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1.
Obes Surg ; 34(3): 836-840, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38282174

RESUMO

PURPOSE: With the increase in obesity epidemic among Asians, it is necessary to evaluate the impact of obesity on this population. Low testosterone levels are known to be associated with obesity. This is the 1st study from Asia to evaluate incidence and magnitude of hypotestosteronemia in young adults with BMI more than 32.5 kg/m2 defined as moderate to severe obesity in Asians. MATERIALS AND METHODS: One hundred thirty-four male patients with BMI more than 32.5 kg/m2, between 18 and 30 years old who visited a single bariatric facility between 2017 and 2020, were evaluated with BMI, total and free testosterone levels and clinical features of gynecomastia, hypogonadism, and thinning of pubic and armpit hair. Statistical analysis was performed using SPSS, Spearman's correlation coefficient, and ANOVA test. RESULTS: 60.4% of patients (84/134) had low testosterone levels (< 300 ng/dl) and 23.9% (32/134) had levels between 300 and 400 ng/dl. 89.6% patients (120/134 had gynecomastia, 60.4% (81/134) had thinning of pubic and arm pit hair, and 62.7% (84/134) had hypogonadism. Testosterone levels showed a decreasing trend with increasing BMI, but it was not statistically significant. CONCLUSION: Obesity is one of the important etiologies of hypotestosteronemia and its manifestations in young adults. The actual incidence may be significantly higher than what is reported in the literature. High-quality research is required to address questions of diagnosis and best treatment options.


Assuntos
Ginecomastia , Hipogonadismo , Obesidade Mórbida , Adulto Jovem , Humanos , Masculino , Adolescente , Adulto , Obesidade Mórbida/cirurgia , Testosterona , Ginecomastia/complicações , Ginecomastia/tratamento farmacológico , Incidência , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/tratamento farmacológico , Hipogonadismo/complicações , Hipogonadismo/epidemiologia
2.
Cureus ; 14(10): e29869, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36348835

RESUMO

By utilizing time study methodologies, one can ascertain how long it takes a skilled person to complete a task with a specific level of quality. Time study aids in the selection of different job execution options as well as in the determination of the workforce required for a certain task, and thus assist in increasing manpower efficiency. It also aids in the acquisition of plants and machinery. By elaborating on the definition of "time-motion studies" (TMSs) as it is used in the biomedical literature and presenting justification based on full knowledge of that definition, this work aims to contribute to the standardization of TMSs. In TMSs, which is a type of quantitative data gathering, an outside observer records the motions and time necessary to complete an activity, together with an analysis aimed at increasing productivity. This paper suggests that, according to the researchers, the term is used to designate a range of investigations, the gathering and/or analysis of the length of one or more occurrences. A detailed analysis of all the available literature is done in this paper to get knowledge about TMS and its use in healthcare. Also, a comprehensive overview of many methodologies applied in works that are classed or referred to as TMSs is provided in this paper. Time motion investigations were first introduced in industrial engineering at the beginning of the twentieth century. Since then, they have been extensively employed by biological researchers, and because there is currently interest in parts of clinical workflow, they have attracted attention. However, combining the findings from different studies has proven challenging because there is a lot of variation in how techniques are used and reported. Although efforts have been made to uniformly publish these data and outcomes, there is still confusion about what TMSs are. A shared understanding of time and motion (TAM) research, as well as a proper acknowledgment of the various approaches it comprises, is a critical step toward standardization and validation. In this review paper literature analysis is done to discover what is known as TMSs to achieve the mentioned purpose.

