The use of novel promotility and prosecretory agents for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation

Chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (C-IBS) are commonly reported gastrointestinal (GI) disorders that have a major impact on health and quality of life. Patients experience a range of symptoms of which infrequency of bowel movement is but one and report that straining, the production of hard stools, and unproductive urges are more bothersome than stool infrequency. Additionally, in C-IBS, patients report abdominal pain and bloating as particularly troubling. Traditional treatments, such as laxatives, are often ineffective, especially in more severe constipation over the long term. In a population-based survey of constipation sufferers, half were not satisfied with their current treatment, due predominantly to poor efficacy. 5-Hydroxytryptamine receptor 4 (5-HT₄) agonists stimulate GI motility and intestinal secretion, and tegaserod has demonstrated efficacy in improving bowel habit. Tegaserod also improves constipationassociated symptoms including bloating, abdominal discomfort, stool consistency, and straining in patients with both CIC and C-IBS. However, tegaserod has been withdrawn due to an association with serious adverse cardiovascular effects. Further 5-HT₄ receptor agonists, including prucalopride and TD-5108 are in development and show exciting results in clinical studies in CIC patients, suggesting further product approvals are likely. Headache and diarrhea are the most commonly reported adverse event with this class of agent. Recently a novel prosecretory agent has been approved for the treatment of both CIC and C-IBS. Lubiprostone stimulates chloride secretion through activation of type-2 chloride channels, increasing intestinal secretion and transit, and its use has been associated with improvements in bowel habit and symptoms of constipation. Nausea, diarrhea, and headache are the most commonly reported adverse events. Linaclotide also stimulates intestinal chloride secretion, but this molecule achieves this indirectly, through the activation of guanylate cyclase C. Data are emerging, but the efficacy and safety profile of this agent in the treatment of CIC and C-IBS appears encouraging.     

Primary retroperitoneal perirenal CIC rearrangement sarcoma: A case report

Primary retroperitoneal perirenal CIC rearrangement sarcoma is rare. The current case report presents a 69-year-old male patient with this pathology, including the clinical features, pathomorphology and immunohistochemistry, and CIC gene rupture detected by fluorescence in situ hybridization (FISH). Furthermore, the relevant literature was reviewed. Histologically, the tumor was composed of diffuse nests of small- to medium-sized juvenile round blue cells with hyperchromatic nuclei, prominent nucleoli and occasional mitotic signs. The tumor involved adipose tissue with no obvious hemorrhagic necrotic foci. Immunohistochemistry indicated scattered expression of CD99 in tumor cells. FISH examination suggested that the CIC gene was fragmented and translocated.     

Chronic Idiopathic Cough: A Discrete Clinical Entity?

STUDY OBJECTIVES: Despite the success of specialist cough clinics, there is increasing recognition of a subgroup of chronic coughers in whom a diagnosis cannot be made even after thorough, systematic investigation. We call this condition chronic idiopathic cough (CIC). The aim of this study is to compare the clinical characteristics of CIC patients with those of coughers in whom a diagnosis has been established (non-CIC) to see if there is a recognizable clinical pattern that distinguishes CIC from non-CIC. DESIGN: Retrospective analysis of the medical records of chronic cough patients. SETTING: The Royal Brompton Hospital Chronic Cough Clinic, London. PATIENTS: One hundred patients with chronic cough referred to the Royal Brompton Hospital Cough Clinic between October 2000 and February 2004. RESULTS: Seventy-one percent of all patients were female. Median age was 57 years (range, 19 to 81 years), with a median duration of symptoms of 48 months (range, 2 to 384 months). The primary diagnoses were CIC (42%), postnasal drip syndromes (22%), gastroesophageal reflux disease (16%), asthma (7%), and others (13%). In CIC patients, the median age at referral, age at onset of cough, and proportion of females did not differ significantly from non-CIC patients. CIC patients had a longer median duration of cough (72 months vs 24 months, p = 0.002), were more likely to report an upper respiratory tract infection (URTI) as the initial trigger of their cough (48% vs 24%, p = 0.0014), and had a significantly lower cough threshold in response to capsaicin (log concentration of capsaicin required to induce five or more coughs, - 0.009 vs 0.592, p = 0.032) than non-CIC patients. CONCLUSIONS: Patients with CIC commonly describe a URTI that initiates their cough, which then lasts for many years, and they demonstrate an exquisitely sensitive cough reflex. We believe that CIC may be a distinct clinical entity with an as-yet unidentified underlying pathology.     

Probiotics in functional bowel disorders

Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.     

贵州部分地区精神分裂症患者血清PBMC博尔纳病病毒CIC及抗体的检测

目的对贵州省部分地区精神分裂症患者血清外周血单个核细胞(PBMC)进行检测,探讨博尔纳病病毒(BDV)感染与精神分裂症的相关性;方法运用新型的三联ELISA测循环免疫复合物(CIC)的方法,检测97例精神分裂症患者组及48例健康对照组PBMC中BDV特异性CIC;结果 97例精神分裂症组中有24例CIC为阳性,阳性率为24.7%(24/97);抗体检出率为14.4%(14/97),48例对照组中CIC及抗体阳性1例,阳性率为2.1%(1/48);精神分裂症组检出率高于健康对照对照组,具有统计学意义(P<0.05);结论贵州省部分地区存在着BDV的感染,BDV感染与精神分裂症可能相关。     

芪蓟肾康颗粒对IgA肾病大鼠肾组织IL-13及血清CIC的影响

目的:观察芪蓟肾康颗粒对IgA肾病大鼠肾组织IL-13的表达及血清循环复合物(CIC)浓度的影响,探讨芪蓟肾康颗粒治疗IgA肾病的机制。方法:采用口服牛血清白蛋白(BSA)制备实验性IgA肾病大鼠模型。芪蓟肾康颗粒及替米沙坦于实验第8周开始灌胃给药,每日1次,连续5周,至实验12周末取血检测CIC含量,取肾脏组织检测IL-13表达。结果:与模型组比较:芪蓟肾康颗粒中、高剂量组IL-13表达下降(P<0.01),芪蓟肾康颗粒各剂量组血清CIC浓度均下降(P<0.01)。与替米沙坦组比较:芪蓟肾康颗粒中、高剂量组IL-13表达差异有统计学意义(P<0.01),中药各剂量组血清CIC浓度差异无统计学意义(P>0.05)。结论:芪蓟肾康颗粒有调节IgA肾病大鼠肾组织IL-13表达及血清CIC浓度的作用。