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Bacterial responses to temperature during aeration of pig slurry.

The temperature effect on total anaerobic and aerobic bacterial growth in pig slurry was studied using low level batch aeration treatments. Five bioreactors were built using Plexiglas tubes to perform five temperature treatments (5 degrees C, 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C). An airflow rate of 0.129 L/min/L manure was used to aerate manure contained in all reactors. Data showed that temperature had a profound impact on the aerobic counts in pig slurry during the aeration process. When the temperature increased from 15 degrees C to 25 degrees C, the average oxidation-reduction potential decreased from +40 mV to -60 mV, accompanied by a 75% reduction of aerobic bacteria in the manure. At 25 degrees C, the anaerobic counts were consistently higher than aerobic counts for most of days. A quadratic relationship was observed between the aerobic counts and the oxidation-reduction potential with a correlation coefficient of 0.8374. To reduce odor generation potential, the oxidation-reduction potential in the manure should be maintained at +35 mV or higher.

Aerobiosis↗

The effect of starch malabsorption on fecal short-chain fatty acid excretion in man.

To study the impact of starch malabsorption on fecal short-chain fatty acid concentrations, 11 healthy volunteers consumed a controlled diet rich in starch for 2 4-week periods. They received the glucosidase inhibitor acarbose (Bay g 5421) in one of the study periods and placebo in the other. Stool wet weight increased by 68% and stool dry weight by 57% with acarbose. The fecal concentration (mumol/g wet weight) of n-butyrate (+58%) rose significantly when acarbose was added to the diet. The fecal excretion (mmol/day) of total short-chain fatty acids (+95%) and of their constituents acetate (+97%) and n-butyrate (+182%) was significantly higher when starch malabsorption was induced by acarbose.

Adult↗

Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora.

Twelve healthy male subjects age range 24-40 y participated in the investigation. The trial was divided into 2 35-d periods. The 2 treatment regimens were: (i) 1 x 400 mg moxifloxacin tablet in the morning and 1 placebo tablet in the evening for 7 d; and (ii) 1 x 500 mg clarithromycin tablet in the morning and 1 x 500 mg clarithromycin tablet in the evening for 7 d. Each subject received firstly I treatment regimen and secondly the other treatment regimen. The wash-out period was 6 weeks between the two treatment regimens. Moxifloxacin caused significant decreases of enterococci and enterobacteria during the administration period while the numbers of staphylococci, streptococci, Bacillus and Candida were not affected. No impact on peptostreptococci, lactobacilli, Veillonella, Bacteroides or fusobacteria was observed, while bifidobacteria and clostridia decreased during moxifloxacin administration. The microflora was normalized after 35 d. Clarithromycin caused significant reduction of Escherichia coli while the numbers of enterococci, Enterobacter, Citrobacter, Klebsiella and Pseudomonas increased markedly. No significant changes in the numbers of staphylococci, streptococci, Bacillus and Candida were noticed. In the anaerobic microflora bifidobacteria, lactobacilli and clostridia were suppressed, while no changes in peptostreptococci, Veillonella, Bacteroides and fusobacteria were found. The microflora was normalized in all volunteers after 35 d.

Administration, Oral↗

The impact of hospitalization on the aerobic fecal microflora.

Quantitative bacteriological analysis of the aerobic fecal microflora of 75 patients indicated that, at the time of admission to hospital, Escherichia coli were the predominant fecal aerotolerant bacteria. Subsequent fecal samples showed a progressive supplantation of E coli by Klebsiella, Enterobacter and Proteus. At the end of 21 days of hospitalization, E coli remained predominant in only 30 patients. None of the patients had received antibiotics, undergone surgery or been subjected to x-ray studies of the gastrointestinal tract. The cause of the change of fecal flora in these patients is unknown, and no change of flora was observed in a control group of nonhospitalized persons, also studied for 21 days. The appearance of Klebsiella, Enterobacter and Proteus as predominant in the fecal flora of hospitalized patients may be an important factor in the natural history of hospital-associated infections.

Bacteria↗

Comparison of fecal flora following administration of two antibiotic protocols for suspected maternofetal infection.

Two protocols are used by French neonatologists for the treatment of suspected maternofetal infection (SMFI). Three groups of premature and term neonates were included to study the impact of antibiotics on fecal flora: 10 infants with SMFI treated with amoxicillin and netilmicin (group BI), 10 infants with SMFI treated with amoxicillin, cefotoxime and netilmicin (group TRI) and 10 infants without antibiotic therapy as controls (group C). Group BI samples were colonized with Klebsiella oxytoca and Escherichia coli resistant to amoxicillin and by Eneterococcus faecium and coagulase-negative staphylococci. In group TRI biodiversity of the intestinal flora was low, with rapid growth of staphyloccoci and occurrence of Candida spp. These modifications of the intestinal flora should encourage us to use antibiotic treatment as targeted as possible.

