G-protein Activation Decreases Isoflurane Inhibition of N-type Ba2+ Currents

Background: G-protein activation mediates inhibition of N-type Ca2+ currents. Volatile anesthetics affect G-protein pathways at various levels, and activation of G-proteins has been shown to increase the volatile anesthetic potency for inhibiting the electrical-induced contraction in ileum. The authors investigated whether isoflurane inhibition of N-type Ba2+ currents was mediated by G-protein activation.

Methods: N-type Ba2+ currents were measured in the human neuronal SH-SY5Y cell line by using the whole cell voltage-clamp method.

Results: Isoflurane was found to have two effects on N-type Ba2+ currents. First, isoflurane reduced the magnitude of N-type Ba2+ currents to a similar extent (IC50 ~ 0.28 mm) in the absence and presence of GDP[beta]S (a nonhydrolyzable GDP analog). Interestingly, GTP[gamma]S (a nonhydrolyzable GTP analog and G-protein activator) in a dose-dependent manner reduced the isoflurane block; 120 [mu]m GTP[gamma]S completely eliminated the block of 0.3 mm isoflurane and reduced the apparent isoflurane potency by ~ 2.4 times (IC50 ~ 0.68 mm). Pretreatment with pertussis toxin or cholera toxin did not eliminate the GTP[gamma]S-induced protection against the isoflurane block. Furthermore, isoflurane reduced the magnitude of voltage-dependent G-protein-mediated inhibition of N-type Ba2+ currents, and this effect was eliminated by pretreatment with pertussis toxin or cholera toxin.     

Components of the IFN-gamma signaling pathway in tumorigenesis

Many features of the interferon gamma (IFN-gamma) signaling pathway would suggest that it is anti-tumorigenic. The IFN-gamma signaling pathway leads to apoptosis and to the expression of immune function proteins that could cooperate with T cells in the destruction of tumor. Various lines of experimental approach have, in general, supported the hypothesis that the IFN-gamma signaling pathway is anti-tumorigenic. However, data also indicate that the idea that the IFN-gamma signaling pathway is exclusively anti-tumorigenic is too simplistic. Also, to date, very little of the knowledge regarding the anti-tumor effects of the IFN-gamma pathway has been useful in the prognosis or therapy of cancer. This review summarizes the current state of knowledge regarding the IFN-gamma signaling pathway in tumorigenesis, with an emphasis on MHC class II induction in tumor cells and the induction of apoptosis in tumor cells. The review also indicates some future areas of investigation that offer hope for applying this knowledge in reducing cancer mortality.     

Induced luteolysis in the primate: rapid loss of luteinizing hormone receptors

The molecular mechanisms involved in luteolysis are still unclear in the primate. This study aimed to investigate the effect of induced luteolysis on the ovarian luteinizing hormone (LH) receptor and the steroidogenic enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the marmoset monkey. Luteolysis was induced in the mid-luteal phase either directly by systemic prostaglandin F2alpha (PGF2alpha), or indirectly by LH withdrawal using systemic gonadotrophin releasing hormone antagonist (GnRHant) treatment. The LH receptor was studied by isotopic mRNA in-situ hybridization and in-situ ligand binding and 3beta-HSD expression was studied using isotopic mRNA in-situ hybridization and immunohistochemistry. Induced luteolysis was associated with a reduction in the expression of LH receptor (P < 0.0001) and 3beta-HSD mRNA, closely followed by a reduction in the LH receptor (P < 0.05) and 3beta-HSD protein concentrations within 24 h. There were no differences in the findings whether luteolysis was induced with PGF2alpha or GnRHant. This study shows that disparate mechanisms to induce luteolysis in the primate result in an identical rapid loss of the LH receptor and 3beta-HSD. In conclusion, induced luteolysis leads to rapid loss of the steroidogenic pathway in luteal cells.      

Semen parameters and testicular pathology in men with testicular cancer and contralateral carcinoma in situ or bilateral testicular malignancies

We evaluated 14 patients with bilateral testicular tumour, one-sided tumour and contralateral carcinoma in situ (CIS) of the testis or testis tumour in single testis with respect to their fertility. We analysed semen parameters, serum hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone], testicular sonography, testicular volumes and testicular histology prior to further anti-cancer treatment. Ten out of 14 patients showed normal or reduced sperm concentrations, while 4/14 patients were azoospermic. Serum FSH levels showed a significant negative correlation with sperm concentrations in patients with testicular malignancies (r = -0.64, P = 0.025). Testicular volumes revealed a significant positive correlation with semen parameters in patients with testes that were affected by CIS (r = 0.733, P = 0.038). We conclude that even bilateral testicular cancer and/or CIS do not preclude fertility and, therefore, patients should be offered andrological investigation and therapy, including possibly surveillance strategy or the chance for cryopreservation of the semen prior to further treatment in order to preserve their chances for paternity.