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July-August 2021
Volume 53 | Issue 4
Page Nos. 261-340

Online since Wednesday, August 18, 2021

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EDITORIAL  

Role of Iron Chelators in Mucormycosis Highly accessed article p. 261
Vidya Mahalmani, Phulen Sarma, Ajay Prakash, Bikash Medhi
DOI:10.4103/ijp.ijp_604_21  PMID:34414902
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RESEARCH ARTICLES Top

Comparative effectiveness of metoprolol, ivabradine, and its combination in the management of inappropriate sinus tachycardia in coronary artery bypass graft patients Highly accessed article p. 264
Parloop Bhatt, Niren Bhavsar, Dhaval Naik, Dhiren Shah
DOI:10.4103/ijp.IJP_478_19  PMID:34414903
BACKGROUND: Inappropriate sinus tachycardia (IST) is an arrhythmic complication observed after coronary artery bypass graft (CABG) surgery which left untreated, commonly increases chances of postoperative stroke. The primary study objective was comparing effectiveness of beta blocker-metoprolol; a specific If blocker-ivabradine and its combination in patients who develop IST as a complication following CABG. MATERIALS AND METHODS: An open-labeled, investigator initiated, clinical study was conducted on 150 patients who developed IST (heart rate [HR] >100 beats/min) following elective CABG surgery. The patients were randomized into three treatment groups. Group I – received ivabradine (5 mg), Group II – metoprolol (25 mg), and Group III – ivabradine (5 mg) and metoprolol (25 mg). Treatment was given orally, twice a day for 7 days in all the three groups postoperatively. Primary endpoints were comparative effectiveness in HR and blood pressure reduction following treatment. RESULTS: IST was diagnosed by an electrocardiogram (12-lead) considering morphological features of P-wave and with 32% increase from baseline HR in all the three groups. Compared to IST arrthymic rate, HR was reduced in all groups following respective treatment (P = 0.05). Reduction in HR was significant (P < 0.05) in combination group followed by ivabradine which was significantly greater than metoprolol treated group. None of the treatments clinically changed the systolic, diastolic and mean blood pressure till discharge. No surgery/treatment-related complications were observed in any groups. CONCLUSION: Ivabradine stands as a pharmacological option for controlling HR and rhythm without associated side effects in postoperative CABG patients with IST.
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Correlation between serum pro inflammatory cytokines and clinical scores of knee osteoarthritic patients using resveratrol as a supplementary therapy with meloxicam Highly accessed article p. 270
Bushra Hassan Marouf, Saad Abdulrahman Hussain, Ziyad Serdar Ali
DOI:10.4103/ijp.IJP_493_20  PMID:34414904
OBJECTIVE: The objective of this study was to analyze the associations between the pro-inflammatory markers with the clinical outcomes of knee osteoarthritis (OA) in patients using resveratrol as an add-on treatment with meloxicam. MATERIALS AND METHODS: This was a double-blind controlled clinical investigation, with 110 eligible patients with OA assigned randomly to receive 15 mg a day meloxicam with either resveratrol 500 mg a day or placebo for 90 days. The standard tools for assessment of pain severity and physical functions were utilized. The tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in the blood were evaluated. Spearman's correlation coefficient test was used to determine the significance of correlations. RESULTS: The regression analysis to determine the correlation between reductions of the inflammatory biomarkers with the amelioration of the clinical scores showed a nonsignificant weak correlation between these variables. Total clinical scores of each assessment tool that was used “Knee Injury and OA Outcome Score (KOOS) and WOMAC” displayed a weak and nonsignificant correlation with TNF-α, IL-1β blood level. The Spearman's correlation shows a relatively nonsignificant association between IL-6 levels and KOOS, WOMAC, and Visual Analog Scale scores after incorporating resveratrol as an adjuvant with meloxicam for 90 days. CONCLUSION: A weak and nonsignificant correlation between serum biomarkers and the clinical outcomes has been suggested in patients with painful knee OA treated with meloxicam and resveratrol.
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Natural product topical therapy in mitigating imiquimod-induced psoriasis-like skin inflammation-underscoring the anti-psoriatic potential of Nimbolide p. 278
Nilesh Barku More, Nivya Sharma, Gauthami Pulivendala, Swarna Bale, Chandraiah Godugu
DOI:10.4103/ijp.IJP_591_20  PMID:34414905
