Involvement of K+ATP and Ca2+ channels in hydrogen sulfide-suppressed ageing of porcine oocytes

BACKGROUND: Hydrogen sulfide has been shown to improve the quality of oocytes destined for in vitro fertilization. Although hydrogen sulfide is capable of modulating ion channel activity in somatic cells, the role of hydrogen sulfide in gametes and embryos remains unknown. Our observations confirmed the hypothesis that the KATP and L-type Ca2+ ion channels play roles in porcine oocyte ageing and revealed a plausible contribution of hydrogen sulfide to the modulation of ion channel activity. RESULTS: We confirmed the benefits of the activation and suppression of the KATP and L-type Ca2+ ion channels, respectively, for the preservation of oocyte quality. CONCLUSIONS: Our experiments identified hydrogen sulfide as promoting the desired ion channel activity, with the capacity to protect porcine oocytes against cell death. Further experiments are needed to determine the exact mechanism of hydrogen sulfide in gametes and embryos.

Potassium channel openers exhibit cross-tolerance with morphine in two experimental models of pain / Los abridores de canales de potasio exhiben tolerancia cruzada con la morfina en dos modelos experimentales de dolor

OBJECTIVE: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa. METHODS: Swiss albino mice of either gender weighing between 25-30 g were used for the study. The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests. RESULTS: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However, reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers. CONCLUSIONS: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However, such interaction occurs at the level of potassium channels rather than at the level of receptors.

OBJETIVO: El estudio fue realizado para evaluar el efecto de los abridores de canales de potasio en la tolerancia a la morfina, y viceversa. MÉTODOS: Para el estudio, se usaron ratones albinos suizos de ambos sexos que pesaban entre 25-30 g. El estudio evalúa el efecto de los abridores de canales de potasio (cromacalina, diazóxido y minoxidil) en la tolerancia a la morfina, y viceversa, usando la prueba de la sacudida de la cola y la prueba de la formalina. RESULTADOS: El efecto antinociceptivo de la cromacalina y el minoxidil fue significativamente reducido cuando se le administró a los ratones tolerantes a la morfina, en ambas pruebas conductuales. Sin embargo, se observó un efecto analgésico reducido de diazóxido sobre la tolerancia a la morfina en la prueba de la formalina, pero no en la prueba de la sacudida de la cola. Se observó tolerancia al administrar morfina a animales crónicamente tratados con cualquiera de los abridores de canales de potasio. El mismo efecto fue observado cuando se inyectó la morfina al grupo tratado con una combinación de morfina y cualquiera de los abridores de canales de potasio. CONCLUSIONES: Por consiguiente, este estudio sugiere que tanto la morfina como los abridores de canales de potasio son tolerantes cruzados. Sin embargo, tal interacción ocurre a nivel de los canales de potasio más bien que a nivel de los receptores.

Utilidad y seguridad del 17-alfa-estradiol 0, 025 por ciento versus minoxidil 2 por ciento en el tratamiento de la alopecia androgenética / Usefulness and safety of 0.025 percent 17-alpha-estradiol versus 2 percent minoxidil in the treatment of androgenetic alopecia

Introducción: La calvicie más común es la alopecia androgenética, la cual consiste en una pérdida progresiva del cabello inducida por la acción de los andrógenos a nivel del folículo piloso. Objetivos: Evaluar la utilidad y seguridad del 17-alfa-estradiol al 0,025 por ciento en el tratamiento de la alopecia androgenética. Material y Métodos: Uso de una solución tópica capilar de 17-alfa-estradiol al 0,025 por ciento versus minoxidil al 2 por ciento en solución tópica capilar, durante 12 semanas, en pacientes chilenos con diagnóstico de alopecia androgenética mediante el análisis cuantitativo del videotricograma. Resultados: Se observó una tendencia al aumento de los cabellos en anágeno y disminución de los cabellos en telógeno en los pacientes tratados con 17-alfa-estradiol al 0,025 por ciento en la zona frontoparietal sin aparición de efectos adversos.

