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1.
World J Urol ; 41(8): 2225-2232, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37358598

RESUMO

AIM: To compare the outcomes of two different protocols of antibiotic prophylaxis in patients with positive urine culture undergoing percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Patients were prospectively enrolled for the randomised study to either group A which included patients where an attempt to sterilise the urine was made with a 1 week course of sensitive antibiotics or group B that included patients who received a shorter duration of prophylaxis using sensitive antibiotics for 48 h prior to procedure which was continued for 48 h postoperatively. Enrolled patients had stones requiring percutaneous nephrolithotomy and had a positive preoperative urine culture. Primary outcome was difference in sepsis rates between the groups. RESULTS: A total of 80 patients randomised into two groups of 40 each based on the antibiotic protocol used were analysed in the study. There was no difference in infectious complication rates between groups on univariate analysis. The rate of SIRS in Group A and Group B was found to be 20% (N = 8) and 22.5% (N = 9) respectively. The rate of septic shock in Group A and Group B was 7.5% and 5% respectively. On multivariate analysis, longer duration of antibiotics did not decrease the risk of sepsis compared to shorter antibiotic course (p = 0.79). CONCLUSION: Attempts to sterilise urine before PCNL may not decrease the risk of sepsis in patients with positive urine culture undergoing PCNL and may only result in unnecessary prolonging of antibiotic usage thereby increasing the chances of antibiotic resistance.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Sepse , Humanos , Antibacterianos/uso terapêutico , Cálculos Renais/etiologia , Nefrolitotomia Percutânea/métodos , Nefrostomia Percutânea/métodos , Complicações Pós-Operatórias/etiologia , Sepse/etiologia
2.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443386

RESUMO

Coronary artery disease is the most common cause of heart disease and the single most important cause of premature death in the world.In 2001,CVD was responsible for 29% of all deaths and 14% of the 1.5 billion lost DALYs.By 2030,when population is expected to reach 8.2 billion,33%of all deaths will be caused by CVD. Over the last decade, cardiovascular disease(CVD) has become the single largest cause of death worldwide. Myocardial necrosis causes release of structural proteins and other intracellular macromolecules into the cardiac interstitium as a consequence of compromise of the integrity of cellular membranes. On the basis of improved sensitivity and superior tissue-specificity compared with the other available biomarkers of necrosis, cardiac troponin is the preferred biomarker for the detection of myocardial injury. Material and Objectives:

  • To determine the correlation between Troponin I with left ventricular ejection fraction in acute coronary syndrome.
Methodology:
  • Source of data: The patients with ACS, who gave written consent for the study, in the IP departments of General Medicine.
  • Study Design: Prospective observational study.
  • Sample size: 75.
Methods of Collection of Data:
  • The present study were conducted on patients diagnosed with ACS. Data regarding patient characteristics including age, sex, gender as well as history of chronic heart disease were collected. Patients evaluated during the hospital stay using daily ECG, troponin I, Ejection fraction of left ventricle measured using echocardiography at the 4th day of admission and catergorised as normal (>50%), mildly reduced(40-50%)and reduced(<40%) EF ced(<40%).
Observation: In this study the mean Troponin I is 8332.47 with a standard deviation of 8371.17. Minimum value is 23 and maximum value is 32000. Maximum Troponin I and Ejection Fraction has been correlated with a Pearson correlation coefficient -0.739,which concludes that Maximum troponin I and EF are highly negatively correlated with a significant p value of <0.001. Conclusion: The present study concludes that serum troponin I level has a strong negative correlation with the left ventricular ejection fraction in patients with acute coronary syndrome and hence can be used to predict the LVEF.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Síndrome Coronariana Aguda/diagnóstico , Biomarcadores , Humanos , Prognóstico , Volume Sistólico , Troponina I , Função Ventricular Esquerda
3.
J Mol Cell Cardiol ; 97: 295-305, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27208880

