Localisation of NK1 receptor immunoreactivity to neurons and interstitial cells of the guinea-pig gastrointestinal tract

Tachykinins, including substance P, neurokinin A, and neuropeptides K and γ, are expressed widely in the peripheral nervous system where they affect smooth muscle contraction, exocrine gland secretion, vascular permeability, and neurotransmission. Substance P, the preferred ligand for the NK1 receptor, is found in high concentrations in the enteric nervous system. In the present study, the localisation and distribution of the NK1 receptor was studied throughout the gastrointestinal tract of the guinea-pig by using a polyclonal antiserum raised against the C-terminal 15 amino acids of the NK1 receptor. Co-localisation with other neuronal markers was examined in the ileum. Nerve cell bodies reactive for the NK1 receptor were found in the myenteric plexus of all regions and the submucous plexus of the small and large intestines. In the small intestine, the interstitial cells of Cajal were also immunoreactive. Immunoreactivity was largely confined to cell surfaces. Almost all immunoreactive myenteric nerve cells had Dogiel type I morphology, and most of these were immunoreactive for nitric oxide synthase, a transmitter of inhibitory neurons to the muscle and of descending interneurons. Neuropeptide Y-containing secretomotor neurons in the submucous and myenteric plexuses also exhibited NK1 receptor immunoreactivity. NK1 receptors were present on a minority of tachykinin immunoreactive neurons of submucous ganglia. The results suggest that receptors on the longitudinal muscle might not be conventional NK1 receptors, that excitation of the circular muscle of the ileum is indirect, perhaps via the interstitial cells of Cajal, and that enteric inhibitory neurons may be excited via NK1 receptors. © 1996 Wiley-Liss, Inc.     

Grey matter volume in adolescents with anorexia nervosa and associated eating disorder symptoms

Anorexia nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN; however, differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of adolescent girls with AN before and after weight recovery and the relationship of any changes with clinical characteristics. We collected high‐resolution T1‐weighted images from 26 underweight girls with AN before weight gain and 20 healthy control volunteers. Clinical features were assessed using the Eating Disorder Examination Questionnaire. AN subjects displayed reduced grey matter volumes in the insula, amygdala, prefrontal, hippocampal and cingulate cortices and the precuneus, relative to healthy controls. In a subset of 10 AN subjects who were followed after weight recovery, grey matter volumes increased to near‐control levels in the orbito‐ and medial prefrontal, insular, left hippocampal and mid‐ and posterior cingulate cortices and precuneus. The recovery of the right anterior thalamus and the left orbitofrontal cortex was correlated with improvements in eating concerns and shape concerns, respectively. However, large parts of the anterior cingulate cortex, caudate nuclei and right hippocampus did not display any grey matter recovery following a short‐term of treatment. These results show that in adolescents with AN, some brain regions display marked recovery in grey matter volume following weight recovery, whereas others do not, considering grey mater recovery possibly linked to symptom improvement.     

Systematic review of evidence for different treatment settings in anorexia nervosa

AIM: To compare outcomes in anorexia nervosa (AN) in different treatment settings: inpatient, partial hospitalization and outpatient.METHODS: Completed and published in the English language, randomized controlled trials comparing treatment in two or more settings or comparing different lengths of inpatient stay, were identified by database searches using terms “anorexia nervosa” and “treatment” dated to July 2014. Trials were assessed for risk of bias and quality according to the Cochrane handbook by two authors (Madden S and Hay P) Data were extracted on trial quality, participant features and setting, main outcomes and attrition.RESULTS: Five studies were identified, two comparing inpatient treatment to outpatient treatment, one study comparing different lengths of inpatient treatment, one comparing inpatient treatment to day patient treatment and one comparing day patient treatment with outpatient treatment. There was no difference in treatment outcomes between the different treatment settings and different lengths of inpatient treatment. Both outpatient treatment and day patient treatment were significantly cheaper than inpatient treatment. Brief inpatient treatment followed by evidence based outpatient care was also cheaper than prolonged inpatient care for weight normalization also followed by evidence based outpatient care.CONCLUSION: There is preliminary support for AN treatment in less restrictive settings but more research is needed to identify the optimum treatment setting for anorexia nervosa.     

Substance P and vasoactive intestinal peptide are reduced in right transverse colon in pediatric slow‐transit constipation

Background Slow‐transit constipation (STC) is recognized in children but the etiology is unknown. Abnormalities in substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide (NO) have been implicated. The density of nerve fibers in circular muscle containing these transmitters was examined in colon from children with STC and compared to other pediatric and adult samples. Methods Fluorescence immunohistochemistry using antibodies to NO synthase (NOS), VIP and SP was performed on colonic biopsies (transverse and sigmoid colon) from 33 adults with colorectal cancer, 11 children with normal colonic transit and anorectal retention (NAR) and 51 with chronic constipation and slow motility in the proximal colon (STC). The percentage area of nerve fibers in circular muscle containing each transmitter was quantified in confocal images. Key Results In colon circular muscle, the percentage area of nerve fibers containing NOS > VIP > SP (6 : 2 : 1). Pediatric groups had a higher density of nerve fibers than adults. In pediatric samples, there were no regional differences in NOS and VIP, while SP nerve fiber density was higher in sigmoid than proximal colon. STC children had lower SP and VIP nerve fiber density in the proximal colon than NAR children. Twenty‐three percent of STC children had low SP nerve fiber density. Conclusions & Inferences There are age‐related reductions in nerve fiber density in human colon circular muscle. NOS and VIP do not show regional variations, while SP nerve fiber density is higher in distal colon. 1/3 of pediatric STC patients have low SP or VIP nerve fiber density in proximal colon.     

What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis

It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity—the testicular dysgenesis syndrome—leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease.