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1.
Environ Sci Technol ; 2021 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-34842427

RESUMEN

Two years of satellite observations were used to quantify methane emissions from coal mines in Queensland, the largest coal-producing state in Australia. The six analyzed surface and underground coal mines are estimated to emit 570 ± 98 Gg a-1 in 2018-2019. Together, they account for 7% of the national coal production while emitting 55 ± 10% of the reported methane emission from coal mining in Australia. Our results indicate that for two of the three locations, our satellite-based estimates are significantly higher than reported to the Australian government. Most remarkably, 40% of the quantified emission came from a single surface mine (Hail Creek) located in a methane-rich coal basin. Our findings call for increased monitoring and investment in methane recovery technologies for both surface and underground mines.

2.
Sci Rep ; 11(1): 4138, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33602990

RESUMEN

Quantifying natural geological sources of methane (CH4) allows to improve the assessment of anthropogenic emissions to the atmosphere from fossil fuel industries. The global CH4 flux of geological gas is, however, an object of debate. Recent fossil (14C-free) CH4 measurements in preindustrial-era ice cores suggest very low global geological emissions (~ 1.6 Tg year-1), implying a larger fossil fuel industry source. This is however in contrast with previously published bottom-up and top-down geo-emission estimates (~ 45 Tg year-1) and even regional-scale emissions of ~ 1-2 Tg year-1. Here we report on significant geological CH4 emissions from the Lusi hydrothermal system (Indonesia), measured by ground-based and satellite (TROPOMI) techniques. Both techniques indicate a total CH4 output of ~ 0.1 Tg year-1, equivalent to the minimum value of global geo-emission derived by ice core 14CH4 estimates. Our results are consistent with the order of magnitude of the emission factors of large seeps used in global bottom-up estimates, and endorse a substantial contribution from natural Earth's CH4 degassing. The preindustrial ice core assessments of geological CH4 release may be underestimated and require further study. Satellite measurements can help to test geological CH4 emission factors and explain the gap between the contrasting estimates.

3.
Sci Adv ; 6(17): eaaz5120, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32494644

RESUMEN

Using new satellite observations and atmospheric inverse modeling, we report methane emissions from the Permian Basin, which is among the world's most prolific oil-producing regions and accounts for >30% of total U.S. oil production. Based on satellite measurements from May 2018 to March 2019, Permian methane emissions from oil and natural gas production are estimated to be 2.7 ± 0.5 Tg a-1, representing the largest methane flux ever reported from a U.S. oil/gas-producing region and are more than two times higher than bottom-up inventory-based estimates. This magnitude of emissions is 3.7% of the gross gas extracted in the Permian, i.e., ~60% higher than the national average leakage rate. The high methane leakage rate is likely contributed by extensive venting and flaring, resulting from insufficient infrastructure to process and transport natural gas. This work demonstrates a high-resolution satellite data-based atmospheric inversion framework, providing a robust top-down analytical tool for quantifying and evaluating subregional methane emissions.