RESUMO

The AT1 receptor (AT1R) mediates the manifold actions of angiotensin II in the cardiovascular system. This study probed the molecular mechanisms that link altered redox status to AT1R expression in cardiac fibroblasts. Real-time PCR and western blot analysis showed that H2O2 enhances AT1R mRNA and protein expression via NADPH oxidase-dependent reactive oxygen species induction. Activation of NF-κB and AP-1, demonstrated by electrophoretic mobility shift assay, abolition of AT1R expression by their inhibitors, Bay-11-7085 and SR11302, respectively, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of AT1R by NF-κB and AP-1 in H2O2-treated cells. Further, inhibition of ERK1/2, p38 MAPK and c-Jun N-terminal kinase (JNK) using chemical inhibitors or by RNA interference attenuated AT1R expression. Inhibition of the MAPKs showed that while ERK1/2 and p38 MAPK suffice for NF-κB activation, all three kinases are required for AP-1 activation. H2O2 also increased collagen type I mRNA and protein expression. Interestingly, the AT1R antagonist, candesartan, attenuated H2O2-stimulated AT1R and collagen mRNA and protein expression, suggesting that H2O2 up-regulates AT1R and collagen expression via local Angiotensin II generation, which was confirmed by real-time PCR and ELISA. To conclude, oxidative stress enhances AT1R gene expression in cardiac fibroblasts by a complex mechanism involving the redox-sensitive transcription factors NF-κB and AP-1 that are activated by the co-ordinated action of ERK1/2, p38 MAPK and JNK. Importantly, by causally linking oxidative stress to Angiotensin II and AT1R up-regulation in cardiac fibroblasts, this study offers a novel perspective on the pathogenesis of cardiovascular diseases associated with oxidative stress.


Assuntos
Angiotensina II/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Animais , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Modelos Biológicos , NADPH Oxidases/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
J Mol Cell Cardiol ; 90: 59-69, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26674152

RESUMO

Delineation of mechanisms underlying the regulation of fibrosis-related genes in the heart is an important clinical goal as cardiac fibrosis is a major cause of myocardial dysfunction. This study probed the regulation of Discoidin Domain Receptor 2 (DDR2) gene expression and the regulatory links between Angiotensin II, DDR2 and collagen in Angiotensin II-stimulated cardiac fibroblasts. Real-time PCR and western blot analyses showed that Angiotensin II enhances DDR2 mRNA and protein expression in rat cardiac fibroblasts via NADPH oxidase-dependent reactive oxygen species induction. NF-κB activation, demonstrated by gel shift assay, abolition of DDR2 expression upon NF-κB inhibition, and luciferase and chromatin immunoprecipitation assays confirmed transcriptional control of DDR2 by NF-κB in Angiotensin II-treated cells. Inhibitors of Phospholipase C and Protein kinase C prevented Angiotensin II-dependent p38 MAPK phosphorylation that in turn blocked NF-κB activation. Angiotensin II also enhanced collagen gene expression. Importantly, the stimulatory effects of Angiotensin II on DDR2 and collagen were inter-dependent as siRNA-mediated silencing of one abolished the other. Angiotensin II promoted ERK1/2 phosphorylation whose inhibition attenuated Angiotensin II-stimulation of collagen but not DDR2. Furthermore, DDR2 knockdown prevented Angiotensin II-induced ERK1/2 phosphorylation, indicating that DDR2-dependent ERK1/2 activation enhances collagen expression in cells exposed to Angiotensin II. DDR2 knockdown was also associated with compromised wound healing response to Angiotensin II. To conclude, Angiotensin II promotes NF-κB activation that up-regulates DDR2 transcription. A reciprocal regulatory relationship between DDR2 and collagen, involving cross-talk between the GPCR and RTK pathways, is central to Angiotensin II-induced increase in collagen expression in cardiac fibroblasts.


