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1.
Nat Commun ; 15(1): 4037, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740793

ABSTRACT

Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.

2.
Bioorg Chem ; 110: 104829, 2021 05.
Article in English | MEDLINE | ID: mdl-33773222

ABSTRACT

Rohitukine (RH) was extracted from the stem bark of Dysoxylum binectariferum Hook. It was derivatized to different arylsulphanmides by treating with the corresponding aryl sulphonyl chlorides. These derivatives were tested in-vitro on protein tyrosine phosphatase 1B (PTP1B) inhibition. Among these the active compounds K2, K3, K5, and K8 significantly inhibited the PTP1B by 51.3%, 65.6%, 71.9%, and 55.9% respectively at 10 µg/ml, the results were also supported by in-silico docking experiments. The most potent compound K5 was analyzed for antidiabetic and antidyslipidemic activity in vivo. It showed a marked reduction in blood glucose level (random and fasting) and serum insulin level in db/db mice. It improved glucose intolerance as ascertained by the oral glucose tolerance test (OGTT). These NCEs (New Chemical Entities) also lowered cholesterol and triglyceride profiles while improved high-density lipoprotein cholesterol in db/db mice. The K5 was further evaluated for antiadipogenic activity on MDI (Methylisobutylxanthine, dexamethasone, and insulin)-induced adipogenesis. where it significantly inhibited MDI-induced adipogenesis in 3 T3-L1 preadipocytes, at 10 µM and 20 µM concentration. These results were compared with the parent compound RH which inhibited 35% and 45% lipid accumulation while the RH analog K5 inhibited the lipid accumulation by 41% and 51% at 10 and 20 µM concentration, respectively. These results well corroborated with in-silico studies.


Subject(s)
Chromones/pharmacology , Enzyme Inhibitors/pharmacology , Piperidines/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , 3T3-L1 Cells , Animals , Cell Differentiation/drug effects , Cells, Cultured , Chromones/chemistry , Chromones/isolation & purification , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Male , Meliaceae/chemistry , Mice , Molecular Structure , Piperidines/chemistry , Piperidines/isolation & purification , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Structure-Activity Relationship
3.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 1): 248-252, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31741968

ABSTRACT

The buccal fat pad (BFP) originally described as an anatomic structure without any obvious function. For long period it was considered to be surgical nuisance. However during the last four decades buccal fat is successively used tool for maxillofacial surgery for reconstruction of small to medium sized acquired or congenital soft tissue and bony defect in oral cavity. The aim of present article is to review the database available regarding BFP including its anatomy, clinical usage in oral malignancy as tool of reconstruction after ablative procedures it's success and its adoptability with other loco-regional flap for oral reconstruction in different scenario and our experience with it in tertiary cancer centre in India.

4.
Int J Tuberc Lung Dis ; 23(4): 450-457, 2019 04 01.
Article in English | MEDLINE | ID: mdl-31064624

ABSTRACT

BACKGROUND The association between respiratory impairment and tuberculosis (TB) treatment outcomes is not clear. METHODS We prospectively evaluated respiratory health status, measured using the Saint George's Respiratory Questionnaire (SGRQ), in a cohort of new adult pulmonary TB cases during and up to 18 months following treatment in India. Associations between total SGRQ scores and poor treatment outcomes of failure, recurrence and all-cause death were measured using multivariable Poisson regression. RESULTS We enrolled 455 participants contributing 619 person-years at risk; 39 failed treatment, 23 had recurrence and 16 died. The median age was 38 years (interquartile range 26-49); 147 (32%) ever smoked. SGRQ scores at treatment initiation were predictive of death during treatment (14% higher risk per 4-point increase in baseline SGRQ scores, 95%CI 2-28, P = 0.01). Improvement in SGRQ scores during treatment was associated with a lower risk of failure (1% lower risk for every per cent improvement during treatment, 95%CI 1-2, P = 0.05). Clinically relevant worsening in SGRQ scores following successful treatment was associated with a higher risk of recurrence (15% higher risk per 4-point increase scores, 95%CI 4-27, P = 0.004). CONCLUSION Impaired respiratory health status was associated with poor TB treatment outcomes. The SGRQ may be used to monitor treatment response and predict the risk of death in pulmonary TB. .


