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1.
J West Afr Coll Surg ; 13(3): 59-64, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37538208

RESUMO

Background: Unicondylar fracture of distal femur accounts for less than 1% of all femoral fractures. As conservative methods have shown substandard results, traditional surgical treatment includes open reduction and internal fixation by Herbert screws, cannulated screws, and conventional lateral locking plates. Though screw fixation has excellent results over long run, there is literature documenting the loosening and loss of articular congruency in elderly patients and in comminuted fracture patterns. Also, the traditional locking plates are precontoured to fit the lateral condyle, whereas there is no specific implant to fix the medial condylar fractures. The merit of the calcaneal plating is that it is easily moldable and can be used for either of the sides irrespective of fracture pattern. Objectives: This study aimed to evaluate the clinical outcome of calcaneal plate (D-shape) fixation in distal femur unicondylar fractures. Materials and Methods: A total of 30 patients were studied, who met the inclusion criteria and consented to the surgery. After appropriate investigations, these patients were treated with calcaneal plating and were followed up postoperatively at 2 weeks, 1 month, 3 months, and 6 months for clinical evaluation. Results: There was a gradual increase in the range of motion (ROM) with subsequent follow-ups. The overall mean ROM evaluated at 6 months was 108.46° ± 28.27° with P < 0.001 and was a statistically significant outcome. Also, the mean ROM for sagittal split fractures (~120°) was comparatively more than the coronally split fractures (~90°). The functional outcome assessed by Neer scoring showed excellent and satisfactory results in 24 (80%) patients, whereas the remaining six (20%) patients had poor results. None of the patients had nonunion, infection, or implant failure. Conclusion: With no specific implant for isolated unicondylar fractures, the use of calcaneal plate in our study has shown promising results probably due to its low profile design reducing the soft-tissue irritation and wide area of bone coverage by the plate offering regions of intermittent fixation due to its spanning design, thereby promoting periosteal preservation and ultimately fracture union.

2.
Sci Rep ; 13(1): 4038, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36899053

RESUMO

The oral cavity of human contains bacteria that are critical for maintaining the homeostasis of the body. External stressors such as high altitude (HA) and low oxygen affect the human gut, skin and oral microbiome. However, compared to the human gut and skin microbiome, studies demonstrating the impact of altitude on human oral microbiota are currently scarce. Alterations in the oral microbiome have been reported to be associated with various periodontal diseases. In light of the increased occurrence of HA oral health related problems, the effect of HA on the oral salivary microbiome was investigated. We conducted a pilot study in 16 male subjects at two different heights i.e., H1 (210 m) and H2 (4420 m). Total of 31 saliva samples,16 at H1 and 15 at H2 were analyzed by utilizing the 16S rRNA high-throughput sequencing, to explore the relationship between the HA environment and salivary microbiota. The preliminary results suggesting that, the most abundant microbiome at the phylum level are: Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Interestingly, 11 genera were identified at the both heights with different relative abundances. In addition, the salivary microbiome was more diverse at H1 compared to H2 as demonstrated by decreased alpha diversity. Further, predicted functional results indicate that microbial metabolic profiles significantly decreased at H2 as compared to H1, including two major metabolic pathways involving carbohydrates, and amino acids. Our findings show that HA induces shifts in the composition and structure of human oral microbiota which can affect host health homeostasis.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Masculino , Altitude , RNA Ribossômico 16S/genética , Projetos Piloto , Microbioma Gastrointestinal/genética , Microbiota/genética , Bactérias/genética
3.
Appl Microbiol Biotechnol ; 106(18): 6225-6238, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35976427

