Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 117
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Microb Pathog ; 174: 105946, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36526038

RESUMO

Viruses utilize clever strategies of interacting with various cellular factors, to remodel an organelle function, for the establishment of successful infection. In recent decades, numerous studies revealed the exploitation of the peroxisomal compartment by viruses. Epstein-Barr virus (EBV) is a ubiquitous virus linked with various cancers and neurological disorders. Till now, there is no report regarding the impacts of EBV infection on peroxisomal compartment. Therefore, we investigate the modulation of peroxisomal proteins in EBV transformed cell lines and during acute EBV infection. EBV positive Burkitt lymphoma cells of different origins as EBV transformed cells along with EBV negative Burkitt lymphoma cells as a control were used in this study. For acute EBV infection experiments, we infected peripheral blood mononuclear cells with EBV for three days. Thereafter, analyzed the gene expression patterns of peroxisomal proteins using qPCR. In addition, quantification of lipid content was performed by using fluorescence microscopy and biochemical assay. Our results revealed that, the peroxisomal proteins were distinctly regulated in EBV transformed cells and during acute EBV infection. Interestingly, PEX19 was significantly upregulated in EBV infected cells. Further, in correlation with the altered expression of peroxisomes proteins involved in lipid metabolism, the EBV transformed cells showed lower lipid abundance. Conversely, the lipid levels were increased during acute EBV infection. Our study highlights the importance of investigating the manipulation of the peroxisomal compartment by putting forward various differentially expressed proteins upon EBV infection. This study provides a base for further investigation to delve deeper into EBV and peroxisomal interactions. The future research in this direction could provide involvement of novel signaling pathways to understand molecular changes during EBV mediated pathologies.


Assuntos
Linfoma de Burkitt , Infecções por Vírus Epstein-Barr , Humanos , Herpesvirus Humano 4/genética , Leucócitos Mononucleares/metabolismo , Lipídeos
2.
J Med Virol ; 94(4): 1696-1700, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34786733

RESUMO

Emerging reports of SARS-CoV-2 breakthrough infections entail methodical genomic surveillance for determining the efficacy of vaccines. This study elaborates genomic analysis of isolates from breakthrough infections following vaccination with AZD1222/Covishield and BBV152/Covaxin. Variants of concern B.1.617.2 and B.1.1.7 responsible for cases surge in April-May 2021 in Delhi, were the predominant lineages among breakthrough infections.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19/administração & dosagem , Feminino , Genoma Viral/genética , Genômica , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Filogenia , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Adulto Jovem
3.
Indian J Med Res ; 155(1): 171-177, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35859442

RESUMO

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region.


Assuntos
COVID-19 , Faringite , Adulto , Anticorpos Antivirais , COVID-19/epidemiologia , Humanos , Imunoglobulina G , Masculino , SARS-CoV-2 , Estudos Soroepidemiológicos
4.
Anaerobe ; 73: 102482, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34861364

RESUMO

OBJECTIVE: To study the spectrum of anaerobic infections and the frequency of clinically relevant anaerobes in various infections in a tertiary care hospital in North India. METHOD: In this two-year (2018-2019) retrospective study, a total of 22,177 samples were processed both anaerobically and aerobically. The samples included blood, pus, body fluids, necrotic tissues, abscess, peritoneal fluids, and other specimens of conditions predisposing to anaerobic infections. The recovered bacterial isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). RESULT: Of the 22,177 samples processed anaerobically, 1094 showed significant anaerobic growth yielding 1464 anaerobes. Bacteroides fragilis (12.7%) and Peptoniphilus harei (12.2%) were the most predominant anaerobes, whereas Escherichia coli (32.6%) and Staphylococcus aureus (13.2%) were the most frequently recovered facultative anaerobes in polymicrobial growth. Both aerobic and anaerobic data were available for 673/1094 samples, of which 68% represented a polymicrobial etiology and 32% as monomicrobial. Of the cases where complete clinical information was available (504/1094), the majority of the anaerobes were recovered from the skin and soft tissue infections (36.3%) and intra-abdominal infections (17.1%). The clinical specimen most frequently growing anaerobes was abscess (29.1%), followed by diabetic foot ulcers (14.1%). CONCLUSION: The study documents the frequency of clinically significant anaerobic bacteria in various infections, and their associations with aerobes in polymicrobial growth. The present study may aid us in devising better therapeutic strategies against both aerobes and anaerobes in anaerobic infections, which is often empirical. Besides, the data can update clinicians with the changing patterns of anaerobic infections, which remains a neglected concern.