4.
Infect Genet Evol ; 80: 104139, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31841700

RESUMEN

Bone marrow stromal cell antigen 2 (BST2) is an interferon induced host restriction factor for HIV-1 that blocks the release of nascent virions from infected T cells. We aimed to characterize BST2 gene variants in HIV-1 positive individuals in Indian cohort and study the association of these variants with disease progression in long term non progressors (LTNPs) and progressors. Archived samples of 32 LTNPs, 17 progressors, and 78 controls were screened for BST2 gene polymorphisms using Sanger's sequencing method. Frequency distribution, survival analysis and bioinformatics tools were used to study the association of BST2 variants with disease progression. Eighteen variants of BST2 gene were observed in Indian cohort. Intronic SNP rs919267T/C (OR = 4.489 [0.8494-27.03], p = .04157) and exonic SNP rs13485C/G (OR = 3.887 [0.8262-25.56], p = .0488) were found to be significantly associated with disease progression. Also, rs13485C/C genotype in combination with rs919267C/T (OR = 9.406 [1.384-111], p = .0085) and rs145303329 Δ19bp (OR = 3.887 [0.826-25.5], p = .048) were found to be significantly associated with disease progression. 19 bp indel rs145303329 and its allele c.1-443_1-442insCGCCCCCAGAC[C/T]CAGGCCC from BST2 promoter also showed association with disease progression (OR = 12.97 [0.9731-850.5], p = .026). Docking of AP2 repressor with above allele showed the total binding energy of LTNPs and progressors to be -2581.42 kcal/mol and -3563.27/-3562.84 kcal/mol respectively. We have identified the novel association of three BST2 gene SNPs; rs919267, rs13485 and indel rs145303329 from Indian cohort to be associated with the risk of HIV-1 disease progression for the first time.


Asunto(s)
Antígenos CD/genética , Susceptibilidad a Enfermedades , Variación Genética , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1 , Alelos , Antígenos CD/química , Antígenos CD/metabolismo , Sitios de Unión , Biología Computacional/métodos , Progresión de la Enfermedad , Exones , Proteínas Ligadas a GPI/química , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/mortalidad , Humanos , India , Estimación de Kaplan-Meier , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Unión Proteica , Relación Estructura-Actividad , Factor de Transcripción AP-2/química , Factor de Transcripción AP-2/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-31843920

RESUMEN

Methane emissions due to accidents in the oil and natural gas sector are very challenging to monitor, and hence are seldom considered in emission inventories and reporting. One of the main reasons is the lack of measurements during such events. Here we report the detection of large methane emissions from a gas well blowout in Ohio during February to March 2018 in the total column methane measurements from the spaceborne Tropospheric Monitoring Instrument (TROPOMI). From these data, we derive a methane emission rate of 120 ± 32 metric tons per hour. This hourly emission rate is twice that of the widely reported Aliso Canyon event in California in 2015. Assuming the detected emission represents the average rate for the 20-d blowout period, we find the total methane emission from the well blowout is comparable to one-quarter of the entire state of Ohio's reported annual oil and natural gas methane emission, or, alternatively, a substantial fraction of the annual anthropogenic methane emissions from several European countries. Our work demonstrates the strength and effectiveness of routine satellite measurements in detecting and quantifying greenhouse gas emission from unpredictable events. In this specific case, the magnitude of a relatively unknown yet extremely large accidental leakage was revealed using measurements of TROPOMI in its routine global survey, providing quantitative assessment of associated methane emissions.

6.
BMC Infect Dis ; 19(1): 1053, 2019 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-31842762

RESUMEN

BACKGROUND: HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. METHODS: The Sanger's method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. RESULTS: Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. CONCLUSION: The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.


Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/genética , Infecciones por VIH/genética , Infecciones por VIH/inmunología , VIH-1/inmunología , Células Asesinas Naturales/inmunología , Polimorfismo de Nucleótido Simple/genética , Receptores de IgG/genética , Adolescente , Adulto , Anticuerpos Monoclonales/uso terapéutico , Femenino , Frecuencia de los Genes/genética , Genotipo , Anticuerpos Anti-VIH/uso terapéutico , Infecciones por VIH/terapia , Humanos , Inmunoterapia , India , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Proteínas del Envoltorio Viral/farmacología , Adulto Joven
7.
Artículo en Inglés | MEDLINE | ID: mdl-30297466

