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1.
Reprod Domest Anim ; 59(1): e14526, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268210

RESUMO

The research utilized data from 662 Murrah buffaloes meticulously recorded over 24 years (1996-2019) from historical pedigree sheets maintained at the buffalo farm of the Department of Livestock Production and Management (LPM) at Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), Hisar. A series of six univariate animal models were employed to calculate estimates of (co)variance components and heritability for first lactation reproduction traits. Among these models, Model 2 was identified as the best fit for age at first calving (AFC) and calving interval (CI), while Model 1 proved optimal for service period (SP) and conception rate (CR). The heritability estimates for AFC, SP, CR and CI across the models were ranged between 0.11 and 0.32, 0.01 and 0.03, 0.05 and 0.06, and 0.01 and 0.06, respectively. Maternal effects (m2 ) were observed in AFC and CI, ranging from 0.10 to 0.20 and 0.01 to 0.03, respectively. Across all three traits, there was a consistent negative genetic correlation (-0.75 to -0.92) between direct additive and maternal effects. The breeding values for AFC, SP, CR and CI varied within specific ranges from -32.85 to 44.33 days, -15.61 to 28.42 days, -7.41 to 6.48% and -20.64 to 35.79 days, respectively. Significantly, Spearman's rank correlation analysis revealed highly significant relationships (p < .01) between the breeding values of different models, indicating strong and consistent associations within these traits. These findings underscore the stable and reliable connections observed within the breeding values for these essential reproductive traits across the various models used in the study. The majority of reproductive traits showed favourable negative trends, indicating a positive outcome. A decrease in AFC, SP and CI suggests an extended economic life for the animals. Additionally, the upward trends in CR reflect positive indications of effective management practices and skilled operational procedures.


Assuntos
Bison , Animais , Feminino , Fazendas , Fertilização , Lactação/genética , Reprodução/genética
2.
J Anim Breed Genet ; 141(4): 415-424, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38284302

RESUMO

The study was done to determine additive, maternal and common permanent environmental effects and best-suited model for some production traits using six univariate animal models that differed in the (co)variance components fitted to assess the importance of maternal effect using likelihood ratio test in Murrah buffaloes. Data from 614 Murrah buffaloes related to production traits were collected from history pedigree sheets maintained at the buffalo farm, Department of Livestock Production and Management (LPM), LUVAS, Hisar. The production traits under this study were 305 days milk yield (305DMY), peak yield (PY), lactation length (LL), dry period (DP), lactation milk yield (LMY) and wet average (WA). The heritability estimates were in the range of 0.33-0.44 for 305DMY, 0.25-0.51 for PY, 0.05-0.13 for LL, 0.03-0.23 for DP, 0.17-0.40 for LMY and 0.37-0.66 for WA. Model 1 was considered best for most of the traits, viz., 305DMY, PY, LL, LMY and WA followed by model 2 for DP. Covariance and correlated values within the traits caused inflation of heritability in model 3 and model 6. The maximum covariance between the additive and maternal effect was found in trait LMY, which was 14,183.90 in model 3 and the minimum value was also reported in the same trait for model 6, valued at -3522.37. Multivariate analysis showed that all production traits were moderate to high and positively correlated with each other except for DP, which was low and negative genetic and phenotypic correlated. Spearman's rank correlation coefficients of breeding value among all six models were high and significant, ranged from 0.78 to 1.00 for all the traits except DP, therefore any of the models could be taken into account depending upon the availability of data.