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has adversely affected humankind and caused millions of deaths globally since January 2020. Robust and quick serological tests such as antibody detection assays for SARS-CoV-2 provide relevant information and aid in the process of vaccine development and diagnostics, as well as in sero-epidemiological monitoring of antibody response to the virus. The receptor-binding domain (RBD) of spike and nucleocapsid protein are specific targets for detecting SARS-CoV-2 antibodies. Here, we present the development of a stable spike (S) and nucleocapsid (N) protein-based ELISA antibody detection test "CoroSuchak," with 99% sensitivity, 98% specificity, cost-effective, and detection in a minimum time for serodiagnosis and mass screening of the population for antibodies against SARS-CoV-2. Blood samples were analyzed from 374 SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) positive, 772 negative and asymptomatic, and 874 random groups of subjects. We found that the antibody titer was significantly higher (p < 0.0001) in infected and vaccinated group compared to the only vaccinated and only infected group. Using enzyme-linked immunosorbent assay (ELISA), we detected SARS-CoV-2 immunoglobulin G (IgG) antibodies in 118/123 (96%) infected individuals, 570/653 (87%) non-infected but vaccinated individuals, 231/237 (97%) individuals who were both infected and vaccinated, and 499/874 (57%) from randomly selected individuals from the first and second waves of the pandemic. Similarly in the third wave, 14/14 (100%) infected and 16/20 (80%) RT-PCR-negative but symptomatic subjects were detected. Thus, the highly sensitive and specific in-house developed ELISA antibody detection kit "CoroSuchak" is extremely useful to determine the seroprevalence of SARS-CoV-2 antibodies in the coronavirus-exposed population. KEY POINTS: •Indigenous kit using a combination of spike and nucleocapsid proteins and peptide sequences. •High sensitivity and specificity to detect variants. •Highly sensitive for mass screening.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/diagnóstico , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G , Programas de Rastreamento , Proteínas do Nucleocapsídeo , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus
4.
J Cell Commun Signal ; 16(4): 547-566, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35260968

RESUMO

Heat stress impairs physiology and overall functionality of the body at tissue and organ level in animals. Liver being a vital organ performs more than hundreds regulatory functions of the body. Present study investigates the modulation of molecular pathways that are responsible for liver damage triggered by heat stress. Male Sprague dawley rats were exposed to heat stress (45 °C) in heat simulation chamber till core temperature reaches 40 °C and 42 °C in 25 and 42 min respectively. For in-depth evaluation of liver functions during severe heat stress, hepatic transcriptome and proteome were analysed by microarray and two dimensional gel electrophoresis respectively. Results revealed major alterations in redox status, inflammation, mitochondrial dysfunction and proteostasis related pathways. Data of molecular pathway analysis demonstrate that nuclear factor erythroid 2-related factor 2 (NRF-2) mediated oxidative stress response and macrophage migration inhibitory factor (MIF) regulated inflammatory pathways were upregulated in severe heat stressed liver. Expression levels of downstream molecules of above pathways such as heat shock protein 90AB 1, peroxiredoxin 5, Jun N-terminal kinases 1/2, heme-oxygenase 1, apolipoprotein 1 and interleukin 10 were examined and result suggested the upregulation of these genes modulates the NRF-2 and MIF regulated pathways in heat stressed liver. Irregularity in molecular signalling networks lead to mitochondrial dysfunction indicated by upregulation of ATP synthase ß and peroxiredoxin 1 along with decreased levels of glucose-6-phosphate dehydrogenase and enhanced activity of cytochrome c in liver mitochondria. Thus, current study demonstrated heat induced alterations in key liver functions were regulated by NRF-2 and MIF pathways.

5.
Sci Rep ; 12(1): 276, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997160

RESUMO

Pearl millet is an important staple food crop of poor people and excels all other cereals due to its unique features of resilience to adverse climatic conditions. It is rich in micronutrients like iron and zinc and amenable for focused breeding for these micronutrients along with high yield. Hence, this is a key to alleviate malnutrition and ensure nutritional security. This study was conducted to identify and validate candidate genes governing grain iron and zinc content enabling the desired modifications in the genotypes. Transcriptome sequencing using ION S5 Next Generation Sequencer generated 43.5 million sequence reads resulting in 83,721 transcripts with N50 of 597 bp and 84.35% of transcripts matched with the pearl millet genome assembly. The genotypes having high iron and zinc showed differential gene expression during different stages. Of which, 155 were up-regulated and 251 were down-regulated while during flowering stage and milking stage 349 and 378 transcripts were differentially expressed, respectively. Gene annotation and GO term showed the presence of transcripts involved in metabolic activities associated with uptake and transport of iron and zinc. Information generated will help in gaining insights into iron and zinc metabolism and develop genotypes with high yield, grain iron and zinc content.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Genes de Plantas , Genoma de Planta , Ferro/metabolismo , Proteínas de Membrana Transportadoras/genética , Pennisetum/genética , Proteínas de Plantas/genética , Transcriptoma , Zinco/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Membrana Transportadoras/metabolismo , Valor Nutritivo , Pennisetum/crescimento & desenvolvimento , Pennisetum/metabolismo , Proteínas de Plantas/metabolismo , RNA-Seq
6.
Orthop Traumatol Surg Res ; 108(2): 102951, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33932577

