Lactobacillus rhamnosus GG and Saccharomyces cerevisiae boulardii exert synergistic antipathogenic activity in vitro against enterotoxigenic Escherichia coli.

Short-term colonic in vitro batch incubations were performed to elucidate the possible synergistic effects of Lactobacillus rhamnosus GG (CNCM-I-4798) and Saccharomyces cerevisiae boulardii (CNCM-I-1079) (associated in Smebiocta/Smectaflora Protect®) on the colonic microbial fermentation process, as well as their antipathogenic activity against enterotoxigenic Escherichia coli (LMG2092) (ETEC). These incubations adequately simulate the native microbiota and environmental conditions of the proximal colon of both adult and toddler donors, including the colonic mucosal layer. Results indicated that both strains were capable of growing together without showing antagonistic effects. Co-cultivation of both strains resulted in increased butyrate (stimulated by L. rhamnosus GG), propionate (stimulated by S. boulardii), and ethanol (produced by S. boulardii) production compared to the control incubations, revealing the additive effect of both strains. After inoculation of ETEC under simulated dysbiotic conditions, a 40 and 46% reduction in the concentration of ETEC was observed upon addition of both strains during the experiments with the adult and toddler donor, respectively. Furthermore, ETEC toxin levels decreased upon S. boulardii inoculation, probably due to proteolytic activity of this strain, with a synergistic effect being observed upon co-cultivation of L. rhamnosus GG and S. boulardii resulting in a reduction of 57 and 46% for the adult and toddler donor, respectively. Altogether, the results suggest that both probiotics together may help microbiota functionality, in both adults and toddlers and under healthy or impaired conditions, which could be of great interest when the colonic microbiota is dysbiotic and therefore sensitive to pathogenic invasion such as during antibiotic treatment.

Inulin-type fructan degradation capacity of Clostridium cluster IV and XIVa butyrate-producing colon bacteria and their associated metabolic outcomes.

Four selected butyrate-producing colon bacterial strains belonging to Clostridium cluster IV (Butyricicoccus pullicaecorum DSM 23266T and Faecalibacterium prausnitzii DSM 17677T) and XIVa (Eubacterium hallii DSM 17630 and Eubacterium rectale CIP 105953T) were studied as to their capacity to degrade inulin-type fructans and concomitant metabolite production. Cultivation of these strains was performed in bottles and fermentors containing a modified medium for colon bacteria, including acetate, supplemented with either fructose, oligofructose, or inulin as the sole energy source. Inulin-type fructan degradation was not a general characteristic among these strains. B. pullicaecorum DSM 23266T and E. hallii DSM 17630 could only ferment fructose and did not degrade oligofructose or inulin. E. rectale CIP 105953T and F. prausnitzii DSM 17677T fermented fructose and could degrade both oligofructose and inulin. All chain length fractions of oligofructose were degraded simultaneously (both strains) and both long and short chain length fractions of inulin were degraded either simultaneously (E. rectale CIP 105953T) or consecutively (F. prausnitzii DSM 17677T), indicating an extracellular polymer degradation mechanism. B. pullicaecorum DSM 23266T and E. hallii DSM 17630 produced high concentrations of butyrate, CO2, and H2 from fructose. E. rectale CIP 105953T produced lactate, butyrate, CO2, and H2, from fructose, oligofructose, and inulin, whereas F. prausnitzii DSM 17677T produced butyrate, formate, CO2, and traces of lactate from fructose, oligofructose, and inulin. Based on carbon recovery and theoretical metabolite production calculations, an adapted stoichiometrically balanced metabolic pathway for butyrate, formate, lactate, CO2, and H2 production by members of both Clostridium cluster IV and XIVa butyrate-producing bacteria was constructed.

Summer Meeting 2013: growth and physiology of bifidobacteria.

Bifidobacteria are a minor fraction of the human colon microbiota with interesting properties for carbohydrate degradation. Monosaccharides such as glucose and fructose are degraded through the bifid shunt, a dedicated pathway involving phosphoketolase activity. Its stoechiometry learns that three moles of acetate and two moles of lactate are produced per two moles of glucose or fructose that are degraded. However, deviations from this 3 : 2 ratio occur, depending on the rate of substrate consumption. Slower growth rates favour the production of acetate and pyruvate catabolites (such as formate) at the cost of lactate. Interestingly, bifidobacteria are capable to degrade inulin-type fructans (ITF) (oligofructose and inulin) and arabinoxylan-oligosaccharides (AXOS). Beta-fructofuranosidase activity enables bifidobacteria to degrade ITF. However, this property is strain-dependent. Some strains consume both fructose and oligofructose, with different preferences and degradation rates. Small oligosaccharides (degree of polymerization or DP of 2-7) are taken up, in a sequential order, indicating intracellular degradation and as such giving these bacteria a competitive advantage towards other inulin-type fructan degraders such as lactobacilli, bacteroides and roseburias. Other strains consume long fractions of oligofructose and inulin. Exceptionally, oligosaccharides with a DP of up to 20 (long-chain inulin) are consumed by specific strains. Also, the degradation of AXOS by α-arabinofuranosidase and ß-xylosidase is strain-dependent. Particular strains consume the arabinose substituents, whether or not together with a consumption of the xylose backbones of AXOS, either up to xylotetraose or higher and either extra- or intracellularly. The production of high amounts of acetate that accompanies inulin-type fructan degradation by bifidobacteria cross-feeds other colon bacteria involved in the production of butyrate. However, bifidobacterial strain-dependent differences in prebiotic degradation indicate the existence of niche-specific adaptations and hence mechanisms to avoid competition among each other and to favour coexistence with other colon bacteria.

