Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons.

AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Avaliação quantitativa e mofométrica dos neurônios mioentéricos da região agrandular do estômago de ratos com Diabetes Mellitus induzido por estreptozootocina e suplementados com ácido ascórbico / Quantitative and morphometric evaluation of myenteric neurons of the forestomach of streptozotocin-induced diabetic rats supplemented with ascorbic acid

O presente trabalho teve como objetivos investigar possíveis alterações no número e a área do corpo celular dos neurônios mioentéricos NADH-diaforase reativos (NADH-dr) da região aglandular do estômago de ratos diabéticos e o efeito da suplementação com AA (1g/L de água) nos referidos parâmetros. Para tanto, 15 ratos (Rattus norvegicus) foram separados em três grupos (n = 5): controle (C); diabético (D); e diabético suplementado com AA (DS). O DM foi induzido por estreptozootocina (35 mg/kg de peso corporal). Após 120 dias de experimento, os animais foram anestesiados para obtenção do estômago. Os neurônios mioentéricos foram evidenciados pelo método da NADH-diaforase. Por meio de microscópio de luz foram contados os neurônios NADH-dr e, pelo programa computadorizado para análise de imagens, foi mensurado o perfil do corpo celular (PCC) desses neurônios. O número de neurônios NADH-dr não variou significativamente entre os três grupos estutados (P>0,05). A média dos PCCs foi maior (P<0,05) para os neurônios dos grupos D e DS do que para o grupo C. Ocorreu aumento na incidência de neurônios com PCC superior a 200 µm2 no grupo D quando comparada aos grupos DS e C. Os resultados sugerem que a suplementação com AA teve efeito neuroprotetor sobre os neurônios mioentéricos NADH-dr representado pela diminuição da freqüência de neurônios grandes na região aglandular A e B do grupo DS

Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret.

BACKGROUND & AIMS: Marijuana and other cannabinoids are effective anti-emetics. Despite ongoing controversy over their usage, the receptor distribution and the site of the anti-emetic action of these compounds are not known. Our aim was to investigate whether the cannabinoid 1 receptor (CB1r) and endocannabinoids play a role in the anti-emetic action of cannabinoids. METHODS: Ferrets were given an emetic stimulus and the number of episodes of retching and vomiting were observed after administration of CB1r agonists and a CB1r antagonist. CB1r and fatty acid amide hydrolase (FAAH), which degrades endocannabinoids, were localized by immunohistochemistry. RESULTS: CB1r and FAAH were localized in the dorsal vagal complex, consisting of the area postrema, nucleus of the solitary tract, and the dorsal motor nucleus of the vagus in the brainstem. CB1r was found in the myenteric plexus of the stomach and duodenum. Activation of CB1r by the agonists (delta)(9)-tetrahydrocannabinol, WIN 55,212-2, and methanandamide inhibited emesis and their action was reversed by a selective CB1r antagonist, which alone had no effect, but potentiated vomiting in response to an emetic stimulus. CONCLUSIONS: CB1r mediates the anti-emetic action of cannabinoids in the dorsal vagal complex. Endocannabinoids are a novel neuroregulatory system involved in the control of emesis.

Sporadic visceral neuropathy.

We encountered three cases of chronic functional colonic obstruction caused by intramural ganglion cell death. Morphologic and pharmacological studies were performed using resected specimens. The patients included a 59-year-old man, a 72-year-old woman, and a 28-year-old man. Barium enema studies revealed segmental stenosis in their left colon. A mecholyl test was positive in all three cases and was useful in diagnosing this disorder. Histopathologic and cytometric examinations disclosed both degeneration and the disappearance of intramural ganglion cells. The number of muscarinic acetylcholine receptors was observed to increase in the muscle layers of the stenotic portion. In addition, the muscle of the affected region showed hypersensitivity to the muscarinic agonist (oxotremorine). These results seem to suggest that this disease is caused by a noncongenital injury to the intramural ganglion cells while the resulting stenosis is considered to reflect the degeneration of the ganglion cells. The etiology of ganglion cell death still remains to be clarified; however, we propose that patients with this disorder may represent a subset of patients with sporadic visceral neuropathy.