RESUMO

BACKGROUND: Acetabular fractures with quadrilateral plate (QLP) involvement have traditionally been treated by buttress plates applied through an Ilio-inguinal approach. Recently, many surgeons prefer the application of infra-pectineal plates through the modified Stoppa approach for this purpose. Whether one method can be preferred over the other is a matter of investigation. HYPOTHESIS: The research question was whether an infra pectineal plate applied through the modified Stoppa approach for acetabular fractures with QLP involvement would result in an equivalent or better outcome than a buttress plate applied through an ilioinguinal approach. PATIENTS AND METHODS: This was a retrospective study of patients with QLP fractures operated by either of the two methods and who had completed at least one year follow up. Demographic and surgical details and the radiological and clinical outcomes at the last follow-up visit were obtained from patient records. RESULTS: A total of 41 patients were treated with a buttress plate applied through an ilioinguinal approach (group A), and 49 patients were treated with an infra-pectineal plate by the modified Stoppa approach (group B). Duration of surgery and intra-operative blood loss was significantly less in group B patients. Radiological and clinical outcomes were better in group B patients than group A patients. Implant loosening was more frequent in group A patients. Injury to the obturator vessels were more common in group B patients. CONCLUSION: With a comparatively lesser surgical duration and blood loss, better clinical and radiological outcomes at least one year after the surgery, an infra-pectineal plate applied through the modified Stoppa approach can be considered the preferred treatment for most acetabular fractures with QLP involvement. LEVEL OF EVIDENCE: III.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Acetábulo/diagnóstico por imagem , Acetábulo/lesões , Acetábulo/cirurgia , Placas Ósseas , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
7.
Trop Doct ; 51(4): 638-639, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34080449

RESUMO

Enteric or typhoid fever is an emerging tropical infectious disease and a global public health problem with a documented spectrum of neuro-psychiatric manifestations especially from endemic countries. Although neuro-psychiatric manifestations are reported in nearly 50-75% of patients at any phase of enteric fever, the chance of their misdiagnosis and deferred diagnosis of the prime illness is quite common. Atypical symptoms are commonly attributed to be a part of 'typhoid toxaemia', the acute febrile phase of the illness. We report a case of young male presenting with catatonia in the aftermath of such.


Assuntos
Catatonia , Febre Tifoide , Catatonia/diagnóstico , Catatonia/etiologia , Febre/diagnóstico , Febre/etiologia , Humanos , Masculino , Síndrome , Febre Tifoide/complicações , Febre Tifoide/diagnóstico , Febre Tifoide/tratamento farmacológico
8.
Trans R Soc Trop Med Hyg ; 115(5): 551-556, 2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33763687

RESUMO

BACKGROUND: There is a paucity of data on risk factors for infection among healthcare workers (HCWs) from India. Our objective was to evaluate the risk factors and frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. METHODS: We conducted this retrospective case-control study of 3100 HCWs between May and July 2020. HCWs positive for SARS-CoV-2 infection were the cases (n=506) and those negative for SARS-CoV-2 were the controls (n=253). Univariate analysis was followed by multivariate analysis of key demographic, clinical and infection control variables. RESULTS: SARS-CoV-2 infection was found in 16.32% of HCWs. Nearly 45% of infected HCWs were asymptomatic. The proportions of sanitation workers (24% vs 8%; p<0.0001) and technicians (10% vs 4%; p=0.0002) were higher and that of doctors was lower among cases as compared with controls (23% vs 43%; p<0.0001). On univariate analysis, the type of HCW, smoking, lack of training, inadequate personal protective equipment (PPE) use and taking no or fewer doses of hydroxychloroquine (HCQ) were found to be significant. On multivariate analysis, the type of HCW (risk ratio [RR] 1.67 [95% confidence interval {CI} 1.34 to 2.08], p<0.0001), inappropriate PPE use (RR 0.63 [95% CI 0.44 to 0.89], p=0.01) and taking fewer doses of HCQ (RR 0.92 [95% CI 0.86 to 0.99], p=0.03) were significant. CONCLUSIONS: The frequency of SARS-CoV-2 infection was 16% among HCWs. Being a sanitation worker, inappropriate PPE use and lack of HCQ prophylaxis predisposed HCWs to SARS-CoV-2 infection.


