1: Am J Psychiatry. 2001 Oct;158(10):1623-30.
Links
Comment in:
ACP J Club. 2002 Jul-Aug;137(1):21.
Am J Psychiatry. 2001 Oct;158(10):1555-7.
Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate.
Seidman SN,
Roose SP,
Menza MA,
Shabsigh R,
Rosen RC.
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. sns5@columbia.edu
OBJECTIVE: Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness. METHOD: Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse. RESULTS: Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders. CONCLUSIONS: Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.
PMID: 11578994 [PubMed - indexed for MEDLINE]
TRADUCCION. OBJETIVO : Los hombres depresivos comunmente tienen disfunción erectile y los hombres con disfución erectilestan frecuentemete deprimidos. Ya que la etiología y las moduladoras relaciones entre depresión y disfunción eréctil ha sido pobremente caracterizada fue conducido un estudio de 12 semanas randomizado doble ciego en 20 clínicas urológicas para evaluar el efecto de sindenafil en hombres con disfunción eréctil y leve a moderada comorbilidades asociadas a depresión. METHOD: Hombres (N=152, mean (mean=5.7 years), a DSM-IV diagnóstico de de desorden depresivo según el score de Hamilton con un valor mayor de 12 (mean at baseline=16.9) fueron randomizadamente asignados a a una dosis flexible de sildenafil o placebo. La evaluación consistió en un autocuestionario respecto de cambios en en la function sexual síntomas depresivos y calidad de vida. La disfunción erectile fue evaluada como respondedores y no respondedores. RESULTS: Sildenafil fue fuertemente asociada con la respuesta a la disfunción eréctil. Un promedio de disminución de 10,6 y 2,3 en el score de Hamilton fue visto en tratados respondedores y no respondedores respectivamente; 76% de los tratados respondedores mostraron un mayor o igual al 50% en la declinación de store de Hamilton versus un 14% en no respondedores. La calidad de vida fue tuvo una similar mejoría en los 2 grupos. En conclusión Sildenafil es eficaz para la disfunción eréctil en hombres con leve a moderada enfermedad depresiva. Mejoría de la disfunción eréctil esta asociada con una marcada mejoría en los síntomas depresivos y calidad de vida.
martes, 22 de mayo de 2007
Envejecimiento masculino
1: J Urol. 2007 Jun;177(6):2267-71.
Links
Is sildenafil citrate associated with an amelioration of the symptomatology of androgen decline in the aging male?
Koulikov D,
Fridmans A,
Chertin B,
Shenfeld O,
Farkas A,
Spitz IM.
Department of Urology, Shaare Zedek Medical Center, Jerusalem, Israel.
PURPOSE: We examined whether treatment of erectile dysfunction with sildenafil citrate is associated with amelioration of the symptomatology of androgen decline in the aging male, and whether this alters the endocrine pattern. MATERIALS AND METHODS: A double-blind, randomized, placebo controlled, crossover study with sildenafil citrate was conducted in 60 men (age range 47 to 75 years old) who presented with erectile dysfunction and screened positively for androgen decline in the aging male by the questionnaire of the same name. The patients were randomized to receive sildenafil citrate or placebo in a 1:1 ratio and were crossed over after 3 months of treatment for an additional 3 months. The evaluation included International Index Erectile Function and Aging Male Symptoms questionnaires, hormonal profiles, total testosterone, and bioavailable testosterone. RESULTS: A total of 40 patients completed the study. Compared to placebo, sildenafil citrate improved erectile function (52.7 +/- 2 vs 39 +/- 1.9, p <0.001) and Aging Male Symptoms score (33.5 +/- 1.3 vs 28.6 +/- 1.3, p <0.001) in the total group. Breakdown into hypogonadal and normal men showed that the International Index of Erectile Function score improved more in normal (Delta 18.5 +/- 3.6) than in hypogonadal men (Delta 6.7 +/- 2.7). There were no differences in improvement on the Aging Male Symptoms questionnaire between hypogonadal and normal men. No treatment changes were observed in total testosterone and bioavailable testosterone. CONCLUSIONS: In the total group of patients sildenafil citrate was associated with expected improvement in erectile function and in the Aging Male Symptoms questionnaire without any alteration in hormonal pattern. The available questionnaires for androgen decline in the aging male are not specific for the diagnosis of biochemical androgen decline in the aging male, although the suboptimal response to sildenafil citrate suggests the presence of hypogonadism.
