Age-associated changes in the expression pattern of cyclooxygenase-2 and related apoptotic markers in the cancer susceptible region of rat prostate

Senescence-associated changes in the prostate are believed to play an important role in the genesis of prostate cancer. In order to provide further information on how aging increases the prostate susceptibility to cancer, we examined the pattern of cyclooxygenase (COX)-2 expression and the concomitant alterations in prostaglandin E(2) (PGE(2)) synthesis in the prostate glands of 4-, 10-, 50- and 100-week-old Fischer 344 rats. This was carried out in the prostatic areas where hormone-induced tumors arise, namely the periurethral ducts of the dorsolateral prostate (DLP). Age-associated changes were also evaluated for pro- and anti-apoptotic factors linked to COX-2 signaling and known to be involved in the normal development of the prostate gland as well as in carcinogenesis. COX-2 expression was increased in the DLP in an age-dependent manner where senescent rats had >3-4-fold higher COX-2 mRNA and protein levels than their juvenile counterparts (P<0.05). The age-related changes in COX-2 were accompanied by a similar up-regulation in the PGE(2) synthesis. Evaluation of mediators of apoptotic signaling showed a significant (P<0.05) decline in the expression levels of the pro-apoptotic BAX (>6-fold) and peroxisome proliferator-activated receptor gamma (>3-fold) and in caspase-3 activity (>2-fold) and an up-regulation of the anti-apoptotic Bcl(2) (>8-fold), PKCalpha (>2-fold) and pAkt (>4-fold) in the 100-week-old rats versus the 4-week-old animals. There was an approximately 15-fold age-dependent decrease in the pro-apoptotic ratio BAX:Bcl(2) and an increase in the anti-apoptotic variable PKCalpha(*)Bcl(2)/BAX in the senescent rats compared with the juvenile ones. These results suggest that increased COX-2 expression can be linked to the decline in the pro-apoptotic signaling in the prostate gland during aging. Subsequently, COX-2 inhibitors can be considered as a promising class of agents to attenuate the increased cell survival and, hence, protect against tumorigenesis in the aging prostate.     

A randomized trial of sublingual misoprostol for cervical priming before hysteroscopy

STUDY OBJECTIVE: To evaluate the effects of sublingual misoprostol on cervical dilatation before hysteroscopy. DESIGN: Prospective randomized study (Canadian Task Force classification I). SETTING: University teaching center. PATIENTS: Forty nulliparous women who received injection of leuprolide acetate 4 weeks before hysteroscopy, of whom 20 were randomized to treatment with misoprostol and 20 to placebo. INTERVENTION: Sublingual misoprostol 100 mug or placebo administered 12 hours before operative hysteroscopy. MEASUREMENTS AND MAIN RESULTS: Misoprostol was associated with mild abdominal cramps in four women (20%) and vaginal bleeding in another. No side effects were reported among women in the placebo group. There was no difference in baseline diameter of the cervical opening between the misoprostol group (4.0 +/- 0.1 mm) and the control group (4.2 +/- 0.2 mm). Time to dilate cervix up to 9 mm was also not significantly different (misoprostol 48.4 +/- 9.2 sec, placebo 37.7 +/- 4.1 sec). We found no difference in degree of difficulty dilating the cervix between groups. Cervical tear occurred in one patient in the misoprostol group. CONCLUSION: Sublingual misoprostol 100 mug does not facilitate cervical dilatation before hysteroscopy. This may be related to leuprolide's hypoestrogenic effect.     