Introduction: Androgenetic alopecia is the most common cause of baldness. It consists of progressive hair loss induced by the action of androgens in the hair follicle. Aim: To evaluate usefulness and safety of 0.025 percent 17-alpha-estradiol in the treatment of androgenetic alopecia. Material and Methods: Use of a topic hair solution of 0.025 percent 17-alpha-estradiol versus 2 percent minoxidil topic hair solution for twelve weeks in Chilean patients with clinically diagnosed androgenetic alopecia through quantitative analysis with videotrichogram. Results: Patients treated with 0.025 percent 17-alpha-estradiol showed a tendency to increase the number of hair follicles in anagen phase and a decrease in telogen phase in the frontoparietal zone with no adverse events.

Role of ion channel modifiers in reversal of morphine-induced gastrointestinal inertia by prokinetic agents in mice.

Prokinetic drugs like mosapride, domperidone etc, are used to treat gastrointestinal delay. Though the receptor-mediated actions of these agents have been studied, involvement of ion channels in reversing morphine-induced gastrointestinal inertia by prokinetic agents has not been explored. Charcoal meal test was used to measure small intestinal transit (SIT) in adult male Swiss albino mice. Animals were given ion channel modifiers and prokinetic drugs intragastrically. Reversal of morphine-induced gastrointestinal delay by mosapride was decreased significantly by CaCl2, minoxidil and glibenclamide. Similarly, domperidone's effect on morphine was decreased by CaCl2, nifedipine, minoxidil and glibenclamide significantly. The results reveal that ion channel modifiers counteract the prokinetic effects of mosapride or domperidone.

Renal humoral modulation of skeletal muscle tone in mice: implications for 'the pulmonary-renal cascade'.

The pulmonary-renal cascade may regulate the respiration and skeletal muscle contractility. To evaluate this working hypothetical model, we conducted experiments to ascertain the skeletal muscle tone of the Swiss mice (20-35 g). The animals were evaluated for their skeletal muscle tone via several techniques i.e. inclined plane test, grip strength test and swim test. Groups of mice (n=6) were pre-treated with mefenamic acid (60 mg/kg, i.p), carbenoxolone (100 mg/kg i.p) or vehicle only 15 minutes before the treatment with heparin (500 U/kg, i.v), urokinase (5500 U/kg, i.v) and erythropoietin (150 U/kg, i.v). Heparin potentiated the loss of skeletal muscle tone induced by mefenamic acid and carbenoxolone while urokinase & erythropoietin significantly enhanced the skeletal muscle tone as evaluated by all or one of the tests. Other groups of mice (n=6) were pretreated with mefenamic acid (1 mg i.c.v), carbenoxolone (160 microg i.c.v) or minoxidil (30 microg i.c.v) and the effects of heparin & urokinase and erythropoietin on skeletal muscle tone were evaluated. To study the effects of heparin and urokinase on nerve regeneration, two groups of mice underwent a sham and sciatic nerve crush procedure. The mice treated with urokinase recovered much faster as compared to those treated with heparin or saline. These experimental results suggest that gap junction blockers and potassium channel openers interact with heparin, urokinase and erythropoietin to control the skeletal muscle tone.

Effect of potassium channel modulators on toxicity of Cleistanthus collinus.

The study was conducted to determine the effects of boiled extract of Cleistanthus collinus on rats by observing ECG changes and electrolyte levels in serum and urine. Influence of minoxidil and glibenclamide on Cleistanthus collinus induced toxicity was determined. ED50 for arrhythmia, changes in contractility and heart rate were recorded using the isolated frog heart. Cleistanthus at low doses caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in rat. LD50 was found to be 1690 mg/kg. Minoxidil potentiated cardiac toxicity, whereas glibenclamide did not produce any significant change. High concentration of potassium in Cleistanthus extract hindered comparison of its levels. There was excretion of sodium even in the presence of hyponatraemia. Cleistanthus at low dose caused transient tachycardia and increase in contractility and at high dose caused arrhythmia and cardiac arrest in isolated frog heart. ED50 for arrhythmia was found to be 1406 mg/kg. Acute toxicity was mainly due to depressive cardiac activity of Cleistanthus. It also caused renal failure. Potassium channel modulators did not have important role in acute cardiac toxicity treatment. Probably in chronic toxicity, electrolyte level changes are involved and potassium channel modulators might have a role.