PMID: 17509338 [PubMed - in process]
MATERIALS AND METHODS: Un studio randomizado controlado doble ciego se realizó con sildenafil citrate con 60 varones ( edad 47 a 75 años ) ) quienes presentaban disfunción erectile y seleccionados positivamente por su declinación de andrógenos mediante un cuestionario. Los pacientes fueron randomizados para recibir sildenafil citrato o placebo en relación 1:1y fueron entrecruzados a los 3 meses para un adiconal tratamiento de 3 meses. La evaluacion incluyó el Indice Internacional de disfunsión erectile y sintomas de envejecimiento masculino, perfil hormonal testosterone total testosterone biodisponible. Los resultados mostrarosn que 40 pacientes completaron el estudio. Comparado con sildenafil citrato mejoraron la disfunción erectil ( 52.7 +/- 2 vs 39 +/- 1.9, p <0.001) y el score de envejecimiento masculino en el grupo total. La separación entre hipogonádicos y normales mostró que el indice de disfuncion erectile mejoró mas en hombres normales (Delta 18.5 +/- 3.6) que en los hombre hipogonádicos No hubo diferencias en la mejoria del indice de envejecimiento entre los 2 grupos. No hubo cambios con el tratamientos en los niveles de testosterona y testosterona biodisponible. Se concluye que en el grupo total de varones en el en que el sildenafil mejoró la disfunción erectile fue asociada CONCLUSIONS: In the total group of patients sildenafil citrate was associated with mejoria de la disfunción eréctil no hubo asociación con los síntomas de envejecimiento y la declinación de los andrógenos. Los cuestionarios para detectar declinación de los andrógenos no guardan relación con la declinación biológica de testosterona aunque la subóptima respuesta al sildenafil citrato sugiere la presencia de hipogonadismo.
Links
Is sildenafil citrate associated with an amelioration of the symptomatology of androgen decline in the aging male?
Koulikov D,
Fridmans A,
Chertin B,
Shenfeld O,
Farkas A,
Spitz IM.
Department of Urology, Shaare Zedek Medical Center, Jerusalem, Israel.
PURPOSE: We examined whether treatment of erectile dysfunction with sildenafil citrate is associated with amelioration of the symptomatology of androgen decline in the aging male, and whether this alters the endocrine pattern. MATERIALS AND METHODS: A double-blind, randomized, placebo controlled, crossover study with sildenafil citrate was conducted in 60 men (age range 47 to 75 years old) who presented with erectile dysfunction and screened positively for androgen decline in the aging male by the questionnaire of the same name. The patients were randomized to receive sildenafil citrate or placebo in a 1:1 ratio and were crossed over after 3 months of treatment for an additional 3 months. The evaluation included International Index Erectile Function and Aging Male Symptoms questionnaires, hormonal profiles, total testosterone, and bioavailable testosterone. RESULTS: A total of 40 patients completed the study. Compared to placebo, sildenafil citrate improved erectile function (52.7 +/- 2 vs 39 +/- 1.9, p <0.001) and Aging Male Symptoms score (33.5 +/- 1.3 vs 28.6 +/- 1.3, p <0.001) in the total group. Breakdown into hypogonadal and normal men showed that the International Index of Erectile Function score improved more in normal (Delta 18.5 +/- 3.6) than in hypogonadal men (Delta 6.7 +/- 2.7). There were no differences in improvement on the Aging Male Symptoms questionnaire between hypogonadal and normal men. No treatment changes were observed in total testosterone and bioavailable testosterone. CONCLUSIONS: In the total group of patients sildenafil citrate was associated with expected improvement in erectile function and in the Aging Male Symptoms questionnaire without any alteration in hormonal pattern. The available questionnaires for androgen decline in the aging male are not specific for the diagnosis of biochemical androgen decline in the aging male, although the suboptimal response to sildenafil citrate suggests the presence of hypogonadism.
PMID: 17509338 [PubMed - in process]
MATERIALS AND METHODS: Un studio randomizado controlado doble ciego se realizó con sildenafil citrate con 60 varones ( edad 47 a 75 años ) ) quienes presentaban disfunción erectile y seleccionados positivamente por su declinación de andrógenos mediante un cuestionario. Los pacientes fueron randomizados para recibir sildenafil citrato o placebo en relación 1:1y fueron entrecruzados a los 3 meses para un adiconal tratamiento de 3 meses. La evaluacion incluyó el Indice Internacional de disfunsión erectile y sintomas de envejecimiento masculino, perfil hormonal testosterone total testosterone biodisponible. Los resultados mostrarosn que 40 pacientes completaron el estudio. Comparado con sildenafil citrato mejoraron la disfunción erectil ( 52.7 +/- 2 vs 39 +/- 1.9, p <0.001) y el score de envejecimiento masculino en el grupo total. La separación entre hipogonádicos y normales mostró que el indice de disfuncion erectile mejoró mas en hombres normales (Delta 18.5 +/- 3.6) que en los hombre hipogonádicos No hubo diferencias en la mejoria del indice de envejecimiento entre los 2 grupos. No hubo cambios con el tratamientos en los niveles de testosterona y testosterona biodisponible. Se concluye que en el grupo total de varones en el en que el sildenafil mejoró la disfunción erectile fue asociada CONCLUSIONS: In the total group of patients sildenafil citrate was associated with mejoria de la disfunción eréctil no hubo asociación con los síntomas de envejecimiento y la declinación de los andrógenos. Los cuestionarios para detectar declinación de los andrógenos no guardan relación con la declinación biológica de testosterona aunque la subóptima respuesta al sildenafil citrato sugiere la presencia de hipogonadismo.
