Effect of feeding yogurt versus milk in children with acute diarrhea and carbohydrate malabsorption.

BACKGROUND: The aim of this study was to compare the effect of infant formula and the same formula subjected to microbial fermentation (yogurt) on the duration of diarrhea in young children with acute watery diarrhea, with or without reducing substances in stools. METHODS: One hundred twelve well-nourished children, aged 3 to 24 months, who were admitted to the hospital with acute watery diarrhea were included in a randomized trial. After appropriate rehydration, they were fed either an infant formula (group M, n = 56) or the same formula fermented with Lactobacillus bulgaricus and Streptococcus thermophilus (group Y, n = 56). The two feedings were comparable in lactose concentration (40 to 42 g/L), pH 4.5, flavor, and texture. The groups were subdivided into those with or without reducing sugars in stools at presentation. The presence of reducing sugars in stool was used as a marker of carbohydrate malabsorption. RESULTS: Group M and group Y had comparable clinical characteristics at admission, including the number of patients with reducing sugars in stools (n = 31 in group M and 27 in group Y). The success rate (cessation of diarrhea and appropriate weight gain 7 days after enrollment into the study) was similar in both groups (82% in group M vs. 84% group Y). Clinical failure was 3.6% in both groups. The percentage of patients withdrawn from the study for medical reasons (5.4% in group M vs. 7.1% in group Y) or withdrawn at the parents' request (8.9% in group M vs. 5.4% in group Y) was similar. Duration of diarrhea and number of stools were significantly less in group Y compared with group M. Forty-eight hours after inclusion, diarrhea was still present in 62% of group M versus in 35% of group Y (P < 0.002). In children with reducing sugars in stools, the rate of success (82%) was similar in groups M and Y, but the duration of diarrhea and number of stools per day were significantly decreased in group Y. Forty-height hours after inclusion, diarrhea was still present in 75% of group M patients and in 20% of group Y patients who had reducing substances in the stool. CONCLUSION: Young children with acute watery diarrhea, without malnutrition or associated disease, can be equally well treated with feeding of either infant formula or yogurt. Yogurt feeding is associated with a clinically relevant decrease in stool frequency and duration of diarrhea in children who have reducing sugars in stools.

Effect of cholera toxin on glutamine metabolism and transport in rabbit ileum.

The aim of the present study was to evaluate the effect of cholera toxin on energy balance from intestinal glutamine metabolism and oxidation, glutamine-dependent sodium absorption, and cholera toxin-dependent ion flux. Cholera toxin-stimulated sodium and L-glutamine ileal transport and metabolism were studied in Ussing chambers. Glutamine (10 mM) transport and metabolism were simultaneously studied using (14)C flux and HPLC. In the same tissues, the flux of each amino acid was studied by HPLC, and glutamine metabolism and oxidation were studied by the determination of amino acid specific activity and (14)CO(2) production. In control tissues, glutamine stimulated sodium absorption and was mainly oxidized. The transepithelial flux of intact glutamine represented 45% of glutamine flux across the luminal membrane. The other metabolites were glutamate and, to a lesser degree, citrulline, ornithine, and proline. Cholera toxin did not alter glutamine-stimulated sodium absorption, glutamine oxidation, transport, and metabolism. In conclusion, the present results indicate that cholera toxin does not alter glutamine intestinal function and metabolism. In addition, approximately 95% of the energy provided by glutamine oxidation remains available to the enterocyte.

Absorption of angiotensin II antagonists in Ussing chambers, Caco-2, perfused jejunum loop and in vivo: importance of drug ionisation in the in vitro prediction of in vivo absorption.

