Rao R.,Jubilee Missions Medical College |
Panghate A.,Sanjeevani Hospital |
Chandanwale A.,Sir JJ Group of Hospitals |
Sardar I.,Nightingale |
And 5 more authors.
Asian Spine Journal | Year: 2012
Study Design: We performed a multicentric, randomized, comparative clinical trial. Eligible patients were randomly assigned to receive 150 mg of Tolperisone thrice daily or 8 mg of Thiocolchicoside twice daily for 7 days.Purpose: To assess the efficacy and tolerability of Tolperisone in comparison with Thiocolchicoside in the treatment of acute low back pain with spasm of spinal muscles. Overview of Literature: No head on clinical trial of Tolperisone with Thiocolchicoside is available and so this study is done.Methods: The assessment of muscle spasm was made by measuring the finger-to-floor distance (FFD), articular excursion in degrees on performing Lasegue's maneuver and modified Schober's test. Assessment of pain on movement and spontaneous pain (pain at rest) of the lumbar spine was made with the help of visual analogue scale score. Results: The improvement in articular excursion on Lasegue's maneuver was significantly greater on day 3 (p = 0.017) and day 7 (p = 0.0001) with Tolperisone as compared to Thiocolchicoside. The reduction in FFD score was greater on day 7 (p = 0.0001) with Tolperisone. However there was no significant difference in improvement in Schober's test score on day 3 (p = 0.664) and day 7 (p = 0.192). The improvement in pain score at rest and on movement was significantly greater with Tolperisone (p = 0.0001). Conclusions: Tolperisone is an effective and well tolerated option for treatment of patients with skeletal muscle spasm associatedwith pain. © 2012 by Korean Society of Spine Surgery.
Ghoshal U.C.,Sanjay Gandhi Post Graduate Institute of Medical Sciences |
Abraham P.,nduja National Hospital and Medical Research Center |
Bhatia S.J.,K E M Hospital |
Misra S.P.,Allahabad University |
And 18 more authors.
Indian Journal of Gastroenterology | Year: 2013
Background: Attempts to diagnose and subtype irritable bowel syndrome (IBS) by symptom-based criteria have limitations, as these are developed in the West and might not be applicable in other populations. Objectives: This study aimed to compare different criteria for diagnosing and subtyping of IBS in India. Method: Manning's and the Rome I, II, and III criteria as well as the Asian criteria were applied to 1,618 patients (from 17 centers in India) with chronic lower gastrointestinal (GI) symptoms with no alarm features and negative investigations. Results: Of 1,618 patients (aged 37.5 [SD 12.6] years; 71.2 % male), 1,476 (91.2 %), 1,098 (67.9 %), 649 (40.1 %), 849 (52.5 %), and 1,206 (74.5 %) fulfilled Manning's, Rome I, II, and III, and the Asian criteria, respectively. The most common reason for not fulfilling the criteria was absence of the following symptoms: "more frequent stools with onset of pain," "loose stool with onset of pain," "relief of pain with passage of stool," "other abdominal discomfort/bloating," and, in a minority, not meeting the duration criterion of 3 months/12 weeks. By stool frequency, constipation-predominant IBS (<3 stools/week) was diagnosed in 319 (19.7 %), diarrhea-predominant IBS (>3 stools/day) in 43 (2.7 %), and unclassified in 1,256 (77.6 %). By Bristol stool form, constipation, diarrhea, and unclassified were diagnosed in 655 (40.5 %), 709 (43.8 %), and 254 (15.7 %) patients, respectively. By their own perception, 462 (28.6 %), 541 (33.4 %), and 452 (27.9 %) patients reported constipation-predominant, diarrhea-predominant, and alternating types, respectively. Conclusion: By Manning's and the Asian criteria, a diagnosis of IBS was made frequently among Indian patients with chronic functional lower GI symptoms with no alarm features; the Rome II criteria gave the lowest yield. By the stool frequency criteria, a majority of patients had unclassified pattern, unlike by the stool form and patients' perception of their symptoms. © 2013 Indian Society of Gastroenterology.