Assuntos
Angiotensina II/farmacologia , Colágeno Tipo I/genética , Fibroblastos/efeitos dos fármacos , Miocárdio/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Mitogênicos/genética , Angiotensina II/genética , Angiotensina II/metabolismo , Animais , Colágeno Tipo I/antagonistas & inibidores , Colágeno Tipo I/metabolismo , Receptores com Domínio Discoidina , Inibidores Enzimáticos/farmacologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Masculino , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miocárdio/citologia , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Cultura Primária de Células , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Mitogênicos/antagonistas & inibidores , Receptores Mitogênicos/metabolismo , Transdução de Sinais , Transcrição Gênica , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Am J Physiol Heart Circ Physiol ; 306(6): H844-55, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24441545

RESUMO

Cardiac fibroblast hyperplasia associated with enhanced matrix deposition is a major determinant of tissue remodeling in several disease states of the heart. However, mechanisms controlling cell cycle progression in cardiac fibroblasts remain unexplored. Identification of cell cycle regulatory elements in these cells is important to develop strategies to check adverse cardiac remodeling under pathological conditions. This study sought to probe the mechanisms underlying ERK1/2-mediated p27(Kip1) regulation in mitogenically stimulated cardiac fibroblasts. Addition of 10% fetal calf serum to quiescent cultures of adult rat cardiac fibroblasts promoted ERK1/2 activation, as evidenced by its phosphorylation status. Reduction in [(3)H]thymidine incorporation into DNA increased population doubling time, flow cytometry, and Western blot analysis showing reduced levels of cyclins D and A, p27(Kip1) induction, and retinoblastoma protein (Rb) hypophosphorylation in ERK1/2-inhibited cells indicated ERK1/2 dependence of G1-S transition in cardiac fibroblasts. Lack of p27(Kip1) protein in serum-stimulated, ERK1/2-active cells was associated with increased levels of Skp2, an E3 ubiquitin ligase for p27(Kip1), whose knockdown by RNA interference induced p27(Kip1) expression. Further, forced expression of Skp2 in ERK1/2-inhibited cells downregulated p27(Kip1). Transcriptional upregulation of p27(Kip1) mRNA in ERK1/2-inhibited cells, demonstrated by real-time PCR, correlated with forkhead box O 3a (FOXO3a) transcription factor activation, shown by gel shift assay. FOXO3a knockdown attenuated p27(Kip1) mRNA and protein expression in ERK1/2-inhibited cells. We provide evidence for the first time that, in cardiac fibroblasts, activated ERK1/2 regulates p27(Kip1) expression transcriptionally and posttranslationally via FOXO3a- and Skp2-dependent mechanisms. Additionally, this study uncovers interesting interactions between critical cell cycle regulatory elements that are only beginning to be understood.


Assuntos
Inibidor de Quinase Dependente de Ciclina p27/fisiologia , Fibroblastos/fisiologia , Fatores de Transcrição Forkhead/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Miócitos Cardíacos/fisiologia , Proteínas Quinases Associadas a Fase S/fisiologia , Animais , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Proteína Forkhead Box O3 , Masculino , Mitógenos/farmacologia , Modelos Animais , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley
7.
Endocr Pract ; 25(6): 624, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30289306
8.
Ann Afr Med ; 23(1): 70-75, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358174

RESUMO

Background The I-LMA ventilates while providing a port for blind insertion of an endotracheal tube. The ILMA Fastrach is used especially for intubating in a difficult airway scenario. Its accompanying endotracheal tube is not economical nor readily available. In comparison, two alternative endotracheal tubes - polyvinyl chloride and wire-reinforced tubes were used for tracheal intubation through the ILMA. AIMS AND OBJECTIVES: The aim of our study was to compare the ease of intubation when using conventional PVC tubes versus the wire-reinforced flexometallic tubes with the ILMA-FastrachTM. The number of attempts, time taken and additional maneuvers were noted. Intra-operative hemodynamic changes, post-operative sore throat, bleeding and hoarseness of voice was recorded over a period of 24 hours. METHODOLOGY: After informed consent, 60 ASA I-II patients undergoing elective surgeries under general anesthesia were allocated to undergo blind intubation with the PVC tube or the wire-reinforced flexometallic tube. RESULTS: More attempts were required for successful intubation using the wire-reinforced tube than the PVC tube with 76.7% passing in the first attempt in the PVC, and 53.3% passing in the first attempt in the flexometallic group. (P = 0.4). Average time for intubation in the PVC group: 28.24 ± 7.22 seconds. Average time for intubation in the flexometallic tube: 45.8 ± 15.78 sec. Occurrence of post-operative sore throat was 13.3% in the PVC group and 26.6% in the flexometallic group, with minimal hoarseness of voice 3.3% in the PVC group and 10% in the flexometallic group. There was also a slightly higher hemodynamic response in those who were intubated with the flexometallic tube than a PVC tube. CONCLUSION: Intubating via the ILMA-Fastrach with the PVC tube offered better intubating conditions with regards to lesser time taken, lesser attempts, less manipulation, and less hemodynamic variations as compared to the patients who were intubated using the wire-reinforced tube.