BACKGROUND: Psoriasis is a chronic inflammatory dermatological disorder having complex pathophysiology with autoimmune and genetic factors being the major players. Despite the availability of a gamut of therapeutic strategies, systemic toxicity, poor efficacy, and treatment tolerance due to genetic variability among patients remain the major challenges. This calls for effective intervention with the superior pharmacological profile. Nimbolide (NIM), a major limonoid is an active chemical constituent found in the leaves of the Indian Neem tree, Azadirachta indica. It has gained immense limelight in the past decades for the treatment of various diseases owing to its anti-proliferative, anti-inflammatory, and anti-cancer potentials. OBJECTIVE: The present study was centered around evaluating the anti-psoriatic effect of NIM in the experimental model of Imiquimod (IMQ)-induced psoriasis-like inflammation model. MATERIALS AND METHODS: Application of IMQ topically on the dorsum of Balb/c mice from day 0-6 prompted psoriasis-like inflammatory symptoms. Treatment groups included topical administration of NIM incorporated carbopol gel formulation and NIM free drug given through subcutaneous route. Protein expression studies such as immunohistochemistry, Western blotting, and ELISA were employed. RESULTS: It was clearly observed from our results that NIM significantly ameliorated the expression of inflammatory and proliferation mediators. Further, NIM in the treatment groups significantly improved classic Psoriasis Area Severity Index scoring when compared to IMQ administered group. CONCLUSION: It is noteworthy that NIM showed a predominant therapeutic effect as compared to other treatment group. To recapitulate, NIM has shown promising activity as an anti-psoriatic agent by remarkably ameliorating inflammation and associated proliferation.
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Desmodium gyrans dc modulates lipid trafficking in cultured macrophages and improves functional high-density lipoprotein in male wistar rats p. 286
MS Indu, Arunaksharan Narayanankutty, Smitha K Ramavarma, Jeksy Jose Manalil, Jose Padikkala, Achuthan Chathrattil Raghavamenon
DOI:10.4103/ijp.IJP_136_17  PMID:34414906
OBJECTIVE: High-density lipoprotein (HDL) cholesterol-mediated atherosclerotic plaque regression has gained wide therapeutic attention. The whole plant methanolic extract of the medicinal plant Desmodium gyrans Methanolic Extract (DGM) has shown to mitigate hyperlipidemia in high fat- and-cholesterol fed rats and rabbits with significant HDL enhancing property. The study aimed to assess the functionality and mechanistic basis of HDL promoting effect of DGM. MATERIALS AND METHODS: Macrophage cholesterol efflux and foam cell formation assays were performed in THP-1 macrophages. Male Wistar rats were given DGM extract over 1 month and assessed the serum HDL, Apolipoprotein A1 (Apo-A1), and paraoxonase activity. Quantitative Polymerase chain reaction was carried out to assess the expression level of Apo-A1, SR-B1 (Scavenger receptor B1), and Cholesteryl ester transfer protein (CETP) on cDNA of HepG2 cells exposed to DGM. RESULTS: Pretreatment of DGM inhibited uptake of oxidized lipids and enhanced the lipid efflux by THP-1-derived macrophages. Oral administration of DGM (100 and 250 mg/kg) progressively enhanced the serum HDL, Apo-A1 level, and associated paraoxonase activity in normal male Wistar rats. In support to this, DGM exposed HepG2 cells documented dose-dependent increase in the expression of SR-B1 and Apo-A1 mRNA, while reduced the CETP expression. CONCLUSION: Overall the results indicated that DGM modulates lipid trafficking and possesses functional HDL enhancing potential through increased Apo-A1 levels and paraoxonase activity. Further, reduced CETP expression and increased expression of SR-B1 suggest the reverse cholesterol transport promoting role of DGM.
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Impact of oral anticholinergic on insulin response to oral glucose load in patients with impaired glucose tolerance p. 294
Sandeep Lahiry, Mitali Chatterjee, Sudip Chatterjee
DOI:10.4103/ijp.IJP_792_19  PMID:34414907
Background: Preliminary data indicates there is a cholinergic basis to insulin secretion. Aims & Objective: To investigate the impact of oral anticholinergics on insulin secretion in subjects with impaired glucose tolerance (IGT), in comparison with volunteers having normal glucose tolerance (NGT). Material & Methods: This prospective observational study recruited 10 IGT and 10 NGT subjects. An oral glucose tolerance test (OGTT) was conducted twice in the absence and presence of hyoscine butyl-bromide (HBB). The plasma glucose (PG) and insulin levels were serially estimated at 30-min increments for 2 h after the OGTT. Early (ΔI30/ΔPG30) & late (insulin/PGAUC 60-120) phase insulin activity were assessed subsequently. Results: The study constituted of 10 IGT (4M/6F, BMI: 28.80 ± 2.30) and 10 NGT (5M/5F, BMI: 23.00 ± 0.80) subjects. In the NGT group, the pre-HBB mean glucose levels (0-120 min) were comparable with those recorded after HBB intake. However, after HBBB, the mean insulin levels decreased significantly at t = 90 and 120min, confirmed by attenuated late phase insulin activity in IGT (P = 0.023) & NGT (P = 0.006) group. On the other hand, in the IGT group, however, HBB did not impact on the mean PG and insulin levels (0-120 min). Conclusions: Our study findings indicate that insulin secretion is influenced by cholinergic system and that oral anticholinergics may attenuate the late phase insulin activity in varying degrees of glycemic status.
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DRUG WATCH Top

