[Constipation and intestinal flora].
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Aged↗
Biomedical subjects
J Schulze
Publications and source records attributed to J Schulze.
Comparative sequence analysis of the Clostridium difficile toxins A and B.
The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf).
Amino Acid Sequence↗
Biliary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the rat.
The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pancreas carcinogen in rats. The biliary excretion of NNK was therefore studied in anesthetized female Sprague-Dawley rats following i.p. administration of 0.7 mumol/kg [carbonyl-14C]NNK. The concentration of radioactivity peaked within 30 min and decreased thereafter exponentially. Cumulative excretion of radioactivity reached a plateau at 6-9% of the total dose. HPLC analysis revealed the presence of 4-hydroxy-4-(3-pyridyl)butyric acid (hydroxy acid), 4-oxo-4-(3-pyridyl)-butyric acid (keto acid), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butyl beta-D-glucopyranosiduronic acid (NNAL Glu), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNK. NNAL Glu was the major metabolite contributing 34 +/- 4% of total radioactivity in bile at 30 min and 58 +/- 4% at 5 h. The percentage of acidic metabolites remained constant at approximately 20%. In contrast, the percentage of NNK and NNAL decreased within the first 2 h to < 5% and < 10% respectively. The elimination kinetics of NNK and its metabolites fitted into a one-compartment model with a half-life of 37 min for NNK, 52 min for NNAL and 110 min for NNAL Glu and acidic metabolites. In three rats dosed with 240 mumol/kg NNK i.p., the concentration of radioactivity peaked after 1-2 h and decreased very slowly thereafter. After 5-8 h a total of 12-17% of the dose has been excreted in the bile with no indication of a plateau. At all time points NNAL Glu was the major metabolite contributing up to 95% of total radioactivity in bile. The percentage of acidic metabolites was < 5% throughout the experiment. Whereas NNK contributed one-third of the radioactivity at 30 min and decreased rapidly, the percentage of NNAL in bile remained rather constant at approximately 5-10%. In conclusion, the detection of NNK, NNAL and NNAL Glu gives support to the hypothesis that tobacco-specific carcinogens could reach the pancreas retrograde from the bile, especially at high NNK concentrations.
Animals↗
Undigested carbohydrates and intestinal micro-ecology.
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Animals↗
[Lactose--a potential dietary fiber. The regulation of its microecological effect in the intestinal tract. 1. Problems, state of knowledge and methods].
Food components of different chemical structure which attain the colon without being attacked by digestion and absorption during their transit through the small intestine are defined as dietary fibre. In the colon they serve as energy or nutrient source for the intestinal microflora or are excreted without change. Not only chemical structure is decisive when a food component has to be assigned to either nutrients or dietary fibre: Substances resisting small intestine digestion due to the lack of corresponding catabolizing enzymes in man are supposed to be "obligate" dietary fibre. "Potential" dietary fibre are nutrients which are only partially digested in the small intestine. Lactose--the main carbohydrate of milk--represents a typical potential dietary fibre. The present paper investigates the factors being responsible for both the degree of lactose utilization in the small intestine and its efficiency in the colon.
Animals↗
[Lactose--a potential dietary fiber. The regulation of its microecological effect in the intestinal tract. 2. The nutrient effect of lactose].
In the small intestine lactose is subjected to the hydrolytic impact of beta-galactosidase originating mainly from the mucosa. In rats about two thirds of the enzyme activity are located in the first part of the small intestine, and one third in the second one. A part of the mucosal enzyme does not remain in the mucosa. It becomes detached and can be determined in the chymus. The ratio of the transient to the resident proportion amounts to 1.8: 1 in germfree and 0.23: 1 in conventional rats. Bacterial settlement causes an increase in the mucosal mass resulting in higher total activity whereas the specific activity of the mucosal enzyme remains unchanged. Microorganisms occurring close to the small intestine mucosa take part in lactose degradation. Lactose-containing diet leads to an increase in both the bacterial and the mucosal activity, the latter one to varying degrees. Lactose concentration in the ileal chymus rises with increasing intake of lactose and decreasing protein and phosphate intake. Following a saturation kinetics the velocity of lactose hydrolysis is correlated with the lactose concentration of the diet. alpha-lactose is hydrolysed more rapidly in the small intestine of both human sucklings and rats than beta-lactose. As the results of a mathematical model show lactose mutarotation does not effect on the degree of lactose degradation in the small intestine. Depending on the intake of lactose and the food composition the rate of lactose hydrolysis amounts to: --max. 50% after small intestine perfusion in human sucklings, --max. 80% after small intestine perfusion in rats, --max. 60% in rats with ileostomata.