Subject(s)
Health Status , Tuberculosis, Pulmonary/drug therapy , Adolescent , Adult , Cohort Studies , Female , Follow-Up Studies , Humans , India , Male , Middle Aged , Recurrence , Surveys and Questionnaires , Treatment Outcome , Tuberculosis, Pulmonary/mortality , Tuberculosis, Pulmonary/physiopathology , Young Adult
5.
Am J Transplant ; 18(9): 2238-2249, 2018 09.
Article in English | MEDLINE | ID: mdl-29900673

ABSTRACT

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.


Subject(s)
Graft Rejection/etiology , Graft Survival/immunology , Immunity, Cellular/immunology , Liver Transplantation/adverse effects , T-Lymphocytes/immunology , Virus Diseases/immunology , Viruses/immunology , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Graft Rejection/pathology , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Infant , Male , Postoperative Complications , Prognosis , Prospective Studies , Risk Factors , Transplant Recipients , Viral Load , Virus Diseases/virology , Virus Replication , Young Adult
6.
Andrologia ; 50(2)2018 Mar.
Article in English | MEDLINE | ID: mdl-28776713

ABSTRACT

The aim of the study was to detect the frequency of the CFTR gene variants poly-T, TG repeats and c.1408A>G p.Met470Val (M470V) in Indian men with congenital bilateral absence of the vas deferens (CBAVD). Men diagnosed with CBAVD (n = 76), their female partners (n = 76) and healthy men from general population (n = 50) were recruited. Genomic DNA was isolated and the polymorphic regions of IVS9- c.1210-12T [5] and M470V were amplified using specific primers followed by Sanger's DNA sequencing. A statistically significant increase in the frequency of heterozygous IVS9- c.1210-12T [5] (39.4%) was observed in CBAVD men as compared to controls (14%). The allelic distribution of c.1210-12T [5], c.1210-12T [7] and c.1210-12T [9] in CBAVD men was 21%, 64.4% and 13% and that in healthy controls was 7%, 73% and 20% respectively. Longest TG repeat c.1210-34TG [13] was found in association with c.1210-12T [5] with an allelic frequency of 5.9% in CBAVD men. We found a significant association of c.1210-34TG [12]/c.1210-34TG [13] - c.1210-12[5] -V470 allele in CBAVD men. Twelve female partners harboured a heterozygous c.1210-12T [5] allele. The study emphasises the need to screen both partners for the polymorphisms M470V, poly-T, TG tract repeats in addition to population-specific known CFTR gene mutations.


Subject(s)
Asian People/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Infertility, Male/genetics , Male Urogenital Diseases/genetics , Polymorphism, Genetic , Vas Deferens/abnormalities , Alleles , Cohort Studies , Female , Genetic Carrier Screening , Genotype , Heterozygote , Humans , Male , Mutation , Sequence Analysis, DNA
7.
Physiol Mol Biol Plants ; 23(3): 663-673, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28878504

ABSTRACT

Foxtail millet [Setaria italica (L.) P. Beauv.] is an important small millet, grown as a short duration, drought tolerant crop across the world. This crop can be grown on wide ranges of soil conditions and has an immense potential for food and fodder in rainfed and arid regions of the India. In the present study, 31 primer pairs (27 SSR and 4 EST-SSR) were used to analyse the genetic diversity in 223 core collection accessions. Analysis resulted in detection of a total of 136 alleles with an average of 4.38 alleles per locus. Among these 136 alleles, 22 were rare, 70 were common and 44 were frequent. The PIC value ranged from 0.01 to 0.86 with an average of 0.31. The average number of observed alleles ranged from 2.0 (northern hills of India accessions) to 4.06 (exotic) with an average of 2.72. The mean Shannon's Information Index ranged from 0.44 (northern hills of India) to 0.69 (exotic) with an average of 0.52. Pair-wise Fst values indicated little to moderate genetic differentiation among the group of accessions. UPGMA clustering grouped the accessions into two major groups while analysis for population substructure indicated presence of four subpopulations. However there was no statistically well supported grouping of the accessions based on eco-geographic specificities. The core collection designated here represented substantial genetic diversity at molecular level, hence may be a good source of diversity for use in foxtail improvement programs in the region.

