Luteinizing hormone-stimulated pituitary adenylate cyclase-activating polypeptide system and its role in progesterone production in human luteinized granulosa cells.

The present study examined the gonadotropin regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP type I receptor (PAC(1)-R) expression, and its role in progesterone production in the human luteinized granulosa cells. The stimulation of both PACAP and PAC(1)-R mRNA levels by LH was detected using a competitive reverse transcription-polymerase chain reaction (RT-PCR). PACAP transcript was stimulated by LH reaching maximum levels at 12 hours in a dose dependent manner. LH treatment also stimulated PAC(1)-R mRNA levels within 24 hours. Addition of PACAP-38 (10(-7) M) as well as LH significantly stimulated progesterone production during 48 hours culture. Furthermore, co-treatment with PACAP antagonist partially inhibited LH-stimulated progesterone production. Treatment with vasoactive intestinal peptide, however, did not affect progesterone production. Taken together, the present study demonstrates that LH causes a transient stimulation of PACAP and PAC(1)-R expression and that PACAP stimulates progesterone production in the human luteinized granulosa cells, suggesting a possible role of PACAP as a local ovarian regulator in luteinization.

Role of hepatocyte growth factor/c-Met signaling in regulating urokinase plasminogen activator on invasiveness in human hepatocellular carcinoma: a potential therapeutic target.

Hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear. This study was designed to investigate the roles of HGF/c-Met in tumor progression and metastasis in HepG2 and Hep3B hepatoma cell lines. Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner. Activity of c-Met phosphorylation peaked 1-3 min after HGF treatment and then declined. HGF enhanced the protein level and the activity of uPA in HepG2 and Hep3B cells, and the uPAR protein level also increased in a HGF dose-dependent manner. HGF increased cell invasion through the Matrigel. A monoclonal antibody against human uPA receptor, mAb 3936, inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down-regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion. These results suggest that hepatoma cells express functional c-Met, which may provide a target for a therapeutic basis to interfere with metastases of cancer cells by inhibiting uPA system-mediated proteolysis.

The effect of pudendal block on voiding after hemorrhoidectomy.

PURPOSE: Urinary retention in common benign anal surgery is a burden to ambulatory surgery. A pudendal nerve block was used in hemorrhoid surgery to reduce voiding complications. METHODS: The effects of a pudendal nerve block in anal surgery were compared with those of spinal anesthesia. In this prospective study, 163 consecutive patients who underwent elective hemorrhoids surgery by a single surgeon were randomized to receive pudendal nerve block (pudendal group) with 0.5 percent bupivacaine (n = 81) with 1:20,000 epinephrine or spinal anesthesia (spinal group) with 0.5 percentbupivacaine (n = 82). RESULTS: There were no statistically significant differences in the patient demographics, total amount of fluid administered, time to the onset of anesthesia, or intraoperative pain. All patients had a successful block during surgery. However, puborectalis muscle relaxation was not complete in the pudendal group. The time from the injection of the anesthetics to the first sensation of pain was longer in the pudendal group (9.1 vs. 3.1 hours; P < 0.001). Urinary catheterization was required in only 6 patients in the pudendal group compared with 57 patients in the spinal group (P < 0.001). The degree of pain was significantly lower in the pudendal group (2.7 vs. 5.2, Visual Analog Scale; P < 0.001). The amount of analgesics injected was significantly lower in the pudendal group (16/81 vs. 45/82; P < 0.001). CONCLUSIONS: A pudendal nerve block with bupivacaine results in fewer postoperative voiding complications and less pain compared with the traditional spinal anesthesia in a hemorrhoidectomy.