Amoxicillin↗

Impact of oral ciprofloxacin on the faecal flora of healthy volunteers.

The intestinal flora was studied in 12 volunteers after the administration of 400 mg ciprofloxacin b.i.d. over seven days. Stool samples were taken prior to and several times after the initiation of therapy, and qualitative and quantitative analyses of microorganisms were performed. Escherichia coli was eliminated in all volunteers after two days of treatment. A selection of resistant enterobacteria could not be observed. A higher incidence of Streptococcus faecium was seen, mainly after the end of drug application. The number of cfu of Bacteroides and Bifidus species remained unchanged during the trial. There was no selection of Clostridium difficile. Based on this pattern of activity on the stool flora we suggest that ciprofloxacin could represent an appropriate drug for the therapy of bacterial intestinal infections as well as for selective decontamination in immunosuppressed patients.

Administration, Oral↗

Digestibility of prairie hay diets supplemented with different levels of magnesium-mica by beef heifers.

Four ruminally fistulated, nonpregnant, nonlactating heifers (515 +/- 7.9 kg) were offered chopped (10-cm screen size) prairie hay for ad libitum consumption with 1.8 kg/d of supplements to provide 0, 45, 113, or 181 g/d of magnesium-mica (MM) in a 4 x 4 Latin square design experiment. Heifers were adapted to diets for 7 d in drylot followed by a 19-d confinement period in individual stalls within a metabolism facility. Total feces and urine were collected for 5 d, daily intake and water consumption were monitored for 16 d, and in situ disappearance of fiber (prairie hay) and CP (soybean meal) were determined during the confinement period. Ruminal samples for fermentation product analyses were collected at feeding and every 2 h thereafter for 12 h on d 18, and rumens were evacuated at 1100 on d 19 to determine rumen fill. Cubic responses (P < .05) to MM level were observed for DM, OM, NDF, and ADF digestion and were characterized by a tendency for improved digestion with 45 g/d compared with the control diet, followed by a suppressive effect on digestion with 113 g/d, then little effect with 181 g/d MM. In situ NDF disappearance at 72 and 96 h tended (P < . 10) to be influenced quadratically by level of MM, but MM level had no apparent effect on ruminal fill and passage rate, ciliated protozoa counts, in situ rate of disappearance of fiber or CP, or nitrogen balance. Therefore, feeding MM at low levels to heifers consuming a prairie hay diet with a 20% CP supplement seemed to be beneficial for feed digestion with no measurable negative impact on intake or ruminal protein or fiber digestion.

Aluminum Silicates↗

Impact of acute diarrhoea on parasite loads.

Parasites and diarrhoea are more frequent in poor populations. Parasite prevalence rates in post-diarrhoeal patients of the International Centre for Diarrhoeal Disease Research (ICDDRB) and in non-diarrhoeal populations of two Dhaka poor socioeconomic communities have been compared to explore if there is any effect of acute diarrhoea on parasite prevalence rates. Stool of a 4% systemic randomly selected sample of diarrhoeal patients and the whole population of two local poor communities have been examined. The results showed that the prevalence of parasites in a post-diarrhoeal population is significantly lower than in a non-diarrhoeal population. These reductions (E. hist. 10.2% vs. 2.03%, G. lamb. 9.7% vs. 3.5%, hookworm 37.4% vs. 4.7% and Ascaris lumbricoides 81% vs. 20.6%) may be attributed mainly to the flushing effect of diarrhoea.

Acute Disease↗

Schistosomiasis mansoni: follow-up of control program based on parasitologic and serologic methods in a Brazilian community of low endemicity.

A field survey on schistosomiasis was carried out in 1998, in the municipality of Pedro de Toledo, a low endemic area in the state of São Paulo, Brazil. According to the parasitologic Kato-Katz method, the prevalence rate was 1.6%, with an infection intensity of 40.9 eggs per gram of stool. By the immunofluorescence test (IFT) for detection of IgG and IgM antibodies in the serum, IgG-IFT and IgM-IFT, respectively, prevalence indices of 33.2% and 33.5% were observed. To assess the impact of the schistosomiasis control program in the area, parasitologic and serologic data obtained in 1998, analyzed according to the age, sex, and residence zone, were compared to previous data obtained in a epidemiologic study carried out in 1980, when prevalence indices were of 22.8% and 55.5%, respectively by Kato-Katz and IgG-IFT. A significant fall of the prevalence was observed, indicating that the control measures were effective. Nonetheless, residual transmission was observed, demonstrating the need for a joint effort to include new approaches for better understanding the real situation and improving the control of the disease in low endemic areas.

