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1.
Hypertension ; : HYPERTENSIONAHA12015504, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32755410

RESUMO

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.

3.
Am J Physiol Regul Integr Comp Physiol ; 318(5): R855-R869, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32186897

RESUMO

Angiotensin II (ANG II) Agtr1a receptor (AT1A) is expressed in cells of the arcuate nucleus of the hypothalamus that express the leptin receptor (Lepr) and agouti-related peptide (Agrp). Agtr1a expression in these cells is required to stimulate resting energy expenditure in response to leptin and high-fat diets (HFDs), but the mechanism activating AT1A signaling by leptin remains unclear. To probe the role of local paracrine/autocrine ANG II generation and signaling in this mechanism, we bred mice harboring a conditional allele for angiotensinogen (Agt, encoding AGT) with mice expressing Cre-recombinase via the Lepr or Agrp promoters to cause cell-specific deletions of Agt (AgtLepr-KO and AgtAgrp-KO mice, respectively). AgtLepr-KO mice were phenotypically normal, arguing against a paracrine/autocrine AGT signaling mechanism for metabolic control. In contrast, AgtAgrp-KO mice exhibited reduced preweaning survival, and surviving adults exhibited altered renal structure and steroid flux, paralleling previous reports of animals with whole body Agt deficiency or Agt disruption in albumin (Alb)-expressing cells (thought to cause liver-specific disruption). Surprisingly, adult AgtAgrp-KO mice exhibited normal circulating AGT protein and hepatic Agt mRNA expression but reduced Agt mRNA expression in adrenal glands. Reanalysis of RNA-sequencing data sets describing transcriptomes of normal adrenal glands suggests that Agrp and Alb are both expressed in this tissue, and fluorescent reporter gene expression confirms Cre activity in adrenal gland of both Agrp-Cre and Alb-Cre mice. These findings lead to the iconoclastic conclusion that extrahepatic (i.e., adrenal) expression of Agt is critically required for normal renal development and survival.


Assuntos
Glândulas Suprarrenais/metabolismo , Proteína Relacionada com Agouti/metabolismo , Angiotensinogênio/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Metabolismo Energético , Rim/metabolismo , Receptores para Leptina/metabolismo , Glândulas Suprarrenais/crescimento & desenvolvimento , Proteína Relacionada com Agouti/deficiência , Proteína Relacionada com Agouti/genética , Angiotensinogênio/deficiência , Angiotensinogênio/genética , Animais , Núcleo Arqueado do Hipotálamo/crescimento & desenvolvimento , Comunicação Autócrina , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Rim/crescimento & desenvolvimento , Masculino , Camundongos Knockout , Miocárdio/metabolismo , Comunicação Parácrina , Receptores para Leptina/deficiência , Receptores para Leptina/genética , Albumina Sérica/genética , Albumina Sérica/metabolismo , Transdução de Sinais
4.
J Neurochem ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32162337

RESUMO

Pannexin-1 (Panx1) is a large pore membrane channel with unique conduction properties ranging from non-selective ion permeability to the extracellular release of signalling molecules. The release of ATP by Panx1 has been particularly well-characterized with implications in purine signalling across a variety of biological contexts. Panx1 activity is also important in inflammasome formation and the secretion of pro-inflammatory molecules such as interleukin-1ß. Within the central nervous system (CNS), Panx1 is expressed on both neurons and glia, and is thought to mediate crosstalk between these cells. A growing body of literature now supports the pathological activity of Panx1 in contributing to disease processes including seizure, stroke, migraine headache and chronic pain. Emerging evidence also reveals a physiological function of Panx1 in regulating neural stem cell survival, neuronal maturation and synaptic plasticity, with possible relevance to normal cognitive functioning. The aim of this review is to summarize the current evidence regarding the roles of Panx1 in the CNS, with emphasis on how putative signalling properties and activation mechanisms of this channel contribute to various physiological and pathophysiological processes.