Résumé Arrière-plan: L'I-LMA ventile tout en fournissant un port pour l'insertion aveugle d'une sonde endotrachéale. L'ILMA Fastrach est utilisé notamment pour l'intubation dans un scénario de voies respiratoires difficiles. La sonde endotrachéale qui l'accompagne n'est ni économique ni facilement disponible. En comparaison, deux tubes endotrachéaux alternatifs ­ du chlorure de polyvinyle et des tubes renforcés de fil ­ ont été utilisés pour l'intubation trachéale via l'ILMA. Buts et objectifs: Le but de notre étude était de comparer la facilité d'intubation lors de l'utilisation de tubes en PVC conventionnels par rapport aux tubes flexométalliques renforcés de fil avec l'ILMA-FastrachTM. Le nombre de tentatives, le temps nécessaire et les manÓuvres supplémentaires ont été notés. Les changements hémodynamiques peropératoires, les maux de gorge postopératoires, les saignements et l'enrouement de la voix ont été enregistrés sur une période de 24 heures. Méthodologie: Après consentement éclairé, 60 patients ASA I-II subissant des interventions chirurgicales électives sous anesthésie générale ont été affectés à une intubation aveugle avec le tube en PVC ou le tube flexométallique renforcé de fil. Résultats: Plus de tentatives ont été nécessaires pour réussir l'intubation à l'aide du tube renforcé par fil métallique qu'avec le tube PVC, avec 76,7 % de réussite lors de la première tentative dans le groupe PVC et 53,3 % de réussite lors de la première tentative dans le groupe flexométallique. (P = 0,4). Temps moyen d'intubation dans le groupe PVC : 28,24 ± 7,22 secondes. Temps moyen d'intubation dans le tube flexométallique : 45,8 ± 15,78 sec. La survenue de maux de gorge postopératoires était de 13,3 % dans le groupe PVC et de 26,6 % dans le groupe flexométallique, avec un enrouement minime de la voix de 3,3 % dans le groupe PVC et de 10 % dans le groupe flexométallique. Il y avait également une réponse hémodynamique légèrement plus élevée chez ceux qui étaient intubés avec le tube flexométallique qu'avec un tube en PVC. Conclusion: L'intubation via l'ILMA-Fastrach avec le tube en PVC offrait de meilleures conditions d'intubation en ce qui concerne moins de temps, moins de tentatives, moins de manipulations et moins de variations hémodynamiques par rapport aux patients intubés à l'aide du tube renforcé de fil Mots-clés: Facilité d'intubation, sonde endotrachéale flexométallique, masque laryngé d'intubation des voies respiratoires, sonde endotrachéale en polychlorure de vinyle.


Assuntos
Máscaras Laríngeas , Faringite , Humanos , Máscaras Laríngeas/efeitos adversos , Cloreto de Polivinila , Rouquidão/etiologia , Intubação Intratraqueal/efeitos adversos , Faringite/etiologia
9.
Front Endocrinol (Lausanne) ; 15: 1416668, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948520

RESUMO

Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively.


Assuntos
Retinopatia Diabética , Terapia de Alvo Molecular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Animais , Terapia de Alvo Molecular/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
J Mol Cell Cardiol ; 62: 217-26, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23837962