Assuntos
Bactérias Aeróbias , Infecções Bacterianas , Anaerobiose , Bactérias Anaeróbias , Infecções Bacterianas/microbiologia , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária
5.
Int J Phytoremediation ; 24(5): 536-556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34340616

RESUMO

This review analyses the account of biological (microalgae) and synthetic (bio-polymeric adsorbents) elements to compass the treatment efficiencies of various water pollutants and mechanisms behind them. While considering pollutant removal, both techniques have their own merits and demerits. Microalgal-based methods have been dominantly used as a biological method for pollutant removal. The main limitations of microalgal methods are capacity, scale, dependence on variables of environment and duration of the process. Biopolymers on the other hand are naturally produced, abundant in nature, environmentally safe and biocompatible with cells and many times biodegradable. Algal immobilization in biopolymers has promoted the reuse of cells for further treatment and protected cells from toxic environment monitoring and controlling the external factors like pH, temperature and salinity can promote the removal process while working with the mentioned technologies. In this review, a mechanistic view of both these techniques along with integrated approaches emphasizing on their loopholes and possibilities of improvement in these techniques is represented. In addition to these, the review also discusses the post-treatment effect on algal cells which are specifically dependent on pollutant type and their concentration. All these insights will aid in developing integrated solutions to improve removal efficiencies in an environmentally safe and cost-effective manner.Novelty statement The main objective of this review is to thoroughly understand the role of micro-algal cells and synthetic adsorbents individually as well as their integrative effect in the removal of pollutants from wastewater. Many reviews have been published containing information related to either removal mechanism by algae or synthetic adsorbents. While in this review we have discussed the agents, algae and synthetic adsorbents along with their limitations and explained how these limitations can be overcome with the integration of both the moieties together in process of immobilization. We have covered both the analytical and mechanistic parts of these technologies. Along with this, the post-treatment effects on algae have been discussed which can give us a critical understanding of algal response to pollutants and by-products obtained after treatment. This review contains three different sections, their importance and also explained how these technologies can be improved in the future aspects.


Assuntos
Microalgas , Poluentes Químicos da Água , Poluentes da Água , Purificação da Água , Biodegradação Ambiental , Microalgas/fisiologia , Águas Residuárias/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos
6.
Indian J Microbiol ; 62(3): 323-337, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35974919

RESUMO

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

7.
Indian J Palliat Care ; 28(4): 354-359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36447506

RESUMO

Objectives: Cancers and various terminal illnesses need integrated palliative care with curative management, but, unfortunately, our health care system mainly focuses on the treatment of disease. Lack of awareness, difficulty in pain management and untrained staff are some of the challenges in palliative care services.The study was done to explore the perception of healthcare workers regarding availability, utilisation and challenges in the delivery of palliative care services. Material and Methods: A mixed method study was conducted at tertiary care teaching hospital in North India. Qualitative approach using interviews and focus group discussions (FGDs) among healthcare workers was done to understand their knowledge, perception, barriers and challenges in implementing palliative care services. One hundred and thirteen healthcare workers were interviewed using a semi-structured questionnaire and FGD was conducted to gain more insight into the issues of palliative care. The data obtained was analysed with the help of computer software Microsoft Excel and SPSS version 23 for windows. The data was presented as proportion and mean (S.D.) as deemed appropriate for qualitative and quantitative variables respectively. Thematic analysis was done with the data of FGD. Results: The knowledge, attitude and practices regarding palliative care were poor across the HCW. During FGD with faculty and residents, the participants showed great concern about the absence of palliative care across many specialties while expressing an acute need for the establishment of a separate interdisciplinary unit on palliative care to improve the quality of life in patients. Conclusion: The study shows that there are gaps that need to be addressed to make palliative services available in our hospital.