5.
Neuron ; 106(1): 108-125.e12, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-31995730

RESUMO

Presynaptic neurexins (Nrxs) and type IIa receptor-type protein tyrosine phosphatases (RPTPs) organize synapses through a network of postsynaptic ligands. We show that leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) differentially engage the protein domains of Nrx but require its heparan sulfate (HS) modification to induce presynaptic differentiation. Binding to the HS of Nrx is sufficient for LRRTM3 and LRRTM4 to induce synaptogenesis. We identify mammalian Nrx1γ as a potent synapse organizer and reveal LRRTM4 as its postsynaptic ligand. Mice expressing a mutant form of LRRTM4 that cannot bind to HS show structural and functional deficits at dentate gyrus excitatory synapses. Through the HS of Nrx, LRRTMs also recruit PTPσ to induce presynaptic differentiation but function to varying degrees in its absence. PTPσ forms a robust complex with Nrx, revealing an unexpected interaction between the two presynaptic hubs. These findings underscore the complex interplay of synapse organizers in specifying the molecular logic of a neural circuit.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Giro Denteado/metabolismo , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Moléculas de Adesão de Célula Nervosa/genética , Neurônios/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Sinapses/metabolismo , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Giro Denteado/patologia , Heparitina Sulfato/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Sinapses/patologia
6.
J Biophotonics ; 13(4): e201960172, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31957205

RESUMO

Approaches for noninvasive bone quality assessment are of great clinical need, particularly in individuals that require close monitoring of disease progression. X-ray measurements are standard approaches to assess bone quality; however, they have several disadvantages. Here, a nonionizing approach for noninvasive assessment of the second metacarpal bone based on near infrared (NIR) spectroscopy was investigated. Transcutaneous bone signal detection was experimentally confirmed with cadaveric hand data, and Monte Carlo modeling further indicated that 50% of the measured signals arise from bone. Spectral data were collected via a NIR fiber optic from the bone of individuals with osteogenesis imperfecta, a disease marked by frequent bone fractures and fragility. Multiple significant correlations were found between spectral parameters related to water, protein and fat, and standard bone quality parameters obtained by X-ray measurements. The results from this preliminary study highlight the potential application of NIR spectroscopy for the noninvasive assessment of bone quality.

7.
J Glob Health ; 9(1): 010408, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30546869

RESUMO

Background: Lack of menstrual knowledge, poor access to sanitary products and a non-facilitating school environment can make it difficult for girls to attend school. In India, interventions have been developed to reduce the burden of menstruation for school girls by government and non-governmental organizations (NGOs). We sought to identify challenges related to menstruation, and facilitators of menstrual management in schools in three states in India. Methods: Surveys were conducted among menstruating school girls in class 8-10 (above 12 years of age) of 43 government schools selected through stratified random sampling in three Indian states (Maharashtra, Chhattisgarh, Tamil Nadu) in 2015. For comparison, ten model schools supported by NGOs or UNICEF with a focussed menstrual hygiene education program were selected purposely in the same states to represent the better-case scenario. We examined awareness about menarche, items used for menstruation, and facilitators on girls' experience of menstruation in regular schools and compared with model schools. Factors associated with school absence during menstruation were explored using multivariate analysis. Findings: More girls (mean age 14.1 years) were informed about menstruation before menarche in model schools (56%, n = 492) than in regular schools (36%, n = 2072, P < 0.001). Girls reported menstruation affected school attendance (6% vs 11% in model vs regular schools respectively, P = 0.003) and concentration (40% vs 45%, P = 0.1) and was associated with pain (31% vs 38%, P = 0.004) and fear of stain or smell (11% vs 16%, P = 0.002). About 45% of girls reported using disposable pads in both model and regular schools, but only 55% and 29% of pad-users reported good disposal facilities, respectively (P < 0.001). In multivariate analysis, reported absenteeism during menstruation was significantly lower in Tamil Nadu (adjusted prevalence ratio (APR) 95% confidence interval (CI) = 0.24, 0.14-0.40) and Maharashtra (APR 0.56, CI = 0.40-0.77) compared to Chhattisgarh, and halved in model compared to regular schools (APR 0.50, CI = 0.34-0.73). Pain medication in school (APR 0.71, CI = 0.51-0.97) and use of disposable pads (APR 0.57, CI = 0.42-0.77) were associated with lower absenteeism and inadequate sanitary facilities with higher absenteeism during menstruation. Conclusions: Menstrual hygiene education, accessible sanitary products, pain relief, and adequate sanitary facilities at school would improve the schooling-experience of adolescent girls in India.


