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1.
Front Cell Infect Microbiol ; 14: 1380736, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716191

RESUMO

Introduction: Chikungunya virus (CHIKV) infection is associated with acute clinical manifestations and chronic joint inflammation. CHIKV has emerged as a significant causative agent of central nervous system (CNS) complications, including encephalitis and related sequelae. Microglial cells, crucial for immune responses and tissue repair in the CNS, play a vital role in the host response to viral infections, with their activation potentially leading to either protection or pathology. In this study, the infection biology of CHIKV in the C20 human microglial cell line was investigated. Methods: The permissiveness of C20 cells to CHIKV infection was assessed, and viral replication kinetics were compared to Vero E6 cells. Cytopathic effects of CHIKV infection on C20 cells were examined, along with ultrastructural changes using transmission electron microscopy. Additionally, apoptosis induction, mitochondrial membrane potential, and alterations in cell surface marker expression were evaluated by flow cytometry. Results: CHIKV infection demonstrated permissiveness in C20 cells, similar to Vero cells, resulting in robust viral replication and cytopathic effects. Ultrastructural analysis revealed viral replication, mature virion formation, and distinctive cytoplasmic and nuclear changes in infected C20 cells. CHIKV infection induced significant apoptosis in C20 cells, accompanied by mitochondrial membrane depolarization and altered expression of cell surface markers such as CD11c, CD14, and HLA-DR. Notably, decreased CD14 expression was observed in CHIKV-infected C20 cells. Discussion: The study findings suggest that CHIKV infection induces apoptosis in C20 microglial cells via the mitochondrial pathway, with significant alterations in cell surface marker expression, particularly CD14 that is linked with apoptosis induction. These observations provide valuable insights into the role of human microglial cells in the host response to CHIKV infection and contribute to the knowledge on the neuropathogenesis of this virus.


Assuntos
Apoptose , Febre de Chikungunya , Vírus Chikungunya , Microglia , Mitocôndrias , Replicação Viral , Microglia/virologia , Vírus Chikungunya/fisiologia , Humanos , Mitocôndrias/ultraestrutura , Linhagem Celular , Chlorocebus aethiops , Animais , Células Vero , Febre de Chikungunya/virologia , Potencial da Membrana Mitocondrial , Efeito Citopatogênico Viral
2.
Infect Dis (Lond) ; 56(2): 145-156, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37966909

RESUMO

BACKGROUND: In this study, we carried out an investigation of Kyasanur Forest Disease (KFD) suspected human cases reported in Karnataka state, India from December 2018 to June 2019. METHODS: The clinical samples of KFD suspected cases (n = 1955) from 14 districts of Karnataka were tested for KFD using real-time RT-PCR and IgM ELISA. Further, the KFD-negative samples were tested for IgM antibodies against dengue and chikungunya viruses. Monkey samples (n = 276) and tick pools (n = 11582) were also screened using real-time RT-PCR. KFD-positive samples were further analysed using next-generation sequencing along with clinico-epidemiological analysis. RESULTS: Of all, 173 (8.8%) cases tested positive for KFD either by real-time RT-PCR (n = 124), IgM ELISA (n = 53) or both tests (n = 4) from seven districts. Among KFD-negative cases, IgM antibody positivity was observed for dengue (2.6%), chikungunya (5.8%), dengue and chikungunya coinfection (3.7%). KFD cases peaked in January 2019 with fever, conjunctivitis, and myalgia as the predominant symptoms and a mortality of 4.6%. Among confirmed cases, 41% received a single dose and 20% received two doses of the KFD vaccine. Of the seven districts with KFDV positivity, Shivamogga and Hassan districts reported KFD viral RNA positivity in humans, monkeys, and ticks. Sequencing analysis of 2019 cases demonstrated a difference of less than 1.5% amino acid compared to prototype KFDV. CONCLUSION: Although the KFD has been endemic in many districts of Karnataka state, our study confirms the presence of KFDV for the first time in two new districts, i.e. Hassan and Mysore. A comparative analysis of KFDV infection among the KFD-vaccinated and non-vaccinated populations demonstrated an insignificant difference.