8.
Environ Res ; 201: 111499, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34146525

RESUMO

The current research focuses on the Intracellular biosynthesis of Ag/AgCl nanohybrids in microalgae, Scenedesmus sp. The effect of biosynthesis process on growth and lipid profile of cells is key element of this study. Ag/AgCl nanohybrids synthesized intracellularly were characterized by UV-Vis spectrophotometer, Powder X-Ray Diffraction (P-XRD), Scanning Electron Microscopy (SEM), High Resolution Transmission Electron Microscopy (HRTEM). 10-20 nm and 10-50 nm sized spherical shaped nanoparticles of polycrystalline nature were grown using 0.5 and 1 mM of AgNO3 precursor, respectively and Scenedesmus sp. as reducing agent. Total lipid content of the cells treated with 0.5 mM and 1 mM AgNO3 was static and found to be 43.2 ± 0.01 µg/mL and 48.2 ± 0.02 µg/mL respectively at 120 h of Ag/AgCl nanoparticles biosynthesis. FAME (Fatty Acid Methyl Ester) profile was improved due to intracellular nanoparticles biosynthesis with maximum C16:0 (palmitic acid) (35.7%) in cells treated with 0.5 mM AgNO3 used for Ag/AgCl nanohybrids synthesis. Palmitic acid in cells exposed to 0.5 mM concentration of metallic precursor increased by 75.86%. Synthesized nanoparticles were tested on four bacterial strains to establish its antibacterial efficiency showing appropriate zone of inhibition at varying concentrations. Present study efficiently demonstrates the utility of microalgae integrating nanoparticles biosynthesis and lipid accumulation.


Assuntos
Nanopartículas Metálicas , Scenedesmus , Antibacterianos/farmacologia , Lipídeos , Prata
9.
Phytother Res ; 35(5): 2296-2316, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33210447

RESUMO

Covid-19 pandemic severely affected human health worldwide. Till October 19, 2020, total confirmed patients of COVID-19 are 39,944,882, whereas 1,111,998 people died across the globe. Till to date, we do not have any specific medicine and/or vaccine to treat COVID-19; however, research is still going on at war footing. So far vaccine development is concerned, here it is noteworthy that till now three major variants (named A, B, and C) of severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) have been recognized. Increased mutational rate and formation of new viral variants may increase the attrition rate of vaccines and/or candidate chemotherapies. Herbal remedies are chemical cocktails, thus open another avenue for effective antiviral therapeutics development. In fact, India is a large country, which is densely populated, but the overall severity of COVID-19 per million populations is lesser than any other country of the world. One of the major reasons for the aforesaid difference is the use of herbal remedies by the Government of India as a preventive measure for COVID-19. Therefore, the present review focuses on the epidemiology and molecular pathogenesis of COVID-19 and explores algal metabolites for their antiviral properties.


Assuntos
Tratamento Farmacológico da COVID-19 , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Índia/epidemiologia , Pandemias/prevenção & controle , SARS-CoV-2
10.
Anaerobe ; 71: 102443, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34492368

RESUMO

OBJECTIVE: To compare the performance of agar dilution and broth microdilution by commercial and in-house prepared plates for the Bacteroides fragilis group. The cost analysis was performed to demonstrate that in-house prepared BMD plates were a suitable alternative to agar dilution given the high cost and low feasibility of incorporating commercial BMD plates in routine, particularly in the tertiary care institutes of many low- and middle-income countries. METHODS: Thirty B. fragilis group isolates were tested against six antibiotics, frequently used as empirical therapy for anaerobic infections including metronidazole, clindamycin, imipenem, piperacillin-tazobactam, cefoxitin, and chloramphenicol. The running consumable expenditure for all methodologies was calculated. RESULTS: The results demonstrated essential and categorical agreement of >90% for all antibiotics except cefoxitin, which showed <90% categorical agreement. No major or very major errors were observed. We observed a high agreement and strong concordance for MIC values between both methods and inter-rate reliability of >0.9 by Cohen's kappa analysis, indicating almost perfect agreement between both methods using either of the plates. In contrast to agar dilution, a 20.5 fold cost reduction was seen in BMD using in-house plates and a 5.8 fold reduction using commercial plates to test a single isolate. However, when testing 30 isolates concurrently the cost significantly increased for commercial BMD plates by 8.4 folds, and only 1.03 fold cost reduction was seen with in-house BMD plates. CONCLUSION: BMD gives comparable results to agar dilution and can be considered a method of choice to test a small number of samples. The technique is an economical option when plates are standardized in-house and could be employed for susceptibility testing of the B. fragilis group.