8.
Phys Chem Chem Phys ; 17(10): 6896-904, 2015 Mar 14.
Article in English | MEDLINE | ID: mdl-25673368

ABSTRACT

A stable photocatalyst, CdS dispersed on zeolite with Pd as both the dopant and the co-catalyst, has been developed. Enhancement of photocatalytic activity for hydrogen generation is observed for CdS when doped with palladium and dispersed on NaY-zeolite (CdPdS-Z). A further increase in the photocatalytic activity of CdPdS-Z is observed when palladium is added as a co-catalyst (Pd-CdPdS-Z). Cd0.95Pd0.05S-Z is synthesized via a facile soft chemical route and the Pd co-catalyst is loaded onto the composite using a wet impregnation method. This composite catalyst exists as two phases consisting of CdPdS and zeolite and CdPdS exists as a highly dispersed phase on zeolite as revealed by TEM studies. The Pd doped CdS-zeolite composite exhibits increased visible light absorption indicating the alteration of the band structure of CdS as a result of doping. Time resolved fluorescence studies reveal that the lifetime of the charge carriers is higher in the composites than in pure CdS. A detailed characterization using XRD, Raman and X-ray photoelectron spectroscopy indicates that Pd has substituted for Cd in the CdS lattice and Pd exists in the Pd(2+) oxidation state. Solid state MAS NMR studies indicate that an interaction exists between CdS (or CdPdS) and zeolite at the interface and Cd selectively interacts with Al of the zeolite framework. The photocatalytic activity of the Pd-CdPdS-Z catalyst remains unchanged with repeated cycles. Characterization of the used catalyst indicates that it is stable under the present experimental conditions. The enhanced photocatalytic activity of Pd-CdPdS-Z is attributed to the enhanced visible light absorption arising due to Pd doping and increased lifetime of the photogenerated charge carriers assisted by zeolite and the Pd co-catalyst. This study highlights the multiple roles played by palladium in enhancing the photocatalytic activity of the CdS-zeolite composite.

10.
J Midlife Health ; 4(3): 172-5, 2013 Jul.
Article in English | MEDLINE | ID: mdl-24672190

ABSTRACT

RESEARCH QUESTION: What is the addiction problems and morbidity profile pattern of geriatric population in rural area? OBJECTIVES: i) To study the morbidity profile of elderly. ii) To study the addiction problems among elderly. MATERIALS AND METHODS: The present study was carried out at the field practice area of Rural Health and Training Center (RHTC), Paithan of Government Medical College, Aurangabad during the period of September 1, 2006 to August 31, 2007. Total elderly population according to the definition at the field practice area of RHTC, Paithan was 3128. Enlisting of the study subjects was done by systematic random sampling by using Loksabha electoral list of 2005. A sample of 20% of total elderly population was taken by including every fifth elderly from the electoral list. STUDY DESIGN: Cross-sectional study. SETTINGS: Field practice area of RHTC, Paithan of Government Medical College, Aurangabad. PARTICIPANTS: Elderly above 60 years of age. SAMPLE SIZE: 625 which was 20% of total elderly at RHTC, Paithan. STATISTICAL ANALYSIS: Chi-square test. RESULTS: a) The study found that the prevalence of addiction among males was 68.34%, the prevalence of various addictions were smoking 29.96%, alcohol 18.18%, tobacco chewing 29.29% and among females, 45.42% elderly females use to chew tobacco. b) Prevalence of cataract was 40.16%, joint pain - 23.04%, chronic obstructive pulmonary disorder (COPD) - 7.52%, senescent forgetfulness - 10.88%, hemorrhoids - 8.64%, benign enlargement of prostate (BEP) - 7.20% in elderly males, hearing impairment - 24.8%, hypertension - 21.6%, diabetes mellitus - 13.92%, and anemia - 8.32%.

11.
Indian J Med Sci ; 66(3-4): 55-61, 2012.
Article in English | MEDLINE | ID: mdl-23603621

ABSTRACT

OBJECTIVE: Adverse drug reactions (ADRs) are associated with significant morbidity and mortality and have a major impact on public health. Pharmacovigilance helps in early detection of ADRs and identification of risk factors. Underreporting of ADRs can be improved by imparting knowledge regarding pharmacovigilance to healthcare professionals. This study was aimed at investigating the knowledge and attitude of resident doctors about ADR reporting and suggesting possible ways of improving ADR reporting. MATERIALS AND METHODS: This study was a cross-sectional, questionnaire-based survey conducted in a tertiary care teaching hospital. The respondents were resident doctors. Study instrument was a self-developed, pre-validated, semi-structured questionnaire consisting of open- and close-ended items. RESULTS: A total of 84 questionnaires were considered for analysis, giving a response rate of 93.33%. In all, 64.28% of the respondents were aware about pharmacovigilance, 52.38% were aware of ADR reporting system in India, 83.33% opined that only serious ADR with any medicine should be reported, and 35.72% believed that ADRs should be reported only for newly marketed agents. Although 67.85% of respondents observed an ADR, only 25% reported it; 44.04% were aware about the complete procedure of ADR reporting. General attitude of the respondents about ADR reporting was as follows: ADR reporting should be compulsory (15.19%), voluntary (41.66%), remunerated (3.57%), identity of prescriber should be concealed (21.42%), and identity of reporter should be concealed (29.7%). CONCLUSION: Increasing awareness about pharmacovigilance will be helpful in improving the status of ADR reporting. Other measures such as making ADR reporting guidelines available in the form of booklets and displaying posters can also play a useful role.