Assuntos
Febre de Chikungunya , Dengue , Doença da Floresta de Kyasanur , Animais , Humanos , Doença da Floresta de Kyasanur/epidemiologia , Doença da Floresta de Kyasanur/diagnóstico , Febre de Chikungunya/epidemiologia , Índia/epidemiologia , Imunoglobulina M , Haplorrinos , Dengue/epidemiologia
3.
Int J Pharm ; 642: 123184, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37379893

RESUMO

Arthritis is an inflammatory disorder that leads to degeneration and swelling in the joints thereby severely affecting mobility. Till date, a complete cure for this disorder remains elusive. Administration of disease modifying anti-rheumatic drugs has not proved effective owing to poor retention of drugs at the site of inflammation in the joints. In most cases, lack of adherence to the therapeutic regimen further aggravates the condition. Localized administration of the drugs through intra-articular injections is highly invasive and painful. A possible solution to overcome these issues will be to ensure sustained release of the anti-arthritic drug at the site of inflammation through a minimally invasive method. The present work focuses on the development of a microneedle patch for localized and minimally invasive delivery of methotrexate to arthritic joints in guinea pig model. The microneedle patch was found to elicit minimal immune response and ensured sustained release of the drug that was manifested through faster restoration of mobility and a distinct reduction in inflammatory and rheumatoid markers at the joints when compared to untreated and those treated through conventional hypodermic injections. Our results demonstrate the promise of microneedle-based platform for an effective arthritic therapy.


Assuntos
Antirreumáticos , Artrite Reumatoide , Animais , Cobaias , Metotrexato , Preparações de Ação Retardada/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico
4.
Indian J Med Microbiol ; 41: 45-52, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36870749

RESUMO

PURPOSE: The study aims to isolate and understand cytopathogenesis, ultrastructure, genomic characteristics and phylogenetic analysis of SARS-CoV-2 virus of B.1.210 lineage, that circulated in India during first wave of the pandemic. METHODS: Clinical specimen from an interstate traveller from Maharashtra to Karnataka, in May 2020, who was positive by RT PCR for SARS-CoV-2 infection was subjected to virus isolation and Whole Genome Sequencing. Vero cells were used to study cytopathogenesis and ultrastructural features by Transmission Electron Microscopy (TEM). Phylogenetic analysis of the whole genome sequences of several SARS-CoV-2 variants downloaded from GISAID was performed in comparison with the B.1.210 variant identified in this study. RESULTS: The virus was isolated in Vero cells and identified by immunofluorescence assay and RT PCR. The growth kinetics in infected Vero cells revealed a peak viral titre at 24 â€‹h post-infection. Ultrastructural studies revealed distinct morphological changes with accumulation of membrane-bound vesicles containing pleomorphic virions in the cytoplasm, with single or multiple intranuclear filamentous inclusions and dilated rough endoplasmic reticulum with viral particles. Whole genome sequence of the clinical specimen as well as the isolated virus revealed the virus to be of lineage B.1.210 with the D614G mutation in the spike protein. Phylogenetic analysis of the whole genome sequence in comparison with other variants reported globally revealed that the isolated SARS-CoV-2 virus of lineage B.1.210 is closely related to the original Wuhan virus reference sequence. CONCLUSIONS: The SARS-CoV-2 variant B.1.210 virus isolated here showed ultrastructural features and cytopathogenesis similar to that of the virus reported during early phase of pandemic. Phylogenetic analysis showed that the isolated virus is closely related to the original Wuhan virus, thereby suggesting that the SARS-CoV-2 lineage B.1.210 that was circulating in India during the early phase of pandemic is likely to have evolved from the original Wuhan strain.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Chlorocebus aethiops , Animais , Pandemias , Filogenia , Células Vero , Índia , Genômica
5.
Int J Pharm ; 632: 122546, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36574913

