Moduladores seletivos dos receptores da progesterona: revisão da literatura / Selective modulators of progesterone receptors: literature review

Os moduladores seletivos dos receptores da progesterona (MSRP) são substâncias sintéticas derivadas dos esteroides que têm a capacidade de ocupar os receptores da progesterona e passam a ter ação como antagonista, agonista-antagonista ou agonista desse hormônio, dependendo do tecido alvo. Essas variedades de ações favorecem a utilização dessas substâncias para o tratamento da miomatose uterina, endometriose, entre outros, tendo também importante aplicação na anticoncepção e na reprodução assistida. O mecanismo de ação dos MSRP não está completamente elucidado, uma vez que intercalam efeitos sinérgicos e antagônicos aos da progesterona. Entretanto, sabe-se que têm efeito antiproliferativo, antiangiogênico, aumentam os índices de apoptose celular e promovem uma diminuição do aporte sanguíneo das artérias uterinas e dos vasos espiralados do endométrio. O tempo de utilização dessas drogas é restrito devido aos seus efeitos adversos relacionados, principalmente, alterações endometriais, propriedades abortivas de alguns compostos e efeitos adversos associados com a dose e a utilização em longo prazo.

The selective modulators of progesterone receptors (MSRP) are synthetic compounds derived from steroids that have the ability to bind the progesterone receptor. These substances can act as an antagonist, agonist-antagonist or agonist of the progesterone, and these effects are specific for each target tissue. These properties favor the use of these substances for the treatment of uterine fibroids and endometriosis. These componds can also be used in assisted reproduction and contraception. The precise mechanism by which MSRP acts is not fully understood. However, it is known that these componds have antiproliferative and antiangiogenic effects. Also, MSRP promotes an increase in the rates of apoptosis and decreased blood supply of uterine arteries and vessels of the endometrium. The time of use of these drugs is restricted due to its adverse effects mainly related to endometrial changes, its abortion properties, and adverse effects associated with dose and long-term use.

Electroacupuncture ameliorates experimental colitis induced by acetic acid in rat

The effect of electroacupuncture (EA) on experimental colitis was investigated in Sprague-Dawley rats. Colitis was induced by intracolonic instillation of 4% acetic acid. EA (2 Hz, 0.05 ms, 2 V for 20min) was applied to bilateral Hoku (LI-4) and Zusanli (ST-36) on 12 hrs and 36 hrs after induction of colitis. EA-treatment significantly reduced the macroscopic damage and the myeloperoxidase activity of colonic samples at 3 days post-induction of colitis. Colitic colon showed a decreased in vitro motility. However, colonic motility of EAtreated group was not significantly different from that of normal group. The anti-inflammatory effect of EA was not inhibited by a glucocorticoid receptor antagonist, RU-486, but suppressed by a beta-adrenoceptor antagonist, propranonol. These results suggest that EA-treatment has a beneficial effect on colitis, and its anti-inflammatory effect is mediated by beta-adrenoceptor activation but not by endogenous glucocorticoiddependent mechanism.

Research in reproduction: the Indian scenario in the last decade [II].

Developing new, improved and totally safe, effective and acceptable contraceptives based on the recent advances in cellular and molecular biology of reproduction is a new challenge to biomedical scientists involved in research in reproductive biology. The present article reviews some of the major contributions made during the last decade by scientists working in India in developing new strategies and technologies for better human reproductive health and fertility regulation.

Exogenous cysteamine increases basal pancreatic exocrine secretion in the rat

To determine whether exocrine pancreatic secretion is regulated by endogenous somatostatin, somatostatin deficiency was induced by cysteamine. Rats were subcutaneously administered a single dose of cysteamine (30 mg/100 g body weight) 12 hr before experiment. Anesthetized rats were prepared with cannulation into bile duct, pancreatic duct, duodenum, and jugular vein and pancreatic juice was collected. For in vitro study, isolated pancreata of rats, pretreated with cysteamine, were perfused with an intraarterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 mL/min, and pancreatic juice was collected in 15-min samples. In vivo experiment of the rat, the mean basal pancreatic secretions, including volume, bicarbonate, and protein output were significantly increased from 18.4+/-0.5 microL/30 min, 0.58+/-0.05 microEq/30 min, and 214.0+/-26.1 microg/30 min to 51.6+/-3.7 microL/30 min, 1.52+/-0.11 microEq/30 min, and 569.8+/-128.9 microg/30 min, respectively (p<0.05). In the isolated perfused pancreas, cysteamine also resulted in a significant increase in basal pancreatic secretion (p<0.05). Simultaneous intraarterial infusion of octreotide (10 pmol/hr) to isolated pancreata partially reversed the effect of cysteamine on basal pancreatic secretion. These findings suggest that endogenous somatostatin play an important role on the regulation of basal pancreatic exocrine secretion.

Secretory response of cultured acinar cells of rat pancreas to cholecystokinin

To determine the adequate models for studying the functions of pancreatic acinar cells, secretory responses to CCK and to CCK receptor antagonist, L-364, 718 were examined in freshly isolated cells and confluent monolayer cells. The results showed that as CCK concentration increased, releases of amylase and lipase increased dose-dependently reaching a maximum at 10(-9) M in acinar cells cultured in serum-containing media as well as in serum-free media. Acinar response to CCK was partially inhibited by L-364, 718, L-364, 718 itself had no effect on the releases of both amylase and lipase. Confluent monolayer of acinar cells released relatively low levels of enzymes and exhibited less response to CCK. In conclusion, short-term culture of acinar cells would be suitable to study the regulation of pancreatic enzyme secretion, and serum factors do not influence acina response to the secretagogues. However, confluency of the acinar cells resulted in the loss of their secretory potential in the aspect of amylase and lipase release.