TESTOSTERONA ENVEJECIMIENTO
1: J Sex Med. 2007 May;4(3):558-66.
Links
Canadian Society for the Study of the Aging Male: Response to Health Canada's Position Paper on Testosterone Treatment.
Bain J,
Brock G,
Kuzmarov I;
for the International Consulting Group.
Department of Medicine, Division of Endocrinology and Metabolism, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Introduction. Testosterone treatment of older symptomatic men with reduced testosterone availability is increasing. There is an expanding body of literature to support such treatment in a large subset of aging men, but there has not yet been a long-term placebo-controlled double-blind study of several thousand men to confirm the efficacy and safety of this treatment as indicated by shorter-term studies. The absence of a long-term study has been used by governmental agencies as a limiting factor in providing full access and payment for this treatment in government-sponsored health care plans. Health Canada issued a testosterone analysis document to the pharmaceutical industry, the implications of which may make it more difficult for appropriate patients to receive such treatment. The Canadian Society for the Study of the Aging Male (CSSAM) believed it had an obligation to advocate on behalf of men requiring this treatment. Aim. To provide an international consensus on the use of testosterone treatment in appropriately selected hypogonadal men. Main Outcome Measure. To determine whether the literature supports the use of testosterone treatment in a selected population of hypogonadal men, to achieve consensus on this point among an international consulting group, and to transmit this view to health care workers and insuring and governmental agencies. Methods. Email communication among the consulting group to prepare a response to Health Canada, followed by a review of appropriate literature and international practice guidelines, incorporating the literature and guidelines together with the CSSAM letter and Health Canada's response. Result. The literature and international guidelines support the initiation of testosterone therapy in symptomatic hypogonadal men, recognizing that there is no universal agreement on the criteria for the diagnosis of hypogonadism in each suspected case. The need for careful monitoring of such men is stressed. Conclusion. CSSAM acted as an advocate for hypogonadal men who may benefit from treatment with testosterone. Short-term studies and 60 years of experience with testosterone therapy attest to its efficacy. Long-term studies are desirable, but it may take many years before results could be forthcoming. There is no evidence to suggest that testosterone treatment increases the risk of prostate cancer or cardiovascular disease. Current evidence suggests, in fact, that testosterone treatment may be cardioprotective. It is important to bring this information to the attention of governments and insuring agencies through the collaboration of groups devoted to the diagnosis and treatment of hypogonadal men.
PMID: 17498097 [PubMed - in process]
TRADUCCION . El tratamiento de hombres viejos sintomáticos con testosterona con reducida disponibilidad de la hormona es creciente. Hay una expansiva literatura que soporta tal tratamiento en un gran grupo de hombres viejos pero aún no existe un estudia a largo plazo placebo y doble ciego para confirmar su eficacia y seguridad como lo indicant los trabajos de corto plazo.
La ausencia de estos trabajos de largo plazo ha sido usada por las agenciaa guvernamentales como un factor limitante en proporcionar el total acceso y el pago por este tratamiento por los auspiciadores de planes de salud. La sociedad canadiense para el estudio de envejecimiento masculino ( CSSAM) cree que tiene la obligación de abocarse al grupo de pacientes que requiern este tratamiento. Nuestro objeto fue proporcionar un consenso internacional acerca de el uso de tratamiento con testosterona en seleccionados varones hipogonádicos. Para determinar si la literatura soporta el uso de testosterona en varones hipogonádicos, para obtener un concenso en este punto y entre un un grupo inter4nacional de consulta y para trasmitir esa visión a los médicos tratantes y asegurar un apoyo de las agencias gubernamentales. Comunicación via e mail entre los grupos consultantes para preparar una respuesta a Health Canadá seguido de una revision de la literature apropiada y gías de practica médica internacional junto con La CSSAM. Concluyeron en lo siguiente;
La CSSAN actua como propiciador de hipogonádicos quienes pueden beneficiarse con el tratamiento con testoster Estudios de corto plazo y sesenta años de wexperiencia con testosterona enfocan hacia su eficacia. Estudios a largo plazo son deseables pero puede tomar muchos años antes que los estudios puedan ser confirmatorios. No hay evidencia de que el tratamiento con testosterona eleve el riesgo de cancer de próstata o accidente vascular de hecho el tratamiento con la hormona puede ser cardioprotector. Es importante destacar esta información para ser tomados en cuenta por los governantes y agencies de seguridad a traves de la colaboración de grupos abocados al tratamiento y el diagnóstico de hombres con hipogonadismo.
Links
Canadian Society for the Study of the Aging Male: Response to Health Canada's Position Paper on Testosterone Treatment.
Bain J,
Brock G,
Kuzmarov I;
for the International Consulting Group.