Mukhopadhyay S.,Christian Medical College |
Niyogi M.,Burdwan Medical College |
Sarkar J.,Kothari Medical Center |
Mukhopadhyay B.S.,Nilratan Sirkar Medical College |
Halder S.K.,IQ City Medical College
Journal of Anaesthesiology Clinical Pharmacology | Year: 2015
Background and Aims: In absence of any published standard guideline for sedation or anesthesia practice for prolonged therapeutic "endoscopic retrograde cholangio-pancreatography (ERCP)," safe and cost-effective sedation protocol is the need of the hour. Our study aims to evaluate the efficacy of a dexmedetomidine as an add-on for prolonged deep sedation for ERCP and to compare three deep sedation regimens regarding safety and efficacy. Material and Methods: Forty-five consecutively enrolled patients planned for therapeutic ERCP and assumed to have prolonged procedural duration (>50 min) were divided into three groups in a randomized assessor blinded fashion. Group 1 received propofol and midazolam, Group 2 received the sedato-analgesic cocktail containing ketamine-propofol-midazolam-pentazocine, and the Group 3 received sedate-analgesic cocktail plus dexmedetomidine infusion under monitoring of vital parameters and according to the judgment of the concerned anesthesiologist. Total propofol requirement, episodes of gagging, oxygen desaturation, changes in mean blood pressure (MBP), recovery and satisfaction score of endoscopist, anesthetist and patient were noted and analyzed statistically using one way ANOVA with Bonferroni correction and Chi-square test. Results: Mean propofol requirement, incidences of gagging and oxygen desaturation was significantly less in Group 2 and 3 compared to Group 1. MBP was more stable and recovery was faster in Group 3. Anesthetist's satisfaction was more with Group 2 and even more with Group 3. Conclusions: The sedato-analgesic cocktail was superior to the conventional propofol-midazolam regimen, dexmedetomidine as add-on increased the efficacy and safety of sedate-analgesic cocktail. It reduces propofol requirement, helps to maintain the patient in a safe and more stable level of sedation and increases satisfaction of the anesthetist.
Mondal S.,Indian Institute of Science |
Chandra S.,Kothari Medical Center |
Mandal C.,Indian Institute of Science
Leukemia Research | Year: 2010
Altered sialylation occurs in essentially all types of human and experimental cancers. Although, aberrant sialylation is believed to mainly due to altered sialyltransferase (ST) level, so far, expression pattern of different STs in acute lymphoblastic leukemia has never been investigated. Accordingly, the aim of our study was to monitor the changes in mRNA expression of ST6Gal I, ST3Gal V and ST8Sia I in patients by real-time PCR, which may provide prognostic information useful in defining appropriate therapeutic options. Our data demonstrated that ST6Gal I and ST3Gal V mRNA were up-regulated in lymphoblasts whereas its presence was negligible in non-malignant donors. In contrast, ST8SiaI was downregulated in patients. The extents of linkage-specific sialylation of glycoconjugates were found to be associated with disease establishment. Additionally, ST6Gal I and ST3Gal V were positively correlated with the high risk of the disease (P = 0.0032 and 0.0016). This differential ST level can be used as biomarker with the molecular method of quantitative PCR and may be useful to discriminate normal and cancer patients. © 2009 Elsevier Ltd. All rights reserved.
Basu S.,Saha Institute of Nuclear Physics |
Banerjee D.,Ramakrishna Mission Seva Prathisthan |
Chandra S.,Kothari Medical Center |
Chakrabarti A.,Saha Institute of Nuclear Physics
Glycoconjugate Journal | Year: 2010
The present work is aimed to study the mechanism of faster erythrocyte clearance in hereditary spherocytosis (HS), a heterogeneous disorders characterized by alterations in the proteins of the red cell membrane skeleton along with different kinds of thalassemia. The maximum exposure of phosphatidylserine (PS) is found in HS compared to those in both α- and β-thalassemia. Interestingly, in HS more PS exposed cells were found in younger erythrocytes compared to normal and the thalassemics where aged cells showed higher loss of PS asymmetry. Loss of sialic acid and GlcNAc bearing glycoconjugates, presumably the glycophorins, was also found upon aging. The loss of PS asymmetry together with the cell surface glycoproteins mediated by membrane vesiculation, seemed to play key role in early clearance of erythrocytes from circulation following a mechanism similar to HbEβ-thalassemia. © 2009 Springer Science+Business Media, LLC.
