Displaying publications 1 - 20 of 140 in total

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  1. Sharma A, Lal SK
    Rev. Med. Virol., 2019 05;29(3):e2036.
    PMID: 30706579 DOI: 10.1002/rmv.2036
    Tetherin, an interferon-inducible gene was first discovered to be an antiviral factor in 2008. A vast range of viruses, such as influenza A virus (IAV), dengue virus, Ebola virus, HIV, and RSV, have been reported to be susceptible to the antiviral activity of tetherin. Multiple reports have been published encompassing the role of tetherin in the IAV life cycle. To date, nine reports have been published regarding the role of tetherin in the IAV life cycle, with four reports supporting tetherin as an antiviral factor while five other reports suggesting no effect. To this end, this review summarizes the list of viruses currently known to be inhibited by tetherin and describes mechanisms used by viruses to overcome the antiviral potential of tetherin. Further, using IAV as disease model, we provide existing evidence in favor and against tetherin being considered as an antiviral candidate. Subsequent analysis of the experimental procedures across IAV-tetherin published reports revealed that the experimental setup (ie, cell lines, transfection reagents, and multiplicity of infection), strain-specific activity of NS1, and differing roles of NS1 in different cell lines may add up to the contributing factors leading to the discrepancies observed.
  2. Sharma A, Lal SK
    Front Microbiol, 2017;8:110.
    PMID: 28217114 DOI: 10.3389/fmicb.2017.00110
    Zika virus (ZIKV) is a mosquito-borne Flavivirus discovered in Uganda in the 1940s. To date, three major ZIKV outbreaks have been reported. ZIKV infections have known to be primarily asymptomatic while causing mild illness in a few cases. However, the recent emergence and spread of ZIKV in the Americas has resulted in the declaration of "Public Health Emergency of International Concern" due to the potential association between the infection and prenatal microcephaly or other brain anomalies. In Brazil, a 20-fold increase in prenatal microcephaly cases and 19% increase in Guillain-Barré Syndrome (GBS) cases were reported in 2015, as compared to the preceding year. The probable deleterious effects of ZIKV infection prompt the urgent development of diagnostics and therapeutics. To this end, the existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review. This review also emphasizes the importance of understanding ZIKV transmission in order to design a sensitive yet cost and time-efficient detection technique. Development of an efficient detection technique would subsequently allow for better surveillance and control of ZIKV infection. Currently, limited literature is available on the pathogenesis of ZIKV, hence, focusing on the modes of ZIKV transmission could potentially contribute to the understanding of the disease spectrum and formulation of targeted treatment and control.
  3. Sharma A, Shukla S, Kiran B, Michail S, Agashe M
    Malays Orthop J, 2018 Mar;12(1):26-30.
    PMID: 29725509 DOI: 10.5704/MOJ.1803.005
    Introduction: We assessed the role of the Pirani score in determining the number of casts and its ability to suggest requirement for tenotomy in the management of clubfoot by the Ponseti method. Materials and Methods: Prospective analysis of 66 (110 feet) cases of idiopathic clubfoot up to one year of age was done. Exclusion criteria included children more than one year of age at the start of treatment, non-idiopathic cases and previously treated or operated cases. Results: The initial Pirani score was (5.5±0.7) for the tenotomy group and the initial Pirani score was (3.3±1.6) for the non-tenotomy group. There was a significant difference between the initial Pirani score for the tenotomy and the non-tenotomy group with t= -7.9, df= 64 p<0.0001. The tenotomy group had a significantly higher number of casts (four to seven) compared to non-tenotomy group (two to five) t=-10.4, df=64, p<0.0001. Spearman's rank correlation coefficient was significant and confirmed positive correlation between the initial Pirani score and the number of casts required to correct the deformity (r = 0.931, p<0.0001). Conclusion: Initial high Pirani score suggests the need for greater number of casts to achieve correction and probable need for tenotomy. The number of casts required in achieving complete correction increases with increase in the initial Pirani score. The initial high hindfoot score (2.5-3) signifies the probable need of a minor surgical intervention of percutaneous tendoachilles tenotomy. Based on the initial Pirani score, parents can be informed about the probable duration of treatment and the need for tenotomy.
  4. Sharma A, Sikka M, Bhankar H, Gomber S, Sharma S
    Malays J Pathol, 2017 Aug;39(2):155-159.
    PMID: 28866697