Assuntos
Búfalos , Lactação , Animais , Búfalos/genética , Búfalos/fisiologia , Feminino , Lactação/genética , Leite/metabolismo , Fenótipo , Modelos Genéticos , Cruzamento , Herança Materna/genética , Característica Quantitativa Herdável
3.
Blood ; 137(8): 1104-1116, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33512471

RESUMO

Acute pulmonary embolism generally resolves within 6 months. However, if the thrombus is infected, venous thrombi transform into fibrotic vascular obstructions leading to chronic deep vein thrombosis and/or chronic thromboembolic pulmonary hypertension (CTEPH), but precise mechanisms remain unclear. Neutrophils are crucial in sequestering pathogens; therefore, we investigated the role of neutrophil extracellular traps (NETs) in chronic thrombosis. Because chronic pulmonary thrombotic obstructions are biologically identical to chronic deep venous thrombi, the murine inferior vena cava ligation model was used to study the transformation of acute to chronic thrombus. Mice with staphylococcal infection presented with larger thrombi containing more neutrophils and NETs but less resolution. Targeting NETs with DNase1 diminished fibrosis and promoted thrombus resolution. For translational studies in humans, we focused on patients with CTEPH, a severe type of deep venous and pulmonary artery fibrotic obstruction after thrombosis. Neutrophils, markers of neutrophil activation, and NET formation were increased in CTEPH patients. NETs promoted the differentiation of monocytes to activated fibroblasts with the same cellular phenotype as fibroblasts from CTEPH vascular occlusions. RNA sequencing of fibroblasts isolated from thrombo-endarterectomy specimens and pulmonary artery biopsies revealed transforming growth factor-ß (TGF-ß) as the central regulator, a phenotype which was replicated in mice with fibroblast-specific TGF-ß overactivity. Our findings uncover a role of neutrophil-mediated inflammation to enhance TGF-ß signaling, which leads to fibrotic thrombus remodeling. Targeting thrombus NETs with DNases may serve as a new therapeutic concept to treat thrombosis and prevent its sequelae.


Assuntos
Armadilhas Extracelulares , Hipertensão Pulmonar/patologia , Neutrófilos/patologia , Embolia Pulmonar/patologia , Trombose/patologia , Animais , Células Cultivadas , Doença Crônica , Feminino , Fibrose , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
4.
Anim Biotechnol ; 34(8): 3867-3876, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37477621

RESUMO

This study aimed to characterize estrus response and to establish relationships between intensity of estrus, preovulatory follicle (POF) size and estradiol (E2) concentrations on day of AI, luteal profiles and pregnancy outcome in lactating Hariana breed of cows. 200 cyclic cows were subjected to Ovsynch (n = 54) and Pre-OV treatment (n = 146). Ovsynch: Buserelin acetate (BA; 10 µg), Cloprostenol (500 µg) and BA (10 µg) were injected i.m. on day 0, 7 and 9, respectively, irrespective of treatment. Pre-OV: BA (10 µg) and Cloprostenol (500 µg) was also injected i.m. simultaneously 7 days prior to initiate Ovsynch. On the basis of estrus behavior, the cows were classified into three groups: weak, moderate and intense. Artificial insemination performed at 18-24 hours after 2nd BA of Ovsynch in both treatments. The average duration of estrus did not differ (p > 0.05) between Ovsynch and Pre-OV treatment. A positive correlation was observed between estrus response and POF size, concentration of E2 on day of AI and luteal profiles on day 12 post-AI. First service conception rate was higher in cows exhibited intense (45.46%) and moderate (42.56%) estrus response than weak (28.57%) estrus response. In conclusion, intensity of estrus expression could be considered as important determinant for deciding pregnancy outcomes in Bos indicus cows.


Assuntos
Sincronização do Estro , Lactação , Feminino , Gravidez , Bovinos , Animais , Lactação/fisiologia , Estro/fisiologia , Fertilidade , Busserrelina/farmacologia , Cloprostenol , Progesterona
6.
J Mater Sci Mater Med ; 33(3): 25, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35190908