3.
J Family Med Prim Care ; 11(7): 4019-4022, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36387681

RESUMO

With increasing travel and immunosuppression, parasitic lung and pleural diseases are increasingly been reported. The diagnosis in certain cases is very challenging because of nonspecific clinical and radiological features. We hereby present a case of a 60-year-old immunocompetent female complaining of difficulty in breathing for 4-5 days for which sputum sample along with the coughed-up fragment of the parasite under investigation was sent to the laboratory. All the blood parameters along with blood and sputum culture were within normal limits. Direct microscopy for sputum and multiple fecal samples did not yield any significant information. Chest X-ray was normal, whereas contrast-enhanced computed tomography scan changes were suggestive of fibrotic changes and mucoid impaction. The histopathological examination showed thick mucus content and no evidence of a parasitic infestation, worm, larva, or ova. So the differential diagnosis of the right lower lobe obstruction probably due to mucus plug was made, and the patient was referred to a pulmonologist for further follow-up. This case highlights the importance of common respiratory disorders characterized by mucus plugs and that some may mimic parasitic segments. Specific clinical, radiological, and pathologic features, microscopic examination, or serological testing can help to narrow the differential diagnosis of infective or noninfective causes and help the patients in early and accurate diagnosis and treatment and save them from unnecessary expensive and invasive investigations.

4.
Cureus ; 14(9): e29372, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36304347

RESUMO

In underserved communities, the community health worker (CHW) concept has been employed to improve health and lessen unfavourable health consequences. In India's rural healthcare delivery system, auxiliary nurse midwives (ANMs), accredited social health activists (ASHA workers), and Anganwadi workers (AWWs) are the primary field-level frontline officials who come into direct contact with the population. They bear a large portion of the burden of carrying out health services. This review investigated the various contributions made by these CHWs, ANMs, ASHA workers, and AWWs to the advancement of basic healthcare in Indian rural areas. The goal of reviewing this paper was to learn more about what CHWs do to provide the target demographic with high-quality healthcare. A thorough literature search was conducted using crucial databases including PubMed, Google, and Google Scholar. Recent studies were examined to determine how well CHWs perform essential healthcare services in low and middle-income nations. Numerous studies demonstrate how their work has a good effect on society. The length of time CHWs spend at work each day and how well they perform as a whole depends on several variables. This review study showed that, globally, there is a growing interest in CHWs' performance. In terms of incentives, pay, and training expenses, CHWs are thought to be a more affordable option than other types of health workers. They are recognised as the main factors in providing promotive, preventive, curative and rehabilitative healthcare services, achieving enhanced neonatal and maternal health and the development of children and adolescents. The current review also examined previous studies on the work done by CHWs and their potential benefits for enhancing primary healthcare in rural India. It focused on the routine work done by these health workers to increase service accessibility and access to high-quality healthcare, particularly for individuals living in rural areas. Hence, it is necessary to evaluate the functions and general status of community health workers (CHWs), as well as recognise their role, to improve their efficiency in providing basic healthcare services to society and make necessary changes in the future.

5.
Viral Immunol ; 35(2): 82-111, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35007431

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which caused the coronavirus disease 2019 (COVID-19) pandemic as declared by the World Health Organization, has created havoc worldwide. The highly transmissible infection can be contained only by accurate diagnosis, quarantining, and exercising social distancing. Therefore, quick and massive deployment of SARS-CoV-2 testing plays a crucial role in the identification and isolation of infected patients. Reverse transcription-polymerase chain reaction is the gold standard for COVID-19 detection; however, it needs expertise, facilities, and time. Hence, for the ease of population-wide screening, serology-based diagnostic assays were introduced. These can help determine the prevalence of infection, understand the epidemiology of the disease, and assist in suitable public health interventions while being user-friendly and less time consuming. Although serological testing kits in markets soared, their sensitivity and specificity were questioned in reports from different parts of the world. In this article, we have reviewed 40 Food and Drug Administration (FDA) and CE-approved clinically evaluated serological kits (8 enzyme-linked immunosorbent assay [ELISA] kits, 10 chemiluminescent immunoassay [CLIA] kits, and 22 lateral flow immunoassay [LFIA] kits) for their sensitivity and specificity and discussed the apparent reasons behind their performance. We observed appreciable sensitivity in the kits detecting total antibodies compared to the kits targeting single isotype antibodies. Tests that determined antibodies against nucleocapsid protein were found to be more sensitive and those detecting antibodies against spike protein were found to have greater specificity. This study was conducted to help the decision-making while acquiring antibody kits and concurrently to be mindful of their shortcomings.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Pandemias , Sensibilidade e Especificidade
6.
Bioresour Technol ; 349: 126757, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35077811

