Atul Rajpurkar

COCAINE INDUCED APOPTOSIS IN RAT TESTES

PURPOSE Exposure of rats to chronic cocaine results in disruption of spermatogenesis including reduction of germ cells. However, the cellular mechanism responsible for the testicular damage in testes is still unknown. We have studied the role of apoptosis in cocaine induced testicular damage. MATERIALS AND METHODS Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg./kg. body weight) subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed at 15, 30, 60, and 90 days of cocaine administration. In situ detection of germ cells with DNA strand breaks in paraffin-embedded testicular section (5 microm.) was achieved by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end-labeling (TUNEL) method. DNA fragmentation was also determined by gel electrophoresis. RESULTS Apoptotic cells were found in the spermatocytes and spermatogonia of germinal epithelium. Less than 7% of seminiferous tubule cross sections showed a high level of apoptosis (> or =3 apoptotic cells per tubule) in control animals compared with experimental group where 25% of the tubules showed a high level of apoptosis (p<0.05). The number of apoptotic cells was significantly increased by 15 days, peaked at 30 days and persisted up to 90 days of cocaine exposure when compared with controls (p<0.05). DNA isolated from the cocaine treated testes displayed a clear ladder pattern whereas the DNA from controls did not. CONCLUSIONS The experimental results presented here suggest that cocaine exposure leads to significant apoptosis in rat testes and the mechanism of cocaine induced testicular injury may be related to the induction of apoptosis.

Assessment of psychosexual adjustment after insertion of inflatable penile prosthesis

OBJECTIVES To evaluate the psychosexual benefit obtained from multicomponent penile implant surgery in patients with erectile dysfunction. METHODS A psychosexual questionnaire was given to 35 patients undergoing penile prosthesis implantation before surgery and at 3 months, 6 months, and 1 year after surgery. The questionnaire consisted of 13 questions scored on a scale from 1 through 5. Results of the questionnaire were statistically analyzed for differences among the preoperative, 3-month postoperative, 6-month postoperative, and 1-year postoperative period. RESULTS The general linear model evaluation showed a significant difference for each overall combination of the following pairs: preoperative versus 3 months postoperative (P=0.0005) and 3 months postoperative versus 6 months postoperative (P=0.002). There was no overall difference between psychosexual total score at 6 months after surgery and 1 year after prosthesis implantation (P=0.85). The patients perceived improvement in their erectile ability and libido. Concern about obtaining and maintaining an erection during intercourse was significantly alleviated. There was an increase in the frequency of sexual activity and an improvement in satisfaction with sex life. A decrease in feelings of sadness, depression, anxiety, anger, frustration, and embarrassment related to sexual activity was also noted. CONCLUSIONS The current study demonstrates significant improvement in the psychosexual well being of multicomponent penile implant recipients, with attainment of a high level of patient satisfaction up to 1 year after surgery.

ANTIBACTERIAL ACTIVITY OF ANTIBIOTIC COATED SILICONE GRAFTS

PURPOSE Postoperative infection remains one of the most serious complications of implantation of penile prostheses. Attempts to reduce the rate of infection by spraying the prosthesis with an antibiotic solution prior to implantation, along with perioperative antibiotics, have failed to eradicate infection. No published studies have evaluated the effect of antibiotic coating of penile prostheses. In this study, we evaluate the antibacterial effect of antibiotic-coated silicone strips as a surrogate for the penile prosthesis. MATERIALS AND METHODS Strips coated with several different antibiotics were dipped in bacterial solutions containing Staphylococcus epidermidis or S. aureus and implanted subcutaneously in adult Sprague-Dawley rats. After a week, the strips were removed, and the number of bacteria on the strips and in the surrounding tissue were determined. The in vitro antibiotic activity of the antibiotic-coated strips against the same organisms was also determined. RESULTS In the group of rats that received silicone strips contaminated in vitro with S. epidermidis, six of nine control rats yielded strips and tissues containing heavy bacterial growth. None of six strips coated with rifampin/minocycline yielded bacterial growth, nor did any of the seven strips coated with vancomycin. One of seven rats that received amikacin-coated strips had infection of the strip. The tissue results were similar to the strip results. In the group using S. aureus as the contaminating bacterium, the strips and tissues from eight of nine control rats yielded bacteria. None of the six rifampin/minocycline-coated strips yielded bacteria, while two of seven vancomycin-treated strips and two of six amikacin-coated strips were infected with S. aureus. The difference in bacterial growth between controls and antibiotic-coated strips reached a level of statistical significance for the rifampin/minocycline and vancomycin groups and was highly significant for the rifampin/minocycline groups. CONCLUSION The experimental results presented here suggest that coating silicone graft material with antibiotics, particularly rifampin/minocycline, can reduce the incidence of graft colonization in contaminated wounds in rats, even in the absence of systemic antibiotics. These graft materials may prove useful in preventing the infection of penile prostheses.

Lipid peroxidation and antioxidant activities in rat testis after chronic cocaine administration

OBJECTIVES Our recent study has shown that cocaine has adverse action on spermatogenesis and fertility in male rats. Adverse effects of cocaine on the testes may be mediated by oxidative damage and subsequent lipid peroxidation. Glutathione is a cellular antioxidant and is found in high concentrations in the rat testes. In this study, the effects of chronic cocaine administration on the activities of glutathione peroxidase, the level of testicular reduced glutathione, and lipid peroxidation were investigated. METHODS Thirty-day-old male Sprague-Dawley rats were given cocaine hydrochloride (15 mg/kg body weight) subcutaneously daily for 90 days. Control animals received equal volumes of normal saline daily for 90 days. Testes were removed at 15, 30, 60, and 90 days after cocaine injection. Tissues were washed and homogenized in ice-cold metaphosphoric acid solution or Tris-HCI buffer. Reduced glutathione, glutathione peroxidase, and malonaldehyde levels were determined by colorimetric assay. Statistical analysis was performed using analysis of variance. RESULTS Testicular reduced glutathione and glutathione peroxidase were significantly decreased in the treatment testes 15, 30, 60, and 90 days after chronic cocaine injection compared with controls (P <0.05). The testicular malonaldehyde level was 20.8% (P <0.05), 22.1% (P <0.05), 31.2% (P <0.05), and 24.7% (P <0.05) above the control value on days 15, 30, 60, and 90, respectively. CONCLUSIONS Our findings demonstrate that chronic administration of cocaine to male rats induces a depletion of reduced glutathione and glutathione peroxidase. Adverse effects of cocaine on the testes are at least in part due to impairment of the function of the antioxidant defense and further enhancement of lipid peroxidation.