Assuntos
COVID-19/diagnóstico , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Equipamento de Proteção Individual , Adulto , COVID-19/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Centros de Atenção Terciária
9.
Life Sci ; 269: 119094, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33482193

RESUMO

AIM: Environmental heat stress alters physiological and biochemical functions which leads to multiorgan dysfunction including severe hepatic injury in animals. We hypothesize that heat preconditioning can be potential intervention in combating heat illnesses. MAIN METHODS: Sprague Dawley rats were exposed to moderate heat stress, severe heat stress and heat preconditioning in heat simulation chamber. Mean arterial pressure, heart rate, skin and core temperature were monitored in pre and post heat exposed animals. After stress exposure, blood for hemodynamic and liver tissue for liver function tests, oxidative stress, inflammatory variables and structural studies were collected from rats. Hepatic mitochondria were isolated to study the key structural alterations and functional changes by transmission electron microscopy. KEY FINDINGS: The effect of heat precondition shows improvement in time to attain the core temperature, weight loss, blood pressure and heart rate in rats. Results exhibited decreased levels of liver function tests, elevated levels of free radicals and inflammatory cytokines in heat exposed liver as compared with heat preconditioned animals. Expression levels of mitochondrial heat shock protein 60, superoxide dismutase 1 and uncoupling protein 1 along with activity of electron transport chain complexes I-V were examined and found to be increased in heat preconditioned as compared to heat stressed animals. Morphological studies of liver parenchyma demonstrated reduction in structural deterioration of hepatic lobules and restoration of mitochondrial structural integrity in heat preconditioned rats. SIGNIFICANCE: Present study suggests that heat preconditioning intervention plays a crucial role in protection against heat induced hepatic injury in animals.


Assuntos
Metabolismo Energético , Transtornos de Estresse por Calor/terapia , Resposta ao Choque Térmico , Temperatura Alta , Fígado/metabolismo , Estresse Oxidativo , Animais , Transtornos de Estresse por Calor/etiologia , Transtornos de Estresse por Calor/metabolismo , Transtornos de Estresse por Calor/patologia , Proteínas de Choque Térmico/metabolismo , Fígado/lesões , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Oxirredução , Ratos , Ratos Sprague-Dawley
10.
J Med Virol ; 93(4): 2499-2504, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33417259

RESUMO

Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.


Assuntos
Anosmia/epidemiologia , COVID-19/epidemiologia , Disgeusia/epidemiologia , Adulto , Anosmia/sangue , Anosmia/fisiopatologia , Anosmia/virologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/fisiopatologia , Estudos de Casos e Controles , Disgeusia/sangue , Disgeusia/fisiopatologia , Disgeusia/virologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pandemias , Contagem de Plaquetas , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Rinite/epidemiologia , Rinite/etiologia , SARS-CoV-2/isolamento & purificação , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia
11.
Behav Brain Res ; 396: 112895, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32890597

RESUMO

Heat exposure is an environmental stress that causes diverse heat related pathophysiological changes under extreme conditions. The brain including hippocampal region which is associated with learning and memory is significantly affected by heat stress resulting in memory impairment. However, the effect of heat on the spatial memory remains unclear. The present study aimed to explore the effect of heat stress on hippocampus and spatial memory in rats. Rat model of acute heat stress was used which was divided into two groups, viz. moderate heat stress (MHS) and severe heat stress (SHS). Redox parameters evaluation revealed that MHS and SHS exposure markedly increase the production of malondialdehyde (MDA), oxidised glutathione (GSSG), reactive oxidative species (ROS), protein oxidation level and decrease the reduced glutathione (GSH) levels in the hippocampal tissue. Furthermore, Cresyl Violet (CV) staining of hippocampal region showed higher pyknosis in rats exposed to SHS. Pronounced increase of caspase3 expression and Fluoro Jade-C (FJ-C) positive cells were observed in SHS resulting in neuronal injury and apoptosis in CA3 region of hippocampus culminating in spatial memory deficit. Our data also suggest that heat stress induces phospho Extracellular signal-regulated kinases (pERK)1/2 activation induced by Brain-derived neurotrophic factor (BDNF) leading to further activation of phospho cAMP-response element binding protein (pCREB) under MHS. However, during SHS, BDNF and pCREB expression were completely dysregulated and not sufficient to rescue cognitive decline in rats. In conclusion, SHS induces pathological alterations that include oxidative damage and apoptosis of hippocampal neurons, disturbing BDNF/ERK1/2/CREB axis that may affect spatial memory.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA3 Hipocampal , Proteína de Ligação a CREB/metabolismo , Resposta ao Choque Térmico/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Transtornos da Memória , Estresse Oxidativo/fisiologia , Memória Espacial/fisiologia , Animais , Comportamento Animal/fisiologia , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Região CA3 Hipocampal/fisiopatologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Ratos , Ratos Sprague-Dawley
12.
Cell Stress Chaperones ; 24(2): 393-407, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30783905