Adolescent↗

Steroid hormone related male biased parasitism in chamois, Rupicapra rupicapra rupicapra.

Parasites are linked with their host in a trophic interaction with implications for both hosts and parasites. Interaction stretches from the host's immune response to the structuring of communities and the evolution of biodiversity. As in many species sex determines life history strategy, response to parasites may be sex-specific. Males of vertebrate species tend to exhibit higher rates of parasites than females. Sex-associated hormones may influence immunocompetence and are hypothesised to lead to this bias. In a field study, we tested the prediction of male biased parasitism (MBP) in free ranging chamois (Rupicapra rupicapra rupicapra), which are infested intensely by gastrointestinal and lung helminths. We further investigated sex differences in faecal androgen (testosterone and epiandrosterone), cortisol and oestrogen metabolites using enzyme immunoassays (EIA) to evaluate the impact of these hormones on sex dependent parasite susceptibility. Non-invasive methods were used and the study was conducted throughout a year to detect seasonal patterns. Hormone levels and parasite counts varied significantly throughout the year. Male chamois had a higher output of gastrointestinal eggs and lungworm larvae when compared to females. The hypothesis of MBP originating in sex related hormone levels was confirmed for the elevated output of lungworm larvae, but not for the gastrointestinal nematodes. The faecal output of lungworm larvae was significantly correlated with androgen and cortisol metabolite levels. Our study shows that sex differences in steroid levels play an important role to explain MBP, although they alone cannot fully explain the phenomenon.

Analysis of Variance↗

The population dynamics of Ostertagia gruehneri in reindeer: a model for the seasonal and intensity dependent variation in nematode fecundity.

The gastrointestinal nematode Ostertagia gruehneri is a parasite of reindeer that can have a significant impact on host population dynamics. To gain a better understanding of the population dynamics of O. gruehneri, we parameterise a model for its fecundity that describes the observed seasonal and intensity dependent pattern of faecal egg counts well. The faecal egg count model is combined with a model for the seasonal faecal production rate of Svalbard reindeer to obtain quantitative estimates of the fecundity of O. gruehneri. The model is used to evaluate the relative contribution to pasture contamination of variation in the abundance of O. gruehneri and variation in reindeer densities. It is concluded that due to the intensity dependence in nematode fecundity, variation in reindeer population densities is likely to be the most important of these factors for pasture contamination.

Animals↗

Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice.

G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) is a novel G protein-coupled receptor for bile acid. Tissue distribution and cell-type specificity of Gpbar1 mRNA suggest a potential role for the receptor in the endocrine system; however, the precise physiological role of Gpbar1 still remains to be elucidated. To investigate the role of Gpbar1 in vivo, the Gpbar1 gene was disrupted in mice. In homozygous mice, total bile acid pool size was significantly decreased by 21-25% compared with that of the wild-type mice, suggesting that Gpbar1 contributes to bile acid homeostasis. In order to assess the impact of Gpbar1 deficiency in bile acid homeostasis more precisely, Gpbar1 homozygous mice were fed a high-fat diet for 2 months. As a result, female Gpbar1 homozygous mice showed significant fat accumulation with body weight gain compared with that of the wild-type mice. These findings were also observed in heterozygous mice to the same extent. Although the precise mechanism for fat accumulation in female Gpbar1 homozygous mice remains to be addressed, these data indicate that Gpbar1 is a potential new player in energy homeostasis. Thus, Gpbar1-deficient mice are useful in elucidating new physiological roles for Gpbar1.

Animals↗

Modification of colonic fermentation by bifidobacteria and pH in vitro. Impact on lactose metabolism, short-chain fatty acid, and lactate production.

Colonic fermentation plays an important role in the prevention of lactose intolerance and intestinal disorders. The objectives of this study were to evaluate whether supplementation with bifidobacteria modify colonic fermentation of lactose and short-chain fatty acid production and to assess influence of the pH in an in vitro continuous culture system. There was a significantly greater reduction in lactose concentrations at pH 6.7 than that at either pH 6.2 or pH 5.7, accompanied by the highest beta-galactosidase activity and D-lactate production. Bifidus supplementation reduced lactose and D-lactate concentrations and increased acetate production at pH 6.7. The study demonstrates that lactose is rapidly metabolized by colonic bacteria and lactose fermentation in vitro is pH dependent with a maximum rate at pH 6.7. Bifidobacteria supplementation may have the potential to improve lactose fermentation and to manipulate SCFA and lactate production.