Assuntos
Ágar/economia , Antibacterianos/farmacologia , Infecções por Bacteroides/microbiologia , Bacteroides fragilis/efeitos dos fármacos , Testes de Sensibilidade Microbiana/economia , Testes de Sensibilidade Microbiana/métodos , Ágar/química , Antibacterianos/economia , Bacteroides fragilis/crescimento & desenvolvimento , Clindamicina/economia , Clindamicina/farmacologia , Humanos , Imipenem/economia , Imipenem/farmacologia , Metronidazol/economia , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana/instrumentação
11.
Mol Biol Rep ; 47(12): 9489-9497, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269434

RESUMO

Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the same. Both Resistin, an adipose derived peptide hormone and Urotensin II a potent vasoconstrictor, are reported to be involved in the development of insulin resistance and T2DM but the results remain contradictory. Therefore, investigations were carried out to study the association of T2DM and single nucleotide polymorphism (SNP) in Resistin (RETN) gene at rs3745367 (+ 299 G > A) and Urotensin II (UTS2) gene at rs228648 (+ 143 G > A) and rs2890565 (+ 3836 C > T) in a North Indian population. Method: The present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs3745367, rs228648 and rs2890565 were amplified from genomic DNA in the studied samples by polymerase chain reaction (PCR) using specific primers. The amplified products were genotyped by restriction fragment length polymorphism (RFLP) using particular restriction endonucleases. Clinical parameters viz. glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusion: A statistically significant association between T2DM and RETN gene at SNP rs3745367 (p = 0.001) and UTS2 gene at SNP rs2890565 (p = 0.001) was observed. In RETN gene SNP rs3745367, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were found to be higher in GA + AA combined genotype than in GG genotype for T2DM subjects. Regression analysis revealed that SNP rs2890565 and HOMA-IR were independently associated with the risk of development of T2DM when three SNPs were taken as independent variable adjusted for clinical variables. Among four haplotypes, A/T was found associated with increased risk of T2DM as determined for rs228648 and rs2890565 of UTS2 gene. It can be concluded from these results that polymorphism at rs3745367 of RETN gene and at rs2890565 of UTS2 gene are associated with risk of T2DM in North Indian population.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Resistência à Insulina/genética , Polimorfismo de Fragmento de Restrição , Resistina/genética , Urotensinas/genética , Fatores Etários , Idoso , Glicemia/metabolismo , Peso Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Feminino , Expressão Gênica , Haplótipos , Humanos , Índia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resistina/metabolismo , Risco , Fatores Sexuais , Urotensinas/metabolismo
12.
Anaerobe ; 57: 32-34, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30872072

RESUMO

Septic arthritis is one of the most serious conditions leading to grave consequences in all age groups, with a number of cases seen in infancy and childhood. Although septic arthritis in neonates is a known clinical entity, it is a diagnostic dilemma for the paediatricians. Of the reported causes of bacterial arthritis, anaerobic bacteria account for only 1%. Anaerobic bacterial septic arthritis may be more common than appreciated and therefore anaerobic as well as aerobic cultures should be done in all cases of septic arthritis. We report the first documented case of spontaneous septic arthritis due to Clostridium septicum in an infant with successful outcome.


Assuntos
Artrite Infecciosa/diagnóstico , Artrite Infecciosa/patologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/patologia , Clostridium septicum/isolamento & purificação , Anti-Infecciosos/administração & dosagem , Artrite Infecciosa/microbiologia , Artrite Infecciosa/terapia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Desbridamento , Feminino , Humanos , Lactente , Metronidazol/administração & dosagem , Resultado do Tratamento
13.
Neurol India ; 66(4): 1052-1059, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30038093

RESUMO

BACKGROUND: Nearly 40%-50% of the individuals fail to respond to first line antiepileptic drug (AED) monotherapy and 30% are refractory, which calls for the need to recognize predictive markers for treatment failure. This study aims to identify clinical factors predictive of a poor prognosis in patients on AED therapy. MATERIALS AND METHODS: A prospective follow-up study involving 1056 patients with epilepsy (PWE) aged 5-67 years from North India on phenytoin (PHT, n = 247), carbamazepine (CBZ, n = 369), valproate (VA, n = 271), phenobarbital (PB, n = 50), and multitherapy (MultiT, n = 119) was conducted between 2005 and 2015. Seizure and epilepsy types were diagnosed based on the classifications by the International League Against Epilepsy (ILAE). Patients remaining seizure-free during the past 1 year were assigned to the "no seizure" group and patients experiencing seizure recurrence were assigned to the "recurrent seizures" group. RESULTS: Of the total, 786 (74.4%) patients were successfully followed up with 60% achieving 1-year seizure remission. Seizure recurrence was observed in the remaining 40% of the patients with a high likelihood in patients with the disease onset at ≤5 years of age [55% vs. 38%, P = 0.0016, odds ratio (OR) = 2.02 (95% confidence interval (CI) = 1.31-3.13)], in patients with cryptogenic epilepsy than with idiopathic/symptomatic epilepsy (48% vs. 32%, P = 0.0049, OR = 1.61 [95% CI = 1.16-2.24]), and in patients with pretreatment seizure frequency ≥12/year (46% vs. 27%, P < 0.0001, OR = 2.21 [95% CI = 1.61-3.05]). Logistic regression analysis also revealed a significant association of seizure recurrence (P < 0.05) with the three variables. CONCLUSION: Our findings suggest that an early disease onset, cryptogenic epilepsy, and a higher pretreatment seizure frequency are related to a poor prognosis or poor remission in people with epilepsy (PWE) on AED therapy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Resultado do Tratamento , Adolescente , Adulto , Idoso , Povo Asiático , Criança , Pré-Escolar , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Convulsões/prevenção & controle , Adulto Jovem
14.
Indian J Microbiol ; 63(3): 231-234, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37781007
15.
PLoS Pathog ; 11(8): e1005105, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26295810