RESUMO

Cardiac fibroblasts are resistant to several pro-apoptotic factors that prevail in the diseased myocardium. Resistance to death signals may, in the short-term, enable these cells to play a central role in tissue repair following myocyte loss but, in the long-term, facilitate their persistence in the infarct scar, resulting in disproportionate stromal growth and pump dysfunction. Surprisingly, the molecular basis of apoptosis resistance in cardiac fibroblasts remains unclear. We explored the recruitment of anti-apoptotic mechanisms in cardiac fibroblasts subjected to oxidative stress, a major component of ischemia-reperfusion injury and heart failure. Cardiac fibroblasts exposed to H2O2 expressed enhanced levels of anti-apoptotic cIAP-2 mRNA and protein, revealed by real time PCR and western blot analysis, respectively. Pulmonary fibroblasts did not express cIAP-2 and were more susceptible than cardiac fibroblasts to H2O2. cIAP-2 knockdown by RNA interference promoted apoptosis in H2O2-treated cardiac fibroblasts. Electrophoretic mobility shift assay showed NF-κB activation in cells under oxidative stress. NF-κB inhibition in H2O2-treated cells resulted in significant attenuation of cIAP-2 mRNA and protein expression and apoptosis, indicating involvement of NF-κB in cell survival via regulation of cIAP-2. Further, pCMV promoter-driven constitutive expression of cIAP-2 reduced viability loss in NF-κB-inhibited cardiac fibroblasts exposed to oxidative stress. H2O2 also caused ERK1/2 activation, which, upon inhibition, prevented IκBα degradation and nuclear translocation of NF-κB. Moreover, ERK1/2 inhibition attenuated H2O2-induced cIAP-2 expression and compromised viability in H2O2-treated cardiac fibroblasts. We propose for the first time that ERK1/2-dependent activation of NF-κB and consequent induction of cIAP-2 protects cardiac fibroblasts from oxidative damage.


Assuntos
Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Células Cultivadas , Ensaio de Desvio de Mobilidade Eletroforética , Peróxido de Hidrogênio/farmacologia , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
11.
Theranostics ; 13(7): 2241-2255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153730

RESUMO

Diabetic retinopathy (DR) is associated with retinal neovascularization, hard exudates, inflammation, oxidative stress and cell death, leading to vision loss. Anti-vascular endothelial growth factor (Anti-VEGF) therapy through repeated intravitreal injections is an established treatment for reducing VEGF levels in the retina for inhibiting neovascularization and leakage of hard exudates to prevent vision loss. Although anti-VEGF therapy has several clinical benefits, its monthly injection potentially causes devastating ocular complications, including trauma, intraocular hemorrhage, retinal detachment, endophthalmitis, etc. Methods: As mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) demonstrated safety in clinical studies, we have tested the efficacy of MSC-derived small EVs (MSC-sEVs) loaded anti-VEGF drug bevacizumab in a rat model of DR. Results: The study identified a clinically significant finding that sEV loaded with bevacizumab reduces the frequency of intravitreal injection required for treating diabetic retinopathy. The sustained effect is observed from the reduced levels of VEGF, exudates and leukostasis for more than two months following intravitreal injection of sEV loaded with bevacizumab, while bevacizumab alone could maintain reduced levels for about one month. Furthermore, retinal cell death was consistently lower in this period than only bevacizumab. Conclusion: This study provided significant evidence for the prolonged benefits of sEVs as a drug delivery system. Also, EV-mediated drug delivery systems could be considered for clinical application of retinal diseases as they maintain vitreous clarity in the light path due to their composition being similar to cells.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Vesículas Extracelulares , Animais , Ratos , Bevacizumab/uso terapêutico , Injeções Intravítreas , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese , Anticorpos Monoclonais Humanizados , Diabetes Mellitus/tratamento farmacológico
12.
Exp Cell Res ; 317(7): 899-909, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21211536