RESUMEN

Southeast Asia, in particular Indonesia, has periodically struggled with intense fire events. These events convert substantial amounts of carbon stored as peat to atmospheric carbon dioxide (CO2) and significantly affect atmospheric composition on a regional to global scale. During the recent 2015 El Niño event, peat fires led to strong enhancements of carbon monoxide (CO), an air pollutant and well-known tracer for biomass burning. These enhancements were clearly observed from space by the Infrared Atmospheric Sounding Interferometer (IASI) and the Measurements of Pollution in the Troposphere (MOPITT) instruments. We use these satellite observations to estimate CO fire emissions within an inverse modelling framework. We find that the derived CO emissions for each sub-region of Indonesia and Papua are substantially different from emission inventories, highlighting uncertainties in bottom-up estimates. CO fire emissions based on either MOPITT or IASI have a similar spatial pattern and evolution in time, and a 10% uncertainty based on a set of sensitivity tests we performed. Thus, CO satellite data have a high potential to complement existing operational fire emission estimates based on satellite observations of fire counts, fire radiative power and burned area, in better constraining fire occurrence and the associated conversion of peat carbon to atmospheric CO2 A total carbon release to the atmosphere of 0.35-0.60 Pg C can be estimated based on our results.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monóxido de Carbono/análisis , Incendios , El Niño Oscilación del Sur , Indonesia , Tecnología de Sensores Remotos
8.
J Assoc Physicians India ; 66(7): 50-54, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31325263

RESUMEN

Background: Herpes zoster (HZ) is caused by varicella-zoster virus ( VZV ) reactivation. In the United States, Zoster vaccine (ZOSTAVAX) is indicated for HZ prevention in patients ≥50 years. Aims: To evaluate the immunogenicity, safety, and tolerability of ZOSTAVAX in healthy Indian subjects, to support its registration in India. Methods: This open-label, single-arm study was conducted at 10 sites in India. Healthy Indians (≥50 years) received a single ZOSTAVAX dose. Immunogenicity was assessed by VZV-specific antibody titer using gpELISA assay. VZV-specific antibody geometric mean titers (GMT; Day 1 pre-vaccination, Week 6 post-vaccination) and geometric mean fold-rise (GMFR; Week 6 post-vaccination) were assessed. Safety was evaluated by the incidence of adverse events (AEs) and serious adverse events (SAEs) within 42 days of vaccination. Two-sided 95% confidence intervals (CIs) were evaluated using t-distribution with natural log-transformed values. Results: Of the 250 subjects (mean age, 58.6 years) enrolled and vaccinated, 244 subjects completed the 6-week follow-up. Overall, subjects in the per-protocol population had GMT of 149.8 gpELISA units/mL (n=250; 95% CI: 132.6, 169.2) at Day 1 pre-vaccination, and 410.8 gpELISA units/mL (n=243; 95% CI: 373.0, 452.6) at Week 6 post-vaccination. GMFR of VZV-specific antibody from Day 1 pre-vaccination to Week 6 post-vaccination was 2.8 (95% CI: 2.5, 3.1). Overall, 67 subjects (26.8%) experienced AEs, with 48 (19.2%) reporting injection-site AEs and 38 (15.2%) reporting non-injection-site AEs. SAE-abdominal pain and bronchitis-was reported in one (0.4%) patient each. There was one death, which was unrelated to the vaccine. Limitations: Since ZOSTAVAX introduces a new live attenuated virus, clinical reactivation of ZOSTAVAX virus and wild-type VZV will need to be differentiated. Conclusions: In healthy Indians ≥50 years, ZOSTAVAX was well tolerated and resulted in expected VZV-specific antibody titer levels at 6 weeks post-vaccination.


Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Adulto , Anticuerpos Antivirales , Herpesvirus Humano 3 , Humanos , India , Persona de Mediana Edad
9.
Nat Commun ; 8(1): 2227, 2017 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-29263323

RESUMEN

Several viable but conflicting explanations have been proposed to explain the recent ~8 p.p.b. per year increase in atmospheric methane after 2006, equivalent to net emissions increase of ~25 Tg CH4 per year. A concurrent increase in atmospheric ethane implicates a fossil source; a concurrent decrease in the heavy isotope content of methane points toward a biogenic source, while other studies propose a decrease in the chemical sink (OH). Here we show that biomass burning emissions of methane decreased by 3.7 (±1.4) Tg CH4 per year from the 2001-2007 to the 2008-2014 time periods using satellite measurements of CO and CH4, nearly twice the decrease expected from prior estimates. After updating both the total and isotopic budgets for atmospheric methane with these revised biomass burning emissions (and assuming no change to the chemical sink), we find that fossil fuels contribute between 12-19 Tg CH4 per year to the recent atmospheric methane increase, thus reconciling the isotopic- and ethane-based results.