Withanolide D induces apoptosis in leukemia by targeting the activation of neutral sphingomyelinase-ceramide cascade mediated by synergistic activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase
Mondal S.,Indian Institute of Science |
Mandal C.,Indian Institute of Science |
Sangwan R.,Central Institute of Medicinal and Aromatic Plants |
Chandra S.,Kothari Medical Center
Molecular Cancer | Year: 2010
Background: Ceramide is an important second messenger that has diverse cellular and biological effect. It is a specific and potent inducer of apoptosis and suppressor of cell growth. In leukemia, chemoresistance generally developed due to deregulated ceramide metabolism. In combinatorial treatment strategies of leukemia, few components have the capability to increases ceramide production. Manipulation in ceramide production by physiological and pharmacological modulators therefore will give additive effect in leukemia chemotherapy.Results: Here, we show that Withanolide D (C 4β-C 5β,C 6β-epoxy-1-oxo-,20β, dihydroxy-20S,22R-witha-2,24-dienolide; WithaD), a pure herbal compound isolated from Withania somnifera could effectively induces apoptosis in a dose and time dependant manner both in myeloid (K562) and lymphoid (MOLT-4) cells being nontoxic to normal lymphocytes and control proliferative cells. WithaD potentially augment ceramide production in these cells. Downstream of ceramide, WithaD acted on MKK group of proteins and significantly increased JNK and p38MAPK phosphorylation. Pharmacological inhibition of p38MAPK and JNK proves their cooperative action on WithaD-induced cell death. Dissecting the cause of ceramide production, we found activation of neutral sphingomyelinase and showed neutral-sphingomyelinase 2 (N-SMase 2) is a critical mediator of WithaD-induced apoptosis. Knockdown of N-SMase 2 by siRNA and inhibitor of N-SMase (GW4869) significantly reduced WithaD-induced ceramide generation and phosphorylation of MKK4 and MKK3/6, whereas phosphorylation of MKK7 was moderately regulated in leukemic cells. Also, both by silencing of N-SMase 2 and/or blocking by GW4869 protects these cells from WithaD-mediated death and suppressed apoptosis, whereas Fumonisin B1, an inhibitor of ceramide synthase, did not have any effect. Additionally, WithaD effectively induced apoptosis in freshly isolated lymphoblasts from patients and the potent cell killing activity was through JNK and p38MAPK activation.Conclusion: Our results demonstrate that WithaD enhance the ceramide accumulation by activating N-SMase 2, modulate phosphorylation of the JNK and p38MAPK and induced apoptosis in both myeloid and lymphoid cells along with primary cells derived from leukemia patients. Taken together, this pure herbal compound (WithaD) may consider as a potential alternative tool with additive effects in conjunction with traditional chemotherapeutic treatment, thereby accelerate the process of conventional drug development. © 2010 Mondal et al; licensee BioMed Central Ltd.
Samanta S.,Indian Institute of Technology Kharagpur |
Mehra S.,Kothari Medical Center |
Maiti T.K.,Indian Institute of Technology Kharagpur |
Ghosh P.,Medical College |
Ghosh S.K.,Indian Institute of Technology Kharagpur
Journal of Public Health (Germany) | Year: 2012
Aim: The aim of this study was to estimate the change in magnitude of intestinal parasitic infestation, distribution of various socio-demographic factors and their possible influence on the parasitic infestation in the community over a period of 4 years. Subject and methods: Two cross-sectional surveys were carried out in 2004 and 2008 in an agriculture-dependent rural community in Singur block of Hooghly district of West Bengal. The changing pattern of socio-behavioural characteristics was compared with intestinal parasitic infestation using univariate and multivariate analysis. Results: A statistically significant decline in intestinal parasitic infestation from 94/246 (38.20%) in 2004 to 56/210 (26.70%) in 2008 was detected. The univariate analysis showed that absence of chronically ill patients at home, use of a sanitary latrine and easier access to medication were important correlates. Laboratory investigation was often negative for symptomatic subjects. A statistically significant decline was noted in the later phase of the study in the proportion of infested persons among illiterates, those using untreated surface water for washing utensils and those using a sanitary latrine. However, multivariate analysis failed to identify the single most important determinant that influences the change; rather the overall decline in 4 years time is the key finding indicating a potential role of multiple factors. Conclusion: The significant decline in parasitic infestation rates probably can be attributed to overall improvement in socio-behavioural factors. With the decline in intestinal parasitic infestation, symptomatic subjects should be screened for other diseases with similar presenting symptoms. © Springer-Verlag 2011.