Animals↗
[Lactose--a potential dietary fiber. The regulation of its microecologic effect in the intestinal tract. 3. Dietary fiber actions of lactose due to microbial activity].
The activity of the mucosal beta-galactosidase of caecum and colon is low in both germfree and conventional rats. beta-Galactosidase activity occurs also in the chymus of germfree rats. It increases after monoassociation and is higher in conventional than in germfree animals. Lactose entering caecum and colon acts like dietary fibre and is hydrolysed mainly by the intestinal flora. Aerobe lactobacilli and bacteroides predominate in the microflora of rat caecum and colon. A lactose-containing diet increases the total number of germs and stimulates the growth of bifidobacteria. After special diets, rich in lactose and low in protein and phosphate (e.g. human milk and similar formulae), the number of bacteroides and other putrefactive germs decreases. Moreover, a lactose-containing diet alters the metabolic activity of intestinal microorganisms (activity of microbial beta-galactosidase, acidification and lowering of ph in the chymus, production of hydrogen, proteolytic activity.) Lactose as dietary fibre decreases the nitrogen excretion in the urine and increases the N-excretion in the faeces of conventional rats.
Animals↗
[Lactose--a potential dietary fiber. The regulation of its microecologic effect in the intestinal tract. 4. Dietary fiber action of lactose: evaluation with multivariate statistical analysis].
The conditions and the intestinal processes responsible for the action of lactose as a potential dietary fibre are described. The beta-galactosidase activity in the rat caecum and colon is influenced by dietary factors: It declines with increasing lactose concentration and it rises with increasing protein and phosphate concentration in the diet. The enzyme activity correlates negatively with the content of lactose, and positively with the content of protein and phosphate in the chymus. The products of lactose hydrolysis are degraded by microbial glycolysis in caecum and colon. The glycolytic products are mainly absorbed and energetically utilized by the macroorganism. Phosphate stimulates the microbial metabolism and, therefore, accelerates the consumption of the energy substrate lactose. Mathematical optimization gives the necessary composition of the diet which causes an intended microecological effect. To minimize the chymus pH (5.1 in the colon ascendens; 4.6 in the colon descendens; 4.3 in the faeces) the lactose content of the diet has to be greater than or equal to 160 mumol/g, the protein content less than or equal to 10 mg/g, and the phosphate content less than or equal to 5.5 mumol/g. The minimal pH value depends to a greater extent on variations in the supply of protein and phosphorus with the diet whereas the response to changes in lactose concentration is less noticeable.
Animals↗
Diabetes Intervention Study. Multi-intervention trial in newly diagnosed NIDDM.
