Prescript-assist probiotic-prebiotic treatment for irritable bowel syndrome: an open-label, partially controlled, 1-year extension of a previously published controlled clinical trial.

OBJECTIVE: The aim of this study was to extend a previous 2-week assessment of a probiotic-prebiotic complex in patients with irritable bowel syndrome (IBS). METHODS: In this open-label, partially controlled, 1-year (14 [2] months) extension study, data were collected from patients with IBS who continued treatment following a 2-week study of the efficacy of the probiotic-prebiotic complex. Data were collected at 2 and approximately 60 weeks after the end of the original study. RESULTS: A total of 25 patients entered the 2-week extension and 22 completed the approximately 60-week follow-up study (20 women, 2 men; age range, 20-70 years; all white). Results in the control group 2 weeks after crossover to treatment were similar to those from the original study, with reductions in IBS subsyndromes, as follows: general ill feelings/nausea (P < 0.001), indigestion/flatulence (P < 0.001), and marginally colitis (P < 0.03 [1-tailed]). Treatment was associated with a continued reduction in general ill feelings/nausea at 4 weeks (P < 0.007). At >or=52-week follow-up, the rate of remissions was 81.5% to 100% (P < 0.003). CONCLUSION: Based on the results from the present 1-year extension study, treatment with this probiotic-prebiotic complex may be an option for short-term (2-4 weeks) and long-term ( approximately 60-week) reductions in IBS symptoms.

A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production.

Mercury (Hg) exposure in various forms remains a persistent public health concern in many parts of the world. In previous studies, we have described a biomarker of mercury exposure characterized by increased urinary concentrations of specific porphyrins, pentacarboxyporphyrin (5-CP) and coproporphyrin (4-CP), and the atypical keto-isocoproporphyrin (KICP), based on selective interference with the fifth (uroporphyrinogen decarboxylase, UROD) and sixth (coproporphyrinogen oxidase, CPOX) enzymes of the heme biosynthetic pathway. Whereas this response occurs in a predictable manner among approximately 85% of subjects with Hg exposure, an atypical porphyrinogenic response (APR) has been observed in approximately 15% of Hg-exposed persons, in which the three porphyrins that are affected by Hg, i.e., 5-CP, 4-CP and, KICP, are excreted in substantial excess of that predicted on the basis of Hg exposure alone. This APR has been attributed to a specific polymorphism in exon 4 of the CPOX gene (CPOX4). In the present study, we sought to further confirm the hypothesis that the observed changes in porphyrin excretion patterns might serve as a biomarker of Hg exposure and potential toxicity by statistically modeling the cascading effects on porphyrin concentrations within the heme biosynthetic pathway of Hg exposure and CPOX4 polymorphism in a human population with long-term occupational exposure to elemental mercury. Our results are highly consistent with this hypothesis. After controlling for precursor porphyrin concentrations, we demonstrated that 5-CP and 4-CP are independently associated with Hg concentration, while KICP is associated only with the CPOX4. An unpredicted association of Hg with heptacarboxyporphyrin (7-CP) may indicate a previously unidentified point of mercury inhibition of UROD. These findings lend further support to the proposed utility of urinary porphyrin changes as a biomarker of exposure and potential toxicity in subjects with mercury exposure. Additionally, these findings demonstrate the successful application of a computational model for characterizing complex metabolic responses and interactions associated with both toxicant exposure and genetic variation in human subjects.

Prescript-Assist probiotic-prebiotic treatment for irritable bowel syndrome: a methodologically oriented, 2-week, randomized, placebo-controlled, double-blind clinical study.