RESUMO

Hollow microneedle arrays (HMNs) are an excellent choice for managing chronic diseases requiring the administration of multiple drug doses over a prolonged duration. However, HMNs have gained partial success due to limitations in their manufacturing capabilities, and cumbersome processes. In the present study, polymeric HMNs were fabricated using a novel single-step drop-casting process without needing cleanroom facilities, and sophisticated instrumentation. When drop casted on the pyramidal tip stainless steel needles, the optimized polymer solution allowed the reproducible formation of desired height HMMs on a detachable acrylic base. To enable broader applications, the base with HMNs was integrated into an experimental package built to deliver a dose of âˆ¼ 5 µL per 30° clockwise rotation of the actuator, allowing multiple metered drug dose administrations. The fabricated HMNs were optically imaged, and tested for mechanical integrity and stability. The working and functional utility of the HMNs package in delivering metered drug doses was demonstrated by delivering vitamin B12 (ex vivo) and insulin (in vivo), respectively. The optimized process can be used for the large-scale manufacturing of HMNs and the experimental package shows the potential to be further developed into a wearable device.


Assuntos
Sistemas de Liberação de Medicamentos , Insulina , Administração Cutânea , Microinjeções , Sistemas de Liberação de Medicamentos/métodos , Agulhas , Polímeros
6.
J Neurovirol ; 28(3): 374-382, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35352315

RESUMO

Chikungunya virus (CHIKV) infection, generally characterised by fever, rash and debilitating polyarthralgia, and/or arthritis, also causes complications of the central nervous system, including encephalitis. However, the role of microglial cells in the neuropathogenesis of CHIKV is poorly understood. The current study characterised the progression of CHIKV infection in the human microglial cell line CHME-3. The susceptibility of these cells to CHIKV and the viral replication kinetics were assessed during the early and late phases of infection. The cell viability was determined using the cell viability assay. Ultrastructural changes in CHIKV infected CHME-3 cells were assessed using transmission electron microscopy. The results showed that CHME-3 cells are susceptible to CHIKV infection and support viral replication with no significant loss in cell viability until 72 h post infection. Ultrastructural studies revealed the formation of cytopathic vacuoles-I (CPV-I) in the early stages and CPV-II in later stages with several virions organized along the membrane of CPV-II. Profuse vacuolation was observed in the later stages of infection. Abnormal giant mitochondria with altered cristae were observed in infected cells with an electron-dense matrix. The study establishes CHME-3 cells as a potential model for investigating the role of human microglial cells in neuropathogenicity of CHIKV.


Assuntos
Febre de Chikungunya , Vírus Chikungunya , Linhagem Celular , Vírus Chikungunya/fisiologia , Humanos , Microglia/patologia , Replicação Viral/fisiologia
7.
Appl Biochem Biotechnol ; 194(1): 517-528, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34637110

RESUMO

Heat shock proteins (HSPs) are available and/or induced for the survival of all organisms, including eukaryotic, prokaryotic, and plants, from higher temperature stresses. They are the chaperone proteins that protect all cells against heat, as the name implies. In addition to thermal stress, they also protect them from chemical, physical, and other stresses, including exposure to oxidative stress, nutritional deficiencies, ultraviolet radiation, ethanol, viral infection, ischemia-reperfusion injury, and cancer-related stresses. They are classified based on their molecular weights in kDa, such as HSP90 and HSP70. In our label-free, high-throughput, quantitative LC-MS/MS-based proteomic studies of MDA-MB-231, human, triple-negative breast cancer cells, treated with electrical pulses (EP) and cisplatin (CsP), we identified a number of HSPs, such as HSP90AA1, and others to be significantly downregulated in EP + CsP, compared to CsP alone. This indicates that cells will undergo apoptotic cell death and hence could cause effective cancer cure/treatment. Considering that over 2 million new cases and over 600,000 deaths in 2020, of which ~ 15% are TNBC, heat shock proteins could be the untapped resources, available for the next biomarkers and/or inhibitors for new/additional therapies.


