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   Table of Contents - Current issue
November-December 2018
Volume 50 | Issue 6
Page Nos. 299-357

Online since Tuesday, January 22, 2019

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Connectomics: A pharmacologic viewpoint p. 299
Dibbanti Harikrishnareddy, Manisha Prajapat, Subodh Kumar, Ajay Prakash, Bikash Medhi
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Management of myasthenia gravis during pregnancy p. 302
Ramandeep Bansal, Manoj Kumar Goyal, Manish Modi
The management of myasthenia gravis (MG) during pregnancy requires special skills as both diseases as well as its treatment can have deleterious effects on mother and fetus. MG often affects women in second and third decades of life during the childbearing age. Exacerbations of MG are likely to occur during the first trimester and postpartum period. The treatment of MG during pregnancy needs to be individualized depending on the severity of MG as well as the efficacy of various treatment modalities and their possible harmful effects on pregnancy. In addition, special attention has to be given to avoid drugs and other factors (such as urinary tract infections) which may worsen MG. The key to successful outcome during pregnancy in myasthenic women lies in multidisciplinary care involving obstetricians, neurologists, anesthetist as well as neonatologist. In this review, we discuss various therapeutic options available for the management of MG during pregnancy and provide recommendations based on the current best evidence.
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Neuroprotective effect of solanesol against 3-nitropropionic acid-induced Huntington's disease-like behavioral, biochemical, and cellular alterations: Restoration of coenzyme-Q10-mediated mitochondrial dysfunction Highly accessed article p. 309
Sidharth Mehan, Vikramdeep Monga, Manju Rani, Rajesh Dudi, Krishna Ghimire
OBJECTIVE: The aim of the present study was to evaluate the solanesol (SNL)-mediated coenzyme-Q10 restoration to ameliorate 3-nitropropionic (3-NP)-induced behavioral, biochemical, and histological changes which resemble Huntington's disease (HD)-like symptoms in men. MATERIALS AND METHODS: Various behavioral and biochemical parameters were carried out to evaluate the activity of SNL on 3-NP-treated rats. To determine the therapeutic significance of SNL on HD, different behavioral tests such as memory task, locomotor activity, grip strength, and beam cross and some biochemical test along with histopathological findings were done. RESULTS: Chronic 3-NP, 10 mg/kg i.p., caused physical and mental abnormalities in animals, including memory impairment, weak grip strength, abnormal posture, and cognitive deficit. Biochemical analysis of brain homogenate in 3-NP-treated rats showed altered mitochondrial complexes, oxidative stress, and elevated lipid biomarkers. Neurohistological alterations of hippocampus, basal ganglia, and cerebral cortex of 3-NP-treated rats exhibit severe neuronal space, irregular damaged cells, and dense pyknotic nuclei-associated marked focal diffused gliosis. SNL administered for 15 days significantly improved motor performance and cognitive behavior task and restored the histopathological changes. Further, SNL treatment significantly improved mitochondrial complexes such as coenzyme-Q10 enzyme activity and attenuated inflammatory and oxidative damage of rat brain. CONCLUSION: In the present research work, SNL (5, 10, and 15 mg/kg p.o.) provided notable neuroprotective effect, which was confirmed by behavioral paradigms and biochemical test. It restored the behavioral and biochemical alteration caused by 3-NP and confirmed the strong neuroprotective mechanism of SNL in 3-NP-intoxicated memory and cognitive abnormalities.
