A ghrelin receptor agonist is an effective colokinetic in rats with diet-induced constipation.

BACKGROUND: Despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. Recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. Here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin. METHODS: Rats were given low-fiber diets for 5 weeks. Their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet. KEY RESULTS: After the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. However, capromorelin was similarly effective in causing defecation in constipated and non-constipated rats. CONCLUSIONS & INFERENCES: Low-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. The effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.

Site and mechanism of the colokinetic action of the ghrelin receptor agonist, HM01.

BACKGROUND: It has been recently demonstrated that the ghrelin receptor agonist, HM01, caused defecation in rats that were treated to provide a model for the constipation of Parkinson's disease. HM01 significantly increased fecal output and increased Fos activity in neurons of the hypothalamus and hindbrain, but not in the spinal defecation center. Other ghrelin agonists act on the defecation center. METHODS: Receptor pharmacology was examined in ghrelin receptor (GHSR1a) transfected cells. Anesthetized rats were used to investigate sites and mechanisms of action. KEY RESULTS: HM01 activated rat GHSR1a at nanomolar concentrations and was antagonized by the GHSR1a antagonist, YIL781. HM01, intravenous, was potent to activate propulsive colorectal contractions. This was prevented by pelvic nerve section and by intravenous YIL781, but not by spinal cord section rostral to the defecation centers. Direct intrathecal application of HM01 to the defecation center at spinal level L6-S1 initiated propulsive contractions of the colorectum. CONCLUSIONS & INFERENCES: HM01 stimulates GHSR1a receptors on neurons in the lumbosacral defecation centers to cause propulsive contractions and emptying of the colorectum. It has greater potency when given systemically, compared with other GHSR1a agonists.

[Prevalence of bacterial vaginitis and vaginosis: association with clinical and laboratory features, and treatment]. / Prevalencia de vaginitis y vaginosis bacteriana: asociación con manifestaciones clínicas, de laboratorio y tratamiento.

This was a cross-sectional study meant to determine the prevalence of vaginitis and bacterial vaginosis among open population females from Cuernavaca City. The relationship between clinical manifestations, laboratory diagnosis and response to therapy were evaluated as well. A group of 405 sexually active women were enrolled between January and July, 1994. The patients were attending the City Hospital for a regular gynecological consultation, upon their informed consent, they answered a specifically designed questionnaire and had a vaginal secretion sampling. Cotton swabs containing such secretions were employed to measure pH, estimate amines production (fishy odor) and perform both direct microscopic examination and Gram stained smears, which allowed the recognition of yeasts, Trichomonas vaginalis, "clue" cells and normal microflora. Treatments were clotrimazole for candidiasis and metronidazole for trichomoniasis and bacterial vaginosis. Data obtained were analyzed with statistical programs SPSS/PC and EGRET. Overall, 193 out of 405 women (47.7%) had some genital infection; most frequent was candidiasis with a prevalence of 105/405 (26%), bacterial vaginosis and trichomoniasis were present in 67/405 (16.5%) and 7/405 (1.7%) of the population, respectively. Clinical features associated to candidiasis were vulvar itching, dyspareunia, vulvar and cervical erythema, cervical inflammation and vaginal secretion. The only sign consistently observed in bacterial vaginosis patients was a yellow secretion. Women with T. vaginalis showed cervical lesions, friability, microhemorragic zones and vaginal secretion. One important factor linked to bacterial vaginosis was to have had premature labor. Therapeutic responses, with clinical and microbiological cure, were 92% for candidiasis; 93% for bacterial vaginosis; and 100% for trichomoniasis. In conclusion, it is of relevance to stimulate sexually active women to care for their genital health to medically diagnose, avoid and control the very common infections assessed in this paper.

Damage to enteric neurons occurs in mice that develop fatty liver disease but not diabetes in response to a high-fat diet.

BACKGROUND: Disorders of gastrointestinal functions that are controlled by enteric neurons commonly accompany fatty liver disease. Established fatty liver disease is associated with diabetes, which itself induces enteric neuron damage. Here, we investigate the relationship between fatty liver disease and enteric neuropathy, in animals fed a high-fat, high-cholesterol diet in the absence of diabetes. METHODS: Mice were fed a high-fat, high-cholesterol diet (21% fat, 2% cholesterol) or normal chow for 33 weeks. Liver injury was assessed by hematoxylin and eosin, picrosirius red staining, and measurement of plasma alanine aminotransaminase (ALT). Quantitative immunohistochemistry was performed for different types of enteric neurons. KEY RESULTS: The mice developed steatosis, steatohepatitis, fibrosis, and a 10-fold increase in plasma ALT, indicative of liver disease. Oral glucose tolerance was unchanged. Loss and damage to enteric neurons occurred in the myenteric plexus of ileum, cecum, and colon. Total numbers of neurons were reduced by 15-30% and neurons expressing nitric oxide synthase were reduced by 20-40%. The RNA regulating protein, Hu, became more concentrated in the nuclei of enteric neurons after high-fat feeding, which is an indication of stress on the enteric nervous system. There was also disruption of the neuronal cytoskeletal protein, neurofilament medium. CONCLUSIONS & INFERENCES: Enteric neuron loss and damage occurs in animals with fatty liver disease in the absence of glucose intolerance. The enteric neuron damage may contribute to the gastrointestinal complications of fatty liver disease.

The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin.

