RESUMEN
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. Among the many mediators implicated in cystitis, the overproduction of reactive oxygen species (ROS) seems to play a key role, although the main source of ROS remains unclear. This study aimed to investigate the contribution of NADPH oxidase (NOX) isoforms in ROS generation and the voiding dysfunction of cyclophosphamide (CYP, 300 mg/Kg, ip, 24 h)-induced cystitis in adult female mice, a well-recognized animal model to study IC/BPS, by using GKT137831 (5 mg/Kg, ip, three times in a 24 h period) or GSK2795039 (5 mg/Kg, ip, three times in a 24 h period) to inhibit NOX1/4 or NOX2, respectively. Our results showed that treatment with GSK2795039 improved the dysfunctional voiding behavior induced by CYP, reduced bladder edema and inflammation, and preserved the urothelial barrier integrity and tight junction occludin expression, besides inhibiting the characteristic vesical pain and bladder superoxide anion generation. In contrast, the NOX1/4 inhibitor GKT137831 had no significant protective effects. Taken together, our in vivo and ex vivo data demonstrate that NOX2 is possibly the main source of ROS observed in cystitis-induced CYP in mice. Therefore, selective inhibition of NOX2 by GSK2795039 may be a promising target for future therapies for IC/BPS.
RESUMEN
Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) (ranging from 10(-9) to 10(-7) m [1-100 nm; 0.39-39 ng ml(-1) ]) and butylparaben (BP) (ranging from 10(-8) to 10(-5) m [10 nm-10 µm; 1.9 ng ml(-1) to 1.9 µg ml(-1) ]), alone and in combination, on isolated mouse preantral follicle and human granulosa cell (hGC) cultures to study direct effects on follicle growth and ovarian steroidogenesis. Our results revealed that, in follicle culture, DEHP and BP attenuate estradiol output but only when present together. DEHP decreases progesterone concentrations in the spent media of hGC cultures, an effect that was attenuated when BP was added together with DEHP. Although changes in steroidogenesis were observed, no effects on follicular development or survival were noted in the culture systems. We suggest that BP and DEHP act with additive effect to decrease estradiol production whereas at later stages of follicle development BP blocks the effect of DEHP in hGCs resulting in decreased progesterone output. Taken together our results suggest that DEHP and BP adversely affect steroidogenesis from the preantral stage onward and the effects of these chemicals are both stage-dependent and modified by co-exposure. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Dietilhexil Ftalato/toxicidad , Folículo Ovárico/efectos de los fármacos , Parabenos/toxicidad , Animales , Células Cultivadas , Disruptores Endocrinos/toxicidad , Estradiol/metabolismo , Femenino , Células de la Granulosa/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos C57BL , Folículo Ovárico/metabolismo , Progesterona/metabolismoRESUMEN
A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we contest [corrected] that epididymal function is the key target for the adverse effects of TCDD.
Asunto(s)
Dibenzodioxinas Policloradas/efectos adversos , Recuento de Espermatozoides , Espermatogénesis/efectos de los fármacos , Animales , Epidídimo , Humanos , Masculino , RatasRESUMEN
A single in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gestation day 15 decreased epididymal sperm count in adult rats and thus was used to establish a tolerable daily intake for TCDD. However, several laboratories have been unable to replicate these findings. Moreover, conflicting reports of TCDD effects on daily sperm production suggest that spermatogenesis may not be as sensitive to the adverse effects of TCDD as previously thought. We performed a PubMed search using relevant search terms linking dioxin exposure with adverse effects on reproduction and spermatogenesis. Developmental exposure to TCDD is consistently linked with decreased cauda epididymal sperm counts in animal studies, although at higher dose levels than those used in some earlier studies. However, the evidence linking in utero TCDD exposure and spermatogenesis is not convincing. Animal studies provide clear evidence of an adverse effect of in utero TCDD exposure on epididymal sperm count but do not support the conclusion that spermatogenesis is adversely affected. The mechanisms underlying decreased epididymal sperm count are unknown; however, we postulate that epididymal function is the key target for the adverse effects of TCDD.