OBJECTIVE: In a randomized 5-yr multi-intervention trial, we tested the efficacy of intensified health education (IHE) in improving metabolic control and reducing the level of coronary risk factors and incidence of ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS: Within the intervention group, the benefit of clofibric acid was evaluated in a double-blind study. One thousand one hundred thirty-nine newly diagnosed middle-aged (30- to 55-yr-old) patients with non-insulin-dependent diabetes mellitus (NIDDM) entered the study. They were classified as diet controlled after a 6-wk screening phase with conventional dietary treatment. During the follow-up, the control group (n = 378) was cared for at different diabetes outpatient clinics with a standardized surveillance. The intervention group (n = 761) had a structured IHE that included dietary advice, antismoking and antialcohol education, and ways to enhance physical activity. RESULTS: Randomly, 379 of the IHE patients received 1.6 g clofibric acid/day, and the others received placebo. IHE resulted in improved glucose control (adjusted fasting blood glucose) levels after 5 yr (control subjects 9.27 mM, IHE group 8.71 mM, and IHE plus clofibric acid group 8.60 mM, P less than 0.01). The better glycemic control was achieved with fewer antidiabetic drugs. After 5 yr, antidiabetic drugs were prescribed to 47% of the control subjects, 28% of the IHE group, and 34% of the IHE plus clofibric acid group (cutoff limit for drug application was postprandial blood glucose of greater than or equal to 13.87 mM). The ratio of polyunsaturated to saturated fatty acids (0.26 vs. 0.40, P less than 0.01) and physical activity (174 vs. 327 scores, P less than 0.01) were increased, and blood pressure, tobacco, and alcohol consumption were significantly reduced by IHE. However, IHE had no effect on calorie intake, percentage of fat in the diet (45%), and body weight. The most important finding was the significant increase of blood cholesterol in all three groups (+0.47, +0.36, and +0.34 mM, respectively). Clofibric acid only prevented the increase of triglyceride levels (+0.56, +0.24, and +0.05 mM, respectively). The incidence rate per 1000 for myocardial infarction was 30.3 for control subjects, 53.6 for the IHE group, and 55.6 for the IHE plus clofibric acid group. The corresponding rates for IHD incidence were 90.9, 97.8, and 98.8, respectively. Men suffered more frequently from myocardial infarction, whereas women developed ECG criteria for IHD more frequently. Among the 35 cases of death, besides cardiovascular diseases, liver cirrhosis and neoplasia were the predominant causes. The death rate per 1000 in control subjects was 46.2, 30.6 in the IHE group, and 27 among patients with IHE plus clofibric acid. CONCLUSIONS: IHE was of substantial benefit for the control of glycemia, significantly diminished the need for antidiabetic drugs, and reduced a cluster of risk factors but had no effect on the control of blood lipids. This could be one major reason for the failure of IHE, effective lowering of blood pressure, and clofibric acid to prevent cardiovascular complications. Clofibric acid was only effective in reducing triglycerides.
Adult↗
Therapeutic potentials of acarbose as first-line drug in NIDDM insufficiently treated with diet alone.
OBJECTIVE: Acarbose inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. Therefore, its efficacy and acceptability as a first-line drug in non-insulin-dependent diabetes mellitus (NIDDM) insufficiently treated with diet alone was tested in a randomized double-blind placebo-controlled study. RESEARCH DESIGN AND METHODS: Ninety-four NIDDM subjects, aged 43-70 yr with average body mass index of 28 kg/m2 and undergoing a pretreatment period of at least 3 mo with diet alone, were treated with 100 mg acarbose three times daily or placebo for 24 wk. The patients were recruited after a 4-wk screening period of dietary reinforcement. The inclusion limits for patients termed diet not satisfactory were fasting blood glucose (FBG) greater than or equal to 7.8 mM and/or postprandial blood glucose (BG) greater than or equal to 10 mM. RESULTS: FBG was lowered in the acarbose group from 9.8 to 8.4 mM and in the placebo group from 10.2 to 9.6 mM after 24 wk (P = 0.007 vs. placebo). The most impressive therapeutic effect was a highly significant reduction of postprandial hyperglycemia for at least 5 h after the test meal (1-h postprandial BG with acarbose 10.4 mM and placebo 13.5 mM at 24 wk, P less than 0.001) accompanied by a significant decrease in HbA1 (acarbose 8.65%, placebo 9.32%, P = 0.003). Whereas C-peptide and fasting serum insulin were not significantly affected by acarbose, postprandial insulin increment was approximately 30% lower after 24 wk compared with placebo. Furthermore, acarbose significantly reduced 1-h postprandial triglyceride levels. After an initial phase of greater than 4 wk (when 76.6% in the acarbose group vs. 28% on placebo complained about flatulence, P less than 0.001), the drug was well accepted. At the end of the study, only 32% showed mild or moderate gastrointestinal sensations. CONCLUSIONS: Extrapolation shows that acarbose is an efficient and acceptable drug for the treatment of NIDDM with poor metabolic control by diet alone. It has beneficial effects on postprandial hyperinsulinemia and postprandial hypertriglyceridemia.