Subject(s)
Adverse Drug Reaction Reporting Systems , Health Knowledge, Attitudes, Practice , Pharmacovigilance , Physicians , Cross-Sectional Studies , Hospitals, Teaching , Humans , India , Mandatory Reporting , Tertiary Care Centers
12.
J Colloid Interface Sci ; 358(1): 238-44, 2011 Jun 01.
Article in English | MEDLINE | ID: mdl-21453926

ABSTRACT

Nearly monodisperse rhodium nanoparticles with adsorbed NH(x) were synthesized at the CCl(4)-water interface. The presence of NH(x)-adsorbed species was confirmed by energy-dispersive X-ray analysis (EDX) and X-ray photoelectron spectroscopy (XPS) studies. The synthesis of controlled size 2-38 nm rhodium particles was studied as a function of reducing agent concentration by transmission electron microscopy (TEM). HRTEM confirmed the formation of rhodium nanoparticles having fringe spacing consistent with reported Rh (111) planes. The continuity of these films over an area of 1×1 µm was revealed by atomic force microscopy (AFM) studies. The electrocatalytic application of these nanostructure Rh-NH(x) thin films for formaldehyde oxidation in 0.5M NaOH was investigated by cyclic voltammetry. The Rh nanoparticles formed by the present strategy are expected to be useful for other catalytic applications also.


Subject(s)
Nanoparticles/chemistry , Nanotechnology/methods , Rhodium/chemistry , Adsorption , Catalysis , Electrochemistry , Nanoparticles/ultrastructure , Nanotechnology/economics , Oxidation-Reduction , Surface Properties , Water/chemistry
14.
Eur J Med Chem ; 44(8): 3350-5, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19272678

ABSTRACT

A series of imidazole based compounds were synthesized by reacting simple imidazoles with alkyl halides or alkyl halocarboxylate in presence of tetrabutylammonium bromide (TBAB). The compounds bearing carbethoxy group undergo amidation with different amines in the presence of DBU to give respective carboxamides. The synthesized compounds were screened against Mycobacterium tuberculosis where compound 17 exhibited very good in vitro antitubercular activity and may serve as a lead for further optimization.


Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Antitubercular Agents/chemistry , Drug Evaluation, Preclinical , Imidazoles/chemistry , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects
15.
Genome ; 52(3): 222-30, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19234550

ABSTRACT

Cashew (Anacardium occidentale L.), introduced into India about 400 years ago, is distributed widely in the coastal regions as spontaneous populations as well as in cultivation. Despite the plant's commercial exploitation, little is known about its actual introduction and diversification. We attempted to construct these events by investigating the level of genetic variation and genetic structure of cashew populations collected from different geographical regions of India. A total of 91 individuals from four populations were analysed using AFLP markers and morphometric data. AFLP analysis based on 354 polymorphic loci revealed Indian cashew to have low but relatively substantial genetic diversity for an introduced species (H(E) = 0.262 and I(S) = 0.404). Twenty-seven qualitative and quantitative traits also revealed the existence of considerable morphometric variation (24% around the mean values). Bayesian cluster analysis based on AFLP data did not indicate the existence of definite population differentiation. Morphometric analysis allocated 12% variation among all four populations, whereas AFLP variation observed in cashew individuals was entirely within populations. The results, supporting the possibility of cashew having been introduced into India repeatedly over a period of time but at a single location (west coast), are discussed and their implications for germplasm management are described.