Department of Medicine, Division of Endocrinology and Metabolism, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Introduction. Testosterone treatment of older symptomatic men with reduced testosterone availability is increasing. There is an expanding body of literature to support such treatment in a large subset of aging men, but there has not yet been a long-term placebo-controlled double-blind study of several thousand men to confirm the efficacy and safety of this treatment as indicated by shorter-term studies. The absence of a long-term study has been used by governmental agencies as a limiting factor in providing full access and payment for this treatment in government-sponsored health care plans. Health Canada issued a testosterone analysis document to the pharmaceutical industry, the implications of which may make it more difficult for appropriate patients to receive such treatment. The Canadian Society for the Study of the Aging Male (CSSAM) believed it had an obligation to advocate on behalf of men requiring this treatment. Aim. To provide an international consensus on the use of testosterone treatment in appropriately selected hypogonadal men. Main Outcome Measure. To determine whether the literature supports the use of testosterone treatment in a selected population of hypogonadal men, to achieve consensus on this point among an international consulting group, and to transmit this view to health care workers and insuring and governmental agencies. Methods. Email communication among the consulting group to prepare a response to Health Canada, followed by a review of appropriate literature and international practice guidelines, incorporating the literature and guidelines together with the CSSAM letter and Health Canada's response. Result. The literature and international guidelines support the initiation of testosterone therapy in symptomatic hypogonadal men, recognizing that there is no universal agreement on the criteria for the diagnosis of hypogonadism in each suspected case. The need for careful monitoring of such men is stressed. Conclusion. CSSAM acted as an advocate for hypogonadal men who may benefit from treatment with testosterone. Short-term studies and 60 years of experience with testosterone therapy attest to its efficacy. Long-term studies are desirable, but it may take many years before results could be forthcoming. There is no evidence to suggest that testosterone treatment increases the risk of prostate cancer or cardiovascular disease. Current evidence suggests, in fact, that testosterone treatment may be cardioprotective. It is important to bring this information to the attention of governments and insuring agencies through the collaboration of groups devoted to the diagnosis and treatment of hypogonadal men.
PMID: 17498097 [PubMed - in process]
TRADUCCION . El tratamiento de hombres viejos sintomáticos con testosterona con reducida disponibilidad de la hormona es creciente. Hay una expansiva literatura que soporta tal tratamiento en un gran grupo de hombres viejos pero aún no existe un estudia a largo plazo placebo y doble ciego para confirmar su eficacia y seguridad como lo indicant los trabajos de corto plazo.
La ausencia de estos trabajos de largo plazo ha sido usada por las agenciaa guvernamentales como un factor limitante en proporcionar el total acceso y el pago por este tratamiento por los auspiciadores de planes de salud. La sociedad canadiense para el estudio de envejecimiento masculino ( CSSAM) cree que tiene la obligación de abocarse al grupo de pacientes que requiern este tratamiento. Nuestro objeto fue proporcionar un consenso internacional acerca de el uso de tratamiento con testosterona en seleccionados varones hipogonádicos. Para determinar si la literatura soporta el uso de testosterona en varones hipogonádicos, para obtener un concenso en este punto y entre un un grupo inter4nacional de consulta y para trasmitir esa visión a los médicos tratantes y asegurar un apoyo de las agencias gubernamentales. Comunicación via e mail entre los grupos consultantes para preparar una respuesta a Health Canadá seguido de una revision de la literature apropiada y gías de practica médica internacional junto con La CSSAM. Concluyeron en lo siguiente;
La CSSAN actua como propiciador de hipogonádicos quienes pueden beneficiarse con el tratamiento con testoster Estudios de corto plazo y sesenta años de wexperiencia con testosterona enfocan hacia su eficacia. Estudios a largo plazo son deseables pero puede tomar muchos años antes que los estudios puedan ser confirmatorios. No hay evidencia de que el tratamiento con testosterona eleve el riesgo de cancer de próstata o accidente vascular de hecho el tratamiento con la hormona puede ser cardioprotector. Es importante destacar esta información para ser tomados en cuenta por los governantes y agencies de seguridad a traves de la colaboración de grupos abocados al tratamiento y el diagnóstico de hombres con hipogonadismo.
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Review: 1
1: Curr Med Chem. 2006;13(24):2889-900.
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Current pharmacological treatment of nonalcoholic fatty liver.
Portincasa P,
Grattagliano I,
Palmieri VO,
Palasciano G.
