Castration of adult male rats reduces by half the penile erectile response to electrical field stimulation (EFS) of the cavernosal nerve, and the activity of penile nitric oxide synthase (NOS). Both changes are prevented by androgen administration. We have now investigated whether other strategies of androgen ablation or competition may act as stronger inhibitors, and, if so, whether the stronger inhibition is due to the depletion of penile NOS content. Rats were castrated or left intact and were treated daily as follows: 1) intact, with the antiandrogen flutamide (25 mg/kg/day, i.p.); 2) castrated, with similar treatment; 3) castrated, with 17 beta-estradiol 3-benzoate (estradiol; via silastic tubing, s.c.). Additional groups of intact rats received injections of a GnRH antagonist (GnRHA, 1.25 mg/kg, s.c.), or were hypophysectomized and left untreated. Controls were untreated intact and castrated animals. After 7 days, rats were subjected to EFS, and the ratios between maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were measured. Penile NOS activity and the contents of neuronal NOS (nNOS) and endothelial NOS (eNOS) were determined. Castration reduced the MIP:MAP ratio and penile NOS activity. Androgen receptor blockade with flutamide induced a similar response in intact rats. When flutamide treatment was combined with castration, the erectile response was nearly abolished, but NOS activity was not decreased below the values in castrated rats. Estradiol given to castrated rats and hypophysectomy or GnRHA treatment in intact rats diminished the erectile response below the level in castrated animals. In hypophysectomized rats, penile NOS activity fell below levels in castrated animals. contents of nNOS and eNOS were not significantly reduced by any treatment. These data suggest that penile erection in the rat is completely dependent on androgens, presumably because of their role in the maintenance of penile NOS activity and of other ancillary factors. However, only the complete blockade of residual androgen effects at the tissue level or a total androgen depletion can abolish the erectile response.

These results indicate that chronic smoking in the rat leads to age-independent moderate hypertension and considerable decreases in penile NOS activity and nNOS content, that are not reflected in a reduction of the erectile response to EFS or accompanied by a decrease in penile eNOS.

Castration in the rat reduces both the erectile response and penile nitric oxide synthase (NOS) activity, and these effects are prevented by androgen administration. In this study we determined that the decrease of penile NOS in the castrated rat is due to NOS enzyme inhibition rather than to a reduction of its content and that this inhibition may be reversed. Adult rats were either castrated or left intact, and, after 1 wk, electrical field stimulation (EFS) was applied to the cavernosal nerve and the penises were excised either at the peak of erection or after detumescence. Penile NOS activity in the non-EFS castrates decreased by 70% as compared with the intact non-EFS-treated controls, but neuronal NOS content remained unaffected despite changes in regional distribution. NOS activity in the castrated penis was restored to normal values by EFS at the peak of stimulation, and then decreased on detumescence. This was in contrast to the intact controls in which EFS did not stimulate penile NOS activity. These data indicate that androgen depletion in the rat reduces penile NOS activity rather than NOS content and that this enzyme inhibition is reversed by cavernosal nerve stimulation.

These results indicate that chronic smoking in the rat leads to age-independent moderate hypertension and considerable decreases in penile NOS activity and nNOS content, that are not reflected in a reduction of the erectile response to EFS or accompanied by a decrease in penile eNOS.

Penile erection is a nitric oxide (NO)-mediated process that has been shown to be androgen dependent in rats. Castration reduces the activity of the penile enzyme involved in NO synthesis, nitric oxide synthase (NOS). To determine whether adrenal androgens and/or corticosteroids contribute to this control, the following groups of Fischer 344 adult male rats (n = 5-7) were studied: 1) intact, 2) castrated, 3) adrenalectomized alone, 4) castrated/adrenalectomized, 5) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.) and hydrocortisone (12 mg/kg, s.c.), 6) castrated/adrenalectomized with dihydrotestosterone (1.2-cm SILASTIC-brand tubing pellet; Dow Corning, Midland, MI), 7) castrated/adrenalectomized with dehydroepiandrosterone (2-cm tubing), 8) castrated/adrenalectomized with aldosterone (1.25 mg/kg, s.c.), and 9) castrated/adrenalectomized with hydrocortisone (12 mg/kg, s.c.). After 1 week, EFS was applied, and the maximal intracavernosal pressure (MIP) and mean arterial pressure (MAP) were recorded. The MIP/MAP ratio in the adrenalectomized group (0.37) was reduced to values found in the castrated group (0.40). The values in both groups were significantly less than those in intact controls (0.75). The most significant reduction in MIP/MAP was seen in the adrenalectomized/castrated group (0.16). Erectile response in animals submitted to adrenalectomy and castration was restored close to intact values with the administration of hydrocortisone and aldosterone (0.63). Similar results were obtained by the administration of either of the substances alone (0.56 and 0.67, respectively). Penile NOS activity assayed by the L-arginine/citrulline conversion was decreased by 55% in the castrated group compared with that in the intact group, but was not further reduced in the adrenalectomized/castrated or adrenalectomized groups. Penile neuronal NOS protein content, estimated by Western blot, was decreased only in the adrenalectomized/castrated animals (35%), and endothelial NOS content was not affected. These data suggest that the rat adrenal gland contributes to the maintenance of the erectile mechanism and may affect neuronal NOS content in the penis in the rat model. The possibility that hypotension may play a role in the erectile dysfunction observed in adrenalectomized rats cannot be discarded.