Assuntos
Higiene , Menstruação , Instituições Acadêmicas/organização & administração , Absenteísmo , Adolescente , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Índia , Produtos de Higiene Menstrual/provisão & distribução , Setor Público , Inquéritos e Questionários
8.
Artigo em Inglês | MEDLINE | ID: mdl-29582850

RESUMO

Expanding mobile telephony in India has prompted interest in the potential of mobile-telephone health (mHealth) in linking health workers in rural areas with specialist medical advice and other professional services. In 2012, a toll-free helpline offering specialist medical advice to community-based health workers throughout Maharashtra was launched. Calls are handled via a 24 h centre in Pune, staffed by health advisory officers and medical specialists. Health advisory officers handle general queries, which include medical advice via validated algorithms; blood on-call services; grievance issues; and mental health support - the latter calls are transferred to a qualified counsellor. Calls requiring more specialist advice are transferred to the appropriate medical specialist. This paper describes the experience of the first 4 years of this helpline, in terms of the services used, callers, nature of calls, types of queries serviced and lessons learnt. In the first 4 years of the helpline, 669 265 calls were serviced. Of these calls, 453 373 (67.74%) needed medical advice and were handled by health advisory officers. Specialist services were required to address 199 226 (29.77%) calls. Blood-bank-related services accounted for 7919 (1.18%) calls, while 2462 (0.37%) were grievance calls. Counselling for mental health issues accounted for 6285 (0.94%) calls. The large-scale mHealth professional support provided by this helpline in Maharashtra has reached many health workers serving rural communities. Future work is required to explore ways to expand the reach of the helpline further and to measure its effectiveness in improving health outcomes.


Assuntos
Call Centers , Agentes Comunitários de Saúde/psicologia , Relações Interprofissionais , Serviços de Saúde Rural , Telemedicina/organização & administração , Agentes Comunitários de Saúde/estatística & dados numéricos , Feminino , Humanos , Índia , Masculino
9.
J Biophotonics ; 11(6): e201700188, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29411949

RESUMO

Renal mass biopsy is still controversial due to imperfect accuracy. Raman spectroscopy (RS) demonstrated promise as an in vivo real-time, nondestructive diagnostic tool in many malignancies. Short wave infrared (SWIR) RS has the potential to improve on previous RS systems for renal mass diagnosis. The aim of this study is to evaluate a SWIR RS system in differentiating normal and malignant renal samples. Measurements were acquired using a benchtop RS system with excitation wavelength at 1064 nm and an InGaAs array detector. Processed spectra were classified with a Bayesian machine learning algorithm, sparse multinomial logistic regression. Sensitivity and receiver operating characteristic curve analyses evaluated the classifier accuracy. Accuracy of the classifier was 92.5% with sensitivity and specificity of 95.8% and 88.8%, respectively. For posterior probability of malignant class assignment, the area under the ROC curve is 0.94 (95% confidence interval: 0.89-0.99, P < .001). SWIR RS accurately differentiated normal and malignant kidney tumors. RS has the potential to be used as a diagnostic tool in kidney cancer.


Assuntos
Raios Infravermelhos , Neoplasias Renais/patologia , Rim/citologia , Rim/patologia , Análise Espectral Raman , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/diagnóstico
10.
J Am Heart Assoc ; 6(10)2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29042425

RESUMO

BACKGROUND: The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system. METHODS AND RESULTS: In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system. CONCLUSIONS: Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term.


