Emergency surgery for patients with severe acute cholangitis carries formidable postoperative morbidity and mortality rates. A retrospective study was conducted on 86 consecutive patients who had exploration for the calculous obstructions to identify the high-risk population to guide better management. Septicemic shock was present in 55 patients before surgery. All patients had ductal exploration under general anesthesia. Additional procedures included cholecystectomy (n = 55), cholecystostomy (n = 5), and transhepatic intubation (n = 2). Complications and deaths occurred in 43 (50%) and 17 (20%) patients, respectively. Multivariate analysis on the 25 clinical (n = 14) and biochemical (n = 11) parameters evaluated yield the following five predictive factors (relative risk): the presence of concomitant medical problems (4.5); pH less than 7.4 (3.5); total bilirubin more than 90 mumol/l (3.1); platelet less than 150 x 10(9)/l (2.9), and serum albumin less than 30 g/L (2.9). In the presence of three or more albumin less than 30 g/L (2.9). In the presence of three or more risk factors, postoperative morbidity and mortality rates were 91% and 55%, respectively, which were significantly higher than those with two or less risk factors (34% and 6%, respectively). As thrombocytopenia developed even with transient hypotension, timely ductal decompression would improve outcome of these patients after surgery. For the high-risk population, application of nonoperative biliary drainage might be considered.

Spermatogenesis, a tightly regulated developmental process of male germ cells in testis, is associated with temporal and spatial expression of gap junction proteins, such as the connexin family members. Perturbation of their expressions may lead to spermatogenic arrest as manifested by disruption of cell-cell interaction. To explore the role(s) of connexins during spermatogenesis, we utilized the small peptide antagonistic approach to specifically deplete connexin 31, connexin 33, and pan-connexin. Three connexin peptides corresponding to the extracellular binding domain of connexin 31 and connexin 33 and to the extracellular conserved domain of connexins were designed and synthesized commercially. Peptides (at single dosage of 0.5, 1, or 2 mg per animal) were injected into rat testes and testes were collected on day 0, 1, 3, 5, 10, 15, and 30 after microinjection. In situ TUNEL assay demonstrated the induction of apoptosis in the testes after pan-connexin peptide treatment in a dose-dependent manner from day 3 and onward. Unlike the pan-connexin peptide, connexin 31 and connexin 33 peptides appeared to have little effect on inducing apoptosis and germ cell loss. CD45 staining also detected the occasional presence of infiltrating lymphocytes in the seminiferous tubules. Accompanied with the apoptotic events, two apoptotic markers, NF-kappaB and caspase 3, demonstrated a general up-regulation in their expressions. In adjacent testis sections, eliminations of connexin 31, 32, and 43 were observed. However, an induction of connexin 33 expression was detected. This suggests the versatility and functional diversity of connexins in the testis. The expression of ZO-1, the only known adaptor of connexins in the testis, was reduced and remained in a low level in the seminiferous epithelium. As such, the alterations of connexins in seminiferous epithelium may induce apoptotic signaling in the testis via the caspase 3 and the NF-kappaB pathway. This demonstrates the significant role of testicular connexins to maintain the survival of germ cells by regulating inter-cellular communications among germ cells and adjacent supporting cells during spermatogenesis. In addition, the inter-relationship between connexins and other junction proteins and associated signaling protein were investigated. After pan-connexin peptide treatment, a dys-localization of N-cadherin, an adherens junction protein, and diminution of occludin, a tight junction protein, level were detected. In addition, inductions of junction regulatory protein, cathepsin L, was observed during the course of peptide-mediated germ cell loss in the testes. In summary, pan-connexin peptide treatment triggered apoptosis and germ cell loss in the testes. This event influenced the localization and expression of different junction proteins and junction-associated protein in the testes.

Together with previous data, the present results indicate synergistic action of melatonin and castration in inhibiting the growth of androgen-sensitive LNCaP tumor. Androgen-sensitive prostate cancer cell proliferation may be modulated by opposite changes in cyclin D1 levels induced by activated MT(1) and EGF receptors. In androgen-insensitive prostate cancer cells, MT(1) receptor-mediated signal transduction may become defective not only through changes in membrane receptor protein expression and/or functions, but also by means of alterations in downstream postreceptor signaling events.