    Sepsis is a common cause of death in infants and children. Haemostatic abnormalities have been reported in such patients. There is scant information on the nature and frequency of these abnormalities in children especially from India. Our aim was to evaluate the nature and frequency of haematological and haemostatic abnormalities in children with sepsis. Fifty children between 1-10 years of age admitted with sepsis and 50 age-matched, healthy controls were included in the study. Complete blood counts, examination of stained peripheral blood film, prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen, C-reactive protein, liver function tests and serum creatinine were done in all patients and controls. Prolonged PT and APTT were seen in 9 (18%) and 24 (48%) patients respectively. Plasma fibrinogen was decreased in 6% and increased in 8% patients. One or more haemostatic parameter was abnormal in 35 (70%) patients and in all patients who died.
  5. Gaur P, Kumar P, Sharma A, Lal SK
    Lett. Appl. Microbiol., 2020 Apr;70(4):252-258.
    PMID: 31990997 DOI: 10.1111/lam.13279
    Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-β levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-β levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-β. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-β response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.
  6. Sharma AK, Sharaf I, Ajay S
    Med. J. Malaysia, 2001 Jun;56 Suppl C:70-2.
    PMID: 11814254
    We report a case of a 12-year-old boy with acute compartment syndrome of the foot following a road-traffic accident. Due to the rarity of the injury, there was a delay in diagnosing the injury. An emergency fasciotomy was performed 19 hours after the injury. The foot healed with a mild extension contracture of the second toe.
  7. Sharma A, Jindal S, Narula MS, Garg S, Sethi A
    Malays Orthop J, 2017 Mar;11(1):74-76.
    PMID: 28435581 DOI: 10.5704/MOJ.1703.011
    The incidence of bilateral gleno-humeral joint dislocation is rare, is almost always posterior and is usually caused by sports injuries, epileptic seizures, electrical shock, or electroconvulsive therapy. Bilateral fracture-dislocation is even rarer, with a few cases reported in the literature. We report an unusual case with dislocation of the both glenohumeral joints in opposite direction after a seizure episode, with fracture of greater tuberosity on one side and of the lesser tuberosity on the contralateral side. Although there have been a few reports of bilateral asymmetric fracture dislocations of the shoulder in the past, an injury pattern resembling our case has, to the best of our knowledge, not been described in the literature so far. This report includes a detailed discussion regarding the mechanism of injury in a case of asymmetrical dislocation following a seizure episode. At final follow-up, the patient had healed fractures, painless near normal range of motion with no redislocations.
  8. Sharma A, Dosajh R, Bedi GS, Gupta K, Jain A
    Malays Orthop J, 2017 Mar;11(1):71-73.
    PMID: 28435580 DOI: 10.5704/MOJ.1703.010
    Dislocation of multiple metatarsophalangeal joint is an uncommon injury. The mechanism of injury is a high energy force distal to proximal with foot in hyperextension at the metatarsophalangeal (MTP) joint. The acute hyperextension of the toe at the moment of injury causes avulsion of the plantar part of the capsule from the junction of head and neck of the metatarsal. If the collateral ligaments remain intact, they maintain the locked fibrocartilaginous plate over the dorsum of the head of the metatarsal, making closed reduction impossible. We report a case of simultaneous 1st and 2nd MTP joint open dislocation. In the present case, we chose the plantar approach utilizing the already present plantar wound. At 18 months post-operative follow-up, there was no instance of redislocations or signs of avascular necrosis of head of metatarsal.
  9. Kumar Y, Sharma A, Mani KR
    Trop Life Sci Res, 2013 Aug;24(1):45-54.
    PMID: 24575241
    Typhoid fever continues to remain a major health problem in the developing world, and the emergence of multidrug-resistant (MDR) strains has further reduced therapeutic options for treatment of the disease. The National Salmonella and Escherichia Centre in Kasauli, India received 128 Salmonella Typhi isolates during 2008-2009. These were evaluated for antimicrobial resistance, prevalent resistotypes and the proportion of MDR strains, using standard methods for 11 antimicrobials. An abrupt decrease in the proportion of MDR strains was observed. Only 4.7% of the isolates were found to be MDR with resistotypes chloramphenicol-ampicillin-streptomycin-nalidixic acid-trimethoprim (C-AS-Na-Tr) and chloramphenicol-ampicillin-nalidixic acid-trimethoprim (C-A-Na-Tr), which is very low compared to other studies from India. Nalidixic acid resistance was found to be present in 93.8% of the isolates. Moreover, the difference in the mean minimum inhibitory concentration (MIC) of ciprofloxacin for nalidixic acid-resistant and nalidixic acid-sensitive strains was found to be statistically significant (p<0.001), which calls into question the further use of ciprofloxacin for the treatment of typhoid fever because of potential treatment failures. The low proportion of MDR strains increases the possibility of first-line drugs for the treatment of typhoid fever.
  10. Sharma A, Ahuja S, Diwaker P, Wadhwa N, Arora VK
    Malays J Pathol, 2019 Aug;41(2):191-194.
    PMID: 31427555
    INTRODUCTION: Acinic cell carcinoma (ACC) represents 1-6% of parotid gland neoplasms.