Subject(s)
Anacardium/genetics , Genetic Variation , Genetics, Population , Amplified Fragment Length Polymorphism Analysis , Anacardium/classification , Geography , Phylogeny
16.
J Med Imaging Radiat Oncol ; 52(2): 148-54, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18373806

ABSTRACT

Retrospective review of the congenital coronary artery (CA) anomalies detected by a 64-slice multidetector row computed tomographic (MDCT) angiography. The type of the anomaly, imaging characteristics, clinical relevance and the superiority of the MDCT over conventional coronary angiography are discussed. Multidetector row computed tomographic coronary angiography was carried out by the usual technique with 70 cc of non-ionic contrast agent and retrospective electrocardiogram gating. The volume data obtained were reconstructed in axial plane, along with volume-rendered three-dimensional reconstruction and virtual angioscopy in selected patients. The images were analysed by a radiologist, experienced in cardiac CT, and an experienced cardiologist. A retrospective review of the records was carried out, and subjects with congenital coronary anomalies were included in the study. Between 15 November 2005 and 27 February 2007, 1495 MDCT coronary angiograms were carried out. Eleven of them were found to have coronary anomalies. Five had absent left main CA. Two had interarterial course of the left main CA artery passing in between the right ventricular outflow tract and the root of aorta. In one patient, there was aberrant origin of right CA from the left aortic sinus with subsequent interarterial course and another one had aberrant origin of circumflex artery from the right aortic sinus. One patient each of congenitally absent circumflex artery and atresia of the right CA were found. Sixty-four slice MDCT coronary angiography provided accurate depiction of anomalous vessel origin and course along with the complex anatomical relation with the adjacent structures. CT can be considered as a first-line imaging method for delineating coronary arterial anomalies.


Subject(s)
Coronary Angiography/methods , Coronary Vessel Anomalies/diagnosis , Tomography, X-Ray Computed/methods , Contrast Media/administration & dosage , Electrocardiography , Female , Humans , Imaging, Three-Dimensional/methods , Iopamidol , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Radiographic Image Enhancement/methods , Retrospective Studies , Tomography, X-Ray Computed/instrumentation
17.
Carbohydr Res ; 343(7): 1153-62, 2008 May 19.
Article in English | MEDLINE | ID: mdl-18346719

ABSTRACT

5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition with different alkynes in the presence of CuSO4 and sodium ascorbate gave the corresponding sugar triazoles in very good yields. The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubercular activity in vitro with MIC 12.5 microg/mL.


Subject(s)
Alkynes/chemistry , Antitubercular Agents/chemical synthesis , Azides/chemistry , Carbohydrates/chemistry , Triazoles/chemical synthesis , Antitubercular Agents/pharmacology , Cyclization , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium tuberculosis/drug effects , Structure-Activity Relationship
18.
Clin Exp Immunol ; 151(3): 414-22, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18234054

ABSTRACT

We aimed to delineate factors operating at the interface of macrophage-mycobacterium interaction which could determine the fate of a 'subclinical' infection in healthy people of a tuberculosis-endemic region. Ten study subjects (blood donors) were classified as 'high' or 'low' responders based on the ability of their monocyte-derived macrophages to restrict or promote an infection with Mycobacterium tuberculosis. Bacterial multiplication between days 4 and 8 in high responder macrophages was significantly lower (P < 0.02) than low responders. All donor sera were positive for antibodies against cell-membrane antigens of M. tuberculosis and bacilli opsonized with heat-inactivated sera were coated with IgG. In low responder macrophages, multiplication of opsonized bacilli was significantly less (P < 0.04) than that of unopsonized bacilli. The levels of tumour necrosis factor (TNF)-alpha and interleukin (IL)-12 produced by infected high responder macrophages was significantly higher (P < 0.05) than low responders. However, infection with opsonized bacilli enhanced the production of IL-12 in low responders to its level in high responders. The antibody level against membrane antigens was also significantly higher (P < 0.05) in high responders, although the antigens recognized by two categories of sera were not remarkably different. Production of certain other cytokines (IL-1beta, IL-4, IL-6 and IL-10) or reactive oxygen species (H2O2 and NO) by macrophages of high and low responders did not differ significantly. The study highlights the heterogeneity of Indian subjects with respect to their capability in handling subclinical infection with M. tuberculosis and the prominent role that TNF-alpha, opsonizing antibodies and, to a certain extent, IL-12 may play in containing it.