Assuntos
Pressão Arterial/efeitos dos fármacos , Terapia de Reposição Hormonal/efeitos adversos , Hipertensão/fisiopatologia , Testosterona/toxicidade , Adiposidade/efeitos dos fármacos , Fatores Etários , Envelhecimento , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Modelos Animais de Doenças , Enalapril/farmacologia , Estradiol/sangue , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Leptina/sangue , Masculino , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/deficiência , Ganho de Peso/efeitos dos fármacos
12.
Physiol Rep ; 5(20)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29051304

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive disorder in premenopausal women, characterized by hyperandrogenemia, metabolic syndrome, and inflammation. Women who had PCOS during their reproductive years remain hyperandrogenemic after menopause. The consequence of chronic hyperandrogenemia with advanced aging has not been studied to our knowledge. We have characterized a model of hyperandrogenemia in female rats and have aged them to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested the hypothesis that chronic exposure to hyperandrogenemia with aging has a deleterious effect on renal function. Female rats were chronically implanted with dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days or placebo pellets, and renal function was measured by clearance methods. Aging DHT-treated females had a threefold higher level of DHT with significantly higher body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT-treated-old females had a 60% reduction in glomerular filtration rate, 40% reduction in renal plasma flow, and significant reduction in urinary nitrate and nitrite excretion (UNOxV), an index of nitric oxide production. Morphological examination of kidneys showed that old DHT-treated females had significant focal segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis compared to controls. Thus chronic hyperandrogenemia that persists into old age in females is associated with renal injury. These data suggest that women with chronic hyperandrogenemia such as in PCOS may be at increased risk for development of chronic kidney disease with advanced age.


Assuntos
Envelhecimento/patologia , Hiperandrogenismo/fisiopatologia , Rim/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Animais , Moléculas de Adesão Celular/metabolismo , Feminino , Fibrose , Taxa de Filtração Glomerular , Rim/metabolismo , Rim/patologia , Ratos , Ratos Sprague-Dawley
13.
J Indian Prosthodont Soc ; 17(3): 295-300, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28936045

RESUMO

AIM: A comparative study for plaque removing efficacy between toothpaste, liquid handwashing soap, and two chemical-soak denture cleansers (clinsodent denture cleansing powder and fittydent denture cleansing tablet). MATERIALS AND METHODS: A total of 140 healthy complete denture patients were selected and checked for denture cleansing using toothpaste, liquid handwashing soap, and two chemical denture cleansers: Clinsodent powder and fittydent tablets. Cleansing with plain water was kept as control for twenty patients. RESULTS: The data were analyzed using Wilcoxon signed ranks test for checking the efficacy. The Kruskal-Wallis test was used for comparing the plaque removing efficacies of each denture cleanser used in the study. All four denture cleansers were significantly effective in removing plaque when compared with plain water, but there was no significant difference among them. CONCLUSIONS: There was no significant difference among action of four denture cleansers used in this study. Thus we can infer that patients can use liquid handwashing soap or commercial products to overcome disadvantages of toothpastes. Recommendation from the results of this study is the use of liquid handwashing soap for cleansing after every meal and soaking of the denture in commercial denture cleanser during the night.

14.
Clin Hemorheol Microcirc ; 67(2): 159-172, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28800323

RESUMO

BACKGROUND: Interaction of von Willebrand factor (VWF) with circulating platelets is the trigger for thrombosis in a region of arterial stenosis. These events are typically studied in vitro under conditions where platelets adhere to a VWF-coated surface. Our approach assesses platelet responses in the absence of adhesion. OBJECTIVE: To characterize extent of platelet activation and erythrocyte lysis in an artificial stenosis model. METHODS: Whole blood is perfused through a length of polyetheretherketone tubing that includes an artificial stenosis, comprising narrow-bore (89-381 µm) tubing. Secretion of [14C] serotonin and hemoglobin release was measured to evaluate platelet activation and hemolysis respectively at various perfusion rates and different stenosis dimensions. RESULTS: Platelet activation and erythrocyte lysis increased progressively with increasing perfusion rate and decreasing stenosis diameter; the length of the stenosis had negligible influence. Modest platelet activation (5-10% secretion of [14C] serotonin) occurred without significant erythrocyte lysis under a limited range of perfusion conditions (4-6 mL/min flow through a 127 µm stenosis). CONCLUSIONS: Our experimental approach mimics conditions in severe arterial stenosis or a mechanical heart valve. It could be a valuable aid in the development of novel drugs to treat arterial thrombosis and in the design of heart valves.