RESUMO

Cardiac fibroblasts are reported to be relatively resistant to stress stimuli compared to cardiac myocytes and fibroblasts of non-cardiac origin. However, the mechanisms that facilitate their survival under conditions of stress remain unclear. We explored the possibility that NF-κB protects cardiac fibroblasts from hypoxia-induced cell death. Further, we examined the expression of the antiapoptotic cIAP-2 and Bcl-2 in hypoxic cardiac fibroblasts, and their possible regulation by NF-κB. Phase contrast microscopy and propidium iodide staining revealed that cardiac fibroblasts are more resistant than pulmonary fibroblasts to hypoxia. Electrophoretic Mobility Shift Assay showed that hypoxia activates NF-κB in cardiac fibroblasts. Supershift assay indicated that the active NF-κB complex is a p65/p50 heterodimer. An I-κB-super-repressor was constructed that prevented NF-κB activation and compromised cell viability under hypoxic but not normoxic conditions. Similar results were obtained with Bay 11-7085, an inhibitor of NF-κB. Western blot analysis showed constitutive levels of Bcl-2 and hypoxic induction of cIAP-2 in these cells. NF-κB inhibition reduced cIAP-2 but not Bcl-2 levels in hypoxic cardiac fibroblasts. The results show for the first time that NF-κB is an important effector of survival in cardiac fibroblasts under hypoxic stress and that regulation of cIAP-2 expression may contribute to its pro-survival role.


Assuntos
Sobrevivência Celular/fisiologia , Fibroblastos/fisiologia , Hipóxia/metabolismo , Miócitos Cardíacos/fisiologia , NF-kappa B/antagonistas & inibidores , Animais , Caspase 3/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Nitrilas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Sulfonas/farmacologia
13.
J Cancer Res Ther ; 18(Supplement): S239-S243, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510971

RESUMO

Background: Oral cavity cancer is estimated to be the third most common malignancy after cancer of cervix and stomach in developing countries. Objectives: The objective of this study is to investigate the relationship between smoking, alcoholic consumption, betel quid chewing, and OPMD in a prospective manner. Materials and Methods: A descriptive, cross-sectional study was conducted among 35-55-year-old adults of Western Maharashtra, India. Oral cavity examination as recommended by the American Dental Association specification was followed. Data recorded were transferred from precoded survey pro forma to the computer. The prevalence of OPMD was assessed by determining the percentage of the study population affected. Analysis was done to find out the risk of oral premalignant disorders. The Chi-square (x2) test and adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated. The Statistical Package for the Social Sciences (SPSS) software version 21.0 was used for the statistical analysis and significance level was set at P < 0.05. Results: Odds of having OPMD are five times higher for those who smoke (OR = 5.78; 95% CI, [6.18, 7.82]) as compared to those who do not. The odds of suffering from OPMD are about five times higher among those who chew as compared to those who do not (OR = 4.98; 95%CI, [2.91, 7.28]). The mean frequency of tobacco chewing per day and duration in years in participants with OPMDs was significantly higher as compared with normal oral mucosa (P < 0.05 and P < 0.05), respectively, in the use of different tobacco forms. Conclusion: These findings can be used to design case control or cohort studies to further understand the relation between habits and OPMD.


Assuntos
Consumo de Bebidas Alcoólicas , Lesões Pré-Cancerosas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Estudos Prospectivos , Fatores de Risco , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Índia/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Prevalência , Areca/efeitos adversos
14.
J Pediatr Urol ; 17(4): 546.e1-546.e8, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33931319

RESUMO

BACKGROUND: Urogenital tuberculosis (UGTB) has traditionally being a diagnosis of adulthood and is supposed to be rare in children, as it is believed that the symptoms of renal tuberculosis do not appear for 10 or more years after the primary infection. While this may be true in developed countries, where childhood pulmonary tuberculosis is a rarity nowadays. In developing countries, childhood pulmonary tuberculosis is still a major issue and hence, UGTB is not an uncommon diagnosis in younger children and adolescents in these countries. Considering this dearth of data on childhood UGTB, we retrospectively evaluated our series of children with this disease, with special emphasis on the role of surgery. OBJECTIVE: To analyze the clinical presentation, management strategies and outcomes of pediatric UGTB managed in a tertiary care center. MATERIALS AND METHODS: Case records of children and adolescents ≤18 years diagnosed with UGTB during the period July 1998 to June 2018 at our center were reviewed. Clinical features, organ involvement, investigations, treatment and outcome of therapy were studied. RESULTS: There were 41 children and adolescents (M: F = 22:19) identified, with a mean age of 14.8 ± 3.9 years who fulfilled the inclusion criteria. The most common presentation was flank pain and irritative storage symptoms. Mycobacterium tuberculosis was identified on urinary examination in only 17 (41.5%) cases. Six patients were lost to follow up after initial diagnosis. A total of 45 procedures (35 primary and 10 secondary) were performed in 35 children. Initial diversion in the form of PCN and DJS were done in 11 and 12 patients respectively, of which 8 were managed with stenting alone. Surgical management was done mostly in the form of nephrectomy (15), nephrectomy along with reconstruction (5) and reconstruction only (6). On univariate analysis, factors associated with nephrectomy were poor initial function and nephrostomy as initial diversion. Overall median follow-up was 25 (IQR 15.5-74.25) months. During follow up, chronic renal failure developed in nearly 53.8% of patients who underwent major reconstruction. CONCLUSIONS: Urogenital tuberculosis presents with a wide spectrum of clinical features and pathological lesions. Diagnosis is often delayed because of late presentation and many children present with cicatrization sequelae. Antitubercular drug therapy and judicious application of minimally invasive diversions and surgery (both ablative and reconstructive) achieve satisfactory results in the majority of cases. Children undergoing major surgical reconstruction in particular need to be followed up rigorously and counselled about possibility of development of renal failure.


Assuntos
Tuberculose Urogenital , Adolescente , Adulto , Criança , Cicatriz , Humanos , Nefrectomia , Estudos Retrospectivos , Stents , Tuberculose Urogenital/diagnóstico , Tuberculose Urogenital/epidemiologia , Tuberculose Urogenital/terapia
15.
BMJ Case Rep ; 14(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782373

RESUMO

In India, bee stings are very common, seen mainly in farmers and honey collectors. Usually, it presents with local reactions and anaphylaxis. It rarely requires urgent hospitalisation. Other major complications seen are acute renal failure, intravascular coagulation, rhabdomyolysis and acute pulmonary oedema. Stroke as a presentation is uncommon. We report a case of a 45-year-old man presenting with right-sided hemiplegia and aphasia due to multiple bee stings. Diffusion MRI showed left middle cerebral artery territory hyperacute infarct.


Assuntos
Anafilaxia , Venenos de Abelha , Mordeduras e Picadas de Insetos , Acidente Vascular Cerebral , Animais , Abelhas , Imagem de Difusão por Ressonância Magnética , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/etiologia , Mordeduras e Picadas de Insetos/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia
16.
Epilepsy Behav ; 19(3): 301-5, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20728411

RESUMO

Psychiatric disorders are a source of significant comorbidity in patients with refractory epilepsy, yet are often underrecognized. We assessed the prevalence of DSM-IV Axis I psychiatric disorders using a short structured clinical interview (Mini-International Psychiatric Interview [MINI]) in patients with medically refractory complex partial seizures. Consecutive patients with refractory epilepsy being evaluated with video/EEG monitoring and imaging for seizure focus localization and lateralization underwent MINI evaluation to assess for the presence of psychiatric disorders. Among 117 patients (74 male, 43 female) studied, 57 (48.7%) had at least one psychiatric disorder; 19 (16.2%) had depression, 10 (8.5%) dysthymia, 27 (23.0%) anxiety disorder, and 11(9.4%) other disorders. Most clinical features and epilepsy-related variables had no significant association with psychiatric disorder on logistic regression analysis. Almost half of the patients with refractory focal seizures have a coexistent psychiatric disorder, and its presence or absence cannot be predicted by their clinical profiles. All patients should be assessed and treated for psychiatric comorbidity to improve overall quality of life.


Assuntos
Epilepsia Parcial Complexa/complicações , Epilepsia Parcial Complexa/epidemiologia , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estatística como Assunto , Adulto Jovem
17.
Urology ; 141: e35-e36, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32305551

RESUMO

Renal replacement lipomatosis is a rare condition characterized by extensive fat deposition in hilum with parenchymal thinning and progressive detoriation of function.1-4 Though uncommon, it should be considered as a possibility in patients with history of intervention for stone disease.5,6 Correct diagnosis can be easily established by cross sectional imaging and is helpful to counsel patients about the possibility of progressive functional detoriation and poor salvageability of the affected kidneys.7-10 Here, we present 2 patients with previous history of intervention for calculus disease who had developed progressive renal damage due to RRL with one patient ultimately needing nephrectomy.


Assuntos
Cálculos Renais/complicações , Nefropatias/complicações , Lipomatose/complicações , Adulto , Progressão da Doença , Feminino , Humanos , Nefropatias/diagnóstico , Lipomatose/diagnóstico , Masculino
18.
J Family Med Prim Care ; 9(5): 2244-2247, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32754481

RESUMO

INTRODUCTION: Cancer is considered as a serious health problem in public with an increasing number of cancer patients reported every year hence public health awareness/knowledge on oral cancers oral potentially malignant disorders (OPMDs) and their risk factors is crucial for prevention and early detection of OPMD and it is important to prevent transformation of oral cancer. MATERIALS AND METHODS: A cross-sectional survey with an interviewer-administered questionnaire was conducted. The questionnaire consists of relevant questions to ascertain sociodemographic information, awareness, and knowledge of Oral cancer and OPMDs, and their associated risk factors, and participants exposure to risk factors. Subjects above the age of 20 years (n = 200) were randomly selected, and the questionnaires were administered by the interviewer while they were waiting for treatment. RESULTS: Results showed lack of awareness for OPMDs based on the evaluation of the questionnaires for sociodemographic data. CONCLUSION: Awareness about oral cancer is relatively significant; however, for OPMDs, awareness is low in our study and the subjects were unaware of the risk factors. So a high level of public awareness and knowledge of OPMDs should be brought to people via mass media as it is a very effective source of information. Early detection of oral cancer is the most effective means to improve survival and to reduce morbidity.

19.
Eur J Obstet Gynecol Reprod Biol ; 250: 231-234, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32480169

RESUMO

Ehlers-Danlos syndrome (EDS) is one of the commonest inheritable connective tissue disorders (CTD) affecting one in 5000 people globally. The incidence of bladder diverticula (BD) is reported to be 1.7% seen more commonly in children without any bladder outlet obstruction. BD are associated with congenital syndromes, namely, EDS. We report a case of huge BD in pregnancy that became symptomatic as the pregnancy progressed to term with urinary retention, recurrent urinary infections and fetal malpresentation. The patient was taken for elective Lower segment cesarean section (LSCS) wherein intra-operative findings of soft abdominal wall, velvety and jelly-like rectus muscle made us suspect connective tissue disorder. A thorough retrospective evaluation of medical history, physical examination along with orthopedic evaluation led to the diagnosis of EDS. To the best of our knowledge, this is the first case report of EDS with huge BD in pregnancy.


Assuntos
Divertículo , Síndrome de Ehlers-Danlos , Cesárea , Criança , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia , Síndrome de Ehlers-Danlos/complicações , Síndrome de Ehlers-Danlos/diagnóstico , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Bexiga Urinária/anormalidades , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/cirurgia
20.
J Oral Maxillofac Pathol ; 24(2): 273-278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33456236

RESUMO

BACKGROUND: Odontogenic keratocyst (OKC) is a benign intraosseous lesions (within the jaw bone) of odontogenic origin that account for about 10% of jaw cysts. They are characterized by an aggressive behavior with a relatively high recurrence rate. Early diagnosis and follow-up of the patient with OKC is important because the possibility of such patient there is develop to other features of Nevoid basal cell carcinoma syndrome in future. Considering the roles and effects of p53, p63 and proliferating cell nuclear antigen (PCNA) in cells proliferation, this study was designed. OBJECTIVES: To understand the behavior of epithelial cells in pathogenesis and biological aspects of OKC in diagnosis. MATERIALS AND METHODS: Immunohistochemical (IHC)technique was performed in 21 cases of OKCs. RESULTS: Immunological stained p53 cells were mainly located in the suprabasal layers. p63 and PCNA-positive cells were found throughout the lining epithelium including basal and suprabasal cell layers. The intensity of staining was more in p63 and PCNA than the p53 expression of the cystic epithelial lining. CONCLUSIONS: It is possible that the biological behavior of OKCs may be related to the suprabasal proliferative compartment in the cystic epithelium as observed. These proteins may participate in the regulation of epithelial cell differentiation. Taken together, these data may favor tumerigenesis on OKCs.

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