Subject(s)
Endemic Diseases , Macrophages/microbiology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Adult , Antibodies, Bacterial/blood , Antigens, Bacterial/immunology , Blood Donors , Cells, Cultured , Humans , Immunity, Innate , India/epidemiology , Interleukin-12/biosynthesis , Lymphocyte Activation/immunology , Macrophages/immunology , Mycobacterium tuberculosis/growth & development , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Tuberculosis/epidemiology , Tumor Necrosis Factor-alpha/biosynthesis
19.
Br J Pharmacol ; 153(6): 1225-31, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18204486

ABSTRACT

BACKGROUND AND PURPOSE: Curcumin has been used to treat cancer, diabetes and other pathologies. However, little is known regarding its role in altering post-translational modifications of histone H3. A recent report suggests that acute hyperglycaemia induces a global down-regulation of gene expression in human tissues and epigenetic regulation of gene expression could be a novel mechanism underlying the pathological processes of hyperglycaemia. The present study was undertaken to examine changes in histone modification by curcumin treatment which prevents development of type I diabetic nephropathy. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were rendered diabetic using a single dose of streptozotocin (55 mg kg(-1), i.p.). Diabetic nephropathy was assessed by measurements of blood urea nitrogen, albumin and creatinine levels. Post-translational modifications of histone H3, heat shock protein-27 (HSP-27) and mitogen-activated protein (MAP) kinase p38 expression were examined by western blotting. KEY RESULTS: Treatment of diabetic rats with curcumin significantly decreased blood urea nitrogen and creatinine and increased albumin; variables associated with the development of diabetic nephropathy. There were also increased levels of HSP-27 and MAP kinase (p38) in diabetic kidney. However, curcumin treatment prevented this increase in HSP-27 and p38 expression. Moreover, at nuclear level curcumin prevented the decrease in dephosphorylation and increases acetylation of histone H3. CONCLUSIONS AND IMPLICATIONS: Our results suggested that protection against development of diabetic nephropathy by curcumin treatment involved changes in post-translational modifications of histone H3, expression of HSP-27 and MAP kinase p38 in diabetic kidney.


Subject(s)
Antioxidants/pharmacology , Curcumin/pharmacology , Diabetic Nephropathies/prevention & control , Gene Expression Regulation/drug effects , Animals , Blotting, Western , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/physiopathology , Heat-Shock Proteins/drug effects , Heat-Shock Proteins/metabolism , Histones/drug effects , Histones/metabolism , Male , Oxidative Stress/drug effects , Protein Processing, Post-Translational , Rats , Rats, Sprague-Dawley , Streptozocin , p38 Mitogen-Activated Protein Kinases/drug effects , p38 Mitogen-Activated Protein Kinases/metabolism
20.
Cell Death Differ ; 14(11): 1948-57, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17690712

ABSTRACT

Avicins, a family of plant triterpene electrophiles, can trigger apoptosis-associated tumor cell death, and suppress chemical-induced carcinogenesis by its anti-inflammatory, anti-mutagenic, and antioxidant properties. Here, we show that tumor cells treated with benzyloxycarbonylvalyl-alanyl-aspartic acid (O-methyl)-fluoro-methylketone, an apoptosis inhibitor, and Bax(-/-)Bak(-/-) apoptosis-resistant cells can still undergo cell death in response to avicin D treatment. We demonstrate that this non-apoptotic cell death is mediated by autophagy, which can be suppressed by chloroquine, an autophagy inhibitor, and by specific knockdown of autophagy-related gene-5 (Atg5) and Atg7. Avicin D decreases cellular ATP levels, stimulates the activation of AMP-activated protein kinase (AMPK), and inhibits mammalian target of rapamycin (mTOR) and S6 kinase activity. Suppression of AMPK by compound C and dominant-negative AMPK decreases avicin D-induced autophagic cell death. Furthermore, avicin D-induced autophagic cell death can be abrogated by knockdown of tuberous sclerosis complex 2 (TSC2), a key mediator linking AMPK to mTOR inhibition, suggesting that AMPK activation is a crucial event targeted by avicin D. These findings indicate the therapeutic potential of avicins by triggering autophagic cell death.


Subject(s)
Autophagy , Multienzyme Complexes/metabolism , Protein Serine-Threonine Kinases/metabolism , Saponins/pharmacology , Ubiquitin-Activating Enzymes/metabolism , AMP-Activated Protein Kinases , Apoptosis/physiology , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Protein 5 , Autophagy-Related Protein 7 , Beclin-1 , Cell Line, Tumor , Chloroquine/pharmacology , Enzyme Activation , Fusion Regulatory Protein 1, Heavy Chain/metabolism , Humans , Membrane Proteins/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering , Sirolimus/pharmacology , Tuberous Sclerosis Complex 2 Protein , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Ubiquitin-Activating Enzymes/genetics
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