RESUMO

Stress-activated and mitogen-activated protein kinases (MAPKs) regulate gene expression by post-translational modifications of transcription factors. Elk-1, a transcription factor that regulates the expression of immediate early genes, is amenable to regulation by all the three mammalian MAPKs. In the present report, using inhibitors specific for different MAPK pathways, we show that during exposure of HeLa cells to heat stress, Elk-1 is SUMOylated with SUMO1 by p38 MAPK pathway-dependent mechanisms. Elk-1-phosphorylation levels were significantly reduced under similar conditions. We also show that transcriptional activity of Elk-1 as assessed by luciferase reporter expression and qPCR estimation of the expression of genes regulated by Elk-1 was downregulated upon exposure to heat stress; this downregulation was reversed when heat exposure was performed in the presence of either SB203580 (p38 MAPK inhibitor) or ginkgolic acid (inhibitor of SUMOylation). Elk-1 induced transcription is also regulated by PIAS2 which acts as a coactivator upon the activation of extracellular signal-regulated kinases (ERKs) and as a corepressor upon its phosphorylation by p38 MAPK. Since heat stress activates the p38 MAPK pathway, we determined if PIAS2 was phosphorylated in heat-stressed HeLa cells. Our studies indicate that in HeLa cells exposed to heat stress, PIAS2 is phosphorylated by p38 MAPK pathway-dependent mechanisms. Collectively, the results presented demonstrate that in heat-stressed HeLa cells, p38 MAPK pathway-dependent SUMOylation of Elk-1 and phosphorylation of PIAS2 correlate with the downregulation of transactivation by Elk-1.


Assuntos
Resposta ao Choque Térmico , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Elk-1 do Domínio ets/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Regulação para Baixo , Células HeLa , Temperatura Alta , Humanos , Fosforilação , Sumoilação
13.
Yeast ; 35(12): 653-667, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30335186

RESUMO

Hsp30 is a plasma membrane localized heat shock protein in Saccharomyces cerevisiae whose expression is induced by numerous environmental stressors. Elucidation of its mechanism of action has remained elusive primarily because hsp30Δ cells do not show a strong phenotype. To identify cellular functions associated with Hsp30, we thus compared the transcriptome of BY4741hsp30Δ with that of its wild type counterpart. Our studies indicate down-regulation of the target of rapamycin complex 1 (TORC1)-dependent gene-expression programme in hsp30Δ cells. We further show that TORC1-signalling through its effectors (Sch9 and Tap42) was down-regulated in the deletion strain. Specifically, (a) phosphorylation levels of Sch9 were lower and nuclear exclusion of Rim15 (Sch9-downstream function) was overridden in hsp30Δ cells, (b) membrane association of Tor1 and Tap42 was lower in hsp30Δ cells, and (c) Tap42-downstream functions were abrogated in the deletion strain. Furthermore, transcription factors Rtg1, Rtg3, Gat1, and Gln3 were localized in the nucleus of the hsp30Δ as observed upon inactivation of TORC1. Studies aimed at determining how TORC1-signalling is down-regulated in hsp30Δ cells indicated that total reducing sugar levels were lower and ADP:ATP ratio was higher in hsp30Δ cells -conditions known to activate the Snf1 kinase and consequently to the inactivation of TORC1. We thus determined if TORC1-signalling could be restored in hsp30Δ cells upon the deletion of SNF1. Sch9 phosphorylation levels (TORC1-signalling) was restored to wild type levels in hsp30Δsnf1Δ cells. TORC1-signalling is thus down-regulated in hsp30Δ cells by SNF1-dependent mechanisms. A probable role for Hsp30 is discussed.