Background:Chronic intestinal pseudo-obstruction can be a rare complication of systemic lupus erythematosus. It is often late to be identified in contrast to other commoner organs involvement in systemic lupus erythematosus such as nervous system, joint and kidney.Objectives:To report a case of uncommon gastrointestinal complication of lupus, with associated hydronephrosis at the ureter, with treatment delay.Methods:We report a case of chronic intestinal pseudo-obstruction.Results:A 34 year old, with ten-year history of lupus nephritis, presented with recurrent abdominal pain and diarrhoea past nine months. The patient had just been diagnosed as end-stage renal failure a year ago, on regular haemodialysis. For the past ten years, the patient was not able to tolerate immunosuppressant due to the multiple episodes of infections, including shin carbuncle, herpes zoster, breast abscess and catheter-related candida/bacterial infections. However, the patient did not have any other major organs manifestations of lupus for the past ten years. The patient was apyretic. Multiple stool cultures were negative including Clostridium difficile. The abdominal radiography showed dilated small bowel with diffuse thickening of large and small bowels on computed tomography. Bilateral uretero-hydronephrosis was also noted without any evidence of obstructive uropathy on imaging. Ileocolic resection was done for presumed intestinal obstruction and the ileocolic biopsy did not reveal any granuloma, malignancy or vasculitis except for non-specific inflammation of cecum. Cytomegalovirus inclusion body was absent as well. Tuberculosis culture was negative. Oesophagoduodenoscopy and colonoscopy were offered in view of persistent unexplained loose stool and abdominal pain. But unremarkable findings were noted from multiple biopsy specimens of the small and large bowels. Second relook of the initial hemicolectomy specimen with special actin immunostain on the smooth muscle revealed degenerative changes of the muscularis propria. These were evidenced by cytoplasmic vacuolation, atrophy and pyknotic nucleus of the smooth muscle cells with surrounding oedema. Smooth muscle dysmotility could be the underlying pathology of this patient presentation. The patient responded well to intravenous immunoglobulin followed by azathioprine in addition to prednisolone and prokinetic agent.Conclusion:Prompt recognition is pivotal in this case could have prevented the unnecessary surgical intervention earlier. It is potentially reversible. Long term prognosis of this rare entity is, however, varying.Disclosure of Interests:None declared

The successful use of a combination of "patch, drain, and wait" (PDW) and home total parenteral nutrition (TPN) in the management of a case of acute, catastrophic midgut volvulus in a 2-year-11-month-old boy with near-total ischemia/necrosis of his small intestine is reported. The PDW approach to the highly effective management of acute midgut ischemia/necrosis in infancy and childhood (necrotizing enterocolitis and midgut volvulus) involves maximum gut salvage by avoidance of resection, stoma formation, or both through the use of extensive peritoneal cavity drainage by Penrose drains, TPN, and broad-spectrum antibiotics. The extensive peritoneal drainage fosters capture of enteric fistulas with the formation of enterostomies at drain exit sites, while adhesions and ischemia/inflammation-induced hypervascular obliteration of the peritoneal cavity diminish the potential for peritonitis (no peritoneal cavity, no peritonitis) and facilitate impressive salvage of seemingly hopelessly lost ischemic/necrotic gut (a simulation of the in utero ischemic gut process leading to atresias and some varying, but generally mild, gut loss) while simultaneously contributing to the resorption of absolutely non-salvageable gut and the creation of a remarkably clean and adhesion-free peritoneal cavity resembling that of a newborn infant with midgut intestinal atresia.

The successful use of a combination of "patch, drain, and wait" (PDW) and home total parenteral nutrition (TPN) in the management of a case of acute, catastrophic midgut volvulus in a 2-year-11-month-old boy with near-total ischemia/necrosis of his small intestine is reported. The PDW approach to the highly effective management of acute midgut ischemia/necrosis in infancy and childhood (necrotizing enterocolitis and midgut volvulus) involves maximum gut salvage by avoidance of resection, stoma formation, or both through the use of extensive peritoneal cavity drainage by Penrose drains, TPN, and broad-spectrum antibiotics. The extensive peritoneal drainage fosters capture of enteric fistulas with the formation of enterostomies at drain exit sites, while adhesions and ischemia/inflammation-induced hypervascular obliteration of the peritoneal cavity diminish the potential for peritonitis (no peritoneal cavity, no peritonitis) and facilitate impressive salvage of seemingly hopelessly lost ischemic/necrotic gut (a simulation of the in utero ischemic gut process leading to atresias and some varying, but generally mild, gut loss) while simultaneously contributing to the resorption of absolutely non-salvageable gut and the creation of a remarkably clean and adhesion-free peritoneal cavity resembling that of a newborn infant with midgut intestinal atresia.