Moxifloxacin-induced oral erythema multiforme: An unusual adverse effect hitherto unreported p. 298
Somnath Das, Olympia Rudra, Surabhi Sharma, Subhadeep Mallick
DOI:10.4103/ijp.ijp_771_19  PMID:34414908
Moxifloxacin is a fluoroquinolone with excellent activity in community-acquired respiratory tract infections. Common adverse effects are gastrointestinal symptoms, headache, dizziness, etc., Some serious adverse effects include tendon rupture, rhabdomyolysis, peripheral neuropathy, and interstitial nephritis. Cutaneous adverse effects include allergic reactions, angioedema, Steven–Johnson syndrome, and toxic epidermal necrosis. Erythema multiforme (EM), an acute self-limiting disease, most commonly occurs due to infection and rarely due to drugs or systemic disease. EM is classified into EM major and minor, both having skin lesions. A third category of EM has also been described with only oral involvement and without any skin lesions. Oral EM itself is an uncommon entity which has been reported due to nonsteroidal anti-inflammatory drugs. Here, we are reporting a case of moxifloxacin-induced oral EM. After extensive search in PubMed-Medline database, we could not find any such co-occurrence of moxifloxacin-induced oral EM. To the best of our knowledge, this is the first reported case.
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REVIEW ARTICLE Top

Current concepts and molecular mechanisms in pharmacogenetics of essential hypertension p. 301
Farhana Rahman, Nagasundaram Muthaiah, Govindasamy Kumaramanickavel
DOI:10.4103/ijp.IJP_593_19  PMID:34414909
Hypertension is a leading age-related disease in our society and if left untreated, leads to fatal cardiovascular complications. The prevalence of hypertension has increased and becomes a significant global health economic burden, particularly in lower-income societies. Many loci associated with blood pressure and hypertension have been reported by genome-wide association studies that provided potential targets for pharmacotherapy. Pharmacogenetic research had shown interindividual variations in drug efficacy, safety, and tolerability. This could be due to genetic polymorphisms in the pharmacokinetics (genes involved in a transporter, plasma protein binding, and metabolism) or pharmacodynamic pathway (receptors, ion channels, enzymes). Pharmacogenetics promises great hope toward targeted therapy, but challenges remain in implementing pharmacogenetic aided antihypertensive therapy in clinical practice. Using various databases, we analyzed the underlying mechanisms between the candidate gene polymorphisms and antihypertensive drug interactions and the challenges of implementing precision medicine. We review the emergence of pharmacogenetics and its relevance to clinical pharmacological practice.
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SYSTEMATIC REVIEW Top