10.
AIDS Res Hum Retroviruses ; 33(11): 1171-1174, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28737979

RESUMEN

HECT domain and RCC1-like domain-containing protein 5 (HERC-5) is one of the novel host restriction factors that is known to inhibit HIV release in vitro. Polymorphisms in other host restriction factors have been associated with HIV infection and disease progression. However, no report is available on the HERC-5 polymorphism in HIV-infected individuals. We studied the HERC-5 gene polymorphism in HIV-infected individuals and explored whether it is associated with different disease outcomes. Genomic DNA was isolated from 41 HIV-1 progressors, 39 long-term nonprogressors, and 74 HIV seronegative healthy donors for amplification of HERC5 Exon-18 and other regulatory regions followed by sequencing. We found no genetic variation in the known single-nucleotide polymorphism (SNP)-rs34457268 (Exon-18) of HERC-5 in HIV-infected individuals. Instead, a synonymous mutation at rs6857425 (T-C) was present in the same region among all study groups (p > .05), irrespective of their HIV status. We further noted two novel SNPs in Intron-18 region. To the best of our knowledge, this is first study to report the HERC5 gene polymorphism among HIV-infected groups.


Asunto(s)
Predisposición Genética a la Enfermedad , Infecciones por VIH/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Polimorfismo Genético , Adolescente , Adulto , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Análisis de Secuencia de ADN , Adulto Joven
11.
Sci Rep ; 7: 45759, 2017 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-28393869

RESUMEN

Year-to-year variations in the atmospheric methane (CH4) growth rate show significant correlation with climatic drivers. The second half of 2010 and the first half of 2011 experienced the strongest La Niña since the early 1980s, when global surface networks started monitoring atmospheric CH4 mole fractions. We use these surface measurements, retrievals of column-averaged CH4 mole fractions from GOSAT, new wetland inundation estimates, and atmospheric δ13C-CH4 measurements to estimate the impact of this strong La Niña on the global atmospheric CH4 budget. By performing atmospheric inversions, we find evidence of an increase in tropical CH4 emissions of ∼6-9 TgCH4 yr-1 during this event. Stable isotope data suggest that biogenic sources are the cause of this emission increase. We find a simultaneous expansion of wetland area, driven by the excess precipitation over the Tropical continents during the La Niña. Two process-based wetland models predict increases in wetland area consistent with observationally-constrained values, but substantially smaller per-area CH4 emissions, highlighting the need for improvements in such models. Overall, tropical wetland emissions during the strong La Niña were at least by 5% larger than the long-term mean.

12.
AIDS Res Hum Retroviruses ; 32(5): 489-502, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26756665

RESUMEN

Although HIV-1 epidemic in India is mainly driven by subtype C, subtype A has been reported for over two decades. This is the first comprehensive analysis of sequences of HIV-1 subtype A from India, based on the near full-length genome sequences of six different HIV-1 subtype A Indian isolates along with available partial gene sequences from India and global sequences. The phylogenetic analyses revealed the convergence of all Indian whole-genome sequences and majority of the partial gene sequences to a single node with the sequences most closely related to African sub-subtype A1. The presence of the signature motifs consistent with those observed in subtype A and CTL epitopes characterized specifically for subtype A1 were observed among the study sequences. Deletion of LY amino acid of LYPXnL motif of p6gag and one amino acid in V3 loop have been observed among the study isolates, which have also been observed in a few sequences from East Africa. Overall, the results are indicative of a monophyletic lineage or founder effect of the Indian epidemic due to sub-subtype A1 and supportive of a possible migration of subtype A1 into India from East Africa.


Asunto(s)
Genoma Viral/genética , Infecciones por VIH/epidemiología , VIH-1/clasificación , VIH-1/genética , Secuencia de Aminoácidos , Secuencia de Bases , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , India/epidemiología , Filogenia , Eliminación de Secuencia/genética
13.
AIDS Res Hum Retroviruses ; 31(12): 1269-73, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26323027

RESUMEN

HIV is known for its genetic variability across the globe. The HIV epidemic in India is primarily driven by subtype C, although sporadic circulating and unique recombinant forms are also reported from a few metropolitan cities in which genotyping facilities are available. Here we report a novel CRF01_AE/C recombinant from a multicenter study on the effectiveness of antiretroviral therapy (ART), 12 months after its initiation. Our subject is a 32-year-old heterosexual female, a native of Pune city in western India. Identification and analyses of recombination breakpoints using jpHMM@Gobics and SimPlot bootscanning revealed six recombination breakpoints, indicating insertion of the CRF01_AE genome at three points in the backbone of subtype C. Both subtype C and CRF01_AE are commonly seen in the population at risk of heterosexual HIV transmission, thereby providing an opportunity for cocirculation and recombination. The emergence of a novel recombinant of CRF01_AE/C is indicative of the increasing genetic diversity of the HIV epidemic in India.


Asunto(s)
Genotipo , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/genética , Recombinación Genética , Adulto , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Ciudades , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Humanos , India , Datos de Secuencia Molecular , ARN Viral/genética , Análisis de Secuencia de ADN
14.
Genome Announc ; 3(4)2015 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-26294622

RESUMEN

We report here three novel HIV-1 intersubtype recombinants from India. One among those is a recombinant between subtype C and CRF01_AE and another two between A1 and C. A recombinant virus with CRF01_AE is reported for the first time from India.

15.
Vaccine ; 32 Suppl 1: A36-44, 2014 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-25091678

RESUMEN

Burden of rotavirus gastroenteritis (RVGE) in outpatient setting in India is not fully understood. A prospective study was undertaken to describe RVGE among Indian children less than 5 years of age presenting in outpatient departments with acute gastroenteritis (AGE). This study was conducted at 11 outpatient departments (OPDs) of private pediatric clinics in urban areas of India. A total of 605 eligible children were enrolled at OPDs. Stool samples of the subjects were collected and tested for presence of rotavirus antigen by enzyme immune assay (EIA) and were typed by reverse-transcriptase polymerase chain reaction (RT-PCR). Physician examined the children and documented the disease particulars. In addition, parents/guardians were interviewed for AGE related symptoms, health care utilization and cost incurred due to AGE, and parental stress associated with AGE. After OPD, parents/guardians completed diary cards and questionnaires to capture the information for 14 days following the enrollment. Complete data for analysis including stool sample results was available from 552 subjects. 23% (127/552; [CI 19.5, 26.5]) of stool samples were rotavirus (RV) positive. RT-PCR was done for 85.8% (109/127) of RV positive samples. G1, G2, G9, and G12 types were identified in 34.9% (38/109), 37.6% (41/109), 8.3% (9/109), and 6.4% (7/109) stool samples, respectively. P[4] and P[8] were identified in 36.7% (40/109) stool samples each, followed by P[6] identified in 15.6% (17/109) stool samples. At the time of enrollment, all three symptoms (vomiting, diarrhea, and fever) were observed concurrently in higher proportion of RV positive subjects compared to RV negative subjects (60.6% [77/127] vs. 42.8% [182/425], p=0.0004). Healthcare resource utilization, costs incurred due to disease, and parental stress were higher for RV positive subjects compared to RV negative subjects. In conclusion, RVGE was found to be a definite burden in AGE cases attending pediatric outpatient clinics in urban areas and it was associated with substantial economic and psychological burden. Introduction of rotavirus vaccine in India may help in reducing this disease burden.