BACKGROUND: Discovery of adequate pharmacological treatments for constipation has proven elusive. Increased numbers of bowel movements were reported as a side-effect of ulimorelin treatment of gastroparesis, but there has been no investigation of the site of action. METHODS: Anesthetized rats were used to investigate sites and mechanisms of action of ulimorelin. KEY RESULTS: Intravenous ulimorelin (1-5 mg/kg) caused a substantial and prolonged (~1 h) increase in colorectal propulsive activity and expulsion of colonic contents. This was prevented by cutting the nerves emerging from the lumbosacral cord, by the nicotinic receptor antagonist hexamethonium and by antagonists of the ghrelin receptor. The effect of intravenous ulimorelin was mimicked by direct application of ulimorelin (5 µg) to the lumbosacral spinal cord. CONCLUSIONS & INFERENCES: Ulimorelin is a potent prokinetic that causes propulsive contractions of the colorectum by activating ghrelin receptors of the lumbosacral defecation centers. Its effects are long-lasting, in contrast with other colokinetics that target ghrelin receptors.

The relationship between glial distortion and neuronal changes following intestinal ischemia and reperfusion.

BACKGROUND: Damage to mucosal epithelial cells, muscle cells and enteric neurons has been extensively studied following intestinal ischemia and reperfusion (I/R). Interestingly, the effects of intestinal I/R on enteric glia remains unexplored, despite knowledge that glia contribute to neuronal maintenance. Here, we describe structural damage to enteric glia and associated changes in distribution and immunoreactivity of the neuronal protein Hu. METHODS: The mouse small intestine was made ischemic for 3 h and reperfused from 1 to 12 h. Immunohistochemical localisation of glial fibrillary acidic protein (GFAP), Hu and TUNEL were used to evaluate changes. KEY RESULTS: At all time points glial cells became distorted, which was evident by their altered GFAP immunoreactivity, including an unusual appearance of bright perinuclear GFAP staining and the presence of GFAP globules. The numbers of neurons per ganglion area were significantly fewer in ganglia that contained distorted glia when compared with ganglia that contained glia of normal appearance. The distribution of Hu immunoreactivity was altered at all reperfusion time points. The presence of vacuoles and Hu granules in neurons was evident and an increase in nuclear Hu, relative to cytoplasmic Hu, was observed in ganglia that contained both normal and distorted glial cells. A number of neurons appeared to lose their Hu immunoreactivity, most noticeably in ganglia that contained distorted glial cells. TUNEL reaction occurred in a minority of glial cells and neurons. CONCLUSIONS & INFERENCES: Structural damage to gliofilaments occurs following I/R and may be associated with damage to neighboring neurons.

The involvement of nitric oxide synthase neurons in enteric neuropathies.

Nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS) is a transmitter of inhibitory neurons supplying the muscle of the gastrointestinal tract. Transmission from these neurons is necessary for sphincter relaxation that allows the passage of gut contents, and also for relaxation of muscle during propulsive activity in the colon. There are deficiencies of transmission from NOS neurons to the lower esophageal sphincter in esophageal achalasia, to the pyloric sphincter in hypertrophic pyloric stenosis and to the internal anal sphincter in colonic achalasia. Deficits in NOS neurons are observed in two disorders in which colonic propulsion fails, Hirschsprung's disease and Chagas' disease. In addition, damage to NOS neurons occurs when there is stress to cells, in diabetes, resulting in gastroparesis, and following ischemia and reperfusion. A number of factors may contribute to the propensity of NOS neurons to be involved in enteric neuropathies. One of these is the failure of the neurons to maintain Ca(2+) homeostasis. In neurons in general, stress can increase cytoplasmic Ca(2+), causing a Ca(2+) toxicity. NOS neurons face the additional problem that NOS is activated by Ca(2+). This is hypothesized to produce an excess of NO, whose free radical properties can cause cell damage, which is exacerbated by peroxynitrite formed when NO reacts with oxygen free radicals.

Peyronie's plaque: excision and graft versus incision and stent.

Nineteen patients with Peyronie's plaque unsuccessfully treated conservatively were considered surgical candidates. Although all patients had erections intercourse was functionally difficult to impossible for most. Only 30 per cent of the patients who underwent plaque excision and grafting became sexually functional postoperatively. Placement of penile prostheses appears to be the most secure method to rehabilitate the male patient who has become a sexual cripple secondary to Peyronie's plaque.

Adenocarcinoma of the rete testis with a spindle cell component. A possible metaplastic carcinoma.

A case of adenocarcinoma of the rete testis was encountered in a 36-year-old white man. The tumor fulfilled established criteria for determining origin in the rete and showed an unusual biphasic morphology with papillary adenocarcinoma mixed with a prominent component of cytologically malignant spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelium for cytokeratin and epithelial membrane antigen, and the cytoplasm of a few of the spindle cells also reacted with these antibodies. Electron microscopic study confirmed the biphasic pattern, showing epithelial gland formation and mesenchymal cells. The results indicate that this tumor is a metaplastic carcinoma of the rete testis. Recognition of this pattern of rete carcinoma may further enhance our knowledge of primary tumors at this unusual site.

Disfunción sexual y epilepsia / Sexual disfunction and epilepsy

Estudamos 100 pacientes do Ambulatório de Epilepsia do Hospital Docente Dr. Carlos J. Finlay, com o objetivo de conhecer sua atividade sexual. Como grupo controle, 100 pacientes com os seguintes requisitos: näo epilépticos, do mesmo sexo, a mesma ocupaçäo e a mesma faixa de idade dos epilépticos. As variáveis estudadas distribuiram-se em: dados gerais, características clínicas da doença e história sexual. Nos pacientes de ambos os grupos com disfunçäo sexual, para determinar se era funcional ou orgânica, realizamos: pletismografia digital peniana, índice pênis-braço e dosagem dos hormônios folículo estimulante e testosterona. Encontramos um número elevado de epilépticos sem parceiro sexual (Z>1.645) e um número menor com parceiro sexual estável. Näo encontramos nos epilépticos um maior número de disfunçöes sexuais do que no grupo controle, e estas näo guardaram relaçäo com o tipo de crise, nem com o tratamento