 3 months of diabetes induction in the kidney homogenate. Histological analysis of renal tissue was also carried out. Results: Linear elevation of BG, urea, mean arterial pressure (MAP), and HR was observed up to 3 months of diabetes induction. In the same manner, inflammatory and oxidative stress markers were also found to be significantly increased. Notably, the histological analysis revealed the signs of nephropathy such as increased mesangial cell number, thickness of basement membrane, and renal artery. Inflammatory and oxidative stress markers positively correlated with elevated BP and BG, but the correlation was better with BP rather than BG. Conclusion: Hypertension has a strong implication in the increased oxidative stress and inflammation of diabetic kidney at the very early stage of diabetes mellitus.
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QTc interval in young Gujarati hypertensives: Effect of disease, antihypertensive monotherapy, and coexisting risk factors p. 165
Jayesh Dalpatbhai Solanki, Bhakti P Gadhavi, Amit H Makwana, Hemant B Mehta, Chinmay J Shah, Pradnya A Gokhale
DOI:10.4103/0976-500X.195900  
Objectives: To study the effect of disease duration, treatment and risk factors on QTc interval among young hypertensives. Materials and Methods: A case-control study was conducted on 142 hypertensives (60 males, 82 females) taking calcium channel blocker (CCB) or angiotensin-converting enzyme inhibitor (ACEI) as monotherapy. After blood pressure measurement, we recorded lead II electrocardiograph with minimum ten waveforms. QTc was derived from average of ten values using Bazett's formula. QTc interval >0.43 s in male and >0.45 s in female was considered abnormal. Results: Cases had mean duration of hypertension 5 years, mean age of 40 years, and poor blood pressure control (systolic blood pressure >140 and diastolic blood pressure >90 mm of Hg). Newly diagnosed hypertensives had significantly higher QTc values than the matched known cases (0.44 vs. 0.42 s, P < 0.05). Known hypertensives did not differ significantly in QTc values by the duration of disease. CCB users showed small, insignificant disadvantage for abnormally prolonged QTc values than ACEI users. With coexisting diabetes, smoking, and positive family history of hypertension, there was odds risk of 7.69, 2.75, and 2.54, respectively for prolonged QTc. Conclusion: Our study showed prolonged QTc in hypertensives more so in newly diagnosed, unaffected by duration or use of ACEI, or CCB but associated with modifiable risk factors. This underscores high risk of repolarization abnormality-induced future events, suggesting early screening of hypertension, strict blood pressure control, optimum use of QTc measurement, and preventive pharmacotherapy to reduce this aftermath.
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Comparison of efficacy, safety, and cost-effectiveness of rupatadine and olopatadine in patients of allergic rhinitis: A prospective, randomized, double-blind, parallel group study p. 171
Ganesh Dakhale, Yogesh Tathod, Seema Patel, Sonali Pimpalkhute, Latesh Raghute, Ajita Khamkar
DOI:10.4103/0976-500X.195901  
Objective: To compare the efficacy, safety, and cost-effectiveness of rupatadine and olopatadine in patients of allergic rhinitis (AR). Materials and Methods: A 2-week, single-centered, randomized, double-blind, parallel group comparative clinical study was conducted on patients with AR. Following inclusion and exclusion criteria, 67 patients were recruited and randomized to two treatment groups and received the respective drugs for 2 weeks. At follow-up, parameters assessed were total nasal symptom score (TNSS), change in total and differential count of eosinophil. Results: In olopatadine group, there was a significantly higher reduction in TNSS (P < 0.05) than that of rupatadine. Both the drugs significantly reduced the absolute eosinophil count, but olopatadine (P < 0.001) was found to be superior. The incidence of adverse effects was found to be less in olopatadine group when compared with rupatadine group. Conclusion: Olopatadine is a better choice in AR in comparison to rupatadine due to its better efficacy and safety profile.
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Inhibition by tadalafil of contractility of isolated nonpregnant human myometrium p. 177
Sumalya Sen, Anitha Thomas, Saibal Das, Jayanta Kumar Dey, Abraham Peedicayil, Vinotha Thomas, Jacob Peedicayil
DOI:10.4103/0976-500X.195902  
Objective: To investigate the inhibitory effect of tadalafil on the contractility of isolated nonpregnant human myometrium. Materials and Methods: The ability of tadalafil (25, 40, and 63 μM) to inhibit 55 mM KCl-induced contractility of isolated nonpregnant human myometrium was studied. The ability of the ATP-sensitive potassium channel blocker glibenclamide (10 μM) and the calcium-sensitive potassium channel (BKCa) blocker iberiotoxin (100 nM) to reverse the inhibitory effect of 40 μM tadalafil on 55 mM KCl-induced myometrial contractility was also studied. Results: Tadalafil produced a concentration-dependent inhibition of myometrial contractility that was statistically significant at 40 and 63 μM concentrations of tadalafil. The inhibition by tadalafil of myometrial contractility was statistically significantly reversed by the concurrent administration of glibenclamide and iberiotoxin. Conclusions: These results suggest that tadalafil inhibits human myometrial contractility by opening ATP-sensitive potassium channels and BKCa channels. The opening of these channels could have been due to the action of raised intracellular levels of cGMP due to inhibition of PDE-5 by tadalafil. The results suggest that tadalafil could be investigated for use in clinical conditions requiring relaxation of the myometrium.
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RESEARCH LETTERS Top