Clinica Medica "A. Murri", Department of Internal Medicine & Public Medicine (DIMIMP), University Medical School, Bari, Italy. p.portincasa@semeiotica.uniba.it
Nonalcoholic fatty liver disease (NAFLD) is a frequent and potentially progressive chronic liver disease that occurs in subjects who do not abuse alcohol. NAFLD is often associated with obesity, metabolic syndrome and insulin resistance and its more aggressive form, nonalcoholic steatohepatitis (NASH) is a major cause of cryptogenic cirrhosis. NAFLD/NASH are commonly detected because of elevated serum aminotransferase levels, ultrasonographic fatty liver and, at liver histology, steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Current management of NAFLD/NASH is largely conservative and includes diet regimen, aerobic exercise, and interventions towards the associated metabolic abnormalities. The main concern is therefore to decrease liver steatosis and its progression toward steatohepatitis and fibrosis, and the risk of "cryptogenic" cirrhosis. Among the most promising medications, weight reducing drugs, insulin sensitizers and lipid-lowering agents, antioxidants, bile salts, co-factors increasing the mitochondrial transport of fatty acids are being considered. Among them, thiazolidinediones are the most promising drug family that act by activating PPARgamma nuclear receptors and by regulating both microsomal and peroxisomal lipid oxidative pathways. Pharmacological treatment of obesity and probiotics should be considered as potential therapeutic options. In this review, after summarizing the general background on fatty liver, the most current and attractive pharmacological approaches to the problem of NAFLD/NASH are discussed.
PMID: 17073635 [PubMed - indexed for MEDLINE]
Traducción resumida. Entre los framacos se usan las thiazolidedionas que actuan activando los PPARgamma receptores y regulando la via microsomal la vía oxidativa de los peroxisomas.
All: 1
Review: 1
1: Curr Med Chem. 2006;13(24):2889-900.
Links
Current pharmacological treatment of nonalcoholic fatty liver.
Portincasa P,
Grattagliano I,
Palmieri VO,
Palasciano G.
Clinica Medica "A. Murri", Department of Internal Medicine & Public Medicine (DIMIMP), University Medical School, Bari, Italy. p.portincasa@semeiotica.uniba.it
Nonalcoholic fatty liver disease (NAFLD) is a frequent and potentially progressive chronic liver disease that occurs in subjects who do not abuse alcohol. NAFLD is often associated with obesity, metabolic syndrome and insulin resistance and its more aggressive form, nonalcoholic steatohepatitis (NASH) is a major cause of cryptogenic cirrhosis. NAFLD/NASH are commonly detected because of elevated serum aminotransferase levels, ultrasonographic fatty liver and, at liver histology, steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Current management of NAFLD/NASH is largely conservative and includes diet regimen, aerobic exercise, and interventions towards the associated metabolic abnormalities. The main concern is therefore to decrease liver steatosis and its progression toward steatohepatitis and fibrosis, and the risk of "cryptogenic" cirrhosis. Among the most promising medications, weight reducing drugs, insulin sensitizers and lipid-lowering agents, antioxidants, bile salts, co-factors increasing the mitochondrial transport of fatty acids are being considered. Among them, thiazolidinediones are the most promising drug family that act by activating PPARgamma nuclear receptors and by regulating both microsomal and peroxisomal lipid oxidative pathways. Pharmacological treatment of obesity and probiotics should be considered as potential therapeutic options. In this review, after summarizing the general background on fatty liver, the most current and attractive pharmacological approaches to the problem of NAFLD/NASH are discussed.
PMID: 17073635 [PubMed - indexed for MEDLINE]
Traducción resumida. Entre los framacos se usan las thiazolidedionas que actuan activando los PPARgamma receptores y regulando la via microsomal la vía oxidativa de los peroxisomas.
jueves, 17 de mayo de 2007
Leptin in embryos from control and diabetic rats during organogenesis: a modulator of nitric oxide production and lipid homeostasis.
· White V,
· Gonzalez E,
· Pustovrh C,
· Capobianco E,
· Martinez N,
· Do Porto DF,
· Higa R,
· Jawerbaum A.
Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155 (1121ABG) Buenos Aires, Argentina.
BACKGROUND: Leptin is involved in many metabolic and reproductive events and its levels are altered by the diabetic pathology. In this study, leptin concentrations and leptin effects on both nitric oxide (NO) and lipid concentrations were investigated in embryos from control and diabetic rats. METHODS: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Embryos from control and diabetic rats were obtained on days 10.5 and 13.5 of gestation, corresponding to early organogenesis and post-placentation periods respectively. Leptin was analysed by enzyme immunoanalysis and immunohistochemistry. Nitrates and nitrites were assessed as an index of NO production. Lipid concentrations were analysed by thin layer chromatography. RESULTS: Leptin concentrations were decreased in embryos obtained from diabetic rats on days 10.5 and 13.5 of gestation when compared to controls. NO concentrations, elevated in diabetic embryopathy, were diminished in the presence of leptin in the embryos obtained from control and diabetic animals both during early organogenesis and after placentation. Leptin additions reduced phospholipid, cholesterol and cholesteryl ester concentrations in embryos obtained from diabetic rats during early organogenesis, although no leptin effects on lipid concentrations were observed in control embryos at this developmental stage. In embryos obtained on day 13.5 of gestation leptin additions reduced cholesteryl ester concentrations in controls, and diminished cholesteryl ester, triglycerides and phospholipids in embryos from diabetic rats. CONCLUSIONS: We demonstrated that leptin plays a role in the regulation of NO concentrations and lipid homeostasis during embryo organogenesis and that the diabetic environment causes a reduction of leptin concentrations in rat embryos. Copyright (c) 2007 John Wiley & Sons, Ltd.