Assuntos
Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico HSP30/deficiência , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Saccharomyces cerevisiae/genética , Transdução de Sinais , Deleção de Genes , Perfilação da Expressão Gênica , Proteínas de Saccharomyces cerevisiae
14.
Indian J Crit Care Med ; 22(4): 306-308, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29743772

RESUMO

Chikungunya fever (CHIK) is an arboviral disease which is transmitted by a mosquito bite (Aedes aegypti). Fever, polyarthralgia, and maculopapular rash are hallmark clinical manifestations of this disease. These manifestations are self-liming and complete recovery is seen in most of the cases. However, atypical and lethal complications such as myocarditis, hepatitis, Guillain-Barre syndrome (GBS), and meningoencephalitis have been reported in few cases of CHIK. We hereby report two cases of chikungunya infection where rare and atypical manifestations of CHIK, i.e., GBS with bilateral lower motor facial nerve palsy, and meningoencephalitis with epidermal necrosis were seen.

15.
Scand J Gastroenterol ; 52(12): 1315-1319, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28906161

RESUMO

Increased environmental temperature exerts a visible impact on an individual's physiology. At the onset of heat stress, there is an increase in core body temperature which triggers peripheral vasodilation and sweating in an effort to dissipate the elevated body heat. The increase in peripheral circulation however reduces blood flow to the internal organs which are thus adversely affected. In particular, the gastrointestinal (GI) tract gets adversely affected during hyperthermia resulting in loosening of the tight junctions (TJs) that finally leads to higher intestinal permeability. At the cellular level, elevated levels of heat shock proteins (HSPs) induced in response to heat stress mediated cytoprotection by maintaining proper protein folding, releasing survival signals and preserving cytoskeleton integrity. Recent studies have indicated that HSPs play a crucial role in maintaining the localization of TJ proteins. Dietary supplements have also shown to have a positive effect on the maintenance of intestinal TJs. Therefore, it becomes imperative to understand the cellular, molecular and physiological alterations in response to heat stress in GI tract. In the present report, the effect of thermal stress on GI tract has been summarized. Specific role of HSPs along with mitogen activated protein (MAP) kinase signaling pathway in response to hyperthermia has also been discussed.


Assuntos
Febre/fisiopatologia , Trato Gastrointestinal/fisiopatologia , Proteínas de Choque Térmico/fisiologia , Junções Íntimas/fisiologia , Animais , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia
16.
Indian J Tuberc ; 64(3): 221-224, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28709493

RESUMO

Tuberculosis (TB) is a chronic disease that may affect any part of the human body. Though the osteoarticular TB is not uncommonly seen, TB of the sternoclavicular joint (SC joint) is an infrequently reported condition. The very fact that many physicians have never seen a single case of SC joint TB in their entire career makes them never think of this condition in cases of chronic swellings of the medial end of clavicle. We are reporting here our experience with nine cases of SC joint TB that were treated by us. Delay in diagnosis in each of the case was a common feature, and they had been treated in line of inflammation elsewhere. Diagnosis was arrived at by clinical, radiological, and microscopic examinations. Six of the reported cases responded well to antitubercular chemotherapy, and in one of the cases, chemotherapy was combined with debridement, which was actually done during biopsy and primarily for tissue diagnosis; in another two cases, immunomodulation therapy for HIV was given along with antitubercular therapy. Tuberculous etiology should be considered for patients presenting with atypical sites of skeletal inflammation, and a high index of suspicion by the treating physician is necessary to make early diagnosis and appropriate treatment.


Assuntos
Articulação Esternoclavicular/patologia , Tuberculose Osteoarticular/diagnóstico , Tuberculose Osteoarticular/tratamento farmacológico , Adulto , Idoso , Antituberculosos/uso terapêutico , Biópsia por Agulha Fina , Diagnóstico Tardio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Tuberculose Osteoarticular/patologia , Adulto Jovem
17.
3 Biotech ; 7(3): 193, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28664376