The aims of this study were (i) to compare the absorption of three closely related inhibitors of angiotensin II, RU60018, RU60079 and HR720, in various in vitro and in vivo models, and (ii) to explain the differences in the results and to assess the importance of drug ionisation to predict absorption. Drug absorption was investigated in Ussing chambers, Caco-2 cell monolayers, perfused rat jejunum loops and in vivo after oral, intraduodenal or intravenous administration. In Ussing chambers, the analogues showed the same site-related absorption profile and a common mechanism involving the paracellular pathway. At pH 7.4 in Ussing chambers, perfused jejunum loop or Caco-2 transport studies, the three compounds exhibited low and comparable permeability values suggesting that a similar level of oral absorption may be expected for all three compounds. However, after oral or intraduodenal administration, only HR720 was significantly absorbed. The in vivo results can be explained by the ionic distribution profile which indicated that only HR720 possessed a significant amount of uncharged species at pH values close to that found in the upper part of intestinal tract. Hence, it is expected that in this part of the intestine, only HR720 absorption is favoured. This is supported by Caco-2 transport studies performed when the pH of the apical medium was lowered from 7.4 to 6.0, in which a dramatic increase in permeability was observed for HR720 compared to those of the other analogues. This study highlights the usefulness of different absorption models for drug screening and demonstrates that ionisation profiles must be carefully considered to avoid rejection of promising compounds.

Effect of sorbin on electrolyte transport in rat and human intestine.

Stimulating water absorption in the colon represents an important target to reduce stool output in secretory diarrhea. Recently, a 153-amino-acid peptide was isolated from porcine upper small intestine and purified, taking into account the increase of water absorption in guinea pig gallbladder. Accordingly, this peptide was named sorbin. The aim of the present study was to determine if the COOH-terminal heptapeptide of sorbin (C7-sorbin) participates in the regulation of electrolyte transport in the colon. Different regions (from duodenum to colon) of stripped intestinal mucosa from rats or humans were mounted in Ussing chambers to measure the changes in short-circuit current (DeltaIsc) and net 22Na and 36Cl fluxes (JNanet and JClnet) after serosal exposure of 10(-7) to 10(-3) M C7-sorbin. In fasted rat intestine, C7-sorbin (10(-4) M) induced an immediate reduction in Isc in the distal ileum and proximal and distal colon but not in the duodenum and jejunum. In the colon, Isc reduction and JNanet and JClnet stimulation were dose dependent (EC50 = 2 x 10(-5) M). At 10(-3) M, maximal effect was observed (DeltaIsc = -1.14 +/- 0.05, DeltaJNanet = +4.97 +/- 1.38, and DeltaJClnet = +9.25 +/- 1.44 microeq. h-1. cm-2). C7-sorbin (10(-3) M) inhibited the increase in Isc induced by a series of 10 secretory agents such as secretin, vasoactive intestinal peptide, PGE2, and serotonin. In HT-29-Cl19A cells, C7-sorbin induced an increase in Isc, with a maximal effect at 10(-3) M (DeltaIsc = 0.29 +/- 0.10 microeq. h-1. cm-2). In human intestine, a dose-dependent decrease in Isc was observed in right and sigmoid colons in basal and stimulated conditions (EC50 congruent with 10(-5) M; at 10(-4) M, DeltaIsc = -2.66 +/- 0.17 microeq. h-1. cm-2) but not in the jejunum. The results indicate that C7-sorbin stimulated NaCl neutral absorption and inhibited electrogenic Cl- in rat and human intestinal epithelia. In addition, the antisecretory effect was essentially observed in the distal part of both rat and human intestine and the magnitude of the proabsorptive effect was directly related to the magnitude of the previously induced secretion.

Comparison of the antisecretory effect of endogenous forms of peptide YY on fed and fasted rat jejunum.