PMID: 17506117 [PubMed - as supplied by publisher]
TRADUCCION.
Leptina esta involucrada en muchos eventos reproductivos y metabólicos y sus niveles estan alterados por la diabetes.
In este studio las concentraciones de leptina y sus efectos sobre la acumulación de oxido nitroso y la concentracion de lípidos fueron investigadas en embriones de controles y ratas diabéticas por ausencia de insulina. Embriones de ratas control y diabéticas fueron obtenidos en los días 10,5 y y 13,5 de gestacion correspondientes a los períodos de la organogénesis precoz y post placentación respectivamente. RESULTADOS. Las concentraciones de leptina fueron reducidas en embriones de ratas diabéticas en ambos períodos de gestación respecto de ratas normales. Los niveles de Oxido nitroso (NO) elevados en la embriopatía diabética estuvieron disminuidos en presencia de leptina en las ratas normales en ambos periodos de la gestación. La adición de leptina redujo los fosfolípidos cholesterol y esters de cholesterol en los embriones de ratas diabéticas durante la organogenesispero no se manifestaron efectos sobre ellos en embriones de rats control en este período de la gestación. En el período de de implantación leptina redujo las concentraciones de esters de cholesterol en controles y redujo los niveles de triglicéridos fosfolipidos y esteres de colesterol de embriones de ratas diabéticas. CONCLUSION: la leptina juega un rol en la regulacion de las concentraciones de y la homeostasis lipidica durante la organogénesis embrionaria y la ausencia de insulina en un ambiente diabético causa una reducción da las concentraciones de leptina en embriones de ratas.
.
· White V,
· Gonzalez E,
· Pustovrh C,
· Capobianco E,
· Martinez N,
· Do Porto DF,
· Higa R,
· Jawerbaum A.
Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155 (1121ABG) Buenos Aires, Argentina.
BACKGROUND: Leptin is involved in many metabolic and reproductive events and its levels are altered by the diabetic pathology. In this study, leptin concentrations and leptin effects on both nitric oxide (NO) and lipid concentrations were investigated in embryos from control and diabetic rats. METHODS: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Embryos from control and diabetic rats were obtained on days 10.5 and 13.5 of gestation, corresponding to early organogenesis and post-placentation periods respectively. Leptin was analysed by enzyme immunoanalysis and immunohistochemistry. Nitrates and nitrites were assessed as an index of NO production. Lipid concentrations were analysed by thin layer chromatography. RESULTS: Leptin concentrations were decreased in embryos obtained from diabetic rats on days 10.5 and 13.5 of gestation when compared to controls. NO concentrations, elevated in diabetic embryopathy, were diminished in the presence of leptin in the embryos obtained from control and diabetic animals both during early organogenesis and after placentation. Leptin additions reduced phospholipid, cholesterol and cholesteryl ester concentrations in embryos obtained from diabetic rats during early organogenesis, although no leptin effects on lipid concentrations were observed in control embryos at this developmental stage. In embryos obtained on day 13.5 of gestation leptin additions reduced cholesteryl ester concentrations in controls, and diminished cholesteryl ester, triglycerides and phospholipids in embryos from diabetic rats. CONCLUSIONS: We demonstrated that leptin plays a role in the regulation of NO concentrations and lipid homeostasis during embryo organogenesis and that the diabetic environment causes a reduction of leptin concentrations in rat embryos. Copyright (c) 2007 John Wiley & Sons, Ltd.
PMID: 17506117 [PubMed - as supplied by publisher]
TRADUCCION.
Leptina esta involucrada en muchos eventos reproductivos y metabólicos y sus niveles estan alterados por la diabetes.
In este studio las concentraciones de leptina y sus efectos sobre la acumulación de oxido nitroso y la concentracion de lípidos fueron investigadas en embriones de controles y ratas diabéticas por ausencia de insulina. Embriones de ratas control y diabéticas fueron obtenidos en los días 10,5 y y 13,5 de gestacion correspondientes a los períodos de la organogénesis precoz y post placentación respectivamente. RESULTADOS. Las concentraciones de leptina fueron reducidas en embriones de ratas diabéticas en ambos períodos de gestación respecto de ratas normales. Los niveles de Oxido nitroso (NO) elevados en la embriopatía diabética estuvieron disminuidos en presencia de leptina en las ratas normales en ambos periodos de la gestación. La adición de leptina redujo los fosfolípidos cholesterol y esters de cholesterol en los embriones de ratas diabéticas durante la organogenesispero no se manifestaron efectos sobre ellos en embriones de rats control en este período de la gestación. En el período de de implantación leptina redujo las concentraciones de esters de cholesterol en controles y redujo los niveles de triglicéridos fosfolipidos y esteres de colesterol de embriones de ratas diabéticas. CONCLUSION: la leptina juega un rol en la regulacion de las concentraciones de y la homeostasis lipidica durante la organogénesis embrionaria y la ausencia de insulina en un ambiente diabético causa una reducción da las concentraciones de leptina en embriones de ratas.