RESUMO

BACKGROUND: There is a continuous research in the area of biomimetic coatings on the titanium (Ti) implant surfaces for improved survival and long-term successful outcomes in the field of dentistry and orthopedics. In-vitro approaches are ideal systems for studying cell-material interactions without complexity and interference observed in in-vivo models. PURPOSE: The present study was undertaken to evaluate the osteoblast characteristics and function on Ti substrates coated with the novel composite coating of ceramic apatite-wollastonite (AW) and polymer chitosan. MATERIALS AND METHODS: Ti substrate coated with composite AW-Chitosan was synthesized, using electrophoretic deposition. MG-63 cells were seeded onto the coated substrates and cellular morphology and growth was assessed using Scanning Electron Microscopy (SEM) and Laser Scanning Microscopy (LSM). Osteocalcin expression of the seeded cells was assessed by FITC tagging and LSM analysis. Alizarin Red S staining and Confocal LSM (CSLM) analysis was used to study the in-vitro mineralization on the titanium samples. RESULTS: The AW-Chitosan coating on Ti samples by electrophoretic deposition exerted significant positive influence on cell proliferation, growth and mineralization as compared to uncoated titanium samples. Scanning electron microscopy and laser confocal microscopy experiments revealed that the coating was non-toxic to cells, enhanced adhesion and proliferation of MG-63 cells. Increased functional activity was observed by increased production of bone-specific protein osteocalcin and mineralized calcium through day 7 and 14. CONCLUSIONS: The present study underscores that optimal inorganic-organic phase nanocomposite crack-free coating created on Ti by simple, cost-effective electrophoretic deposition technique may have osteoconductive potential and may have wide application in the field of implantology. Graphical abstract.


Assuntos
Quitosana , Nanocompostos , Apatitas , Compostos de Cálcio , Materiais Revestidos Biocompatíveis , Osteoblastos , Silicatos , Propriedades de Superfície , Titânio
7.
Environ Monit Assess ; 195(1): 68, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331697

RESUMO

A simple and efficient analytical methodology was standardised for the estimation of forchlorfenuron residues in rice leaves, grains, husk, straw and soil using LC-MS/MS. The methodology was validated in terms selectivity, sensitivity, linearity, limit of detection, limit of quantification, matrix effect, repeatability and reproducibility. The limit of detection and limit of quantification of forchlorfenuron in rice leaves, grains, straw, husk and soil were worked out to be 0.003 and 0.01 mg kg-1, respectively. Recoveries ranged between 81.54 and 99.05% with RSDr below 4.57 and RSDR below 4.19%. This validated method was applied for the determination of forchlorfenuron residues in paddy leaves after foliar application. The residues persisted for 0, 3 and 7 days after application of forchlorfenuron 0.12% EC @ 1.25, 2.50 and 5.00 ppm a.i. The half-life values were estimated to be 1.91 and 2.11 days for 2.50 and 5.00 ppm a.i. concentration. The residues were found to be below the limit of quantification of 0.01 mg kg-1 in straw, grain, husk and soil samples collected at harvest time.


Assuntos
Oryza , Resíduos de Praguicidas , Cromatografia Líquida , Monitoramento Ambiental/métodos , Espectrometria de Massas em Tandem , Reprodutibilidade dos Testes , Solo/química , Oryza/química , Resíduos de Praguicidas/análise
8.
Circulation ; 141(5): 376-386, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31896275

RESUMO

BACKGROUND: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of small-vessel disease in patients with chronic thromboembolic pulmonary hypertension undergoing PEA to predict postoperative outcome before surgery. METHODS: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned pulmonary vascular resistance in larger arterial (upstream resistance [Rup]) and small arterial plus venous components (downstream resistance) in 90 patients before PEA. For validation, lung wedge biopsies were taken from nonobstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured in each patient. Percent media (%MT; arteries) and intima thickness (%IT; arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter. RESULTS: Decreased Rup was an independent predictor of persistent PH (odds ratio per 10%, 0.40 [95% CI, 0.23-0.69]; P=0.001) and survival (hazard ratio per 10%, 0.03 [95% CI, 0.00-0.33]; p=0.004). Arterial %MT and %IT of nonobstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and nonsurvivors. Rup correlated inversely with %MT (r=-0.72, P<0.001) and %IT (r=-0.62, P<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, P=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, whereas Rup <60% identified patients with poor prognosis after PEA. CONCLUSIONS: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in chronic thromboembolic pulmonary hypertension.