It is intriguing that the antisecretory peptide YY is present in plasma in two forms: PYY1-36 and PYY3-36. PYY3-36 has been found in human and rabbit blood within 30 min of the beginning of the meal, when the peak of water and electrolyte secretion occurs in the duodeno-jejunum. The aim of this study was therefore to compare the antisecretory effect of PYY1-36 and PYY3-36 in fed and fasted rat jejunum. The variations in electrolyte secretion were assessed by measuring the variations in short-circuit current (delta Isc) and transepithelial isotopic chloride fluxes in jejunal mucosa isolated from fed and fasted animal, and mounted in Ussing Chambers. In fasted animals, 2 x 10(-7) M PYY3-36 induced a reduction in Isc of -0.50 +/- 0.01 microEq/hr.cm2, which was not statistically different from that induced by 2 x 10(-7) M PYY1-36 (-0.60 +/- 0.01 microEq/h cm2). In contrast, in fed animals, 2 x 10(-7) M PYY3-36 did not trigger a significant response on Isc and net chloride flux, while the response to PYY1-36 was present but blunted. The absence of response was probably not related to the presence of secretory peptides because PYY3-36 was still able to induce a reduction in Isc after stimulation by a series of 10 different secretory peptides. After 10(-8) M PYY3-36 addition to an epithelium from the fasted animal, response to 10(-7) M PYY3-36 was blunted for 30 min and returned to control value after 60 min. Plasma concentration of PYY was higher in the fed rats compared to fasted (213.78 +/- 38 vs. 53.62 +/- 11.47 pg/ml p < 0.01). After incubation of crypt cells with or without 0.1 microM of unlabeled PYY for 60 min, Scatchard analysis of equilibrium binding data show that binding capacity (Bmax) of receptors was reduced when crypt cells were previously incubated with unlabeled PYY without significant modification of dissociation constants. Bmax were 183 +/- 27 in control vs. 56 +/- 11 fmol/mg protein. These results confirm the antisecretory activity of PYY1-36 in the jejunum of fasted and fed rats. They further indicate that PYY3-36 displays similar activity to PYY1-36 in fasted animals, but lack of activity in fed animals. These results suggest that the two circulating forms of PYY act as antisecretory peptides by two different mechanisms, implying a C-terminal specificity.

Alternative medicine use in fibromyalgia syndrome.

OBJECTIVE: To record the prevalence, extent, cost, and satisfaction with use of alternative medicine practices by patients with fibromyalgia syndrome (FMS), compared to control rheumatology patients. METHODS: An interviewer-based questionnaire was administered to 221 consecutive rheumatology patients and 80 FMS patients. RESULTS: Alternative medicine interventions were currently being used extensively by rheumatology patients overall, and by FMS patients in particular. All categories of alternative practices were used more often by FMS patients, compared to controls, including overall use 91% versus 63% (P = 0.0001), over-the-counter products 70% versus 54% (NS), spiritual practices 48% versus 37% (NS), and alternative practitioners 26% versus 12% (P = 0.003), respectively. Two-thirds of patients using alternative medicine practices were concurrently using multiple interventions. Patient satisfaction ratings were highest for spiritual interventions. CONCLUSIONS: Alternative medicine practices were currently being used by almost all FMS patients. This observation might indicate that traditional medical therapies are inadequate in providing symptomatic relief to FMS patients.

Sodium fluoride inhibits the antisecretory effect of peptide YY and its analog in rabbit jejunum.

The antisecretory peptide YY (PYY) inhibits jejunal secretion through and inhibitory protein (Gi), whereas sodium fluoride (NaF) is a potent activator of G-proteins. This work was conducted to characterize the role of NaF in the antisecretory effect of PYY. For this purpose, electrogenic chloride secretion was assessed by measuring the in vitro variations in short-circuit current (delta Isc) due to alterations in ionic transport, using Ussing chambers Results: 1) NaF induced a transient increase in Isc at concentrations exceeding 5 mM. 2) 2 mM NaF inhibited the antisecretory effect of 0.1 microM PYY and of its analog P915. 3) stimulation of secretion by forskolin and dbcAMP was halved in the presence of 2 mM NaF. 4) Inhibition of protein kinase C by 0.1 mM bisindolylmaleimide caused a sustained increase in Isc in the presence of 5 mM NaF. In conclusion, these results confirm that PYY inhibits electrogenic chloride secretion and show that NaF stimulates it, and suggest that NaF reduces PYY-induced inhibition via a G-dependent and a G-independent functional pathway.