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1: Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):70-6. Epub 2006 Nov 9.
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Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance.
· Bodary PF,
· Shen Y,
· Ohman M,
· Bahrou KL,
· Vargas FB,
· Cudney SS,
· Wickenheiser KJ,
· Myers MG Jr,
· Eitzman DT.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
BACKGROUND: Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear. METHODS AND RESULTS: Arterial injury was induced in wild-type (wt), leptin-deficient (lep(ob/ob)), and leptin receptor-deficient (lepr(db/db)) mice. Compared with wt mice, lep(ob/ob) and lepr(db/db) mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and lepr(db/db) mice indicated that the vascular protection in lepr(db/db) mice was not attributable to lack of leptin receptor expression on bone marrow-derived elements. To investigate the role of the lepr-mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, lepr(s/s) mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in lepr(s/s) mice was significantly increased compared with lepr(db/db) mice. CONCLUSIONS: The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.
PMID: 17095713 [PubMed - indexed for MEDLINE]
TRADUCCION:
Leptina es una hormona derivada del tejido adiposo crítica en la homeostasis energética e implicada en proceso de la enfermedad vascular. El pool de receptores celulares y sus señales involucrados en los fenotipos de asociación de leptina y estado vascular in vivo hasta ahora no estan claros. Fue inducido daño arterial en ratas normales , deficientes de leptina ( lep ob/ob) y en ratas con ausencia del receptor para leptina ( lepr(db/db). Comparadas con las normales las ratas Lep (ob/ob y Lepr( db/db fueron protegidas del desarrollo de la neoíintima. El trasplante de médula entre ratas normales y leprdb/db indicó que la protección vascular en estas ratas no es atribuible a la ausencia del receptor de leptina en elementos derivados de la médula.
Para investigar la causa de este resultado fueron investigadas ratas con ausencia del gen de receptor y del gent SAT3. Las ratas sufrieron daño vascular. En conclusión. El mecanismo molecular mediante el cual el receptor de leptina media la formación de noeíntima y proliferación de músculo liso vascular es independiente de las señales dependientes de SAT3, la vía involucrada en el balance energético.
Links
Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance.
· Bodary PF,
· Shen Y,
· Ohman M,
· Bahrou KL,
· Vargas FB,
· Cudney SS,
· Wickenheiser KJ,
· Myers MG Jr,
· Eitzman DT.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.
BACKGROUND: Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear. METHODS AND RESULTS: Arterial injury was induced in wild-type (wt), leptin-deficient (lep(ob/ob)), and leptin receptor-deficient (lepr(db/db)) mice. Compared with wt mice, lep(ob/ob) and lepr(db/db) mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and lepr(db/db) mice indicated that the vascular protection in lepr(db/db) mice was not attributable to lack of leptin receptor expression on bone marrow-derived elements. To investigate the role of the lepr-mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, lepr(s/s) mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in lepr(s/s) mice was significantly increased compared with lepr(db/db) mice. CONCLUSIONS: The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.
PMID: 17095713 [PubMed - indexed for MEDLINE]
TRADUCCION:
Leptina es una hormona derivada del tejido adiposo crítica en la homeostasis energética e implicada en proceso de la enfermedad vascular. El pool de receptores celulares y sus señales involucrados en los fenotipos de asociación de leptina y estado vascular in vivo hasta ahora no estan claros. Fue inducido daño arterial en ratas normales , deficientes de leptina ( lep ob/ob) y en ratas con ausencia del receptor para leptina ( lepr(db/db). Comparadas con las normales las ratas Lep (ob/ob y Lepr( db/db fueron protegidas del desarrollo de la neoíintima. El trasplante de médula entre ratas normales y leprdb/db indicó que la protección vascular en estas ratas no es atribuible a la ausencia del receptor de leptina en elementos derivados de la médula.
Para investigar la causa de este resultado fueron investigadas ratas con ausencia del gen de receptor y del gent SAT3. Las ratas sufrieron daño vascular. En conclusión. El mecanismo molecular mediante el cual el receptor de leptina media la formación de noeíntima y proliferación de músculo liso vascular es independiente de las señales dependientes de SAT3, la vía involucrada en el balance energético.
OBESIDAD
1: Front Biosci. 2007 May 1;12:3531-44.
Links
Elevated leptin: consequence or cause of obesity?
· Scarpace PJ,
· Zhang Y.