Assuntos
Hemodinâmica/fisiologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Doenças Vasculares/fisiopatologia , Adulto , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Artéria Pulmonar/patologia , Embolia Pulmonar/complicações , Embolia Pulmonar/fisiopatologia , Doenças Vasculares/diagnóstico , Resistência Vascular/fisiologia
9.
Appl Microbiol Biotechnol ; 105(9): 3611-3623, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33860835

RESUMO

Bacterial cell has always been an attractive target for anti-infective drug discovery. MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) enzyme of Escherichia coli (E.coli) is crucial for peptidoglycan biosynthetic pathway, as it is involved in the early stages of bacterial cell wall biosynthesis. In the present study we aim to identify novel chemical structures targeting the MurA enzyme. For screening purpose, we used in silico approach (pharmacophore based strategy) for 52,026 library compounds (Chembridge, Chemdiv and in house synthetics) which resulted in identification of 50 compounds. These compounds were screened in vitro against MurA enzyme and release of inorganic phosphate (Pi) was estimated. Two compounds (IN00152 and IN00156) were found to inhibit MurA enzyme > 70% in primary screening and IC50 of 14.03 to 32.30 µM respectively. These two hits were further evaluated for their mode of inhibition studies and whole-cell activity where we observed 2-4 folds increase in activity in presence of Permeabilizer EDTA (Ethylenediaminetetraacetic acid). Combination studies were also performed with known antibiotics in presence of EDTA. Hits are reported for the first time against this target and our report also support the use of OM permeabilizer in combination with antibacterial compounds to address the permeability and efficacy issue. These lead hits can be further optimized for drug discovery. KEY POINTS: • Emerging Gram negative resistant strains is a matter of concern. • Need for new screening strategies to cope with drying up antibiotics pipeline. • Outer membrane permeabilizers could be useful to improve potency of molecules to reach its target.


Assuntos
Alquil e Aril Transferases , Escherichia coli , Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Peptidoglicano
10.
Basic Res Cardiol ; 115(6): 58, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880713

RESUMO

Pulmonary arterial hypertension is a severe and progressive disease characterized by a pulmonary vascular remodeling process with expansion of collateral endothelial cells and total vessel occlusion. Endothelial cells are believed to be at the forefront of the disease process. Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor-2 (VEGFR-2), play a central role in angiogenesis, endothelial cell protection, but also in the destabilization of endothelial barrier function. Therefore, we investigated the consequences of altered VEGF signaling in an experimental model, and looked for translational correlates of this observation in patients. We performed an endothelial cell-specific conditional deletion of the kinase insert domain protein receptor (kdr) gene, coding for VEGFR-2, in C57/BL6 mice (Kdr∆end) and held them in an environmental chamber with 10% FiO2 or under normoxia for 6 weeks. Kdr knockout led to a mild PH phenotype under normoxia that worsened under hypoxia. Kdr∆end mice exhibited a significant increase in pulmonary arterial wall thickness, muscularization, and VEGFR-3+ endothelial cells obliterating the pulmonary artery vessel lumen. We observed the same proliferative vasculopathy in our rodent model as seen in patients receiving anti-angiogenic therapy. Serum VEGF-a levels were elevated both in the experimental model and in humans receiving bevacizumab. Interrupted VEGF signaling leads to a pulmonary proliferative arteriopathy in rodents after direct ablative gene manipulation of Kdr. Histologically, similar vascular lesions can be observed in patients receiving anti-VEGF treatment. Our findings illustrate the importance of VEGF signaling for maintenance of pulmonary vascular patency.