BACKGROUND: The symptomatic efficacy of Prescript-Assist (Safer Medical, Inc., Fort Benton, Montana), a treatment combining probiotic and prebiotic components, has previously been evaluated clinically only in an open-label study in patients with various gastrointestinal conditions, including irritable bowel syndrome (IBS). OBJECTIVES: This study was conducted primarily to compare the effects of Prescript-Assist with placebo in patients with a diagnosis of IBS. Toward this objective, a secondary methodologic goal was to determine the number and nature of symptom clusters ("subsyndromic factors") that characterize IBS. METHODS: This was a double-blind, placebo-controlled clinical study in which patients were randomly assigned to receive either Prescript-Assist one 500-mg capsule BID or 1 placebo capsule BID for 2 weeks. Thirteen IBS symptoms identified from the clinical literature were embedded in a larger research instrument. Using a scale from 0 to 5, patients rated the intensity of these symptoms for the 7-day period immediately before the start of treatment, at the end of each study week, and after each of the 2 subsequent weeks (during which all patients received open-label Prescript-Assist as part of a larger study evaluating methodologic approaches to enhancing assessments of medication efficacy/safety). The symptom-intensity data were subjected to maximum likelihood factor analysis with varimax rotation to identify any IBS subsyndromic factors, and the effect of treatment on each of the identified factors was evaluated using analyses of covariance with appropriate baseline-week assessments as covariate controls. RESULTS: The study included 25 patients with IBS (23 women, 2 men; age range, 20-70 years). Three subsyndromic factors were identified that together accounted for 60.2% of total IBS symptom variance: factor 1, general ill feelings/nausea; factor 2, indigestion/flatulence; and factor 3, colitis. Treatment with Prescript-Assist was associated with significant reductions in each of the subsyndromic factors. Factor 1 was significantly reduced by 0.345 standard score units (F(1,46) = 4.26; P = 0.042), factor 2 by 0.544 standard score units (F(1,46) = 7.83; P = 0.008), and factor 3 by 0.826 standard score units (F(1,46) = 10.20; P = 0.003). CONCLUSIONS: This study identified 3 subsyndromic factors of IBS: general ill feelings/nausea, indigestion/flatulence, and colitis. In this methodologically oriented double-blind study in patients with IBS, combined probiotic-prebiotic treatment with Prescript-Assist was associated with significant reductions in these factors.

Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function.

Potential cognitive and motor effects from exposure to elemental mercury (Hg(0)) were examined in the presence and absence of a polymorphism (Val66Met) in brain-derived neurotrophic factor (BDNF). A group of 194 male dentists (DDs) and 233 female dental assistants (DAs) were occupationally exposed to mercury and had no history of kidney or nervous system disorders. Acute exposure was measured using spot urinary Hg (HgU) concentrations (average 3.32 and 1.98 microg/l, respectively) and indices of chronic occupational exposure (26.3 and 14.9 years, respectively, weighted for historical exposures). The BDNF status was 68% and 66% wild type, 26% and 30% single substitution, and 5% and 4% full mutation for DDs and DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant adverse associations with HgU (p<.05) were found for nine measures among DDs (Digit Span (Forward), Digit and Spatial Span(Backward), Visual Reproduction, Finger Tapping(Dominant, Alternate, and Alternate Partialed), Hand Steadiness, and Tracking), and eight measures among DAs (Digit Span(Forward), Visual Reproduction, Pattern Discrimination(Rate), Symbol Digit(Rate), Trailmaking B, Finger Tapping(Dominant and Alternate Partialed), and Hand Steadiness). The BDNF status was associated with four measures in DDs and three measures in DAs. Joint effects were found for Finger Tapping(Alternate and Alternate Partialed) in DDs and Hand Steadiness and Trailmaking B in DAs. Joint effects were additive in all cases. Performance on verbal intelligence and reaction time were not associated with either HgU or BDNF status. A test of threshold effect for the association of Hand Steadiness with HgU demonstrated no lower boundary in both DDs and DAs. No associations were observed with estimates of chronic mercury exposure. Our findings are applicable to exposure levels of the general population and identify a potentially vulnerable group with a BDNF polymorphism.

Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood.

Recent reports have described neurobehavioral impairments in human subjects carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with this BDNF polymorphism are similar to those observed among subjects with chronic exposure to elemental mercury (Hg degrees ), we examined the potential effect of this BDNF polymorphism on symptoms and mood in an established cohort of dental practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms and mood were obtained by computerized questionnaire from 193 male dentists (DTs) and 230 female dental assistants (DAs). Spot urine samples were analyzed for mercury concentrations to evaluate recent exposure. Detailed work histories were obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current and 12 recent and chronic symptom groups, along with six mood factors, were evaluated with respect to recent and chronic Hg degrees exposure and BDNF polymorphism. Multiple regression analysis controlled for age, race, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for DTs and DAs. Twenty-three associations between recent or chronic Hg degrees exposure and BDNF status and self-reported symptoms were observed with p < 0.10. All but three were in the expected direction (symptom scores increasing with Hg degrees exposure or BDNF polymorphism), and all but six were among DAs. All eight correlations between chronic exposure indices and recent and chronic symptoms among DAs were in the expected direction. All seven associations between BDNF and symptoms were in the expected direction and split between DTs and DAs. All three associations with mood factors were among DAs and in the expected direction. These results indicate that among DAs very low levels of occupational Hg degrees exposure are associated with increased symptoms. The BDNF polymorphism is also associated with increased symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive with respect to their associations with the same symptom group.