RESUMO

Kaposi's sarcoma (KS), caused by Kaposi's sarcoma herpesvirus (KSHV), is a highly vascularised tumour of endothelial origin. KSHV infected endothelial cells show increased invasiveness and angiogenesis. Here, we report that the KSHV K15 protein, which we showed previously to contribute to KSHV-induced angiogenesis, is also involved in KSHV-mediated invasiveness in a PLCγ1-dependent manner. We identified ßPIX, GIT1 and cdc42, downstream effectors of PLCγ1 in cell migration, as K15 interacting partners and as contributors to KSHV-triggered invasiveness. We mapped the interaction between PLCγ1, PLCγ2 and their individual domains with two K15 alleles, P and M. We found that the PLCγ2 cSH2 domain, by binding to K15P, can be used as dominant negative inhibitor of the K15P-PLCγ1 interaction, K15P-dependent PLCγ1 phosphorylation, NFAT-dependent promoter activation and the increased invasiveness and angiogenic properties of KSHV infected endothelial cells. We increased the binding of the PLCγ2 cSH2 domain for K15P by substituting two amino acids, thereby creating an improved dominant negative inhibitor of the K15P-dependent PLCγ1 activation. Taken together, these results demonstrate a necessary role of K15 in the increased invasiveness and angiogenesis of KSHV infected endothelial cells and suggest the K15-PLCγ1 interaction as a possible new target for inhibiting the angiogenic and invasive properties of KSHV.


Assuntos
Invasividade Neoplásica/patologia , Neovascularização Patológica/metabolismo , Fosfolipase C gama/metabolismo , Sarcoma de Kaposi/patologia , Proteínas Virais/metabolismo , Western Blotting , Células Endoteliais , Imunofluorescência , Herpesvirus Humano 8/metabolismo , Humanos , Imunoprecipitação , Neovascularização Patológica/patologia , Sarcoma de Kaposi/metabolismo , Ressonância de Plasmônio de Superfície , Transfecção
17.
PLoS Pathog ; 9(11): e1003737, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24244164

RESUMO

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells.


Assuntos
Células Endoteliais/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 8/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas Serina-Treonina Quinases/biossíntese , Sarcoma de Kaposi/metabolismo , Ativação Viral/fisiologia , Ciclo-Oxigenase 2/biossíntese , Ciclo-Oxigenase 2/genética , Células Endoteliais/patologia , Células Endoteliais/virologia , Feminino , Células HEK293 , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/virologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Metaloproteinase 13 da Matriz/biossíntese , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 7 da Matriz/biossíntese , Metaloproteinase 7 da Matriz/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/genética , Proteínas Serina-Treonina Quinases/genética , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/patologia
18.
Med Mycol ; 53(3): 248-57, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25587084