Asunto(s)
Gastroenteritis/epidemiología , Infecciones por Rotavirus/epidemiología , Preescolar , Costo de Enfermedad , Femenino , Gastroenteritis/virología , Costos de la Atención en Salud , Humanos , India , Lactante , Masculino , Pacientes Ambulatorios , Estudios Prospectivos , Rotavirus/genética , Rotavirus/aislamiento & purificación , Población Urbana
16.
AIDS Res Hum Retroviruses ; 29(9): 1245-53, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23742670

RESUMEN

An increasing number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) all over the world has necessitated being vigilant about new recombinants. Since the first report of a recombinant virus with an A1/C mosaic in 1998 more and more B/C and A/C recombinant viruses are being reported from India. Here we report the identification and characterization of a unique HIV-1 A1/C recombinant circulating in Western India. Analysis of the full-length genome using RIP, SimPlot, and jpHMM@Gobics has confirmed its mosaic structure with insertion of subtype A1 in the backbone of subtype C at three positions: gag-pol (1973±15-2617±47), pol-vif (4879±37-5582±32), and gp41 (8437±106-8811±8); however, RIP and SimPlot showed one more small insertion in integrase (4343-4519). Phylogenetic analysis confirmed that the recombinant virus has an insertion of clade A1 in the backbone of subtype C, which has come from Indian subtype C.


Asunto(s)
Proteína gp41 de Envoltorio del VIH/genética , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/genética , Adulto , Secuencia de Bases , Genoma Viral , Integrasa de VIH/genética , VIH-1/clasificación , VIH-1/aislamiento & purificación , Humanos , India , Masculino , Datos de Secuencia Molecular , Filogenia , ARN Viral/genética , Análisis de Secuencia de ARN
17.
Int J Antimicrob Agents ; 40(6): 549-53, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23063097

RESUMEN

A dramatic increase in the number of quinolone-resistant Neisseria gonorrhoeae isolates in India and worldwide has been reported recently. This study was undertaken to identify and characterise mutations in the gyrA and parC genes of N. gonorrhoeae resistant to six different quinolone antibiotics. In total, 64 N. gonorrhoeae clinical isolates were obtained during 2007-2009 from patients attending sexually transmitted diseases clinics (New Delhi, 35; Pune, 16; Mumbai, 6; Hyderabad, 6; and Nagpur, 1). Antimicrobial susceptibility was determined by Etest and mutation patterns in gyrA and parC were determined by sequencing analysis. All strains showed varying resistance to different quinolone analogues, ranging from 17.2% (gatifloxacin) to 98.4% (ofloxacin and norfloxacin). Sequencing of gyrA and parC revealed that 100% of strains showed mutations in gyrA and 46.9% showed mutations both in gyrA and parC. All strains showed single or double mutations at Ser-91→Phe, Ser-91→Thr and Asp-95→Gly/Asn in gyrA and at Glu-91→Gly in parC. Asp-95→Asn mutation was the most prevalent in strains isolated from New Delhi, whilst Asp-95→Gly was prevalent in strains isolated from Pune. Strains were categorised into eight different mutation patterns. Resistant strains with high minimum inhibitory concentrations (≥8 µg/mL) showed mutations both in gyrA and parC. The difference in the proportion of strains showing mutations in gyrA and parC was found to be significant (P<0.001). The mutation Asp-95→Asn was restricted to Pune strains only. These results indicate that mutations in quinolone target enzymes may have resulted in the high-level resistance seen in these isolates.