Assuntos
Pressão Arterial , Proliferação de Células , Células Endoteliais/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Artéria Pulmonar/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/deficiência , Remodelação Vascular , Inibidores da Angiogênese/uso terapêutico , Animais , Apoptose , Bevacizumab/uso terapêutico , Modelos Animais de Doenças , Células Endoteliais/patologia , Feminino , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipóxia/complicações , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/patologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Função Ventricular Direita , Pressão Ventricular
11.
J Nutr ; 150(10): 2818-2824, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32805040

RESUMO

BACKGROUND: Minimum Dietary Diversity (MDD) is a widely used indicator of adequate dietary micronutrient density for children 6-23 mo old. MDD food-group data remain underutilized, despite their potential for further informing nutrition programs and policies. OBJECTIVES: We aimed to describe the diets of children meeting MDD and not meeting MDD in India using food group data, nationally and subnationally. METHODS: Food group data for children 6-23 mo old (n = 73,036) from the 2015-16 National Family Health Survey in India were analyzed. Per WHO standards, children consuming ≥5 of the following food groups in the past day or night met MDD: breast milk; grains, roots, or tubers; legumes or nuts; dairy; flesh foods; eggs; vitamin A-rich fruits and vegetables; and other fruits and vegetables. Children not meeting MDD consumed <5 food groups. We analyzed the number and types of foods consumed by children meeting MDD and not meeting MDD at the national and subnational geographic levels. RESULTS: Nationally, children not meeting MDD most often consumed breast milk (84.5%), grains, roots, and tubers (62.0%), and/or dairy (42.9%). Children meeting MDD most often consumed grains, roots, and tubers (97.6%), vitamin A-rich fruits and vegetables (93.8%), breast milk (84.1%), dairy (82.1%), other fruits and vegetables (79.5%), and/or eggs (56.5%). For children not meeting MDD, district-level dairy consumption varied the most (6.4%-79.9%), whereas flesh foods consumption varied the least (0.0%-43.8%). For children meeting MDD, district-level egg consumption varied the most (0.0%-100.0%), whereas grains, roots, and tubers consumption varied the least (66.8%-100.0%). CONCLUSIONS: Children not meeting MDD had low fruit, vegetable, and protein-rich food consumption. Many children meeting MDD also had low protein-rich food consumption. Examining the number and types of foods consumed highlights priorities for children experiencing the greatest dietary deprivation, providing valuable complementary information to MDD.


Assuntos
Fenômenos Fisiológicos da Nutrição Infantil , Dieta , Proteínas Alimentares , Alimentos/classificação , Frutas , Verduras , Criança , Inquéritos sobre Dietas , Comportamento Alimentar , Humanos , Índia
14.
Altern Ther Health Med ; 24(2): 36-43, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28646806

RESUMO

Context • Coronary heart disease (CHD) is a major public health problem in developing and developed countries. Elevated cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, and the emergence of CHD, have been positively correlated in many clinical and epidemiological studies. The health benefits of probiotics have received a great deal of attention, including their blood cholesterol-lowering effects on humans. Objective • The research team intended to determine the current state of research examining the effects of various probiotic strains on lipid profiles, including measures in serum of total cholesterol, LDL cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. Design • The review examined studies, in both animal and human models and focused on the potential of various probiotic strains to be dietary adjuncts in lowering levels of serum cholesterol with the aim of reducing the risk of cardiovascular disease (CVD) and CHD. Articles were reviewed systematically from Web search bases including PubMed and Cochrane Clinical Trial Registry. Articles meeting the inclusion search criteria were selected for further review and analysis. Only randomized controlled trials evaluating the effects of probiotics on lipid profiles in animals or humans were considered for inclusion in the review. Setting • The selection of articles and further inclusion in the review was performed in Institute of Home Economics, University of Delhi (New Delhi, India). Results • Some of the studies, in both animal and human models, have revealed that several strains were able to improve at least 1 lipid fraction. Although the results from animal studies have been fairly consistent, the findings from studies on humans have varied. Some strains when evaluated in human studies have shown insignificant effects on lipid fractions. Conclusions • Although several mechanisms for cholesterol removal by probiotics have been proposed, they need further investigation to be validated.