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Analysis of glycemic status in diabetes-naïve patients on statins: A hospital-based cross-sectional study p. 320
Sereen Rose Thomson, Bharti Chogtu, Ranjan Shetty, Tom Devasia
INTRODUCTION: Randomized controlled trials, observational studies, and meta-analysis suggest risk of hyperglycemia in patients on statins, and this association is being viewed with renewed interest globally. The present study has tried to explore the possible diabetogenic effect of statins, the mechanism of this effect, and various comorbidities associated with this causation. MATERIALS AND METHODS: This cross-sectional study was carried out at the Department of Cardiology from October 2015 to March 2017. Patients on statins for at least 1 year and normoglycemic at the time of statin initiation were recruited in the study. The outcome of the present study was development of new-onset diabetes mellitus (NODM). Blood glucose levels and insulin levels were estimated. Other adverse reactions of statins and associated comorbidities in the patients were recorded. Descriptive statistics were used to analyze adverse drug reactions. RESULTS: A total of 104 patients met the inclusion criteria, of which eight patients (7.7%) developed NODM and 4 (3.8%) developed prediabetes. Atorvastatin 40 mg was most commonly prescribed statin. About 25% of patients taking atorvastatin 80 mg developed diabetes CONCLUSION: Statins have a mild-to-moderate risk of developing NODM. The dose of statins is an important factor that increases the risk of diabetes in statin users
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Evaluation of Rasna panchaka (indigenous drug) as oxidative stress down-regulator using serum-free explant culture system p. 326
Manjula Talluri, Srinivasa Reddy Yathapu, Dinesh Kumar Bharatraj
CONTEXT: The importance of phytochemicals/natural products as potential therapeutic agents in the present context is gaining a lot of importance. India with a rich heritage of such preparations needs evaluation as potent drugs. Explant culture system is a method, which is sensitive, reliable, reproducible and is capable of mimicking the in situ conditions maintaining the tissue in sufficiently high level of integration. AIM: The current study aimed to test the antioxidant activity of test compounds, namely, traditional aqueous (4212) and aqueous-methanolic (4308) extracts of Rasna panchaka using liver explant cultures. MATERIALS AND METHODS: Dose-response optima of extracts (0.2–10 μg/mL) were determined using mouse liver explant culture system up to 48 h. The antioxidant property of extracts was assessed by primary oxidative defense parameters, namely, superoxide-dismutase (SOD), catalase, reduced glutathione (GSH), and malondialdehyde (MDA). RESULTS: The results indicated that the cellular architecture of the cultured tissue was well conserved in the first 6 h with a gradual display of specific changes in the next 24 h. There was a significant increase in MDA levels in experimental groups indicating the oxidative stress induction in explants. A dose of 2.0 μg/mL extracts have shown statistically significant (P < 0.05) protection against oxidative stress. MDA levels, a measure of lipid peroxidation, were significantly (P < 0.01) reduced by 50% in extract treated explants compared to control. This effect was accompanied by the increase in the first defense enzymes SOD (50%) and catalase (18%) with no change in reduced GSH levels. CONCLUSION: The study enforces the importance of “explant culture system,” as it not only reduces the use of nonclinical/animal model but also is rapid and sensitive. Further, results of the current study also suggest that aqueous-methanolic extract of Rasna panchaka is having superior antioxidant activity compared to traditional water extract.
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Efficacy ratio: A tool to enhance optimal antimicrobial use for intra-abdominal infections p. 332
Priyanka Sabu, Divyaa Elangovan, Agila Kumari Pragasam, Yamuna Devi Bakthavatchalam, Camilla Rodrigues, DS Chitnis, Bhaskar Narayan Chaudhuri, Balaji Veeraraghavan
BACKGROUND: Antimicrobial resistance and inappropriate antibiotic regimen hamper a favorable outcome in intra-abdominal infections. Clinicians rely on the minimum inhibitory concentration (MIC) value to choose from the susceptible antimicrobials. However, the MIC values cannot be directly compared between the different antibiotics because their breakpoints are different. For that reason, efficacy ratio (ER), a ratio of susceptible MIC breakpoint and MIC of isolate, can be used to choose the most appropriate antimicrobial. MATERIALS AND METHODS: A prospective, observational study conducted during 2015 and 2016 included 356 Escherichia coli and 158 Klebsiella spp. isolates obtained from the intra-abdominal specimens. MIC was determined by microbroth dilution method, and ER of each antibiotic was calculated for all the isolates. RESULTS: For both E. coli and Klebsiella spp., ertapenem, amikacin, and piperacillin/tazobactam had the best activities among their respective antibiotic classes. DISCUSSION: This is the first study calculating ER for deciding empiric treatment choices. ER also has a potential additional value in choosing the use of susceptible drugs as monotherapy or combination therapy. A shift in ERs over a period of time tracks rising MIC values and predicts antimicrobial resistance development. CONCLUSION: Estimation of ER could be a meaningful addition for the interpretation of an antimicrobial susceptibility report, thus helping the physician to choose the best among susceptible antimicrobials for patient management.
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Sulfated polysaccharides of seagrass Halophila ovalis suppresses tumor necrosis factor-α-induced chemokine interleukin-8 secretion in HT-29 cell line p. 336
Neelakandan Yuvaraj, Venkatesan Arul
OBJECTIVES: The present study aims to investigate the anti-oxidant and anti-inflammatory properties of seagrass Halophila ovalis sulfated polysaccharide on HT-29 cell line. SUBJECTS AND METHODS: Monosaccharides composition was identified using liquid chromatography-mass spectrometry (LC-MS) and the functional groups were analyzed using Fourier transform-infrared (FT-IR) spectroscopy. The antioxidant and anti-inflammatory potential of crude extract and purified fractions was investigated in vitro. RESULTS: FT-IR spectra revealed that the presence of different functional groups and the presence of galactose (82.4%), xylose (7.6%), fructose (4.0%), mannose (2.0%), fucose (1.6%), glucose (1.2%), and arabinose (1.0%) was observed using LC-MS. Ho-SP and its fractions showed radical scavenging activity in hydroxyl, 2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid, and ferric reducing antioxidant power assay in a dose-dependent manner. Noticeable anti-inflammatory activity of purified fraction Ho FrIV (IC50= 43.85 μg/ml) was observed in a noncytotoxic range of concentrations and inhibited the tumor necrosis factor-α (TNF-α)-induced interleukin-8 (IL-8) secretion (0.27 ng/ml) in HT-29 cell line. CONCLUSION: Overall, the results presented in this study suggest that purified fraction Ho FrIV of Ho-SP could suppress the TNF-α-induced secretion of IL-8 in HT-29 and thus could be used as a promising antioxidant and anti-inflammatory candidate with potential benefits.