Assuntos
Cisplatino/farmacologia , Regulação para Baixo/efeitos dos fármacos , Eletroquimioterapia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP90/biossíntese , Proteínas de Neoplasias/biossíntese , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo
8.
J Food Sci Technol ; 58(4): 1389-1400, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33746267

RESUMO

Recombined milk (RM) can be prepared by blending of butteroil, skim milk powder and water and used for variety of purposes in dairy industry. The present work was undertaken to investigate the feasibility of a custom designed and fabricated universal disperser unit for the preparation of recombined milk. Water, SMP and butteroil were used to manufacture the recombined milk. Three levels of fat viz 1.5%, 3.0% and 4.5% were evaluated to study the effect of fat content on the recombination efficiency of the universal disperser using a high shear saw tooth impeller to impart the required shear and disperse the fat in water-SMP matrix to form a stable emulsion. Two independent parameters i.e. temperature at three different levels (20, 35 and 50 °C) and impeller speed (10,000, 15,000 and 20,000 rpm) were selected for the study. All operations were carried out in heating cum process vessel having working capacity of 3 L. The efficiency of the operation was judged based on the dependent parameters namely, mixing time, mixing index, creaming index, power consumption and overall acceptability. Experiments were designed as per RSM in Design Expert V.10.0 software and results obtained were optimized and predicted solutions were compared with observed data. From the study, the optimal combinations for preparation of recombined milk were obtained as 1.5% Fat RM (17,820 rpm, 48 °C), 3.0% Fat RM (15,701 rpm, 48 °C) and 4.5% Fat RM (15,459 rpm, 48 °C).

9.
EClinicalMedicine ; 32: 100717, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33521608

RESUMO

BACKGROUND: The huge surge in COVID-19 cases in Karnataka state, India, during early phase of the pandemic especially following return of residents from other states and countries required investigation with respect to transmission dynamics, clinical status, demographics, comorbidities and mortality. Knowledge on the role of symptomatic and asymptomatic cases in transmission of SARS-CoV-2 was not available. METHODS: The study included all the cases reported from March 8 - May 31, 2020. Individuals with a history of international or domestic travel from high burden states, Influenza-like Illness or Severe Acute Respiratory Illness and high-risk contacts of COVID-19 cases were included. Detailed analysis based on contact tracing data available from the line-list of state surveillance unit was performed using cluster network analysis software. FINDINGS: Amongst the 3404 COVID-19 positive cases, 3096 (91%) were asymptomatic while 308 (9%) were symptomatic. Majority of asymptomatic cases were in the age range of 16 and 45 years while symptomatic cases were between 31 and 65 years. Mortality rate was especially higher among middle-aged and elderly cases with co-morbidities, 34/38 (89·4%). Cluster network analysis of 822 cases indicated that the secondary attack rate, size of the cluster and superspreading events were higher when the source case was symptomatic as compared to an asymptomatic. INTERPRETATION: Our findings indicate that both asymptomatic and symptomatic SARS-CoV-2 cases transmit the infection, although symptomatic cases were the main driving force within the state during the beginning of the pandemic. Considering the large proportion of asymptomatic cases, their ability to spread infection cannot be overlooked. Notwithstanding the limitations and bias in identifying asymptomatic cases, the findings have major implications for testing policies. Active search, early testing and treatment of symptomatic elderly patients with comorbidities should be prioritized for containing the spread of COVID-19 and reducing mortality. FUNDING: Intermediate Fellowship, Wellcome Trust-DBT India Alliance to Giridhara R Babu, Grant number: IA/CPHI/14/1/501499.

10.
Vaccine ; 39(6): 876-881, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33423836

RESUMO

Rubella, is a contagious disease caused by Rubella virus (RuV) that manifests as fever with skin-rashes in children and adults along with complications in pregnant women. WHO-SEAR has set a target for Rubella elimination by 2023. This is the first report of antigenic characterization and genome sequencing of nine RuVs sampled during 1992, 2007-9, and 2015-17 from four Indian states. Comparative analysis of Indian RuVs (2B) with that of global isolates and vaccine strain RA 27/3 (1a) revealed that the observed mutations in structural proteins have no major impact on the 3D structure, function and antigenicity. Indian RuVs formed three major clusters (Pune-1992, Kannur-2009 and Chitradurg-2007) in genome-based phylogeny of global isolates. Neutralizing antibody titers in a panel of serum samples from measles negative cases were significantly higher to the vaccine strain compared to a wild-type 2B isolate (Kannur) with concordance of 91.9%, thereby substantiating the use of current vaccines.