Adult↗

Resistant starch types 2 and 4 induce distinct and reversible changes in the human gut microbiome.

Resistant starch (RS) can confer benefits for the gut microbiome and host cardiometabolic health. However, different types of resistant starch can differentially affect gut microbiome composition and functional capacity, especially given interindividual variability in responses, thus limiting the application of resistant starch in dietary strategies. We used shotgun metagenomics to perform a secondary analysis of samples collected during a previously reported randomized clinical trial to determine the effects of dietary supplementation with two types of resistant starch (RS2 and RS4) and a digestible starch (control) on the gut microbiome. Both resistant starch types induced distinct but transient alterations in the gut microbial community. RS2 enriched the keystone degrader, Ruminococcus bromii, and Blautia glucerasea, whereas RS4 favored Parabacteroides distasonis and known but uncharacterized microbial species such as a Lachnospiraceae bacterium. Moreover, we detected strain-level differences in the response of Bifidobacterium adolescentis to resistant starch. Microbial functional profiling revealed an enhanced capacity for complex carbohydrate utilization following resistant starch intake, including increased abundance of specific &#x3b1;-amylases, glycoside hydrolases, starch utilization systems, and other currently uncharacterized genes. Identifying the bacterial strains and genes that respond to different RS types will help to more accurately predict who will benefit from a given RS type. Our findings demonstrate that RS2 and RS4 differentially shape microbial ecology and metabolic capacity and provide a foundation for microbiome-informed personalization of resistant starch-based dietary interventions.IMPORTANCEDietary intake influences human health by modulating metabolism, partly by shaping the microbiota inhabiting the gut. Resistant starch (RS), a dietary fiber, is associated with metabolic improvements. While previous research has explored how RS alters the gut microbiome, RS comprises five types with differing physical and chemical characteristics, and the distinct impacts of each type on the microbiome and host health have not been fully characterized, particularly using high-resolution approaches such as shotgun metagenomics. In this secondary analysis of samples from a longitudinal crossover intervention study, we link dietary supplementation with RS2 and RS4 with distinct and transient changes in the composition and functional potential of the human gut microbiome. Specifically, we identify species that increase in abundance with each RS type, accompanied by increases in genes and pathways involved in complex carbohydrate utilization. The findings support the development of precision nutrition strategies utilizing RS supplementation to improve metabolic health.This study is registered with ClinicalTrials.gov as NCT05743790.

Humans↗

Contrasting occurrence of Chromobacterium violaceum in tropical drinking water springs of Uganda.

Occurrence of Chromobacterium violaceum in six protected drinking water springs in Uganda was investigated. C. violaceum showed a contrasting occurrence, which was independent of human impact as assessed by faecal pollution indicators. It was isolated from two springs (S1 and S2) that were located close to each other (3 km) but not in the rest. In S1 C. violaceum was continuously detected, in concentrations ranging from 6 to 270 cfu 100 ml(-1), while in S2 it was detected on only one sampling occasion. C. violaceum was never detected in the investigated upper soil layers (down to 15 cm) in the immediate surroundings (50 m radius) of the springs, despite continued isolation of faecal indicators. The results of the study indicate that C. violaceum may not be ubiquitous in spring water, but could occur in significant numbers in particular potable groundwaters as an autochthonous member.

Chromobacterium↗

Pharmacokinetics, antifolate activity and tissue distribution of PT523 in SCC VII tumor-bearing mice.