RESUMO

Advances such as cell-on-cell immobilization, multi-stage fixed bed tower (MFBT) bioreactor, promotional effect on fermentation, extremely low temperature fermentation, freeze dried immobilized cells in two-layer fermentation, non-engineered cell factories, and those of recent papers are demonstrated. Studies for possible industrialization of ICB, considering production capacity, low temperatures fermentations, added value products and bulk chemical production are studied. Immobilized cell bioreactors (ICB) using cellulose nano-biotechnology and engineered cells are reported. The development of a novel ICB with recent advances on high added value products and conceptual research areas for industrialization of ICB is proposed. The isolation of engineered flocculant cells leads to a single tank ICB. The concept of cell factories without GMO is a new research area. The conceptual development of multi-stage fixed bed tower membrane (MFBTM) ICB is discussed. Finally, feasible process design and technoeconomic analysis of cellulose hydrolysis using ICB are studied for polyhydroxybutyrate (PHB) production.


Assuntos
Celulose , Desenvolvimento Industrial , Reatores Biológicos , Células Imobilizadas/metabolismo , Celulose/metabolismo , Análise Custo-Benefício , Fermentação , Hidrólise
7.
Bioresour Technol ; 345: 126464, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34864183

RESUMO

The aim of this study is the consolidated bioprocessing of lactose into lactic acid and ethanol using non-engineered Cell Factories (CFs). Therefore, two different types of composite biocatalysts (CF1-CF2) based on Saccharomyces cerevisiae with immobilized microorganism or enzyme on starch gel (SG) were prepared for 5% w/v lactose fermentation. In CF1, S. cerevisiae was covered with SG containing Lactobacillus casei, Lactobacillus bulgaricus, Kluyveromyces marxianus CF1a-c. S. cerevisiae/SG-ß-galactosidase (CF1d) was also used for simultaneous saccharification and fermentation (SSF) of lactose. In CF2, S. cerevisiae immobilized on tubular cellulose (TC) was covered with SG containing the aforementioned microorganisms (CF2a-c). The wet CF1d resulted in 96% of the theoretical ethanol yield while the wet CF1b and freeze-dried CF2b resulted in 89% of the theoretical lactic acid yield. The repeated batches using the CF2a-c exhibited better results than using CF1a-c. Subsequently, the freeze-dried CF2 as preservative and more manageable were verified for future exploitation of whey.


Assuntos
Kluyveromyces , Lactose , Etanol , Fermentação , Ácido Láctico , Saccharomyces cerevisiae
8.
Bioresour Technol ; 344(Pt B): 126415, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34838977

RESUMO

The bioprocessing of lignocellulosic biomass to produce bio-based products under biorefinery setup is gaining global attention. The economic viability of this biorefinery would be inclined by the efficient bioconversion of all three major constituents of lignocellulosic biomass i.e. cellulose, hemicellulose, and lignin for value-added biochemicals and biofuels production. Although the lignocellulosic biorefinery setup has a clear value proposition, the commercial success at the industrial scale is still inadequate. This can be attributed mainly to irregular biomass supply chain, market uncertainties, and scale-up challenges. Global research efforts are underway by public and private sectors to get deeper market penetration. A comprehensive account of important factors, limitations, and propositions are worth consideration for the commercial success of lignocellulosic biorefineries. In this article, the importance of integration of lignocellulosic biorefineries with existing petrochemical refineries, the technical challenges of industrialization, SWOT analysis, and future directions have been reviewed.