Assuntos
Vírus da Rubéola/genética , Vírus da Rubéola/imunologia , Rubéola (Sarampo Alemão) , Adulto , Anticorpos Antivirais , Antígenos Virais , Criança , Feminino , Humanos , Índia/epidemiologia , Gravidez , Rubéola (Sarampo Alemão)/epidemiologia , Rubéola (Sarampo Alemão)/prevenção & controle
11.
PLoS One ; 15(12): e0243412, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332472

RESUMO

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 91 genomes of SARS-CoV-2 which clustered into seven lineages (Pangolin lineages-A, B, B.1, B.1.80, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 17 contact clusters and 24 cases with no known contacts. We found 14 of the 17 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (12/17) were contained within a single district, reflecting local spread. In most of the 17 clusters, the index case (12/17) and spreaders (11/17) were symptomatic. Of the 91 sequences, 47 belonged to the B.6 lineage, including eleven of 24 cases with no known contact, indicating ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka suggests multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.


Assuntos
COVID-19 , Surtos de Doenças , Genoma Viral , Filogenia , Síndrome do Desconforto Respiratório , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/genética , COVID-19/transmissão , Busca de Comunicante , Feminino , Humanos , Índia/epidemiologia , Masculino , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/virologia , Viagem
12.
PLoS Negl Trop Dis ; 14(3): e0008112, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32150565

RESUMO

The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNß were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection.


Assuntos
Dengue/complicações , Imunidade Celular , Imunidade Inata , Infecção por Zika virus/imunologia , Adolescente , Adulto , Feminino , Citometria de Fluxo/métodos , Ensaios de Triagem em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Middle East Afr J Ophthalmol ; 27(3): 195-197, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488020

RESUMO

Bullous retinal detachment (RD) is a rare manifestation of chronic central serous chorioretinopathy and may be associated with an underlying retinal pigment epithelial (RPE) tear. It may be confused with rhegmatogenous RD or serous RD from conditions such as Harada disease. Appropriate diagnosis is essential as this may prevent unnecessary surgery or treatment with medication that may worsen the condition. We present the case of a young male Indian patient with unilateral bullous RD and a tentative diagnosis of rhegmatogenous RD. He underwent RD surgery, however a large RPE tear was discovered intraoperatively.


Assuntos
Coriorretinopatia Serosa Central/complicações , Perfurações Retinianas/etiologia , Epitélio Pigmentado da Retina/patologia , Adulto , Coriorretinopatia Serosa Central/diagnóstico por imagem , Angiofluoresceinografia , Humanos , Masculino , Descolamento Retiniano/diagnóstico por imagem , Descolamento Retiniano/etiologia , Perfurações Retinianas/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Tomografia de Coerência Óptica , Campos Visuais
14.
Cytometry B Clin Cytom ; 98(3): 270-281, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-30450685