Assuntos
Análise Química do Sangue/métodos , Plaquetas/fisiologia , Eritrócitos/metabolismo , Ativação Plaquetária/fisiologia , Adesividade Plaquetária/fisiologia , Humanos , Estresse Mecânico
15.
Lung India ; 34(4): 341-348, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28671165

RESUMO

BACKGROUND: Mediastinum is a "Pandora's box" with many neoplastic and nonneoplastic lesions. The purpose of this study was to analyze our institutional experience of mediastinal lesions on fine-needle aspiration cytology (FNAC) and/or biopsy. MATERIALS AND METHODS: This study was an analysis of 144 patients who had undergone ultrasound-guided FNAC and/or core biopsy for mediastinal lesions. RESULTS: A total of 144 cases of suspected mediastinal masses were seen, and in 139 cases, tissue diagnosis was attempted. Out of 139 cases, 93 cases were neoplastic in nature (67%), 32 were nonneoplastic (23%), and 14 remained inconclusive (10%). Among neoplastic mediastinal lesions, metastatic carcinoma (37.4%) was the most common neoplastic lesion, followed by non-Hodgkin's lymphoma (12.2%), Hodgkin's lymphoma (7.1%), thymic lesions (3.5%), etc. Among nonneoplastic conditions, tuberculosis was the most common lesion (20.1%). An accurate tissue diagnosis was made in 89.9% cases by FNAC or core biopsy of mediastinal lesions in this study. Procedure-related mortality was nil. Complications were mostly minor and included chest pain in 24.5%, small pneumothorax in 13.6% requiring closed tube thoracostomy in 1.4%, and scanty hemoptysis in 9.3% cases. CONCLUSION: Neoplastic mediastinal lesions are more common than nonneoplastic lesions, with metastatic carcinoma being the most common cause followed by tuberculosis. A wide variety of lesions observed in this study stress on the importance of cytohistological diagnosis in all cases of mediastinal lesions for the final diagnosis and management planning. A guided FNAC or core biopsy is still accurate, well tolerated, and devoid of major complications.

16.
Lung India ; 34(2): 160-166, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28360465

RESUMO

Malignant pleural effusion (MPE) denotes an advanced malignant disease process. Most of the MPE are metastatic involvement of the pleura from primary malignancy at lung, breast, and other body sites apart from lymphomas. The diagnosis of MPE has been traditionally made on cytological examination of pleural fluid and/or histological examination of pleural biopsy tissue that still remains the initial approach in these cases. There has been tremendous advancement in the diagnosis of MPE now a day with techniques i.e. characteristic Ultrasound and computed tomography features, image guided biopsies, fluorodeoxyglucose-positron emission tomography imaging, thoracoscopy with direct biopsy under vision, tumor marker studies and immunocytochemical analysis etc., that have made possible an early diagnosis of MPE. The management of MPE still remains a challenge to pulmonologist and oncologist. Despite having various modalities with better tolerance such as pleurodesis and indwelling pleural catheters etc., for long-term control, all the management approaches remain palliative to improve the quality of life and reduce symptoms. While choosing an appropriate management intervention, one should consider the clinical status of the patient, life expectancy, overall cost, availability and comparative institutional outcomes, etc.