Uma única exposição in utero a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) no 15º dia de gestação diminuiu a contagem de esperma epididimal em ratos adultos e por isso foi utilizada para estabelecer uma dosagem diária tolerável para TCDD. No entanto, diversos laboratórios não conseguiram reproduzir esses resultados. Além disso, relatórios conflitantes dos efeitos de TCDD na produção diária de esperma sugere que espermatogênese pode não ser tão sensível aos efeitos adversos do TCDD como antes se pensava. Foi feita uma pesquisa no PubMed usando termos de pesquisa relevantes, relacionados à exposição à dioxina com efeitos adversos na reprodução e na espermatogênese. Exposição em desenvolvimento ao TCDD é consistentemente relacionada à diminuição da contagem da cauda epididimal de esperma, mas não apoia a conclusão de que a espermatogênese é afetada. Os mecanismos por trás da diminuição da contagem de esperma epididimal são desconhecidos; no entanto, contestamos que a função epididimal é a chave para efeitos adversos do TCDD.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Recuento de Espermatozoides , Espermatogénesis/efectos de los fármacos , Dibenzodioxinas Policloradas/efectos adversos , EpidídimoAsunto(s)
Humanos , Articulación de la Muñeca/anomalías , Articulación de la Muñeca/fisiopatología , Nervio Radial/anomalías , Nervio Radial/fisiopatología , Nervio Radial/lesiones , Traumatismos de la Muñeca/fisiopatología , Traumatismos de la Muñeca/rehabilitación , Articulaciones de los Dedos/anomalías , Articulaciones de los Dedos/fisiopatología , Pulgar/fisiopatología , Pulgar/lesionesAsunto(s)
Humanos , Enfermedades del Desarrollo Óseo/complicaciones , Enfermedades del Desarrollo Óseo/diagnóstico , Enfermedades del Desarrollo Óseo/fisiopatología , Enfermedades del Pie/diagnóstico , Enfermedades del Pie/fisiopatología , Enfermedades del Pie/rehabilitación , Osteotomía/métodos , Osteotomía/tendencias , Úlcera del Pie/complicaciones , Úlcera del Pie/diagnóstico , Úlcera del Pie/fisiopatología , Cuidados de la Piel/instrumentación , Cuidados de la Piel/métodos , Cuidados de la Piel/normas , Remodelación Ósea/fisiologíaAsunto(s)
Humanos , Cirugía Plástica , Cirugía Plástica/métodos , Cirugía Plástica/tendencias , Deformidades Adquiridas Nasales/cirugía , Deformidades Adquiridas Nasales/diagnóstico , Deformidades Adquiridas Nasales/rehabilitación , Nariz/anatomía & histología , Nariz/anomalías , Nariz/cirugía , Cejas/anatomía & histología , Cejas/cirugía , Cejas/fisiopatología , Cara/anomalías , Cara/cirugíaAsunto(s)
Humanos , Atención al Paciente/métodos , Atención al Paciente/tendencias , Apósitos Biológicos , Apósitos Biológicos/tendencias , Mecanismos Defensivos y Curativos , Procedimientos Quirúrgicos Mínimamente Invasivos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/tendenciasAsunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , ElectrocardiografíaRESUMEN
We document the loss of all but the youngest member of a troop of six howler monkeys due to probable jaguar predation during a 7-month period in 1988. The formation of Guri Lake resulted in forest fragmentation which forced monkeys into new and unfamiliar areas and altered the balance of predator and prey populations, and may thus have contributed indirectly to the success of the jaguar. The selection of defoliated (dead) trees for sleeping sites by the howlers may have directly increased the risk of predation. © 1992 Wiley-Liss, Inc.
RESUMEN
A survey was conducted among U.S. dental schools to determine the status of geriatric dentistry in the curriculum. Since a comparable, independent study was done in 1979, there has been significant growth in formalized didactic courses and less reliance on incorporating geriatric content as lectures or other components of existing courses. The growth in specialized courses was accompanied by an increased tendency to supplement the clinical topics with others relating to social and behavioral aspects of treating geriatric patients.