RESUMO

Mucormycosis is an emerging angioinvasive infection caused by the ubiquitous filamentous fungi of the Order Mucorales and class of Mucormycetes. We conducted a prospective study of 38 patients who were diagnosed as having mucormycosis in a tertiary care hospital during January 2010 to June 2011. The cases were analyzed regarding the site of involvement, underlying disease and species of fungi isolated, antifungal susceptibility pattern of the isolates, and outcome of therapy. The mean age of the patients was 40.43 years, with 72% male. Rhino-orbital mucormycosis (61.5%) was the most common presentation followed by cutaneous manifestations (31%), gastrointestinal symptoms (5%), and pulmonary (2.5%). Diabetes mellitus (56%) was the significant risk factor in rhino-orbito-cerebral presentation (OR = 7.55, P = 0.001). Among 23 culture isolates, Rhizopus arrhizus (37.5%) was the most common, followed by Apophysomyces variabilis (29.2%), Lichtheimia ramosa (16.7%), Rhizopus microsporus (4.2%), Rhizomucor pusillus (4.2%), and Apophysomyces elegans (4.2%). Rhizopus arrhizus was most commonly isolated from rhino-orbito-cerebral mucormycosis and Apophysomyces species were generally obtained from cutaneous mucormycosis. In vitro antifungal susceptibility showed that 16 isolates were sensitive to amphotericin B (MIC less than 1 µg/ml), while in contrast, all isolates were found to be resistant to voriconazole (MIC- 0.25 to >8), fluconazole (MIC > 32), flucytosine (MIC > 32). Treatment regimens included antifungal therapy, reversal of underlying predisposing risk factors, and surgical debridement. Combination of surgery and medical treatment with amphotericin B was significantly better (OR = 0.2, P < 0.04) than amphotericin B alone (61.5% vs. 10.3% patient survival). The awareness of fungal diseases amongst clinicians is required to decrease the fatal outcome of disease.


Assuntos
Mucorales/isolamento & purificação , Mucormicose/epidemiologia , Mucormicose/patologia , Adulto , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Criança , Desbridamento , Feminino , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Mucorales/classificação , Mucormicose/microbiologia , Mucormicose/terapia , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento
19.
Mycoses ; 58(7): 437-44, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26058420

RESUMO

Phaeohyphomycosis refers to infections caused by phaeoid fungi that can have an aggressive course in normal hosts. We report a case of left-sided renal phaeohyphomycosis due to Bipolaris spicifera in a 7-year-old immunocompetent male child. He presented with fever, dysuria, nausea, vomiting and flank pain. Examination revealed tenderness at the left costovertebral angle. Histological examination and culture of biopsy from left kidney and blood yielded the fungal pathogen Bipolaris spicifera. His past history revealed that he was diagnosed perinatally with bilateral hydronephrosis due to bilateral pelvic ureteric junction obstruction. He underwent an open dismembered pyeloplasty on the left side followed by the right side pyeloplasty at the age of 6 months and 1.5 years respectively. He was on a regular follow-up for 5 years and had been doing well. Now he was diagnosed as a case of unilateral renal phaeohyphomycosis. The patient was managed successfully with antifungal drugs amphotericin B and itraconazole. A review of previously reported bipolaris cases with their clinical manifestations, treatment and outcome is presented. Renal phaeohyphomycosis remains an unusual disease. Aggressive diagnostic approaches and careful management helped in survival of the patient.


Assuntos
Nefropatias/microbiologia , Rim/microbiologia , Fungos Mitospóricos/isolamento & purificação , Feoifomicose/microbiologia , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Biópsia , Criança , Humanos , Imunocompetência , Itraconazol/uso terapêutico , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Masculino , Feoifomicose/diagnóstico , Feoifomicose/tratamento farmacológico
20.
Mycopathologia ; 180(3-4): 223-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25894510

RESUMO

We present the case of an 18-year-old male patient admitted with complaints of fever and rapid weight loss since 3 months. Patient had multiple umbilicated papular to nodular lesions over chin and forehead region. Complete blood count revealed bicytopenia. An excisional biopsy of the skin lesions had revealed cutaneous histoplasmosis. On further investigations for bicytopenia, histoplasmosis had been diagnosed on bone marrow trephine biopsy. For the immune status, patient's serology against HIV was negative and his CD4 lymphocyte counts were low at 161. Patient received antifungal therapy including amphotericin B and itraconazole. He showed remarkable improvement in his general condition and blood counts. A repeat CD4 count showed normal counts, and idiopathic CD4 lymphocytopenia was excluded. Disseminated histoplasmosis presenting as cutaneous lesions in an immunocompetent host is very rare, and we are not aware of any case report in the literature where there is reversible depletion of CD4 counts following antifungal treatment in an immunocompetent host of nonendemic area.


Assuntos
Antifúngicos/administração & dosagem , Linfócitos T CD4-Positivos/imunologia , Histoplasmose/diagnóstico , Histoplasmose/patologia , Depleção Linfocítica , Dermatopatias/diagnóstico , Dermatopatias/patologia , Adolescente , Anfotericina B/administração & dosagem , Histoplasmose/tratamento farmacológico , Histoplasmose/imunologia , Humanos , Itraconazol/administração & dosagem , Masculino , Dermatopatias/tratamento farmacológico , Dermatopatias/imunologia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA