RESUMO
The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κß and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κß, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κß, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.
Assuntos
Curcumina/análogos & derivados , Curcumina/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Piperazinas/administração & dosagem , Sulfonamidas/administração & dosagem , Animais , Disponibilidade Biológica , Curcumina/farmacocinética , GMP Cíclico/análise , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Estimulação Elétrica , Disfunção Erétil/etiologia , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Masculino , NF-kappa B/análise , Óxido Nítrico Sintase/metabolismo , Pênis/química , Pênis/enzimologia , Pênis/inervação , Pressão , Purinas/administração & dosagem , Ratos , Citrato de Sildenafila , Solubilidade , ÁguaRESUMO
OBJECTIVE: To study the effect of mesenchymal stem cells (MSC) on experimental liver fibrosis in rats. DESIGN AND METHOD: MSC were derived from bone marrow obtained from femoral and tibial bones of male albino rats. MSC were separated, grown, and propagated in culture for 4 weeks and were characterized morphologically and by detection of CD29 by RT-PCR. They were then infused into the tail vein of female rats that received CCl4 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and MSC. Liver tissue was examined histopathologically and liver functions (ALT and serum albumin) were estimated for all groups. Y-chromosome gene (sry) was assessed by PCR in liver tissue of the female rats to confirm uptake of the male stem cells. Hydroxyproline content in liver tissue was assessed by chemical methods and expression of the collagen gene (type I) was detected as a marker for liver fibrosis. Results of the present study showed that MSC have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in hydroxyproline content in the CCl4/MSC group (p<0.001) compared to the CCl4 group. The Y-chromosome gene (sry) was detected by RT-PCR in the CCl4/MSC group, but was not detected in control group and other groups. The CD29 gene was expressed in MSC culture, and this confirmed the efficiency of isolation and propagation of MSC in culture. With regard to liver function, there was also a significant improvement and elevation of serum albumin in the CCl4/MSC group compared to the CCl4 group (p<0.05). As regard to the liver enzyme ALT, there was a decrease of its level in the CCl4/MSC group compared to the CCl4 group. However, this was statistically nonsignificant (p>0.05). In conclusion, MSC have a potential therapeutic effect against the fibrotic process through their effect in minimizing collagen deposition in addition to their capacity to differentiate into hepatocytes.
Assuntos
Células da Medula Óssea/citologia , Terapia Baseada em Transplante de Células e Tecidos , Cirrose Hepática Experimental/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Actinas/genética , Animais , Colágeno/genética , Feminino , Regulação da Expressão Gênica , Hidroxiprolina/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Cirrose Hepática Experimental/fisiopatologia , Testes de Função Hepática , Masculino , Ratos , Proteína da Região Y Determinante do Sexo/genéticaRESUMO
The relationship between essential fatty acid (EFA) status and degree of hyperbilirubinaemia and oxidant stress in infants and children with chronic liver diseases was evaluated. Thirty patients with chronic cholestasis and 30 with liver cirrhosis were examined; 30 healthy subjects served as controls. Patient groups had significant decreases in EFAs and significant elevation of total bilirubin. Levels of thiobarbituric acid reactive substances were significantly raised and were significantly inversely correlated to decreased EFA levels. There were also significant decreases in retinol, alpha-tocopherol and alpha-tocopherol/total lipids ratio, which had significant positive correlations with decreased EFA levels. Infants and children with chronic liver diseases have a high risk of EFA deficiency correlated with progressive elevation of serum bilirubin and progressive deterioration of oxidant status.
Assuntos
Colestase/metabolismo , Ácidos Graxos Essenciais , Cirrose Hepática/metabolismo , Adolescente , Atresia Biliar/complicações , Bilirrubina/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Colestase/etiologia , Doença Crônica , Egito , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Essenciais/deficiência , Feminino , Doença de Depósito de Glicogênio Tipo III/complicações , Hepatopatia Veno-Oclusiva/complicações , Hepatite Crônica/complicações , Degeneração Hepatolenticular/complicações , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/etiologia , Cirrose Hepática/etiologia , Masculino , Estresse Oxidativo/fisiologia , Veia Porta , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Trombose Venosa/complicações , Vitamina A/sangue , Deficiência de alfa 1-Antitripsina/complicações , alfa-Tocoferol/sangueRESUMO
The relationship between essential fatty acid [EFA] status and degree of hyperbilirubinaemia and oxidant stress in infants and children with chronic liver diseases was evaluated. Thirty patients with chronic cholestasis and 30 with liver cirrhosis were examined; 30 healthy subjects served as controls. Patient groups had significant decreases in EFAs and significant elevation of total bilirubin. Levels of thiobarbituric acid reactive substances were significantly raised and were significantly inversely correlated to decreased EFA levels. There were also significant decreases in retinol, alpha-tocopherol and alpha-tocopherol/total lipids ratio, which had significant positive correlations with decreased EFA levels. Infants and children with chronic liver diseases have a high risk of EFA deficiency correlated with progressive elevation of serum bilirubin and progressive deterioration of oxidant status
Assuntos
Atresia Biliar , Bilirrubina , Estudos de Casos e Controles , Pré-Escolar , Doença Crônica , Ácidos Graxos Essenciais , Doença de Depósito de Glicogênio Tipo III , Hepatopatia Veno-Oclusiva , Hiperbilirrubinemia , Estresse Oxidativo , ColestaseRESUMO
The role of homocysteine as an independent risk factor for vascular endothelial damage, and the possible link between homocysteine and tumour necrosis factor-alpha (TNF-alpha) as two synergistic risk factors for beta-cell apoptosis in type 1 diabetes mellitus was studied. Plasma homocysteine levels were significantly elevated in all diabetic patients compared with controls and diabetic patients with vascular complications showed higher elevations. Furthermore, homocysteine levels showed significant positive correlation with the degree of microalbuminuria. TNF-alpha levels were elevated in all diabetic patients compared with controls. These results may have therapeutic implications.
Assuntos
Diabetes Mellitus Tipo 1 , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Albuminúria/etiologia , Apoptose/fisiologia , Estudos de Casos e Controles , Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Angiopatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Egito/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/etiologia , Hiper-Homocisteinemia/prevenção & controle , Ilhotas Pancreáticas/metabolismo , Masculino , Fatores de TempoRESUMO
The ratio of stearic to oleic acids, i.e. the fatty acid saturation index, in red blood cell membranes was assayed in 60 patients with chronic hepatitis C virus infection before and after interferon-alpha therapy. Results were compared with 20 healthy controls. Hepatitis C virus titre was also assayed before and after interferon-alpha therapy. Within 2-5 months following interferon-alpha therapy, a significant inverse correlation was observed between saturation index and hepatitis C virus load. We conclude that hepatitis C virus infection enhances the degree of desaturation of 18-carbon fatty acids and that interferon-alpha is involved in their metabolism by increasing the degree of saturation and subsequent decrease in membrane fluidity.
Assuntos
Membrana Eritrocítica , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/metabolismo , Interferon-alfa/uso terapêutico , Ácidos Oleicos , Ácidos Esteáricos , Antivirais/uso terapêutico , Biomarcadores , Estudos de Casos e Controles , Cromatografia , Quimioterapia Combinada , Membrana Eritrocítica/química , Membrana Eritrocítica/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/farmacologia , Fluidez de Membrana/efeitos dos fármacos , Fluidez de Membrana/fisiologia , Ácidos Oleicos/análise , Ácidos Oleicos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Ribavirina/uso terapêutico , Índice de Gravidade de Doença , Ácidos Esteáricos/análise , Ácidos Esteáricos/metabolismo , Estearoil-CoA Dessaturase/efeitos dos fármacos , Estearoil-CoA Dessaturase/metabolismo , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
The ratio of stearic to oleic acids, i.e. the fatty acid saturation index, in red blood cell membranes was assayed in 60 patients with chronic hepatitis C virus infection before and after interferon-alpha therapy. Results were compared with 20 healthy controls. Hepatitis C virus titre was also assayed before and after interferon-alpha therapy. Within 2-5 months following interferon-alpha therapy, a significant inverse correlation was observed between saturation index and hepatitis C virus load. We conclude that hepatitis C virus infection enhances the degree of desaturation of 18-carbon fatty acids and that interferon-alpha is involved in their metabolism by increasing the degree of saturation and subsequent decrease in membrane fluidity
Assuntos
Antivirais , Biomarcadores , Estudos de Casos e Controles , Cromatografia , Quimioterapia Combinada , Membrana Eritrocítica , Hepatite C Crônica , Ácidos Oleicos , Índice de Gravidade de Doença , Ácidos Esteáricos , Estearoil-CoA Dessaturase , Carga Viral , Interferon-alfaRESUMO
The role of homocysteine as an independent risk factor for vascular endothelial damage, and the possible link between homocysteine and tumour necrosis factor-alpha [TNF-alpha] as two synergistic risk factors for beta-cell apoptosis in type 1 diabetes mellitus was studied. Plasma homocysteine levels were significantly elevated in all diabetic patients compared with controls and diabetic patients with vascular complications showed higher elevations. Furthermore, homocysteine levels showed significant positive correlation with the degree of microalbuminuria. TNF-alpha levels were elevated in all diabetic patients compared with controls. These results may have therapeutic implications