Phase II study of temsirolimus (CCI-779) in women with recurrent, unresectable, locally advanced or metastatic carcinoma of the cervix. A trial of the NCIC Clinical Trials Group (NCIC CTG IND 199).

OBJECTIVE: HPV infection has been associated with deregulation of the PI3K-Akt-mTOR pathway in invasive cervical carcinomas. This 2-stage phase II study assessed the activity of the mTOR inhibitor, temsirolimus, in patients with measurable metastatic and/or locally advanced, recurrent carcinoma of the cervix. METHODS: Temsirolimus 25mg i.v. was administered weekly in 4 week cycles. One response among the first 18 patients was required to proceed to the second stage of accrual. Correlative molecular studies were performed on archival tumor tissue. RESULTS: Thirty-eight patients were enrolled. Thirty-seven patients were evaluable for toxicity and 33 for response. One patient experienced a partial response (3.0%). Nineteen patients had stable disease (57.6%) [median duration 6.5 months (range 2.4-12.0mo)]. The 6-month progression free survival rate was 28% (95% CI: 14-43%). The median progression free survival was 3.52 months [95% CI (1.81-4.70)]. Adverse effects were mild-moderate in most cases and similar to other temsirolimus studies. No toxicity>grade 3 was observed. Assessment of PTEN and PIK3CA by IHC, copy number analyses and PTEN promoter methylation status did not reveal subsets associated with disease stability. CONCLUSION: Single agent temsirolimus has modest activity in cervical carcinoma with about two-thirds of patients exhibiting stable disease. Molecular markers for treatment benefit remain to be identified.

Weekly intravenous methotrexate with folinic acid for nonmetastatic gestational trophoblastic neoplasia.

OBJECTIVE: The objective of this study was to determine the complete response rate to weekly intravenous methotrexate at 100 mg/m(2) with folinic acid for patients with nonmetastatic gestational trophoblastic neoplasia. METHODS: From 1988 to 1999, 22 women with nonmetastatic gestational trophoblastic neoplasia were treated with weekly intravenous methotrexate with folinic acid at the Hamilton Regional Cancer Centre. Complete response was defined as the attainment of a serum beta-hCG level <5 IU/L for 3 consecutive weeks. Toxicity was graded according to the National Cancer Institute of Canada-Clinical Trials Group criteria for chemotherapy toxicity. RESULTS: There were 10 women who achieved complete response with weekly intravenous methotrexate alone (45.5%). Of the 12 who did not achieve complete response with methotrexate, 10 received actinomycin D and 2 received EMA as second-line chemotherapy. Patients successfully treated with methotrexate required a median of 6.5 cycles (including 2 cycles for consolidation) to achieve complete response. The only significant prognostic factor for failure with methotrexate was pretreatment beta-hCG (P = 0.01). CONCLUSIONS: Only a select group of patients with low pretreatment beta-hCG titers would be expected to achieve complete response with this regimen. Large randomized studies are required to determine the optimal treatment for nonmetastatic gestational trophoblastic neoplasia.

Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a patient with renal failure.

Platinum-based chemotherapy is the standard treatment for ovarian cancer. Since carboplatin elimination occurs largely through the kidneys, its use in patients with hemodialysis-dependent renal failure requires dose adjustments befitting the level of renal function. We employed the AUC (area under the concentration-time curve)- directed dosing strategy (the Calvert formula) to determine the carboplatin dose appropriate for an ovarian cancer patient with renal failure. Our approach is compared and defended against the empiric and thrombocyte nadir-directed dosing strategies. Since carboplatin clearance follows creatinine clearance, we also provide a review of methods and formulas used to determine creatinine clearance. An accurate method to determine creatinine clearance will enable others to use the AUC-directed dosing strategy to establish the carboplatin dose appropriate for patients with some residual renal function.

Design, implementation, and evaluation of a community financing scheme for hospital care in developing countries: a pre-paid health plan in the Bwamanda health zone, Zaire.

Unless scarce resources can be mobilized and used efficiently, health for all by the year 2000 will remain a vain attempt. Innovative financing schemes exploring increased cost recovery from the users of the health system are explored throughout the world. In Bwamanda, Zaire, a community financing scheme for hospital care was developed through the application of operations research. A preference heuristic with considerable involvement of health providers and the community was used to identify the type of financing scheme and resulted in a pre-paid health plan, while a mathematical model was developed to determine the premiums to charge. The implementation of the health plant is briefly described. An evaluation of the effects of the pre-paid plan on the accessibility and equity of health care, as well as on the financial sustainability of the hospital, is presented and discussed: a steadily increasing membership of the health plan illustrates its appropriateness, while a doubling of the cost recovery of the hospital's operating costs after two years seems promising; the hospitalization rate of members of the health plan was significantly higher than for non-members. These findings suggest that a health zone may be an appropriate level for the organization of a regional pre-paid health plan. Problems of equity, full cost recovery, and replicability of the financing scheme are discussed.

A comparison of the anaesthetic properties of propofol and methohexitone when used as the sole induction agent for thermocoagulation of the gasserian ganglion.

Methohexitone and propofol were compared when used as the sole induction agent for thermocoagulation of the Gasserian ganglion. Sleeping and apnoea times were not significantly different for both drugs, nor were they for the same drug during repetitive inductions. However, the haemodynamic data showed a better stability when propofol was used. Amnesia may be in favour of propofol. There were no significant differences concerning pre- and post-operative side-effects in both groups.