Update on geographical variation and distribution of SARS-nCoV-2: A systematic review p. 310
Manisha Prajapat, Vrishbhanu Handa, Phulen Sarma, Ajay Prakash, Hardeep Kaur, Saurabh Sharma, Anusuya Bhattacharyya, Subodh Kumar, Amit Raj Sharma, Pramod Avti, Bikash Medhi
DOI:10.4103/ijp.ijp_483_21  PMID:34414910
Knowledge of a new mutant strain of SARS-coronavirus (CoV-2) is enormously essential to identify a targeted drug and for the development of the vaccine. In this article, we systematically reviewed the different mutation strains (variant of concern [VOC] and variant of interest [VOI]) which were found in different countries such as the UK, Singapore, China, Germany, Vietnam, Western Africa, Dublin, Ireland, Brazil, Iran, Italy, France, America, and Philippines. We searched four literature databases (PubMed, EMBASE, NATURE, and Willey online library) with suitable keywords and the time filter was November 2019 to June 16, 2021. To understand the worldwide spread of variants of SARS-CoV-2, we included a total of 27 articles of case reports, clinical and observational studies in the systematic review. However, these variants mostly spread because of their ability to increase transmission, virulence, and escape immunity. So, in this paper is we found mutated strains of SARS-CoV-2 like VOCs that are found in different regions across the globe are ALPHA strain in the U.K, BETA strain in South Africa, GAMMA strain in Brazil, Gamma and Beta strains in European Countries, and some VOIs like Theta variant in the Philippines.
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Rhino-orbital-cerebral-mucormycosis in COVID-19: A systematic review p. 317
Anusuya Bhattacharyya, Phulen Sarma, Dibya Jyoti Sharma, Karuna Kumar Das, Hardeep Kaur, Manisha Prajapat, Subodh Kumar, Seema Bansal, Ajay Prakash, Pramod Avti, Prasad Thota, Dibbanti Harikrishna Reddy, Bhaswati Sharma Gautam, Bikash Medhi
DOI:10.4103/ijp.ijp_419_21  PMID:34414911
Since the onset of COVID-19 pandemic, parallel opportunistic infections have also been emerging as another disease spectrum. Among all these opportunistic infection, mucormycosis has become a matter of concern with its rapid increase of cases with rapid spread as compared to pre-COVID-19 era. Cases have been reported in post-COVID-19-related immune suppression along with the presence of comorbidity which adds on the deadly outcome. There is no systematic review addressing the issue of COVID-19-associated mucormycosis. This is the first systematic review of published studies of mucormycosis associated with COVID-19. The aim was to analyze the real scenario of the disease statement including all the published studies from first November 2019 to 30th June to analyze the contemporary epidemiology, clinical manifestations, risk factor, prognosis, and treatment outcome of COVID-19 associated rhino-orbito-cerebral-mucormycosis. A comprehensive literature search was done in following databases, namely, PubMed, Google Scholar, Scopus, and EMBASE using keywords mucormycosis, rhino orbital cerebral mucormycosis, COVID-19, and SARS-CoV-2 (from November 01, 2019 to June 30, 2021). Our study shows that, while corticosteroids have proved to be lifesaving in severe to critical COVID-19 patients, its indiscriminate use has come with its price of rhino-orbito-cerebral mucormycosis epidemic, especially in India especially in patients with preexisting diabetes mellitus with higher mortality. Corticosteroid use should be monitored and all COVID-19 patients should be closely evaluated/monitored for sequelae of immunosuppression following treatment.
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LETTERS TO THE EDITOR Top

Apremilast induced tinnitus: An unreported side effect p. 328
Rajiv Ramesh Sule, Paras Choudhary, Tejaswini Sopanrao Salunke
DOI:10.4103/ijp.IJP_533_20  PMID:34414912
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Nilotinib-induced generalized keratosis pilaris: Report of a rare case p. 330
Priyanka Arun Kowe, Vaishali H Wankhade, Sakshi S Malpani, Rajesh P Singh
DOI:10.4103/ijp.IJP_553_20  PMID:34414913
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A successful protocol for desensitization to iron salts p. 332
Kadriye Terzioglu, Kürşat Epöztürk
DOI:10.4103/ijp.IJP_581_20  PMID:34414914
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Prolonged sertraline use related carcinoembryonic antigen increase p. 334
Mehmet Emin Ceylan, Baris Önen Ünsalver, Alper Evrensel, Fatma Duygu Kaya Yertutanol, Aslihan Dönmez
DOI:10.4103/ijp.ijp_370_21  PMID:34414915
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Knowledge, attitude, and practice of mothers regarding immunization p. 336
Rubleen Kaur, Diksha Jassal, Naveenta Sharma, Kamaljeet Kaur, Sukhjot Kaur, Manjula Thakur, Sushma K Saini, Madhu Gupta, Anjali Sharma
DOI:10.4103/ijp.IJP_486_18  PMID:34414916
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Iron nanoparticles and its potential application: A literature review p. 339
Pradip Kumar Saha, Lekha Saha
DOI:10.4103/ijp.ijp_785_20  PMID:34414917
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