Assuntos
Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Probióticos , Animais , Doenças Cardiovasculares , Modelos Animais de Doenças , Humanos , Probióticos/farmacologia , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
15.
J Infect Dis ; 214(10): 1531-1538, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27601622

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a potentially fatal parasitic disease associated with fever, cachexia and impaired protective T-cell responses against the parasite. METHODS: Peripheral blood leukocytes from 105 subjects with VL and healthy control subjects from the endemic region of Muzaffarpur, Bihar, India, were compared using flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. Findings were correlated with clinical data. RESULTS: An expanded population of low-density neutrophils that expressed HLA-DR, CD80 and CD86 was observed in subjects with VL. This neutrophil population contracted after successful treatment of disease. Plasma from patients with acute VL was able to induce similar high-level HLA-DR expression in neutrophils from healthy subjects. HLA-DR+ neutrophils from subjects with VL did not stimulate T-cell proliferation, but they did express higher programmed cell death ligand-1 (PDL1) than other neutrophils, and lymphocytes of the same subjects expressed high programmed cell death 1 (PD1). CONCLUSIONS: Patients with acute VL have expanded circulating low-density neutrophils expressing markers of antigen presentation, which diminish after treatment. Development of HLA-DR+ neutrophils is stimulated, at least in part, by components of plasma from patients with acute disease. Although we found no evidence that they act as antigen-presenting cells, these neutrophils expressed markers implicating a role in T-cell exhaustion.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Neutrófilos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Índia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
16.
Indian J Public Health ; 60(4): 280-286, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27976649

RESUMO

Human studies on the effects of probiotics on lowering blood cholesterol levels have not yielded conclusive results. A meta-analysis of randomized controlled trials evaluating the effect of probiotics on lipid profile was conducted. Articles were reviewed systematically from web search bases; PubMed, Cochrane Clinical Trial Registry. Those studies which were meeting the inclusion criteria-providing matching placebo, at least single blind for probiotics and placebo, providing mean and standard deviations and not involving the use of probiotics were selected. 14 studies from 12 randomized controlled trials were analyzed providing information of 606 normo/hypercholesterolemic patients using Review Manager 5.3 (The Cochrane Collaboration, Oxford, UK). The pooled mean net change for total cholesterol (TC) is -8.40 mg/dl (-13.63, -3.61), for low-density lipoprotein (LDL) is -6.63 mg/dl (-10.63, -2.63), for high-density-lipoprotein-cholesterol is 0.59 mg/dl (-0.92, 2.09), and for triglycerides is -1.32 mg/dl (-6.49, 3.85). The findings of the analysis conclude that probiotics supplementation does lower serum TC and LDL-cholesterol levels significantly and hence a reduction in the risk factor of developing coronary heart disease.


Assuntos
Hipercolesterolemia , Probióticos , LDL-Colesterol , Humanos , Hipercolesterolemia/tratamento farmacológico , Índia , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
17.
Proteins ; 83(10): 1836-48, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26211916

RESUMO

Myoglobin (Mb) uses strong electrostatic interaction in its distal heme pocket to regulate ligand binding. The mechanism of regulation of ligand binding in soybean leghemoglobin a (Lba) has been enigmatic and more so due to the absence of gaseous ligand bound atomic resolution three-dimensional structure of the plant globin. While the 20-fold higher oxygen affinity of Lba compared with Mb is required for its dual physiological function, the mechanism by which this high affinity is achieved is only emerging. Extensive mutational analysis combined with kinetic and CO-FT-IR spectroscopic investigation led to the hypothesis that Lba depended on weakened electrostatic interaction between distal HisE7 and bound ligand achieved by invoking B10Tyr, which itself hydrogen bonds with HisE7 thus restricting it in a single conformation detrimental to Mb-like strong electrostatic interaction. Such theory has been re-assessed here using CO-Lba in silico model and molecular dynamics simulation. The investigation supports the presence of at least two major conformations of HisE7 in Lba brought about by imidazole ring flip, one of which makes hydrogen bonds effectively with B10Tyr affecting the former's ability to stabilize bound ligand, while the other does not. However, HisE7 in Lba has limited conformational freedom unlike high frequency of imidazole ring flips observed in Mb and in TyrB10Leu mutant of Lba. Thus, it appears that TyrB10 limits the conformational freedom of distal His in Lba, tuning down ligand dissociation rate constant by reducing the strength of hydrogen bonding to bound ligand, which the freedom of distal His of Mb allows.