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A prospective randomized study to evaluate safety and efficacy of heparin topical solution (1000 IU/ml) compared to heparin topical gel (200 IU/g) in prevention of infusion-associated phlebitis p. 344
Vikas Saini, Tanvir Samra, Nitin Ahuja, Sameer Sethi
OBJECTIVES: Thrombosis and thrombophlebitis of the superficial venous system are common in hospitalized patients. Efficacy and safety of topical quick penetrating solution (QPS) of heparin were compared to heparin sodium topical gel for the prevention of infusion-associated phlebitis. MATERIALS AND METHODS: Patients aged 18–65 years undergoing intravenous cannulation for at least 72 h were enrolled and randomized to receive 6–8 drops of topical solution of heparin (Group sodium topical solution [QPS]) or1 g of topical gel (Group GEL) over the cannulated vein every 8 hourly for a total of 10 doses. Enrolled patients were monitored every 8 ± 1 h for phlebitis using visual infusion phlebitis scale. The primary aim was to compare the proportion of patients with Grade 0, I, and II phlebitis at the end of 72 h of treatment period. RESULTS: Number of patients assessed for eligibility was 110; 26 excluded and 84 randomized. Analysis was done for 41 administered heparin QPS and 33 administered heparin gel as the rest were lost to follow-up. No phlebitis was reported in 32% of patients in QPS group and 9% in GEL group (P =0.0019). Proportion of patients with Grade I and Grade II phlebitis was 22.9% and 13.5% with QPS and 35.13% and 22.97% with gel, respectively, and the difference was statistically significant. Mean time to develop Grade I (Group QPS = 59.7 h; Group GEL = 58.46 h; P = 0.949) and Grade II (Group QPS = 62.4 h; Group GEL = 61.17 h; P = 0.732) phlebitis was comparable no adverse effects were reported in either group. CONCLUSION: Heparin QPS was more effective in he prevention of infusion-associated phlebitis with similar safety profile as heparin gel.
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A case of capecitabine-induced dermatomyositis p. 350
Neerja Saraswat, Rajesh Verma, Shekha Neema, Sushil Kumar
Dermatomyositis (DM) is an idiopathic, inflammatory connective tissue disorder characterized by symmetrical proximal myopathy and characteristic skin involvement. The pathogenesis of DM is widely debated; however, it is postulated to be an end result of immune-mediated cascade, triggered by multiple environmental factors in a genetically predisposed individual. In addition to underlying malignancies, many drugs have been reported to be associated with DM. Capecitabine is a chemotherapeutic agent, approved by the United States-Food and Drug Administration for the management of colonic, metastatic colonic, and metastatic breast carcinoma. It is converted into 5-fluorouracil after oral intake. Common dose-limiting toxicities associated with the usage of the capecitabine include increased bilirubin levels, diarrhea, and hand-foot syndrome. DM-induced by capecitabine has rarely been reported. Herein, we describe a patient of metastatic carcinoma breast, who developed DM after capecitabine intake. The patient had accidental re-challenge with capecitabine resulting in the reappearance of the cutaneous and musculoskeletal system, thereby confirming our diagnosis of drug-induced DM in the setting of underlying malignancy.
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Digital gangrene induced by inadvertent intra-arterial cocktail injection of anesthetic agents such as pentazocine, promethazine, and atropine: A serious adverse drug experience p. 354
Sonia Shinde Mahajan, Vishal R Tandon, Rajat Sarin, Roshi , Akhil Kumar Gupta, Arvind Kohli
Gangrenous changes in skin due to accidental intra-arterial injection of promethazine and pentazocine have been reported. Accidental intra-arterial injection is most commonly encountered in the antecubital fossa. However, recent reports in the radial and ulnar arteries have also been encountered. We hereby report a serious, preventable adverse drug experience in the form of digital gangrene induced by inadvertent intra-arterial cocktail injection of anesthetic agents such as pentazocine, promethazine, and atropine, which seems to be in the radial artery as the lateral three digits and dorsum of the hand are affected.
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