17.
Lung India ; 33(5): 502-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27625443

RESUMO

BACKGROUND: Medical thoracoscopy is a minimally invasive procedure used in diagnostic and therapeutic applications for pleural diseases. In this study, we describe our experience in the outcome and analysis of thoracoscopy in undiagnosed pleural effusion presenting to our center. MATERIALS AND METHODS: This is a prospective study conducted over last 2 years. We performed thoracoscopy in 129 cases of undiagnosed exudative pleural effusions using rigid thoracoscope. Clinical, radiological, cyto and histopathological data of the patients were collected prospectively and analyzed. RESULTS: The overall diagnostic yield of thoracoscopic pleural biopsy was 110/129 (85.2%) in patients with undiagnosed pleural effusion, and 19/129 (14.8%) patients remained unexplained. Histopathological diagnosis confirmed malignancy in 66.4% patients (both primary and metastatic pleural carcinoma), tuberculosis in 28.2%, others including parapneumonic effusion in 4 cases followed by multiple myeloma, lupus pleuritis, and pulmonary langerhans cell histiocytosis in one case each. Procedure-related mortality was nil. Minor complications related to the procedure include hemorrhage, subcutaneous emphysema, etc. CONCLUSION: Thoracoscopy is relatively a safe and well-tolerated procedure with high diagnostic accuracy in undiagnosed pleural effusions, decreasing the need of formal diagnostic thoracotomy. Every chest physician must, therefore, consider this procedure to decrease the time lag in achieving the final diagnosis and to initiate the treatment as early as possible.

18.
Am J Physiol Renal Physiol ; 311(2): F395-403, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27252490

RESUMO

Renal ischemia-reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 h postreperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R, and that acute low-dose testosterone is protective by the following: 1) increasing renal IL-10 and reducing TNF-α; 2) its effects on nitric oxide; and 3) reducing intrarenal T-cell infiltration. Rats were subjected to renal I/R, followed by intravenous infusion of vehicle or testosterone (20, 50, or 100 µg/kg) 3 h postreperfusion. Low-dose testosterone (20 µg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10, and reduced intrarenal TNF-α, whereas 50 µg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-α. A higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-α compared with other groups. Low-dose nitro-l-arginine methyl ester (1 mg·kg(-1)·day(-1)), given 2 days before I/R, prevented low-dose testosterone (20 µg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4(+) and CD8(+) T cells were significantly increased with I/R, but were attenuated with low-dose testosterone, as were effector T helper 17 cells. The present studies suggest that acute, low-dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T-cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than proinflammatory cytokines.


Assuntos
Interleucina-10/metabolismo , Nefropatias/prevenção & controle , Rim/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Linfócitos T/efeitos dos fármacos , Testosterona/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Creatina/sangue , Citocinas/biossíntese , Inibidores Enzimáticos/uso terapêutico , Nefropatias/patologia , Masculino , NG-Nitroarginina Metil Éster/uso terapêutico , Nitratos/sangue , Óxido Nítrico Sintase/antagonistas & inibidores , Nitritos/sangue , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Testosterona/administração & dosagem , Células Th17/efeitos dos fármacos
19.
Endocrinology ; 157(7): 2920-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27145003

RESUMO

Postmenopausal women who have had polycystic ovary syndrome (PCOS) and chronic hyperandrogenemia may be at a greater risk for cardiovascular disease than normoandrogenemic postmenopausal women. The cardiometabolic effect of chronic hyperandrogenemia in women with PCOS after menopause is unclear. The present study was performed to test the hypothesis that chronic hyperandrogenemia in aging female rats would have more deleterious effects on metabolic function, blood pressure, and renal function than in normoandrogenemic age-matched females. Female Sprague Dawley were implanted continuously, beginning at 4-5 weeks, with dihydrotestosterone (postmenopausal hyperandrogenemic female [PMHAF]) or placebo pellets (controls), and were studied at 13 months of age. Plasma DHT was 3-fold higher, and estradiol was 90% lower in PMHAF than controls. Body weights were higher; EchoMRI showed greater fat and lean mass; and computed tomography showed more sc and visceral adiposity in PMHAF, but with similar femur length compared with controls. Insulin resistance was present in PMHAF with higher plasma insulin, normal fasting blood glucose, abnormal oral glucose tolerance test, and higher nonfasting blood glucose. Blood pressure (radiotelemetry) was significantly higher and heart rate was lower, and renal function (glomerular filtration rate) was reduced by 40% in PMHAF. Thus the aging chronically hyperandrogenemic female rat is a new model of postmenopausal PCOS, which exhibits insulin resistance and visceral obesity, hypertension, and impairment in renal function. This new model provides a unique tool to study the deleterious effects of chronic androgen excess in postmenopausal females rats.