Analgesics self-medication among undergraduate students of a Rural Medical College p. 182
Amit Kumar, Vandana , Ahmad Nadeem Aslami
DOI:10.4103/0976-500X.195903  
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CASE REPORTS Top

Clozapine-induced cataract in a young female p. 184
Md. Shahid Alam, KV Praveen Kumar
DOI:10.4103/0976-500X.195904  
A variety of systemic drugs including corticosteroids, amiodarone and antipsychotics have been known to cause cataract formation. Typical antipsychotics such as chlorpromazine have been reported to cause cataract formation in varying rates ranging from 22% to 80%. Cataract as an adverse effect resulting from the long term use of atypical antipsychotic has rarely been mentioned in literature, and there is only a single case report of cataract formation from prolonged use of clozapine. We report a rare case of clozpine induced cataract in a young female. The patient was advised to consult her psychiatrist for a change of drug and to undergo cataract surgery.
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Presumed isotretinoin-induced extraocular myopathy p. 187
Md. Shahid Alam, Swati Agarwal
DOI:10.4103/0976-500X.195905  
Isotretinoin a synthetic analogue of vitamin A is primarily used for cystic acne not responding to conventional treatment. Several ocular side effects including blurring of vision, decreased dark adaptation, corneal opacities and meibomian gland atrophy have been reported with prolonged use of isotretinoin. There have been reports of muscular damage caused by isotretinoin. Extra ocular myopathy as an adverse effect of long term used of isotretinoin has never been mentioned in literature. We report a case of a young male who presented to us with complaints of diplopia after using isotretinoin for a prolonged period. He was diagnosed as a case of presumed isotretinoin extraocular myopathy after imaging and other blood investigations.
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MOLECULES OF MILLENNIUM Top

Proprotein convertase subtilisin/kexin type 9 enzyme inhibitors: An emerging new therapeutic option for the treatment of dyslipidemia p. 190
Faizan Mazhar, Nafis Haider
DOI:10.4103/0976-500X.195906  
The treatment of hypercholesterolemia entered in a new phase of development with the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the market. The Food and Drug Administration and European Medicines Agency recently approved the alirocumab and evolocumab, subcutaneously injectable monoclonal antibody every 2 or 4 weeks against PCSK9, for the treatment of hypercholesterolemia in patients with intolerance or inadequate response to statins, especially for the secondary prevention or in the case of familial hypercholesterolemia. This decision is based on several clinical trials demonstrating that inhibitors of PCSK9 lower the low-density lipoprotein cholesterol compared to placebo while studies are underway to assess their role in secondary prevention of major cardiovascular events.
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Lifitegrast: A novel drug for treatment of dry eye disease p. 194
Afroz Abidi, Pooja Shukla, Ali Ahmad
DOI:10.4103/0976-500X.195920  
Dry eye disease (DED) is an inflammatory disorder of ocular surfaces leading to severe disability, especially in the elderly age group. The mainstay of therapy includes artificial tears, punctual plugs, topical anti-inflammatory agents, and corticosteroids. In the past few years, only cyclosporine-A emulsions have been added to the existing therapy, but it is discontinued by most patients as it causes burning sensation in the eye. Hence, progress in new research for a better therapeutic option led to the discovery of lymphocyte function-associated antigen intercellular adhesion molecule 1 antagonist, lifitegrast. It hinders the T-cell activation, release of inflammatory mediators, and consequently inhibits the inflammatory pathways in DED. It was approved by the US Food and Drug Administration in July 2016 for the treatment of DED. This review highlights the development process and approval of lifitegrast.
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