Effects of peptide YY and its analogues on chloride ion secretion in fed and fasted rat jejunum.

The aim of our study was to determine whether a meal modifies the antisecretory response induced by PYY and the structural requirements to elicit antisecretory effects of analogue PYY(22-36) for potential antidiarrhea therapy. The variations in short-circuit current (Isc) due to the modification of ionic transport across the rat intestine were assessed in vitro, using Ussing chambers. In fasted rats, PYY induced a dose- and time-dependent reduction in Isc, with a sensitivity threshold at 5 x 10(-11) M (delta Isc -2 +/- 0.5 microA/cm2). The reduction was maximal at 10(-7) M (Isc -23 +/- 2 microA/cm2), and the concentration producing half-maximal inhibition was 10(-9) M. At 10(-7) M, reduction of 1sc by PYY reached 90% of response to 5 x 10(-5) M bumetanide. The PYY effect was partly reversed by 10(-5) M forskolin (Isc + 13.43 +/- 2.91 microA/h.cm2, p < 0.05) or 10(-5) M dibutyryl adenosine 3',5' cyclic monophosphate (Isc + 12 +/- 1.69 microA/cm2, p < 0.05). Naloxone and tetrodotoxin did not alter the effect of PYY. In addition, PYY and its analogue P915 reduced net chloride ion secretion to 2.85 and 2.29 microEq/cm2 (p < 0.05), respectively. The antisecretory effect of PYY was accompanied by dose- and time-dependent desensitization when jejunum was prestimulated by a lower dose of peptide. The antisecretory potencies exhibited by PYY analogues required both a C-terminal fragment (22-36) and an aromatic amino acid residue (Trp or Phe) at position 27. At 10(-7) M the biological activity of PYY was lower in fed than fasted rats (p < 0.001). Our results confirm the antisecretory effect of PYY, but show that the fed period is accompanied by desensitization, similar to the transient desensitization observed in the fasted period with cumulative doses. This suggests that PYY may act as a physiological mediator that reduces intestinal secretion.

Hepatitis C virus (HCV)-specific in vitro antibody secretion by peripheral blood lymphocytes: correlation with progression of disease and HCV RNA in HCV antibody-positive patients.

Hepatitis C virus-specific in vitro antibody production (HCV IVAP) by peripheral blood lymphocytes in 53 HCV antibody-positive patients was investigated in comparison with alanine aminotransferase (ALT) levels and HCV RNA in serum samples. All 29 HCV IVAP-positive patients were HCV RNA positive; 26 had elevated ALT levels. Among the 24 HCV IVAP-negative patients, 16 were HCV RNA negative, with 12 presenting normal ALT values. These data indicate that HCV IVAP results are highly correlated (P < 0.001) with HCV RNA results and ALT levels. Our study indicates that HCV IVAP can be used as a novel assay in the diagnosis and pathogenesis exploration of HCV infection.

Studies on the mechanism of intestinal passage of the food comutagen harman, in the rabbit.

The passage of harman (Ha) across rabbit jejunum and its effects on electrical parameters of the intestinal epithelium were studied in vitro using Ussing chambers. A linear relationship between mucosal to serosal flux (Jm-s) and the concentration of Ha (0.25-2 mM) was found. Ha elicited a dose-related decrease in short-circuit current, but did not affect transmural potential difference. At 2 mM, Ha decreased tissue conductance. Despite changes of electrical parameters, Jm-s of Ha was not modified by metabolic effectors such as glucose, colchicine, 2,4-dinitrophenol and ouabain, indicating that passage was dependent neither on membrane movements nor on cell energy. The transport of Ha was not dependent on Na+, but Ha inhibited in a dose-related manner the cotransport of Na+ and glucose. Luminal sodium taurocholate or beta-lactoglobulin had no appreciable effect on transport of Ha, but ethanol elicited a 45% increase in Ha permeability. These results indicate (1) that substantial amounts of Ha can cross the intestinal epithelium by the transcellular pathway and (2) that the passage of Ha, which appears to be diffusional, is not affected by luminal solutes such as glucose, sodium taurocholate and beta-lactoglobulin, but is markedly enhanced by ethanol.