PURPOSE: To monitor the pharmacokinetics of PT523 and methotrexate in C3H mice with transplanted SCC VII tumors; to compare the impact of PT523 and methotrexate on tumor and normal host 5,10-methylenetetrahydrofolate levels; and to synthesize [14C]PT523 and determine its time-dependent tissue distribution in tumor and host tissues. METHODS: C3H mice bearing SCC VII tumors were given i.p. PT523 or methotrexate. Plasma drug levels and tumor, gut and marrow 5,10-methylenetetrahydrofolate were assayed. [14C]PT523 was synthesized and administered i.v. to tumor-bearing mice for tissue distribution analysis. RESULTS: Areas under the curve, mean residence times, whole body clearances, apparent distribution volumes, and plasma protein binding of PT523 vs methotrexate were, respectively, 4311 vs 6472 microM x min(-1); 20 vs 16 min; 0.56 vs 0.36 ml min(-1); 532 vs 325 ml x kg(-1); and 70% vs 30%. Both PT523 and methotrexate caused time-dependent declines in 5,10-methylenetetrahydrofolate in tumor and marrow, but not in gut mucosa [corrected]. Gut levels began to recover within 4 h in the PT523-treated group only. [14C]PT523 distributed mainly into the liver, duodenum, kidneys, lungs, tumor, pancreas and muscle; less into the spleen, blood cells, heart, brain and testicles; and very little into gut [corrected. Only 35% of the dose was excreted, and 2.9-fold more in feces than urine. CONCLUSIONS: Despite its more rapid clearance, accumulation of PT523 in extravascular tissues was greater than that of methotrexate. Consequently, less PT523 was recovered in feces and urine and its apparent volume of distribution was greater. PT523 selectively depleted 5,10-methylenetetrahydrofolate pools in tumor and, less persistently, in marrow, but spared the gut mucosa [corrected]. [14C]PT523 tissue distribution correlated with organ mass and blood supply.

Animals↗

P450 induction alters paclitaxel pharmacokinetics and tissue distribution with multiple dosing.

PURPOSE: Paclitaxel (Taxol) is an effective agent against a broad range of human cancers. Studies on the metabolism and disposition of paclitaxel have shown that it is primarily eliminated via hepatic metabolism by P450 enzymes (2C8 and 3A4) to essentially inactive metabolites, and that biliary and gut transport by P-glycoprotein (PGP) as well as urinary elimination of the parent compound play relatively minor roles. Recent studies in vitro have shown that paclitaxel treatment increases the level of CYP2C8 and CYP3A4 in human hepatocytes as well as PGP in colon tumor cells. The data suggest that previous paclitaxel exposure may influence metabolism and elimination of subsequent doses. Further, since weekly paclitaxel dose schedules are becoming more common as opposed to the original every 21-day dosing, the likelihood of enzyme induction from previous doses impacting that from subsequent doses is increased. METHODS: To study the potential for such sequence-dependent alterations in paclitaxel pharmacokinetics, we carried out pharmacokinetic studies in mouse plasma and tissues following day 1 and days 1 and 5 dosing at 20 mg/kg. Paclitaxel concentrations were determined by a sensitive LC/MS/MS assay out to 16 h post-dosing in plasma, liver, kidney, gut and heart. The effect of paclitaxel treatment on hepatic expression of PGP and P450 isoforms (CYP2C and CYP3A) was determined to elucidate the mechanism by which paclitaxel disposition is altered by previous drug exposure. RESULTS: Pharmacokinetic analysis of the data showed that plasma and tissue AUC values after treatment on day 5 following a dose on day 1 were between 50% and 74% of those determined following a single dose on day 1. The terminal elimination half-life was not different. Activity and protein levels for CYP2C in liver were elevated at 24 and 96 h after paclitaxel dosing. Cremophor EL, a carrier solvent for paclitaxel, also caused elevated CYP2C activity. Neither CYP3A nor PGP levels in liver were altered by paclitaxel or Cremophor EL treatment at the 24-h and 96-h time points. The levels of 6alpha-OH-paclitaxel in feces were increased on day 5 as opposed to day 1 while paclitaxel levels in feces were unchanged. CONCLUSIONS: The results of our studies showed that paclitaxel pharmacokinetics are altered by previous paclitaxel exposure up to 96 h earlier.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Recent advances in the diagnosis and treatment of colorectal cancers].

We review recent developments in the diagnosis and treatment of colorectal cancer. In diagnosis, the detection of the APC gene mutation in stool samples has had a strong impact because of its practical usage for mass screening. Several reports have indicated that the molecular detection of a very small number of cancer cells in the peripheral blood, bone marrow, or lymph nodes yields adequate information on recurrent disease. Several new markers were reported as a significant indicators of cancer development, invasion, or metastasis. In treatment, determination of microsatellite instability may be useful to select good candidates for 5-fluorouracil-based chemotherapy. New molecular targets have been reported, including epidermal growth factor receptor inhibitor, matrix metalloproteinase inhibitors, etc. Gene therapy with p53 or FHIT had undergone successful clinical trials. Tumor-specific immunotherapy with dendritic cell vaccination has also been achieved. In conclusion, many efforts to overcome colorectal cancer will soon open new therapeutic windows.

Antineoplastic Combined Chemotherapy Protocols↗