    CASE REPORT: We report cytomorphological features of two uncommon variants of acinic cell carcinoma. The first case was an eleven-year-old female with a nodular mass in parotid and the FNA smears demonstrated a lymphoepithelial lesion composed of epithelial tumour cells with features of acinar cells in a lymphoid background. The second case was a 62-year-old male with a large parotid mass. The FNA smears revealed presence of extracellular, acellular amyloid-like material with tumour cells arranged in follicles.

    DISCUSSION: Awareness of cytomorphological features of these unusual variants of acinic cell carcinoma may help to avoid diagnostic pitfall.

  11. Monika, Sharma A, Suthar SK, Aggarwal V, Lee HB, Sharma M
    Bioorg. Med. Chem. Lett., 2014 Aug 15;24(16):3814-8.
    PMID: 25027934 DOI: 10.1016/j.bmcl.2014.06.068
    The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
  12. Singh M, Sharma A, Duthie G, Balasingh D, Kandasamy P
    Asian J Surg, 2005 Jul;28(3):189-91.
    PMID: 16024313
    Treatment of anal fissures has changed dramatically in the past decade. This is primarily due to a better understanding of its pathophysiology and the implications of the various available options. Only a few anal fissures fail to respond to medical therapy. Sphincterotomy and anal dilatation have fallen out of favour due to the risk of incontinence. Island flaps have been proposed to address this, but 60-70% of the flap donor sites break down with complications. We propose using a rotation flap to overcome this problem.
  13. Sharma A, Sethi G, Tambuwala MM, Aljabali AAA, Chellappan DK, Dua K, et al.
    Curr Neuropharmacol, 2020 Apr 28.
    PMID: 32348224 DOI: 10.2174/1570159X18666200429013041
    All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
  14. Sharma A, Kamble SH, León F, Chear NJ, King TI, Berthold EC, et al.
    Drug Test Anal, 2019 Aug;11(8):1162-1171.
    PMID: 30997725 DOI: 10.1002/dta.2604
    Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self-treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1-200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%-38.7% w/w), paynantheine (0.3%-12.8% w/w), speciociliatine (0.4%-12.3% w/w), and speciogynine (0.1%-5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.
  15. Singh D, Yeou Chear NJ, Narayanan S, Leon F, Sharma A, McCurdy CR, et al.
    J Ethnopharmacol, 2019 Dec 07.
    PMID: 31816368 DOI: 10.1016/j.jep.2019.112462
    ETHNOPHARMACOLOGICAL RELEVANCE: Kratom (Mitragyna speciosa) is a native medicinal plant of Southeast Asia widely reported to be used to reduce opioid dependence and mitigate withdrawal symptoms. There is also evidence to suggest that opioid poly-drug users were using kratom to abstain from opioids.

    AIM OF THE STUDY: To determine the patterns and reasons for kratom use among current and former opioid poly-drug users in Malaysia.

    MATERIALS AND METHODS: A total of 204 opioid poly-drug users (142 current users vs. 62 former users) with current kratom use history were enrolled into this cross-sectional study. A validated UPLC-MS/MS method was used to evaluate the alkaloid content of a kratom street sample.

    RESULTS: Results from Chi-square analysis showed that there were no significant differences in demographic characteristics between current and former opioid poly-drug users except with respect to marital status. Current users had higher odds of being single (OR: 2.2: 95%CI: 1.21-4.11; p 

  16. Chindera K, Mahato M, Kumar Sharma A, Horsley H, Kloc-Muniak K, Kamaruzzaman NF, et al.
    Sci Rep, 2016;6:23121.
    PMID: 26996206 DOI: 10.1038/srep23121
    To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance.
  17. Tsapaki V, Faruque Ghulam M, Lim ST, Ngo Minh H, Nwe N, Sharma A, et al.
    Heart Asia, 2011;3(1):16-24.
    PMID: 27325974 DOI: 10.1136/ha.2009.001180
    Increasing use of interventional procedures in cardiology with unknown levels of radiation protection in many countries of Asia-Pacific region necessitates the need for status assessment. The study was part of an International Atomic Energy Agency (IAEA) project for achieving improved radiation protection in interventional cardiology (IC) in developing countries.
  18. Obeng S, Kamble SH, Reeves ME, Restrepo LF, Patel A, Behnke M, et al.
    J. Med. Chem., 2020 Jan 09;63(1):433-439.
    PMID: 31834797 DOI: 10.1021/acs.jmedchem.9b01465
    Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.
  19. Soon SS, Chia WK, Chan ML, Ho GF, Jian X, Deng YH, et al.
    PLoS ONE, 2014;9(9):e107866.
    PMID: 25250815 DOI: 10.1371/journal.pone.0107866
    Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older.
  20. Cheng AL, Cornelio G, Shen L, Price T, Yang TS, Chung IJ, et al.
    Clin Colorectal Cancer, 2017 06;16(2):e73-e88.
    PMID: 27780749 DOI: 10.1016/j.clcc.2016.08.005
    BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed.

    PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated.

    RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations.

    CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

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