Mandal P.,National Institute of Biomedical Genomics |
Bhattacharjee B.,Indian Statistical Institute |
Bhattacharjee B.,University of Massachusetts Medical School |
Das Ghosh D.,Indian Statistical Institute |
And 5 more authors.
PLoS ONE | Year: 2013
We tested the hypothesis that (i) synonymous variations within the coding regions, and (ii) variations within the non-coding regions of HPV, influence cervical cancer (CaCx) pathogenesis under the impact of intact HPV16 genomes. Whole genome sequence analysis of HPV16 isolates within 70 CaCx cases and 25 non-malignant samples revealed that synonymous variations were significantly higher within the E6 (p = 0.014), E5 (p = 0.001) and L2 (p = 0.0002) genes of HPV16 isolates within cases, compared to isolates within non-malignant samples. All of the 25 (100%) humanized codons identified within L2 ORF of the samples analyzed, were harbored by CaCx cases, while 8 out of 25 (32%) were harbored by HPV16 positive non-malignant samples (p = 3.87105E-07). L2 (mRNA and protein) expression was evident only among cases with episomal viral genomes and L2 mRNA expression correlated significantly with E2 gene copy numbers suggesting expression from all episomal genomes. Among such cases, Asian American (AA) isolates portrayed all of the humanized codons (100%; 4-6/sample) recorded within L2, which was significantly higher (p = 2.02E-7) compared to the European (E) isolates (22.8%; none or 1-2/sample). Additionally, majority of E variant isolates within cases (54/57; 94.7%) portrayed a variation (T4228C) within the short non-coding region (NCR2) between E5 and L2 genes, which portrays a weak promoter activity specific for L2 mRNA expression. This resulted in loss of 9 out of 14 miRNA binding sites (hsa-miR-548 family), despite the significant overexpression of miR548a-5p and miR548d-5p among such cases (28.64 and 36.25 folds, respectively), in comparison to HPV negative control samples. The findings exemplify the biological relevance of sequence variations in HPV16 genomes and highlight that episomal HPV16 in CaCx cases employ multiple mechanisms to sustain L2 expression, thereby justifying the potential role of L2 in such cancers, as opposed to those harboring viral integration. © 2013 Mandal et al.
Mandal C.,Indian Institute of Chemical Technology |
Tringali C.,University of Milan |
Mondal S.,Indian Institute of Chemical Technology |
Anastasia L.,University of Milan |
And 2 more authors.
International Journal of Cancer | Year: 2010
Membrane-linked sialidase Neu3 is a key enzyme for the extralysosomal catabolism of gangliosides. In this respect, it regulates pivotal cell surface events, including trans-membrane signaling, and plays an essential role in carcinogenesis. In this report, we demonstrated that acute lymphoblastic leukemia (ALL), lymphoblasts (primary cells from patients and cell lines) are characterized by a marked down-regulation of Neu3 in terms of both gene expression (-30 to 40%) and enzymatic activity toward ganglioside GD1a (-25.6 to 30.6%), when compared with cells from healthy controls. Induced overexpression of Neu3 in the ALL-cell line, MOLT-4, led to a significant increase of ceramide (166%) and to a parallel decrease of lactosylceramide (-55%). These events strongly guided lymphoblasts to apoptosis, as we assessed by the decrease in Bcl2/ Bax ratio, the accumulation of Neu3 transfected cells in the sub G0-G1 phase of the cell cycle, the enhanced annexin-V positivity, the higher cleavage of procaspase-3. Therefore, the reduced expression of Neu3 in ALL could help lymphoblasts to survive, maintaining the cellular content of ceramide below a critical level. Interestingly, we found that Neu3 activity varied in relation to disease progression, increasing in clinical remission after chemotherapy, and decreasing again in patients that relapsed. In addition, a negative correlation was observed between Neu3 expression and the percentage of the ALL marker 9-OAcGD3 positive cells. Consequently, Neu3 could represent a new potent biomarker in childhood ALL, to assess the efficacy of therapeutic protocols and to rapidly identify an eventual relapse. © 2009 UICC.