Assuntos
Biocombustíveis , Lignina , Biomassa , Celulose
10.
Enzyme Microb Technol ; 145: 109750, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33750540

RESUMO

The objective of this project was to ferment lactose and whey to ethanol in one-step process. Models of cell factory of non-engineered S.cerevisiae have been proposed to ferment lactose. The cell factory of non-engineered S. cerevisiae/SG-lactase was prepared by the addition, of a starch gel solution containing lactase on non-engineered S. cerevisiae, and freeze drying of it. The 2-layer non engineered S.cerevisiae-TC/SG-lactase factory was prepared by immobilizing S. cerevisiae on the internal layer of tubular cellulose (TC), and the lactase enzyme was contained in the upper layer of starch gel (SG) covering cells of S. cerevisiae. Using such cell factory for the fermentation of lactose, alcohol yield of 23-32 mL/L at lactose conversion of 71-100%. The improvement in alcohol yield by cell factory versus co-immobilization of lactase enzyme and S. cerevisiae on alginates, was found in the range of 28-78%. Likewise, the cell factories are more effective than engineered S. cerevisiae. The fermentation of whey instead of lactose resulted in a significant reduction of the fermentation time. Freeze-dried cell factories led to improved results as compared with non-freeze dried. When lactase was substituted with L. casei, ethanol and lactic acid were produced simultaneously at high concentrations, but in a much longer fermentation time. The cell factories can be considered as models for white biotechnology using lactose containing raw materials. This suggested cell factory model can be applied for other bioconversions using the appropriate enzymes and cells, in the frame of White Biotechnology without genetic modification.


Assuntos
Lactose , Saccharomyces cerevisiae , Fermentação , Lactase/genética , Saccharomyces cerevisiae/genética , Soro do Leite
11.
Acta Neuropathol ; 141(4): 605-617, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33585982

RESUMO

Low-grade gliomas (LGGs) are the most common childhood brain tumor in the general population and in individuals with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. Surgical biopsy is rarely performed prior to treatment in the setting of NF1, resulting in a paucity of tumor genomic information. To define the molecular landscape of NF1-associated LGGs (NF1-LGG), we integrated clinical data, histological diagnoses, and multi-level genetic/genomic analyses on 70 individuals from 25 centers worldwide. Whereas, most tumors harbored bi-allelic NF1 inactivation as the only genetic abnormality, 11% had additional mutations. Moreover, tumors classified as non-pilocytic astrocytoma based on DNA methylation analysis were significantly more likely to harbor these additional mutations. The most common secondary alteration was FGFR1 mutation, which conferred an additional growth advantage in multiple complementary experimental murine Nf1 models. Taken together, this comprehensive characterization has important implications for the management of children with NF1-LGG, distinct from their sporadic counterparts.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Neurofibromatose 1/complicações , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Camundongos , Mutação
12.
Anticancer Agents Med Chem ; 20(7): 909-916, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32188389

RESUMO

BACKGROUND: The derivatives of xanthene are known to have promising anticancer properties, in comparison to xanthene itself. OBJECTIVE: The object of our study was to develop few xanthene derivatives (a family of fifteen novel 3,4,6,7- tetrahydro-3,3-dimethyl-9-phenyl-2H-xanthene-1,8(5H, 9H)-diones encoded as 4a-4m), which were effectively prepared through regioselective synthesis approach, and to test their anticancer effects. METHODS: A series of cell lines were used in this study, first to assess the cytotoxicity and then the drug efficacy of target compounds, consecutively. Prior to MTT assay, the compounds were analysed for their antioxidant properties, since oxidative stress is an important factor in the development of many cancer types. The anticancer properties of 4a-m have been assessed over in silico (molecular docking and ADMET assessments) and in vitro (MTT assay) methods. RESULTS: Compounds 4h and 4i showed a relative percentage anticancer activity of 86.25±1.25 & 89.74±1.64 against BT474 (ER+HER2+), and 90.56±1.18 & 93.24±1.80 against MCF-7 (ER-HER2), respectively. CONCLUSION: The animal model and pre-clinical studies for 4h and 4i should be performed in order to develop them as future anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Xantenos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células K562 , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Xantenos/química
13.
Proc Natl Acad Sci U S A ; 116(30): 14961-14970, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31296563