RESUMO

BACKGROUND: Neurotuberculosis is one of the commonest HIV associated opportunistic infections of the central nervous system in India. HIV-TB coinfection may lead to altered frequencies of T cells, thereby influencing the course and progression of the disease. METHODS: We examined the frequencies of T cell subsets in HIV infected individuals with neurotuberculosis (HIV+nTB+) as compared to individuals with HIV associated systemic TB (HIV+sTB+), asymptomatic HIV (HIV+TB-), non-HIV neuro TB (HIV-nTB+), non-HIV systemic TB (HIV-sTB+), and healthy controls (HIV-TB-). Activation and senescence profiles of CD4 and CD8 T cells and memory subsets in peripheral blood mononuclear cells were studied by flow cytometry. RESULTS: The significant observations among the T cell subsets in HIV+nTB+ were: (1) Naïve T cells: decreased CD4 T cells compared to HIV-sTB+ (P = 0.005); decreased CD8 T cells compared to HIV-nTB+ and HIV-TB- (P ≤ 0.007), (2) Memory T cells: expanded CD4 TEMRA cells compared to HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.003); expanded CD8 TEMRA cells compared to HIV-nTB+ and HIV-TB- (P ≤ 0.005), (3) Activated T cells: higher CD4 T cells compared to HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.004); higher CD8 T cells compared to HIV + TB-, HIV-nTB+, HIV-sTB+, and HIV-TB- (P ≤ 0.001), and (4) Senescent T cells: increased CD8 T cells compared to HIV-nTB+ and HIV-TB- groups (P = 0.000). CONCLUSIONS: Increased activation compared to HIV+TB-, HIV-nTB+, HIV-sTB+, and HIV-TB- groups and increased senescence compared to HIV-nTB+ and HIV-TB- groups were observed in CD8 T cells in HIV+nTB+, suggesting that the frequencies of these T cell subsets are altered to a greater extent in these individuals. © 2018 International Clinical Cytometry Society.


Assuntos
Citometria de Fluxo , Infecções por HIV/diagnóstico , Leucócitos Mononucleares/ultraestrutura , Ativação Linfocitária/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/microbiologia , Linfócitos T CD8-Positivos/virologia , Feminino , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Índia/epidemiologia , Leucócitos Mononucleares/microbiologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/microbiologia , Subpopulações de Linfócitos T/ultraestrutura , Subpopulações de Linfócitos T/virologia , Adulto Jovem
15.
ACS Med Chem Lett ; 10(10): 1480-1485, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31620237

RESUMO

We report a novel benzimidazole (BI) based DprE1 inhibitor that resulted from scaffold morphing of a 1,4-azaindole series. The clinical progression of the 1,4-azaindole series from our previous work validates the potential of exploring newer chemical entities with antimycobacterial activity driven via a noncovalent inhibition of the decaprenylphosphoryl-ß-d-ribose-2'-epimerase (DprE1). The representative compounds from the new scaffold reported in this study exhibited an improved solubility and higher free plasma fraction, while retaining potent DprE1 inhibition and antimycobacterial activity. A representative compound from the benzimidazole series demonstrated good efficacy in a murine model of tuberculosis. Furthermore, molecular modeling of the BI scaffold suggests plausible modes of binding in the active site of DprE1 enzyme from Mycobacterium tuberculosis that can be used for further exploration of the series.

16.
Schizophr Res ; 212: 47-53, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31439420

RESUMO

The immune hypothesis of schizophrenia has gained significant popularity in recent years in schizophrenia research. Evidence suggests that the peripheral immune system communicates with central nervous system and the effect propagates through microglial and lymphocyte crosstalk, especially during neuro-inflammation. Although, there is previous literature indicating changes in lymphocyte population in schizophrenia, detailed studies with respect to T and B cells are scarce. Mucosal associated invariant T (MAIT) cells are functionally associated with the gut microbiome. The gut microbiome has been implicated in the pathogenesis of schizophrenia. However, there is no information on the frequency of MAIT cells in schizophrenia. Hence, we investigated changes in proportions of T cells, B cells and MAIT cells in peripheral blood mononuclear cells derived from antipsychotic-free patients with schizophrenia in comparison to healthy controls. In line with earlier reports, we noted perturbations in Th17 cells. This study for the first time reports changes in frequencies of MAIT cells in a homogenous population of antipsychotic-free patients with schizophrenia. These changes, though not common across all patients nevertheless point to the fact that inflammation is prevalent in a significant subset of schizophrenia cases.


