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Idiopathic Constipation (idiopathic + constipation)

Distribution by Scientific Domains

Medical Sciences	85%

Selected Abstracts

Effects of female steroid hormones on A-type K+ currents in murine colon

THE JOURNAL OF PHYSIOLOGY, Issue 2 2006
Elizabeth A. H. Beckett
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause. [source]

Chronic constipation in children: Organic disorders are a major cause

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2005
BR Southwell
Abstract: Diagnostic tools for paediatric chronic constipation have been limited, leading to over 90% of patients with treatment-resistant constipation being diagnosed with chronic idiopathic constipation, with no discernible organic cause. Work in our institution suggests that a number of children with intractable symptoms actually have slow colonic transit leading to slow transit constipation. This paper reviews recent data suggesting that a significant number of the children with chronic treatment-resistant constipation may have organic causes (slow colonic transit and outlet obstruction) and suggests new approaches to the management of children with chronic treatment-resistant constipation. [source]

Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain

NEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2010
H. Eutamene
Abstract Background, Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). Methods,Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. Key Results,In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. Conclusions & Inferences,These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C. [source]

Rectal sensorimotor characteristics in female patients with idiopathic constipation with or without paradoxical sphincter contraction

NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2003
C. E. J. Sloots
Abstract, Patients with chronic constipation fulfilling the Thompson criteria can show paradoxical sphincter contraction. Aim of this study was to evaluate rectal sensorimotor characteristics in patients with constipation with or without paradoxical sphincter contraction. Thirty female patients with chronic constipation and 22 female controls were investigated with anal manometry and rectal barostat. Paradoxical sphincter contraction was shown with manometry as a paradoxical increase of anal pressure during straining. Visceral sensitivity and compliance were tested by intermittent and continuous pressure-controlled distension. Patients were classified according to their sensations and compliance into normal, hypersensitive, reduced compliant, insensitive or excessive compliant rectum. Postprandial rectal response (PRR) and phasic volume events (PVEs) were registered for 1 h after a 600-kCal meal. Paradoxical sphincter contraction was found in 13 (43%) patients. In these patients, rectal sensitivity scores were higher (P = 0.045) than in patients without paradoxical contractions, but rectal compliance was not different. In 90% of patients an abnormal rectal sensitivity or compliance was found: excessively compliant in 35%, reduced compliant in 10%, hypersensitive in 27% and hyposensitive in 17%. Both patients with constipation (11%; P = 0.042) and controls (25%; P = 0.002) exhibited the presence of a postprandial rectal response. This response was not significantly different between idiopathic constipation, paradoxical sphincter contraction and controls. Patients with rectal hypersensitivity had lower response than other patients (P = 0.04). Patients with constipation had fewer basal PVEs compared controls (P = 0.03). Postprandial PVEs increased in both patients (P = 0.014) and controls (P < 0.001). Postprandial rectal response and PVE were not different in patients with or without paradoxical sphincter contraction. A total of 90% of female patients with idiopathic constipation show an abnormality in rectal sensation or compliance. The postprandial rectal response was comparable between patients with constipation and controls, however, PVEs were diminished. Patients with paradoxical sphincter contraction had higher rectal sensitivity but an unaltered compliance and postprandial rectal response. Future trials should investigate whether the classification of rectal abnormalities in patients with constipation has clinical importance. [source]

Permanent sacral nerve stimulation for treatment of idiopathic constipation

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2002
N. J. Kenefick
Background: Constipation can usually be managed using conservative therapies. A proportion of patients require more intensive treatment. Surgery provides variable results. This paper describes an alternative approach, in which the neural control of the bowel and pelvic floor is modified, using permanent sacral nerve stimulation. Methods: Four women (aged 27,36 years), underwent temporary and then permanent stimulation. All had idiopathic constipation, resistant to maximal therapy, with symptoms for 8,32 years. Clinical evaluation, bowel diary, Wexner constipation score, symptom analogue score, quality of life questionnaire and anorectal physiology were completed. Results: There was a marked improvement in all patients with temporary, and in three with permanent, stimulation. Median follow-up was 8 (range 1,11) months. Bowel frequency increased from 1,6 to 6,28 evacuations per 3 weeks. Improvement occurred, at longest,follow,up, in median (range) evacuation score (4 (0,4) versus 1 (0,4)), time with abdominal pain (98 (95,100) versus 12 (0,100) per cent), time with bloating (100 (95,100) versus 12 (5,100) per cent), Wexner score (21 (20,22) versus 9 (1,20)), analogue score (22 (16,32) versus 80 (20,98)) and quality of life. Maximum anal resting and squeeze pressures increased. Rectal sensation was altered. Transit time normalized in one patient. Conclusion: Permanent sacral nerve stimulation can be used to treat patients with resistant idiopathic constipation. © 2002 British Journal of Surgery Society Ltd [source]