Acarbose↗
Beneficial effects on serum lipids in noninsulin dependent diabetics by acarbose treatment.
Acarbose (Bay g 5421, Glucobay; CAS 56180-94-0) inhibits alpha-glucosidases of the small intestine and thus delays glucose release from complex carbohydrates. It is therefore efficient as a first-line drug in the treatment of noninsulin-dependent diabetics (NIDDM) insufficiently treated with diet alone. Information is scarce whether under acarbose treatment the lipid metabolism can also be improved. Therefore the changes of triglycerides, cholesterol and HDL-cholesterol were analyzed in a randomized double-blind placebo-controlled trial. In brief, 94 NIDDM aged 43 to 70, after a pretreatment period of at least 3 months, were treated with 100 mg acarbose t.i.d. or placebo for 24 weeks. The patients were recruited after a 4-week screening phase with reinforcement of diet. The most impressive results of acarbose treatment were lowering of blood glucose and insulin, especially in the postprandial state, and of HbA1 (glycosylated hemoglobin). Results on lipids: The initial serum cholesterol levels showed a broad spectrum. Low concentrations remained unchanged under acarbose, while high concentrations (the upper tercile) decreased from 273 to 251 mg/dl. This effect was statistically significant compared to placebo. HDL-cholesterol levels increased continuously under acarbose and placebo as well thus indicating some study effect. Similarly, fasting triglycerides leveled down under acarbose and placebo. However, drastic differences appeared in postprandial triglycerides which were checked 1 and 5 h after a test meal given at entry and at finish of the study. The lowering by acarbose compared to placebo was highly significant for the 1 h postprandial concentrations. It is concluded that acarbose treatment can reduce elevated cholesterol concentrations and postprandial triglyceride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Acarbose↗
Cloning of Clostridium difficile toxin B gene and demonstration of high N-terminal homology between toxin A and B.
High titered Clostridium sordellii lethal toxin antiserum, cross-reactive with C. difficile cytotoxin B (ToxB), was used to isolate toxB fragments from a C. difficile expression library. Recombinant clones containing toxB fragments of the 5' and 3' end were isolate. A 2.5-kb HincII fragment of chromosomal DNA overlaps both groups of clones. A partial restriction map of the total toxB gene is presented. The gene is positioned upstream of utxA and toxA, toxB has a size of 6.9 kb, corresponding to a 250-kDa polypeptide. A partial sequence of the 5' end of toxB was determined. The sequence contains 398 bp upstream of toxB with a putative Shine-Dalgarno box (AGGAGA) and 609 bp of the toxB open reading frame. The N-terminal 203 amino acids of ToxB were compared with the N-terminal amino acids of the enterotoxin A (ToxA). A homology of 64% of the residues was detected, which proves the relatedness of ToxA and ToxB of C. difficile.
Amino Acid Sequence↗
[The modification of ciliary motility by salbutamol: a comparative study on subjects: oral vs inhalation administration].
15 healthy adults received for 3 days twice daily 8 mg salbutamol orally. Ciliary beat frequency was measured before, on the day of drug administration, 1 and 3 days after the beginning of the treatment, by means of nasal brush biopsy. In the same subjects ciliary beat frequency was determined before and 10 minutes following to the inhalation of 2.5 mg salbutamol with 2 ml of 0.9% saline. Findings suggest that by orally administered salbutamol a positive effect on ciliary beat frequency is yielded. The increase of frequency is more distinct in patients suffering from bronchial hyperreactivity. There was no statistically significant effect after inhalative administration of the drug.
Administration, Inhalation↗
[Coronary heart diseases and associated risk factors in newly manifested type II diabetic patients over the course of 5 years].