Evaluation of a therapeutic conversion from amlodipine to felodipine

STUDY OBJECTIVES: To determine patient satisfaction with and tolerability of a conversion from a long-acting calcium channel blocker, amlodipine, to felodipine. Secondary objectives were to compare the effect of the change on blood pressure and heart rate and the economic impact of the change. DESIGN: Retrospective study. SETTING: Veterans Affairs health care system. PATIENTS: Two hundred eighty-three men who were taking amlodipine to manage hypertension. INTERVENTION: Patients who were converted to felodipine were mailed a survey quantifying subjective symptoms; the survey also included questions specific to the change program. Transitory blood pressure and heart rate measurements retrieved by electronic chart review were evaluated during therapy with both amlodipine and felodipine. MEASUREMENTS AND MAIN RESULTS: Ninety-five percent of patients were satisfied with the conversion process and tolerated the switch from amlodipine to felodipine. Mean systolic and diastolic blood pressures were reduced by 4.4 and 2.6 mm Hg, respectively (p=0.166 and 0.187, respectively). Heart rate was reduced significantly by 4.2 beats/minute (p=0.008). The conversion realized a net annual drug cost savings of approximately dollars 16,000. CONCLUSION: Our patient population was satisfied with the conversion from amlodipine to felodipine, and the new drug was found to be effective, well tolerated, and associated with a modest cost reduction.     

Management of the sensitized adult heart transplant candidate

Eckman PM, Hanna M, Taylor DO, Starling RC, Gonzalez‐Stawinski GV. Management of the sensitized adult heart transplant candidate.
Clin Transplant 2010: 24: 726–734. © 2010 John Wiley & Sons A/S. Abstract: Heart transplant recipients sensitized to human leukocyte antigens comprise a challenging subgroup of patients. Sensitization has been associated with a variety of effects that determine short‐term and long‐term outcomes. These include a higher rate of acute rejection and graft loss, and a heightened risk for developing cardiac allograft vasculopathy. Because of improvements in both tissue typing and immunomodulatory therapies coupled with the growing population receiving mechanical circulatory support/LVAD, the percent of sensitized patients listed for heart transplantation has increased, inflicting a greater burden to the already scarce donor pool. Despite these potentially adverse developments, pre‐transplant immunologic management has resulted in decreased waiting times and outcomes that were not possible over 10 yr ago. The following review will focus on the contemporary management of the sensitized heart transplant candidate and highlight therapies that have allowed the successful transplantation of this growing and challenging patient population, including several approaches in development.     

A COMPARISON OF THE ANTICONVULSANT EFFECTS OF PROPOFOL AND THIOPENTONE AGAINST PENTYLENETETRAZOL-INDUCED CONVULSIONS IN THE RAT

1. The anticonvulsant effects of subanaesthetic doses of propofol and thiopentone against PTZ-induced seizures and mortality were examined in the rat. 2. Administration of propofol (50 mg/kg, i.p.) 5 min prior to PTZ treatment increased the 2 h CD50 and the 24 h LD50 of PTZ by 3.4-fold, whereas thiopentone pretreatment (20 mg/kg, i.p.) increased these values by more than five-fold. 3. Both propofol and thiopentone prolonged the latency to the onset of clonic seizure but the effects of the former were more marked. 4. The data demonstrate that propofol was more effective than thiopentone in providing complete protection against PTZ-induced seizures for the first 30-40 min of observation and that thiopentone, because of its sustained effects, was more effective in reducing the cumulative incidence of seizures and mortality over 2 and 24 h, respectively. 5. We conclude that propofol is a very effective anticonvulsant and provides complete protection of short duration against PTZ-induced seizures in the rat.     

Surgical correction of congenital constriction band syndrome in children: Replacing Z-plasty with direct closure

Congenital constriction band syndrome is a sporadic condition that may also be present in association with other congenital anomalies. It has an incidence varying from one in 1200 to one in 15,000 live births. There is a significant predilection for the upper extremities and distal limbs. The two main objectives for the treatment of congenital constriction band syndrome are improvement of function and improvement of cosmetic appearance. Different surgical techniques, such as Z-plasty, have been described and used for decades; however, direct closure after the excision of the constricting band seems to be the simplest and most appropriate, allowing the fatty tissue to naturally reposition itself under the skin. This technique is used in a two-stage approach to avoid affecting distal circulation to the limb.