Assuntos
Monóxido de Carbono/metabolismo , Glycine max/química , Histidina/química , Leghemoglobina/química , Leghemoglobina/metabolismo , Tirosina/química , Monóxido de Carbono/química , Histidina/metabolismo , Simulação de Dinâmica Molecular , Oxigênio/química , Oxigênio/metabolismo , Ligação Proteica , Tirosina/metabolismo
18.
Bioorg Chem ; 59: 91-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25727263

RESUMO

Ligand-based and structure-based methods were applied in combination to exploit the physicochemical properties of 2,3-dideoxy hex-2-enopyranosid-4-uloses against Mycobacterium tuberculosis H37Rv. Statistically valid 3D-QSAR models with good correlation and predictive power were obtained with CoMFA steric and electrostatic fields (r(2) = 0.797, q(2) = 0.589) and CoMSIA with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2) = 0.867, q(2) = 0.570) based on training set of 33 molecules with predictive r(2) of 0.808 and 0.890 for CoMFA and CoMSIA respectively. The results illustrate the requirement of optimal alkyl chain length at C-1 position and acceptor groups along hydroxy methyl substituent of C-6 to enhance the anti-tubercular activity of the 2,3-dideoxy hex-2-enopyranosid-4-uloses while any substitution at C-3 position exert diminishing effect on anti-tubercular activity of these enulosides. Further, homology modeling of M. tuberculosis alpha-mannosidase followed by molecular docking and molecular dynamics simulations on co-complexed models were performed to gain insight into the rationale for binding affinity of selected inhibitors with the target of interest. The comprehensive information obtained from this study will help to better understand the structural basis of biological activity of this class of molecules and guide further design of more potent analogues as anti-tubercular agents.


Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Desoxiaçúcares/química , Desoxiaçúcares/farmacologia , Mycobacterium tuberculosis/enzimologia , alfa-Manosidase/antagonistas & inibidores , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , alfa-Manosidase/química , alfa-Manosidase/metabolismo
19.
Altern Ther Health Med ; 21 Suppl 3: 34-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26348612

RESUMO

Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. Modifiable risk factors of CHD have been identified, including high levels of low-density lipoproteins (LDLs) and triglycerides (TGs). Attempts by various researchers have been made to alter them. Several approaches, both pharmacological and nonpharmacological, have been identified to deal with the soaring numbers of individuals with those high levels. Current CHD treatment includes dietary interventions and use of statins, fibrates, niacin, cholesterol absorption inhibitors, and bile acid sequestrants. Those formulations have limitations and can possess long-term, unwanted side effects, and, therefore, other cholesterol-lowering, dietary adjuncts need to be identified and supplemented. Prebiotics are indigestible, fermented food substrates that selectively stimulate the growth and increase the activity of 1 or a limited number of microbial genus species, thereby changing the composition of the gut microbiota to confer health benefits to the hosts. Prebiotics are also nondigestible carbohydrates with specific fermentative properties, stimulating specific microbial growth associated with health and well-being. Some animal and human studies have provided strong evidence that suggests that prebiotics, as functional foods, can positively alter an individual's serum lipid profile, thereby lowering his or her risk of developing CHD. Therefore, the current review focuses on evaluating the role of prebiotics as potential dietary adjuncts in lowering cholesterol levels, with the aim of reducing the risks of cardiovascular and CHD.

20.
Antimicrob Agents Chemother ; 58(6): 3530-2, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24687500

RESUMO

A promising modified sugar molecule was identified which was active against multidrug-resistant (MDR) strains of Mycobacterium tuberculosis, suggesting involvement of a new target. The compound was demonstrated to be bactericidal, inhibited the growth of M. tuberculosis in mice, and targeted alpha-mannosidase as a competitive inhibitor with a Ki value of 353.9 µM.


Assuntos
Antituberculosos/farmacologia , Desoxiaçúcares/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , alfa-Manosidase/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/crescimento & desenvolvimento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
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