RESUMO

O-GlcNAc transferase (OGT) is an X-linked gene product that is essential for normal development of the vertebrate embryo. It catalyses the O-GlcNAc posttranslational modification of nucleocytoplasmic proteins and proteolytic maturation of the transcriptional coregulator Host cell factor 1 (HCF1). Recent studies have suggested that conservative missense mutations distal to the OGT catalytic domain lead to X-linked intellectual disability in boys, but it is not clear if this is through changes in the O-GlcNAc proteome, loss of protein-protein interactions, or misprocessing of HCF1. Here, we report an OGT catalytic domain missense mutation in monozygotic female twins (c. X:70779215 T > A, p. N567K) with intellectual disability that allows dissection of these effects. The patients show limited IQ with developmental delay and skewed X-inactivation. Molecular analyses revealed decreased OGT stability and disruption of the substrate binding site, resulting in loss of catalytic activity. Editing this mutation into the Drosophila genome results in global changes in the O-GlcNAc proteome, while in mouse embryonic stem cells it leads to loss of O-GlcNAcase and delayed differentiation down the neuronal lineage. These data imply that catalytic deficiency of OGT could contribute to X-linked intellectual disability.


Assuntos
Domínio Catalítico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Deficiência Intelectual/genética , Mutação com Perda de Função , N-Acetilglucosaminiltransferases/genética , Animais , Linhagem Celular , Drosophila , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Fator C1 de Célula Hospedeira/metabolismo , Humanos , Deficiência Intelectual/patologia , Camundongos , N-Acetilglucosaminiltransferases/química , N-Acetilglucosaminiltransferases/metabolismo , Neurogênese , Mutação Puntual , Gêmeos Monozigóticos
14.
BMC Immunol ; 20(1): 2, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30616506

RESUMO

BACKGROUND: The use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases such as HIV-1 and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes in the mouse glycoproteins' chemistry affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection are not known. RESULTS: We mutated mouse CMAH in the NOD/scid-IL2Rγc-/- (NSG) mouse strain, which is widely used for the transplantation of human cells, using the CRISPR/Cas9 system. The new strain provides a better environment for human immune cells. Transplantation of human hematopoietic stem cells leads to broad B cells repertoire, higher sensitivity to HIV-1 infection, and enhanced proliferation of transplanted peripheral blood lymphocytes. The mice showed no effect on the clearance of human immunoglobulins and enhanced transduction efficiency of recombinant adeno-associated viral vector rAAV2/DJ8. CONCLUSION: NSG-cmah-/- mice expand the mouse models suitable for human cells transplantation, and this new model has advantages in generating a human B cell repertoire. This strain is suitable to study different aspects of the human immune system development, provide advantages in patient-derived tissue and cell transplantation, and could allow studies of viral vectors and infectious agents that are sensitive to human-like sialylation of mouse glycoproteins.


Assuntos
Glicoproteínas/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1 , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/virologia , Animais , Sistemas CRISPR-Cas , Modelos Animais de Doenças , Loci Gênicos , Infecções por HIV/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/virologia , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Knockout , Fenótipo
16.
J Anaesthesiol Clin Pharmacol ; 34(2): 242-246, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30104837

RESUMO

BACKGROUND AND AIMS: Adductor canal block (ACB) is now an established component of multimodal analgesia for knee replacement surgery and is slowly replacing femoral nerve block (FNB). It is also gaining popularity for providing pain relief in knee arthroscopies including anterior cruciate ligament reconstruction surgery (ACLR). Data is lacking from the Indian subcontinent on comparing ACB to the traditional FNB for ACLR. Hence, we conducted the present study to compare ACB and FNB in ACLR under general anesthesia. MATERIAL AND METHODS: Sixty patients were randomized to receive either ACB or FNB under ultrasound guidance. Postoperatively, quadriceps muscle strength (straight leg raise and time up and go; TUG test) and quality of analgesia (numeric rating scale; NRS and patient satisfaction score) were assessed every 6 hour, and thereafter, up to 48 hours. The time of rescue analgesia and total analgesic consumption (tramadol) were also recorded. Data was statistically analyzed and P < 0.05 was considered to be significant. RESULTS: Patients receiving ACB had significantly less quadriceps weakness (P < 0.001) compared to FNB on postoperative day (POD) 1. In addition, patient satisfaction score was statistically higher (P < 0.05) in FNB on POD1. Both the above parameters were comparable on POD2. No statistically significant difference was recorded in NRS, time for rescue analgesia, and total analgesic consumption among the two groups. CONCLUSION: ACB preserves quadriceps motor strength while providing analgesia comparable to FNB in patients undergoing ACLR. However, patient satisfaction score is better with FNB than ACB.