Asunto(s)
Girasa de ADN/genética , Topoisomerasa de ADN IV/genética , Farmacorresistencia Bacteriana , Gonorrea/microbiología , Mutación Missense , Neisseria gonorrhoeae/efectos de los fármacos , Quinolonas/farmacología , Antibacterianos/farmacología , Femenino , Humanos , India , Masculino , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Análisis de Secuencia de ADN
18.
Blood Press Suppl ; 2: 5-12, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22352120

RESUMEN

AIM: To compare two strengths of a fixed drug combination (FDC) containing metoprolol XL and amlodipine (metoprolol/amlodipine 50/5; and metoprolol/amlodipine 25/2.5) with its components in hypertension. METHODS: We conducted this multicentre, randomized, open-label, trial in Indian patients with hypertension (140-180 mmHg/90-114 mmHg) in 11 centres from nine cities. Eligible patients (n = 402) were randomized into one of five treatment groups (metoprolol XL 50 mg + amlodipine 5 mg, metoprolol XL 25 mg + amlodipine 2.5 mg, metoprolol XL 50 mg, metoprolol XL 25 mg or amlodipine 5 mg) and treated for 8 weeks with five follow-up visits to record blood pressure (BP) and clinical status. RESULTS: At baseline, treatment groups were well balanced; mean +/- SD BP was 154.87 +/- 11.91/96.63 +/- 6.97 mmHg. The greatest reduction in BP from baseline to 8 weeks was seen in the high-dose FDC group (23.61/14.91 mmHg; p<0.001). The remaining 4 groups too demonstrated a significant reduction (p< 0.001): low-dose FDC - 22.29/ - 14.66; metoprolol 50, - 23.17/ - 13.37; metoprolol 25,- 18.41/ 12.50 and amlodipine 5, - 23.01/- 13.08. BP reductions by FDCs, however, were not statistically superior to monotherapies. Responder rates (sitting diastolic BP< 90 mmHg or reduction > or =10 mmHg) were 93% in the high-dose FDC group and 97% in the low-dose FDC group, and control rates (sitting BP < 140/90 mmHg) were 66% and 58%, respectively. These rates were higher than that seen in individual components. There were no reports of serious adverse events related to study medications. One each from the low-dose FDC and metoprolol 25 mg group discontinued because of adverse events. CONCLUSIONS: FDCs of metoprolol and amlodipine are effective and safe in mild to moderate hypertension.


Asunto(s)
Amlodipino/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Metoprolol/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amlodipino/efectos adversos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Metoprolol/efectos adversos , Persona de Mediana Edad
19.
Virus Res ; 144(1-2): 306-14, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19409946

RESUMEN

HIV-1 subtype C is predominantly circulating in India and has been reported to be strictly CCR5 tropic irrespective of disease stages. In the present study, we examined env clones obtained from a late stage Indian patient with a history of multiple sexual partners and opportunistic infections for coreceptor usage and V3 loop sequence. The env clones were found to exploit several coreceptors in addition to CCR5 in a cell-associated and cell-free manner. Analysis of V3 loop sequence revealed that the NARI-VB105 env clones were presented with unique amino acid substitutions with GPGR motif, atypical of clade C envelope. Further genetic analysis showed the V3 sequences albeit belonging to subtype C; however clustered distinctly to that of other clade C envelopes originated in different geographical regions. Modelling data revealed that NARI-VB105 V3 loop contained several basic residues giving rise a high net positive charge of +8 to these envelopes.


Asunto(s)
Sustitución de Aminoácidos/genética , Infecciones por VIH/virología , VIH-1/genética , Mutación Missense , Receptores del VIH/metabolismo , Acoplamiento Viral , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Secuencia de Aminoácidos , Análisis por Conglomerados , Genotipo , VIH-1/aislamiento & purificación , Humanos , India , Datos de Secuencia Molecular , Filogenia , Alineación de Secuencia , Análisis de Secuencia de ADN , Electricidad Estática , Productos del Gen env del Virus de la Inmunodeficiencia Humana/química
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