Using the baseline data of the diabetes intervention study (DIS) from 1126 newly manifested type II-diabetics our analysis demonstrates higher mean-values of some components of the so-called metabolic syndrome in patients with ECG-abnormalities indicating coronary heart disease (CHD) in diagnosis of diabetes compared with subjects without ECG-findings. The impact of general risk factors for the prevalence of CHD in diagnosis and after a 5-year follow-up is obviously different in both sexes. In multivariate analysis only systolic blood pressure was persistently a significant predictor in both sex groups. With increasing age life-duration gets as time-related factor importance for the development of CHD. The mathematically demonstrated association of triglyceride levels to the presence of ECG-abnormalities agrees with the results of WHO multinational study of vascular disease in diabetes mellitus. In the interventions as well as in the control-groups diabetic subjects with CHD after 5 year follow-up showed in comparison to diabetics without CHD higher levels of investigated risk factors which develop their pathogenetic effect probably by their clustering impact, because the differences of their mean-values are only in some cases significant. The common lower level of the most risk factors at the intervention group compared with the conventionally treated group is the result of the intervention measures.
Adult↗
Pathogenetic role of adipose tissue lipase deficit for development of hypertriglyceridaemia.
In 87 patients (74 males, 13 females; age 43 +/- 9.2 years) covering a wide range of triglyceride (TG) concentrations (8.8 to 80.7 mmol/l) the turnover of total serum TG has been measured using the technique of labelling endogenously synthesized TG with 3H-glycerol. In parallel, lipoprotein lipase activity in adipose tissue and the adipose-tissue lipase activity in post-heparin plasma have been assessed following an oral 50 g glucose load. Despite the well-recognized function of this enzyme for intravascular lipolysis no direct relationship between lipase activities and fractional catabolic rates (FCR), reflecting TG removal processes, was found. On the other hand, relative enzyme activities (per TG moles) are positively correlated with the FCR. However, a detailed analysis of this relationship revealed that only in HTG patients whose FCR are below 0.210 h-1 a rate-limiting influence of a relative lipase deficit can be shown. In these patients, a statistically significant elevation of concentrations of free fatty acids is supposed to contribute to the impairment of the TG removal.
Adipose Tissue↗
Breast cancer: one woman's perspective.
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Breast Neoplasms↗
Clinical study on the effect of biotin on skin conditions in dogs.
In a collaborative study with small-animal veterinary surgeons, dogs with fur and skin conditions were treated with biotin (approximately 5 mg biotin/10 kg body weight/day) for 3 to 5 weeks. In total 119 cases could be treated which were reported to show symptoms such as dull coat, brittle hair, loss of hair, scaly skin, pruritus or dermatitis. Cases requiring other treatments with e.g. glucocorticoids, were excluded from the study. In 60% of the cases all symptoms were reported to be cured after the biotin treatment and in a further 31% an improvement was noted; in only 9% no effect was recorded. All breeds responded but to a variable extent: e.g. in Poodles the response was lower (no response in 6 out of 11 cases) than in Alsatians where all improved and 14 out of 29 were completely cured. The results confirm the favourable effect of biotin for treatment of fur and skin conditions in dogs.
Animals↗
[Intensive basic therapy decreases the need for drug treatment and improves glucose control: an important result of the diabetes intervention study].
In a period of five years in the diabetes intervention study (DIS), 1,139 diabetics aged 30-55 years, who in a 6-week screening phase had been classified as dietetically manageable, were treated in a controlled randomized study with intensified non-medicamentous basic therapy and--in a double blind trial--with 1,6 g clofibric acid. The essential components of the basic therapy were a fat-modified diet (so-called prudent diet) and recommendations for endurance training. Thus in comparison to the control group we succeeded in performing a ca. 40% decrease of the application of oral antidiabetic drugs. The fasting blood values were, nevertheless, with 155 mg% significantly lower than in the control group (169 mg%). Clofibric acid had no influence neither on the necessity to use insulin or oral antidiabetic drugs nor to the control of glycaemia.
Clinical Trials as Topic↗