Excessive dietary selenium decreases the vitamin A storage and the enzymatic antioxidant defence in the liver of rats.

This study investigated the influence of selenium intake, over 8 weeks, on vitamin A level and on enzymatic antioxidant defence in the liver of young rats. Deficient animals were fed a well-balanced diet but without selenite addition; the Se content of this diet which originated from natural Se content of ingredients was 0.05 mg/kg. Controls were fed the same diet with 0.40 mg/kg added Se. The two other groups received high levels of Se, 2.05 or 4.05 mg/kg. Excessive Se intake decreased the concentrations of retinol and retinyl palmitate in the liver. The linear regression analysis indicated a significant (P < 0.001) dose-dependent vitamin A decline. As expected, Se deficit lowered glutathione peroxidase activity. The highest Se excess decreased the enzymatic antioxidation: Zn,Cu superoxide dismutase, catalase, glutathione peroxidase activities. Data showed that high dietary Se can sometimes enhance carcinogenesis and our results suggest that it is best to be cautious in administrating Se to humans with the aim of preventing diseases.

Alternative medicine use by rheumatology patients in a universal health care setting.

OBJECTIVE: To assess the prevalence, extent of use, and cost of alternative medicine by patients attending a rheumatology clinic. METHODS: Two hundred and thirty-five unselected consecutive patients attending a rheumatology clinic were evaluated by questionnaire to record their current use of alternative medicine practices. RESULTS: Sixty-six percent of patients had used alternative medicine interventions in the preceding 12 months; 54% used over the counter products, 39% spiritual aids (including prayer, relaxation, meditation), and 13% each had visited alternative practitioners or used dietary interventions. Patients in the upper middle income group and French speaking patients used more bought products, but no other differences were observed when the groups were analyzed according to level of education, income or cultural background. The current annual cost for the patients of alternative medical therapies was $100. CONCLUSION: Our results demonstrate a moderate use of alternative medicine by rheumatology patients, mostly inexpensive products and no cost spiritual aids. Universal health care may have a negative impact on the extent of use of more costly practices.

Effect of phenoclor DP6 on enzyme-altered foci and lipid peroxidation in livers of aflatoxin B1-initiated rats.

This study investigates the capacity of phenoclor DP6 to promote aflatoxin B1 (AFB1)-induced putative preneoplastic foci in the liver. In male Sprague-Dawley rats pretreated with AFB1 (ip injection of 1 or 2 mg/kg body weight once weekly for 3 consecutive wk) and given a diet containing 50 ppm phenoclor DP6 for 11 days, the number of area of putative liver preneoplastic lesions were increased approximately four-fold as indicated by the number and gamma-glutamyl transpeptidase activity of enzyme-altered foci; this change was also accompanied by an increase in hepatic microsomal lipid peroxidation and a decrease in Se-glutathione peroxidase and superoxide dismutase activities. The results indicate that phenoclor DP6 exerts a promoting effect in AFB1-initiated rats.

Lipid peroxidation of rat liver microsomes membranes related to a protein deficiency and/or a PCB treatment.

In this study, we investigated the influence of protein deficiency on lipid peroxidation (LP) and cellular defense systems against oxidative damage in control or polychlorinated biphenyl (PCB) treated rats. Rats were fed either a standard diet (22% casein) or a low protein diet (3.5% casein) for 1, 2 and 6 weeks. Five days prior to killing, one half of the animals were given a single i.p. injection of Phenoclor DP6 (50 mg/kg body weight). In protein deficient rats, liver vitamin E was depressed and ascorbate level was lowered. Total and selenium-dependent glutathione peroxidases (GSH-Px) activities were decreased whereas glutathione reductase (GSH-red) was enhanced. Enzymatic and non enzymatic LP ('spontaneous' or with ADP-Fe2+) were increased. Phenoclor DP6 treatment enhanced liver ascorbate concentration. Microsomal LP was increased. Total and selenium-GSHPx remained unmodified while GSH-red was increased. Liver glutathione and alpha-tocopherol contents appeared to be independent of the PCB injection. Our data suggest that low protein intake and PCB exposure may reduce liver defensive protection against electrophilic species.

