Gynecological Disorders in Patients with Non-celiac Wheat Sensitivity.

BACKGROUND: Non-celiac wheat sensitivity (NCWS) most frequently presents clinically with irritable bowel syndrome (IBS)-like symptoms, although many extra-intestinal manifestations have also been attributed to it. No studies to date have evaluated the presence and frequency of gynecological symptoms in NCWS. AIM: To evaluate the frequency of gynecological disorders in patients with NCWS. PATIENTS AND METHODS: Sixty-eight women with NCWS were included in the study. A questionnaire investigating gynecological symptoms and recurrent cystitis was administered, and patients reporting symptoms were then examined by specialists. Three control groups were selected: 52 patients with IBS not related to NCWS, 56 patients with celiac disease (CD), and 71 healthy controls. RESULTS: 59% of the patients with NCWS showed gynecological symptoms, a higher frequency than in healthy controls (P = 0.04), IBS controls (P = 0.01) and CD controls (P = 0.02). Menstrual cycle alterations were more frequent in patients with NCWS than in healthy controls (26.5% vs 11.3%; P = 0.03); the patients with NCWS suffered from recurrent vaginitis (16%) and dyspareunia (6%) significantly more frequently than healthy controls. Twenty-nine percent of patients with NCWS reported recurrent cystitis, a finding higher than in the control groups (vs healthy P = 0.0001, vs IBS P = 0.001, vs CD controls P = 0.04). Microbiological examinations were negative in most of the patients with NCWS and recurrent vaginitis or cystitis. During the 1-year follow-up, 46% of patients with menstrual disorders and 36% with recurrent vaginitis reported resolution of symptoms on a wheat-free diet. CONCLUSIONS: Patients with NCWS showed a significantly higher frequency of gynecological symptoms and recurrent cystitis than patients with IBS.

The effect of a therapeutic urinary stress diet on the short-term recurrence of feline idiopathic cystitis.

The aim of this cohort study was to evaluate the effect of a therapeutic urinary stress diet on recurrent clinical signs of lower urinary tract disease in cats with idiopathic cystitis. The effects of feeding a therapeutic urinary stress diet were compared with feeding a non-therapeutic diet for a duration of 5 weeks. The owners selected themselves which food to feed their cat. Of 31 cats with acute non-obstructive idiopathic cystitis, 17 were fed the test food and 14 the control food. An episode of recurrence was defined as a minimum of one day with at least two clinical signs; i.e. stranguria, periuria, haematuria, dysuria and pollakiuria. The number of cats fed the therapeutic urinary stress diet that had an episode of recurrence (5/17) was significantly lower compared with cats that were fed other commercial diets (11/14). The formulation of the foods fed to the participating cats (dry, moist or a combination of both) was not found significant compared with the recurrence of idiopathic cystitis. Apart from type of diet, no other risk factors affected the short-term recurrence of FIC. A prospective clinical trial is needed to confirm these findings.

Urinary K+ promotes irritative voiding symptoms and pain in the face of urothelial barrier dysfunction.

The internal surface of the bladder is lined by the urothelium, a stratified epithelium that forms an impermeable barrier to water and urine constituents. Abnormalities in the urothelial barrier have been described in certain forms of cystitis and were hypothesized to contribute to irritative voiding symptoms and pain by allowing the permeation of urinary K+ into suburothelial tissues, which then alters afferent signaling and smooth muscle function. Here, we examined the mechanisms underlying organ hyperactivity and pain in a model of cystitis caused by adenoviral-mediated expression of claudin-2 (Cldn2), a tight junction protein that forms paracellular pores and increases urothelial permeability. We found that in the presence of a leaky urothelium, intravesical K+ sensitizes bladder afferents and enhances their response to distension. Notably, dietary K+ restriction, a maneuver that reduces urinary K+, prevented the development of pelvic allodynia and inflammation seen in rats expressing Cldn2. Most importantly, intravesical K+ causes and is required to maintain bladder hyperactivity in rats with increased urothelial permeability. Our study demonstrates that in the face of a leaky urothelium, urinary K+ is the main determinant of afferent hyperexcitability, organ hyperactivity and pain. These findings support the notion that voiding symptoms and pain seen in forms of cystitis that coexist with urothelial barrier dysfunction could be alleviated by cutting urinary K+ levels.

Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase-2 inhibitor.

Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non-steroidal anti-inflammatory drugs, anti-allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase-2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase-2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase-2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.

Comparison of foods with differing nutritional profiles for long-term management of acute nonobstructive idiopathic cystitis in cats.

OBJECTIVE: To evaluate the effect of nutrition on recurrent clinical signs of lower urinary tract (LUT) disease in cats with idiopathic cystitis. DESIGN: Randomized, controlled, masked clinical trial. ANIMALS: 31 cats with acute nonobstructive idiopathic cystitis. PROCEDURES: Cats were assigned to receive 1 of 2 foods (a cystitis prevention or control food) that differed in mineral (calcium, phosphorous, and magnesium), antioxidant, and fatty acid profiles. Owners documented LUT signs daily for up to 1 year. The primary endpoint was the number of recurrent episodes in which a cat had multiple (≥ 2 concurrent) LUT signs within a day (defined as multiple-sign day). Consecutive days in which a cat had multiple LUT signs were considered as a single episode. RESULTS: 4 cats fed prevention food and 2 cats fed control food were excluded from analysis because of noncompliance, gastrointestinal signs, food refusal, or owner voluntary withdrawal. The proportion of cats fed prevention food that had ≥ 1 recurrent episode of multiple-sign days (4/11) was not significantly lower than that of cats fed control food (9/14). However, cats fed prevention food had significantly lower mean incidence rates for recurrent episodes of multiple-sign days (0.7 episodes/1,000 cat-days) and episodes of hematuria (0.3 episodes/1,000 cat-days), dysuria (0.2 episodes/1,000 cat-days), and stranguria (0.2 episodes/1,000 cat-days) as single LUT signs, compared with cats fed control food (5.4, 3.4, 3.1, and 3.8 episodes/1,000 cat-days, respectively). Significantly fewer cats fed prevention food required analgesics (4/11), compared with cats fed control food (12/14). CONCLUSIONS AND CLINICAL RELEVANCE: Foods with differing nutritional profiles appeared to impact mean incidence rates of recurrent feline idiopathic cystitis-associated signs.

Clinical evaluation of commercially available urinary acidification diets in the management of idiopathic cystitis in cats.

OBJECTIVE: To compare recurrence of signs of lower urinary tract disease (LUTD) in cats with idiopathic cystitis that were fed the dry or canned formulation of a commercial diet designed to result in production of an acidic urine. DESIGN: Prospective trial. ANIMALS: 54 client-owned cats with idiopathic cystitis that was diagnosed on the basis of a history of abnormal micturition, abnormal results on urinalysis, radiography, or cystoscopy, and lack of an alternative diagnosis. PROCEDURE: Cats were assigned to be fed the canned or dry formulation of the diet. Reevaluations conducted at 2 and 16 weeks, and at 6 and 12 months included a physical examination, CBC and serum biochemical analysis (except week 2), blood gas analysis, and urinalysis. Regular telephone contacts were also made. The study was discontinued after 12 months or if signs of LUTD recurred. RESULTS: Signs of LUTD did not recur in 16 of 18 cats fed the canned diet, and 17 of 28 cats fed the dry diet (chi 2, P < 0.05). Seven cats were reevaluated at recurrence. Owners of remaining cats in which signs of LUTD recurred declined to have their pets reexamined. A different problem (bacterial urinary tract infection) was identified in only 1 cat on reevaluation. Eight cats were lost to follow-up evaluation. CLINICAL IMPLICATIONS: Feeding this commercial canned urinary acidifying diet may reduce the proportion of cats with idiopathic cystitis that will have recurrence of signs of LUTD within a 12-month period.

Metabolic appraisal of the effects of dietary modification on hypersensitive bladder symptoms.

The concentration of certain metabolites and amino acids appears to be changed in patients with the painful bladder syndrome interstitial cystitis. A study of the metabolism of the arylalkylamines (tryptophan, tyrosine, tyramine, phenylalanine) was carried out in 250 patients (237 females, 13 males), revealing an inability to synthesise normal amounts of serotonin and MHPG, a noradrenaline metabolite. Furthermore, the absence of ammonia and tryptophan in urine confirmed the presence of a membrane leak. Dietary restriction lessened the symptoms but did not alter specific abnormalities in dopamine metabolism. Dietary management offers a cost-effective therapeutic approach.