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610, USA. scarpace@ufl.edu
Leptin is an adipocyte-derived, satiety-regulating hormone that acts within the hypothalamus and other brain sites. Obese humans and animals are largely resistant to central actions of leptin. Rising leptin levels associated with progressing obesity are generally regarded as simply a consequence rather than a causative factor in the leptin resistance and obesity. Several lines of evidence suggest otherwise. Chronic overexpression of central leptin induces a leptin resistance that mimics many of the characteristics associated with diet-induced or adult-onset obesity including reduced leptin receptors, diminished signaling, and impaired responsiveness to exogenous leptin. Moreover, these animals have increased susceptibility to diet-induced obesity. New data with a leptin antagonist demonstrate that blockade of leptin receptors also exaggerates diet-induced obesity. These findings suggest an important role for elevated leptin in the development of leptin resistance and obesity, especially in today's society with an overabundance of readily available high caloric food. Once leptin resistance takes hold, each subsequent exposure to high-density food faces diminished counter-regulatory responses, leading to exacerbated weight gain.
PMID: 17485319 [PubMed - in process]
TRADUCCION
Leptina is un hormona regulante de la saciedad derivada de los adipocitos que actua en el hipotálamo y otros sitios del cerebro. Los obesos humanos y animales son largamente resistentes a la acción central de la leptina. Elevados niveles de leptina asociados a progresión de la obesidad son considerados como una consecuencia mas que una causa en la obesidad resistente a la leptina . Varias lineas de evidencia lo sugieren. La sobreexpresión crónica de leptina a nivel central induce un estado de resistencia que se parece a las características de la obesidad de comienzo en la adultez inducida por la dieta, incluyendo reducidos receptores para leptina, reducción de las señales y alteración de la respuesta a la leptina exógena. Más aún estos animales tienen elevada susceptibilidad a la dieta inductora de obesidad. Nuevos datos con antagonistas de la leptina demuestran que el bloqueo de los recptores de leptina también exageran la obesidad inducida por la dieta. Estos hallazgos sugieren un importante rol de elevados niveles de leptina en el desarrollo de nla obesidad resistente a la leptina especialmente en la sociedad actual con un a sobreabundancia y ampliamente disponibilidad de hidratos de carbono. Una vez que la la leptino resistencia toma lugar cada subsecuente exposición a ndietas de alta densidad calórica dfisminuye la respuesta contraregulatoria determinando una exacerbación de la gamnancia de peso
1: Front Biosci. 2007 May 1;12:3531-44.
Links
Elevated leptin: consequence or cause of obesity?
· Scarpace PJ,
· Zhang Y.
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610, USA. scarpace@ufl.edu
Leptin is an adipocyte-derived, satiety-regulating hormone that acts within the hypothalamus and other brain sites. Obese humans and animals are largely resistant to central actions of leptin. Rising leptin levels associated with progressing obesity are generally regarded as simply a consequence rather than a causative factor in the leptin resistance and obesity. Several lines of evidence suggest otherwise. Chronic overexpression of central leptin induces a leptin resistance that mimics many of the characteristics associated with diet-induced or adult-onset obesity including reduced leptin receptors, diminished signaling, and impaired responsiveness to exogenous leptin. Moreover, these animals have increased susceptibility to diet-induced obesity. New data with a leptin antagonist demonstrate that blockade of leptin receptors also exaggerates diet-induced obesity. These findings suggest an important role for elevated leptin in the development of leptin resistance and obesity, especially in today's society with an overabundance of readily available high caloric food. Once leptin resistance takes hold, each subsequent exposure to high-density food faces diminished counter-regulatory responses, leading to exacerbated weight gain.
PMID: 17485319 [PubMed - in process]
TRADUCCION
Leptina is un hormona regulante de la saciedad derivada de los adipocitos que actua en el hipotálamo y otros sitios del cerebro. Los obesos humanos y animales son largamente resistentes a la acción central de la leptina. Elevados niveles de leptina asociados a progresión de la obesidad son considerados como una consecuencia mas que una causa en la obesidad resistente a la leptina . Varias lineas de evidencia lo sugieren. La sobreexpresión crónica de leptina a nivel central induce un estado de resistencia que se parece a las características de la obesidad de comienzo en la adultez inducida por la dieta, incluyendo reducidos receptores para leptina, reducción de las señales y alteración de la respuesta a la leptina exógena. Más aún estos animales tienen elevada susceptibilidad a la dieta inductora de obesidad. Nuevos datos con antagonistas de la leptina demuestran que el bloqueo de los recptores de leptina también exageran la obesidad inducida por la dieta. Estos hallazgos sugieren un importante rol de elevados niveles de leptina en el desarrollo de nla obesidad resistente a la leptina especialmente en la sociedad actual con un a sobreabundancia y ampliamente disponibilidad de hidratos de carbono. Una vez que la la leptino resistencia toma lugar cada subsecuente exposición a ndietas de alta densidad calórica dfisminuye la respuesta contraregulatoria determinando una exacerbación de la gamnancia de peso
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