Assuntos
Inflamação/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Esquizofrenia/imunologia , Células Th17/imunologia , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Feminino , Humanos , Imunidade Celular/imunologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológico , Adulto Jovem
17.
J Food Sci Technol ; 56(5): 2764-2770, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31168158

RESUMO

Vacuum impregnation of sugar syrup into sub-baric fried Gulabjamun was evaluated as a technological approach to prepare a product of most acceptable quality. Sugar syrup concentrations (40, 50 and 60 °Brix) in combination with process time (2, 4 and 6 min) were analyzed for their effect on product quality in terms of its overall acceptability, expansion ratio, hardness, juiciness and sugar content. The effect of the process conditions on the five listed responses during the vacuum impregnation process was evaluated using response surface methodology and modelled using a second order polynomial equation. The optimum combination was obtained as soaking in a syrup of 55 °Brix for 5 min and was experimentally validated for its real time adequacy. The experimental values of the quality parameters thus obtained were found to be in close agreement with the predicted values.

18.
J Food Sci Technol ; 56(4): 1715-1722, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30996407

RESUMO

An attempt was made to design, fabricate and evaluate a heat exchanger for controlling the matting temperature of Paneer during pressing. Based on preliminary investigations, the range of process parameters to be evaluated during the pressing of Paneer was selected as: pressure (2, 3, and 4 kg/cm2), matting temperature (63, 66 and 69 °C) for pressing time of 8, 10 and 12 min. Experiments were designed in a central composite design for 20 runs and the Paneer was evaluated for its moisture content, hardness, springiness, chewiness, cohesiveness, bulk density, porosity and sensory attributes. It was observed that with increasing pressure and matting temperature, the hardness of the product increased; this corresponded with reduced moisture content and porosity of the product. The springiness of the samples correlated linearly with increasing matting temperature and pressing time. Increasing the pressure during pressing resulted in poorer sensory scores. The process conditions for pressing of Paneer under controlled matting conditions were optimised using Response Surface Methodology for moisture content, overall acceptability, hardness and springiness of the pressed product. It was observed that the moisture content of Paneer pressed under controlled matting temperature was marginally lower than the control Paneer, the overall acceptability for the experimental samples was higher with superior body and texture scores.

19.
J Food Sci Technol ; 56(4): 2320-2325, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30996466

RESUMO

The present study was undertaken to develop a protocol for acquisition and analysis of images of ghee samples to derive mathematical parameters related to adulteration of cow ghee with vegetable fat and to develop a model to predict the adulteration levels. The images acquired using a flatbed scanner were quantified in terms of their pixel intensity, colour, morphological, textural and skeleton parameters using ImageJ software. The selected parameters were measured for images of pure cow ghee and compared with that obtained for ghee adulterated with 5%, 10%, 15% and 20% vegetable fat. The parameters were assessed for their ability to detect the fixed adulteration levels on a discrete scale was assessed using discriminant analysis and the adulteration levels of the samples were correctly classified to the extent of 92.2%. An equation for predicting adulteration levels on a continuous scale using regression analysis (adjusted R 2 value 0.94) was developed, tested and further validated using a fresh data set including a commercially popular market sample of ghee giving a good fit (R 2 value of 0.85).

20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2018: 2024-2027, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30440798

RESUMO

This study described the use of Kernel Least Square Tracker based estimation for 3-dimensional shoulder, elbow motion kinematics from surface Electromyogram (EMG) and a two-stage multiclass Support Vector Machine based classification of different wrist, grip and finger motions from Electroencephalogram (EEG). The advantage of employing hybrid EEG-EMG strategy for upper limb motion estimation was demonstrated for a transhumeral subject. The method utilized EMG from upper arm muscles for elbow motion (and shoulder motion in case of higher degree amputation scenario) and used EEG for discerning basic wrist, grip and finger motions. The results showed that the hybrid scheme could estimate shoulder, elbow motion with more than 90% accuracy and wrist, grip and finger motion with 65%-70% accuracy. This strategy of using hybrid EEG-EMG motion estimation, thus, could be employed in developing a more intuitive upper limb prosthesis controller with multiple degrees of freedom.


Assuntos
Braço , Membros Artificiais , Eletroencefalografia , Eletromiografia , Movimento , Humanos , Desenho de Prótese
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