Effect of ATP-dependent K+ channel openers and blockers on serum concentration of aldosterone in rats

There are many reports for involvement of ATP-sensitive potassium channels in pancreatic, cardiac and vascular smooth muscle cells. This study examined the effect of single doses of K+ channel openers; diazoxide, minoxidil and K+ channel blockers; chlorpropamide, glibenclamide on serum concentration of aldosterone in male rats. Blood samples were obtained 60 minutes after drug treatment and serum aldosterone level was determined by RIA. The basal serum aldosterone was 659.32 +/- 71.48 pg/ml and after diazoxide or minoxidil administration increased to 1188.53 +/- 99.45 pg/ml and 1392.69 +/- 177.83 pg/ml, respectively. Chlorpropamide or glibenclamide treatment did not produce any change in basal serum aldosterone concentration, but in early streptozotocin-induced diabetic rats decreased serum aldosterone level significantly [P<0.001]. Pretreatment with glibenclamide blocked aldosterone response to diazoxide but did not affect aldosterone response to exogenous ACTH to the same extent. Effect of diazoxide in insulin-treated rats was approximately similar to that of normal rats. Comparison of blood glucose concentration determined in normal, insulin treated and diabetic rats after different drug administration showed that there is no correlation between blood glucose level and the responses observed in serum hormone concentration. The results indicate that regulatory processes involved in the secretion of aldosterone are responsive to drugs affecting glibenclamide-sensitive K+ channels

Comparison of skin permeability of drugs in mice and human cadaver skin.

In vitro percutaneous absorption of four antihypertensive drugs were carried out across the mice and human cavader skin in order to compare their skin permeability. An interesting trend was noticed in these experiments. Poorly water soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice skin whereas the steady-state flux of the water soluble drug propranolol hydrochloride was almost same in both human cadaver and mice skin. The permeation rate of prazosin hydrochloride and propranolol hydrochloride through the human cadaver skin fluctuated widely over time, but in mice skin, distinct trends were noticed. The study indicates that the overall permeation rate in mice skin is higher than that in the cadaver skin and the meeting of the target-flux in mice skin does not guarantee its good permeability in human skin.

Minoxidil alopécias / Minoxidil in alopecia

Este trabalho é uma revisåo bibliográfica sobre o uso do minoxidil nas alopécias androgênica e areata, abordando o histórico, os mecanismos de açåo, as aplicaçöes terapêuticas e os efeitos colaterais desta droga

Tratamento da alopécia areata: Revisäo bibliográfica de 10 anos / Treatment of alopecia areata: review bibliografic of 10 years

Os autores fazem uma revisäo do tratamento da alopécia areata durante um período de 10 anos e concluem pela näo existência ainda de um medicamento eficaz para curar esta afecçäo

Minoxidil tópico na alopecia androgenética: atualizaçäo e experiência pessoal / Topical minoxidil in adrogenetic alopecia: actualization and personal experience

Esse trabalho faz uma atualizaçäo sumária das publicaçöes sobre o minoxidil tópico no tratamento da alopecia androgenética. Säo analisados diferentes aspectos: mecanismo de açäo, metodologia das investigaçöes, promoçäo da resposta de cabelos, diminuiçäo ou cessaçäo da queda de cabelos, eficácia da droga a longo prazo, resultados cosméticos e reaçöes adversas. É relatada a experiência pessoal de um dos autores no tratamento de 44 pacientes com alopecia androgenética, pela soluçäo tópica de minoxidil a 2%. Os resultados näo diferem dos relatados da literatura, evidenciando a eficácia da droga na induçäo do crescimento de cabelos terminais. Entretanto, um efeito cosmético significativo ocorreu em número reduzido de pacientes. Houve ausência de reaçöes adversas, observando-se freqüência pequena de reaçöes locais

Ensaios com minoxidil / Experiments with minoxidil

A dissoluçäo de minoxidil sob forma de pó microcristalino foi avaliada em diversas temperaturas. A avaliaçäo de minoxidil em soluçöes com diferentes concentraçöes foi feita espectrofotometricamente (U.V.)

O uso de Minoxidil Tópico no tratamento da alopécia: uma revisäo / The use of topic minoxidil in treatment of alopecia: a review

Os autores revisam o uso tópico do minoxidil na alopécia areata e androgênica, avaliando aspectos farmacológicos, formas de utilizaçäo, efeitos adversos, duraçäo e resultados da descontinuaçäo da terapêutica. Analisam criticamente os resultados obtidos pelos diversos autores e indagam sobre a validade deste tipo de tratamento