17.
Int Immunopharmacol ; 62: 237-243, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30032048

RESUMO

Dengue virus (DENV) infections are straining public health systems worldwide. Vitamin D, a secosteroid hormone, is currently being investigated for its immunomodulatory effects in DENV infections. The objectives of the present study was to study the effect of 1, 25 dihydroxy vitamin D3 (1,25(OH)2D3) on the expression of genes coding for RNA sensing pattern recognition receptors, downstream signaling components including oligoadenylate synthetases (OAS) and interferon stimulated gene 15 (ISG15) and T helper (Th)1, Th2 and Th17 cytokine response in DENV infected U937-DC-SIGN cells and THP-1 macrophages. U937-DC-SIGN RNA was investigated for the expression of TLR3, DDX58, IFIH1, OAS1, OAS2, OAS3, CAMP and ISG15 genes using gene expression assays. Interleukin (IL)-12p70, IL-10, IL-4 and IL-17A levels were assessed in the THP-1 macrophage culture supernatants. The results revealed that 1,25(OH)2D3 increased the expression of DDX58, OAS1, OAS2 and OAS3 at 0.1 µM while higher concentration had diminishing effect. 1,25(OH)2D3 enhanced the expression of ISG15 and CAMP genes. 1,25(OH)2D3 suppressed the levels of IL-4 and IL-17A. Lower concentration of 1,25(OH)2D3 suppressed IL-12p70 and IL-10 levels while a higher concentration enhanced the levels. The results suggest that 1,25(OH)2D3 may have concentration dependent immunomodulatory effects. Higher dose of 1,25(OH)2D3 might have an immunoregulatory role in ameliorating inflammation during dengue infections. Further studies are needed to evaluate the efficacy of different doses of 1,25(OH)2D3 in preventing severe dengue.


Assuntos
Calcitriol/farmacologia , Moléculas de Adesão Celular/genética , Citocinas/imunologia , Vírus da Dengue/efeitos dos fármacos , Lectinas Tipo C/genética , Macrófagos/efeitos dos fármacos , Receptores de Superfície Celular/genética , Receptores de Reconhecimento de Padrão/genética , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/fisiologia , Expressão Gênica/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Macrófagos/imunologia , Macrófagos/virologia , RNA/genética , Células U937 , Replicação Viral/efeitos dos fármacos
18.
J Pharmacol Exp Ther ; 365(2): 272-280, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29476044

RESUMO

Antiretroviral drug (ARV) metabolism is linked largely to hepatic cytochrome P450 activity. One ARV drug class known to be metabolized by intestinal and hepatic CYP3A are the protease inhibitors (PIs). Plasma drug concentrations are boosted by CYP3A inhibitors such as cobisistat and ritonavir (RTV). Studies of such drug-drug interactions are limited since the enzyme pathways are human specific. While immune-deficient mice reconstituted with human cells are an excellent model to study ARVs during human immunodeficiency virus type 1 (HIV-1) infection, they cannot reflect human drug metabolism. Thus, we created a mouse strain with the human pregnane X receptor, constitutive androstane receptor, and CYP3A4/7 genes on a NOD.Cg-Prkdcscid Il2rgtm1Sug /JicTac background (hCYP3A-NOG) and used them to evaluate the impact of human CYP3A metabolism on ARV pharmacokinetics. In proof-of-concept studies we used nanoformulated atazanavir (nanoATV) with or without RTV. NOG and hCYP3A-NOG mice were treated weekly with 50 mg/kg nanoATV alone or boosted with nanoformulated ritonavir (nanoATV/r). Plasma was collected weekly and liver was collected at 28 days post-treatment. Plasma and liver atazanavir (ATV) concentrations in nanoATV/r-treated hCYP3A-NOG mice were 2- to 4-fold higher than in replicate NOG mice. RTV enhanced plasma and liver ATV concentrations 3-fold in hCYP3A-NOG mice and 1.7-fold in NOG mice. The results indicate that human CYP3A-mediated drug metabolism is reduced compared with mouse and that RTV differentially affects human gene activity. These differences can affect responses to PIs in humanized mouse models of HIV-1 infection. Importantly, hCYP3A-NOG mice reconstituted with human immune cells can be used for bench-to-bedside translation.


Assuntos
Fármacos Anti-HIV/farmacologia , Citocromo P-450 CYP3A/genética , Receptor de Pregnano X/genética , Receptores Citoplasmáticos e Nucleares/genética , Animais , Fármacos Anti-HIV/farmacocinética , Receptor Constitutivo de Androstano , Interações Medicamentosas , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Distribuição Tecidual , Pesquisa Translacional Biomédica
19.
Anesth Essays Res ; 11(2): 499-502, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28663649

RESUMO

BACKGROUND AND AIMS: Ultrasound-guided transversus abdominis plane (TAP) block has been proven as a safe and effective analgesic technique for several lower abdominal surgeries. Various adjuvants have been used to intensify the quality and prolong the local anesthetic effect. We evaluated the analgesic efficacy of dexamethasone addition to ropivacaine in TAP block following open abdominal hysterectomy. MATERIALS AND METHODS: After clearance from the Institutional Ethics Committee, a double-blind, prospective, randomized study was carried out on sixty patients aged 40-60 years posted for elective open abdominal hysterectomy comparing bilateral TAP block using 20 ml of 0.5% ropivacaine + 1 ml of 0.9% saline (control Group R) or 20 ml of 0.5% ropivacaine + 4 mg dexamethasone (Group RD). The aim of our study was to observe postoperative pain score (visual analog scale [VAS]), time for first analgesic (TFA) demand, total analgesic consumption, and incidence of nausea or vomiting. STATISTICAL ANALYSIS: Chi-square test and Student's t-test were used, and P < 0.05 was considered as statistically significant. RESULTS: Postoperative VAS pain scores were significantly lower at 4, 6, and 12 h in Group RD as compared to Group R (P < 0.05). Significantly longer TFA (13.2 ± 7.6 vs. 7.1 ± 4.6 h, P < 0.001) with lesser tramadol requirement in first 24 h (50.2 ± 34 vs. 94 ± 35 mg, P < 0.001) were observed in Group RD as compared to Group R. Incidence of nausea or vomiting was statistically insignificant between the groups (P > 0.05). CONCLUSIONS: Addition of dexamethasone to ropivacaine TAP block prolonged the postoperative analgesia and reduced analgesic requirement following abdominal hysterectomy.

20.
J Appl Microbiol ; 123(1): 194-203, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28403558

RESUMO

AIMS: To assess glutathione (GSH) biosynthesis ability and activity of dependent enzymes in food-grade lactic acid bacteria (LAB) and correlating with genomic information on GSH system in LAB. METHODS AND RESULTS: Whole-genome sequences of 26 food-grade LAB were screened for the presence/absence of a set of genes involved in de novo GSH system. Multiple strains of Streptococcus thermophilus (37), Lactobacillus casei (37), Lactobacillus rhamnosus (4), Lactobacillus paracasei (8) Lactobacillus plantarum (23) and Lactobacillus fermentum (22) were screened for biochemical evidence of the GSH system. Multiple sequence analysis of GshF sequences was carried out for comparing the genomic signatures between GSH-producing and nonproducing species. CONCLUSIONS: Streptococcus thermophilus was found to have de novo GSH biosynthesis as well as import ability. Lactobacillus sp. were negative for GSH synthesis but could import it from the medium. All the species exhibited prolific GSH reductase and peroxidase activity. Sequence analysis revealed the absence of key amino acid residues as well as a truncated N-terminal region in lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides a comprehensive view on the status of an important antioxidative system (the GSH system) in LAB and is expected to serve as a primer for future work on the mechanistic role of GSH in the group.

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