The effects of vitamin A nutritional status on microsomal lipid peroxidation and alpha-tocopherol level in rat liver.

In vitamin A-deficient rats, liver glutathione peroxidase activity was decreased, alpha-tocopherol content was strongly enhanced, but microsomal liquid peroxidation remained unchanged.

Pre- and postweaning development of drug-metabolizing enzyme activities in small intestine and liver of rats.

The postnatal development of NADPH-cytochrome c reductase, UDP-glucuronosyltransferase, selenium-dependent glutathione peroxidase, glutathione-S-transferase activities, total non-protein sulfhydryls, and cytochrome P-450 contents was compared in small intestine and liver of male Wistar rats from 18 to 60 days of life. In the intestine, main age-related changes affected conjugation enzymes which were increased rapidly by a factor of 4 during the weaning time and remained unchanged thereafter. Development in the rat was accompanied by changes in cytochrome P-450 content and NADPH-cytochrome c reductase activity only in the liver. In both organs, glutathione concentration and selenium-dependent glutathione peroxidase activity were not significantly modified between 18 and 60 days. In the liver, we observed discontinuities in the developmental pattern of UDP-glucuronosyltransferase, and the ontogenesis of glutathione-S-transferase activities differed according to the substrate metabolized.

Effect of pretreatment with cimetidine or phenobarbital on lipoperoxidation in carbon tetrachloride- and trichloroethylene-dosed rats.

Lipid peroxidation (LP) in vivo as reflected by the exhalation of ethane and n-pentane and by thiobarbituric acid reactive substances (TBARS) in liver microsomes was studied in rats injected with carbon tetrachloride (CCl4) and trichloroethylene (TCE), each at 2 dose levels. Interactions between these chlorinated solvents and cimetidine (CM), an inhibitor of cytochrome P-450-dependent monooxygenases, or phenobarbital (PB) the well known inducer of microsomal enzyme activities were also assessed. A non-hepatotoxic dose of CCl4 did not cause a significant increase in ethane production except in PB-induced rats but did enhance n-pentane elimination, whereas an hepatotoxic dose increased the emission of both hydrocarbons. No interaction between CM and CCl4 could be shown but, as expected, PB potentiated the effect of CCl4. TCE administration led to a moderate dose-independent elevation of n-pentane production but did not affect that of ethane and the effect of TCE was smaller in PB-induced than in CM- or non-pretreated rats. There was no difference in microsomal TBARS content in rats injected with the chlorinated hydrocarbons. The use of butylated hydroxytoluene (BHT) and ethylene diaminetetraacetic acid (EDTA) revealed that direct measurement of TBARS gave inadequate results due to substantial chemical LP in vitro during the whole procedure. With the "ethane-pentane test" it was established that: CM cannot prevent CCl4-induced LP; and TCE hepatotoxicity does not involve increased LP of membrane lipids.

[Kinetics of the pulmonary clearance of inhaled cadmium and its accumulation in rat liver and kidneys]. / Cinétique de l'épuration pulmonaire du cadmium inhalé et de son accumulation dans le foie et les reins, chez le rat.

Pulmonary clearance rate of cadmium (Cd), inhaled in the form of an aerosol of Cd acetate, is very slow (half-life 53 days). However, results demonstrate that an important part of Cd cleared from the lung is recovered in liver and kidney. Liver binds this metal rapidly but to a limited extent, whereas renal accumulation is slow but continuous throughout the three months following exposure.