Inhibition of HIV-1 integrase-catalysed reaction by new DNA minor groove ligands: the oligo-1,3-thiazolecarboxamide derivatives

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme in the life cycle of the retrovirus, responsible for catalysing the insertion of the viral genome into the host cell chromosome. For this reason it provides an attractive target for antiviral drug design. We synthesized a series of novel thiazole (Tz)-containing oligopeptides (TCOs; oligo-1,3-thiazolecarboxamides), specifically interacting within the minor groove of DNA. The oligocarboxamide derivatives contained 1-4 Tz rings and different N- and C-terminal groups. The effect of these oligocarboxamides on the HIV-1 IN-catalysed reaction was investigated. Some of the compounds were able to inhibit the reaction. The inhibitory effect of the TCOs increased with the number of Tz units. The structure of various additional positively and/or negatively charged groups attached to the N- and C-termini of TCOs had a pronounced effect on their interaction with the DNA substrate complexed to IN. Modified TCOs having a better affinity for this complex should provide a rationale for the design of drugs targeting the integration step.     

Partial penectomy. Technique to eliminate meatal stricture.

A surgical technique for partial penile amputation is described which prevents meatal retraction and stenosis, and results in a functionally and cosmetically acceptable phallus.     

Laparoscopic management of symptomatic and large adrenal cysts

PURPOSE: We present the feasibility and results of the laparoscopic management of symptomatic and large adrenal cysts. MATERIALS AND METHODS: From June 1993 to April 2004 we performed 149 laparoscopic adrenalectomies. In this series 8 patients with symptomatic adrenal cysts or pseudocysts were treated laparoscopically. Surgical indications for laparoscopic management of adrenal cysts were abdominal pain in 5 cases and cyst size 5 cm or greater in 3. RESULTS: The incidence of adrenal cyst was 5.4% (8 of 149 cases). Six patients underwent laparoscopic adrenal cyst decortication and marsupialization, 1 underwent laparoscopic partial adrenalectomy and 1 underwent laparoscopic adrenalectomy. Mean operative time was 77.5 minutes. There were no intraoperative or postoperative complications. Mean hospital stay was 1.7 days. At a mean followup of 18.5 months all patients were asymptomatic and without radiographic evidence of cyst recurrence. CONCLUSIONS: Laparoscopic conservative management of adrenal cysts is safe and feasible. Laparoscopic decortication and marsupialization should be the preferred treatment option for symptomatic adrenal cysts. Laparoscopic partial adrenalectomy or a total adrenalectomy can be performed in cases of larger cysts which compromise most of the adrenal gland. To our knowledge, this represents the largest series of symptomatic adrenal cysts managed laparoscopically.