RESUMO

Increased drug resistance in Candida glabrata (a model non-albicans Candida) calls for the identification of potential molecular targets for the development of effective drugs. Hypoxia (a state of low oxygen) is an important host factor, which affects the virulence of the pathogen and efficacy of drugs. In the present study, in vitro characterization of 13 null mutants of C. glabrata were done under hypoxic condition (1% O2). These mutants have a major role to play in cellular pathways, viability and pathogenesis (cell wall biosynthesis, ergosterol synthesis, calcium-calcineurin, etc.). The in vitro growth, biofilm formation and susceptibility of biofilm to antifungal drugs of these mutants were compared with the control. Hypoxia reduced the susceptibility of planktonic cells to fluconazole. The mutants ecm33Δ, kre1Δ, rox1Δ, and kre2Δ showed maximum reductions in their biofilm activities (>20%). The selected mutants (upc2BΔ, kre2 Δ, ecm7Δ, rox1 Δ, mid1Δ, ecm33Δ, cch1Δ, kre1Δ) showed reduced biofilm activities (>30%) in the presence of 16 µg ml-1 fluconazole under hypoxia. Functional analysis revealed that Kre1, Ecm33, Upc2B, Kre2, Ecm7, Cch1, Mid1 and Rox1 can be explored as a potential drug target for developing novel antifungal drugs.

18.
J Orthop Traumatol ; 16(3): 203-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25588847

RESUMO

BACKGROUND: Extra-articular proximal tibial fractures account for 5-11 % of all tibial shaft fractures. In recent years, closed reduction and minimally invasive plating and multidirectional locked intramedullary nailing have both become widely used treatment modalities for proximal and distal tibial metaphyseal fractures. This study was performed to compare plating and nailing options in proximal tibia extra-articular fractures. MATERIALS AND METHODS: This randomized prospective clinical study was conducted on 58 skeletally mature patients with a closed extra-articular fracture of the proximal tibia treated with minimally invasive proximal tibial plating (PTP) or intramedullary nailing (IMN) by trained surgeons at a tertiary trauma center. RESULTS: Postoperative hospital stay (p = 0.035), time to full weight-bearing, and union time (p = 0.004) were significantly less in the IMN group than in the PTP group, but there was no clear advantage of either technique in terms of operative time (p = 0.082), infection rate (p = 0.738), range of motion of the knee (p = 0.462), or degrees of malunion and nonunion. CONCLUSION: Both implants have shown promising results in extra-articular proximal tibial fractures, and provide rigid fixation that prevents secondary fracture collapse. LEVEL OF EVIDENCE: Level 2, randomized controlled trial.


Assuntos
Pinos Ortopédicos , Placas Ósseas , Fixação Intramedular de Fraturas , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Feminino , Consolidação da Fratura , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fraturas da Tíbia/diagnóstico , Resultado do Tratamento , Adulto Jovem
19.
Case Rep Pulmonol ; 2014: 685406, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25389505

RESUMO

Background. Tuberculosis is a chronic disease which may have varied presentations. Though pulmonary tuberculosis is the commonest, extrapulmonary tuberculosis involving skeletal system is often seen. Individuals with poor nourishment and immunological status are especially susceptible for disseminated and multicentric tuberculosis. Case Report. We here present a case of tuberculosis involving multiple anatomical locations in an immune-competent patient which was diagnosed with radiological studies and confirmed with histological examination. Patient was put on multidrug antitubercular therapy and responded well to the treatment with improvement in clinical and radiological picture. Clinical Relevance. This report of a rare case makes us aware of the varied presentations which tuberculosis can present with. It should be kept as a differential diagnosis in patients with cough and fever but not responding to conventional treatment. This is even more important in countries with poor socioeconomic conditions.

20.
Indian J Microbiol ; 52(2): 209-14, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23729884

RESUMO

DNA repair functions are essential for the maintenance of genetic integrity and are regulated in response to both environmental and chemical stressors in mammalian and yeast cells in culture. The inhibitory effect of limited O2 availability on DNA repair functions in general and on homologous recombination (HR) in particular, correlates with increased chromosomal abnormalities in hypoxic cancer cells. Given the above, we have investigated the effects of CoCl2,--a hypoxia mimetic agent on HR and genetic aberrations in Saccharomyces cerevisiae. Our studies demonstrate that both acute and chronic exposure to CoCl2 activated HR and increased genetic aberrations in S. cerevisiae D7 cells. At early time points following addition of CoCl2 to the growth media, cells were briefly arrested in the G1-S boundary concomitant with a transient increase in Rad52-GFP foci formation and induction of low levels of DNA damage. The mode of action of CoCl2 is thus similar to that of DNA synthesis inhibitors, the later are known to induce HR and cause G1-S arrest. We propose that the activation of HR in the presence of the hypoxia mimetic agent may be attributed to the replication stress and/or DNA damage induced by the stressor.

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