Assuntos
Glicemia/metabolismo , Hiperandrogenismo/metabolismo , Síndrome do Ovário Policístico/metabolismo , Pós-Menopausa , Animais , Peso Corporal/fisiologia , Doenças Cardiovasculares/metabolismo , Modelos Animais de Doenças , Feminino , Teste de Tolerância a Glucose , Resistência à Insulina/fisiologia , Ratos , Ratos Sprague-Dawley
20.
Am J Physiol Renal Physiol ; 311(1): F71-7, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27194719

RESUMO

In male rats, androgen supplements increase 20-hydroxyeicosatetraenoic acid (20-HETE) via cytochrome P-450 (CYP)4A ω-hydroxylase and cause an increase in blood pressure (BP). In the present study, we determined the roles of 20-HETE and CYP4A2 on the elevated BP in hyperandrogenemic female rats. Chronic dihydrotestosterone (DHT) increased mean arterial pressure (MAP) in female Sprague-Dawley rats (96 ± 2 vs. 108 ± 2 mmHg, P < 0.05) and was associated with increased renal microvascular CYP4A2 mRNA expression (15-fold), endogenous renal 20-HETE (5-fold), and ω-hydroxylase activity (3-fold). Chronic DHT also increased MAP in low salt-fed Dahl salt-resistant female rats (81 ± 4 vs. 95 ± 1 mmHg, P < 0.05) but had no effect on MAP in Dahl salt-sensitive female rats (154 ± 3 vs. 153 ± 3 mmHg), which are known to be 20-HETE deficient. To test the role of CYP4A2, female CYP4A2(-/-) and SS.5(Bn) (wild type) rats were treated with DHT. DHT increased MAP in SS.5(Bn) female rats (104 ± 1 vs. 128 ± 1 mmHg, P < 0.05) but had no effect in CYP4A2(-/-) female rats (118 ± 1 vs. 120 ± 1 mmHg). Renal microvascular 20-HETE was reduced in control CYP4A2(-/-) female rats and was increased with DHT in SS.5(Bn) female rats (6-fold) but not CYP4A2(-/-) female rats. ω-Hydroxylase activity was 40% lower in control CYP4A2(-/-) female rats than in SS.5(Bn) female rats, and DHT decreased ω-hydroxylase activity in SS.5(Bn) female rats (by 50%) but significantly increased ω-hydroxylase activity in CYP4A2(-/-) female rats (3-fold). These data suggest that 20-HETE via CYP4A2 contributes to the elevation in BP in hyperandrogenemic female rats. The data also suggest that 20-HETE synthesis inhibition may be effective in treating the elevated BP in women with hyperandrogenemia, such as women with polycystic ovary syndrome.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Ácidos Hidroxieicosatetraenoicos/metabolismo , Hiperandrogenismo/metabolismo , Hipertensão/metabolismo , Androgênios/toxicidade , Animais , Peso Corporal/genética , Sistema Enzimático do Citocromo P-450/genética , Di-Hidrotestosterona/toxicidade , Feminino , Deleção de Genes , Técnicas de Inativação de Genes , Ácidos Hidroxieicosatetraenoicos/genética , Hiperandrogenismo/genética , Hipertensão/genética , Microcirculação/genética , Ratos , Ratos Endogâmicos Dahl , Circulação Renal/genética , Esteroides/sangue
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