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PubMed2026

Targeting Microbial Bile Salt Hydrolase Reprograms Bile Acid Metabolism and Ameliorates Metabolic Dysfunction-Associated Steatohepatitis in Mice.

Microbial bile salt hydrolase (BSH) plays a central role in shaping bile acid composition and gut-liver metabolic signaling, yet its therapeutic potential in metabolic dysfunction-associated steatohepatitis (MASH) remains incompletely defined. Here, we evaluated the efficacy of the non-absorbable BSH inhibitor GR-7 in a diet induced mouse model of steatohepatitis using early and late intervention strategies with different dosing regimens. GR-7 reduced food intake and exerted stage- and dose-dependent therapeutic effects, with early intervention robustly suppressing hepatic fibrosis even at low dose, whereas late-stage administration of high-dose GR-7 markedly reduced hepatic steatosis and inflammation, as evidenced by decreased liver weight, hepatic triglyceride and cholesterol levels, and plasma ALT. Although late intervention did not result in statistically significant histological reversal of fibrosis, a trend toward improvement was observed, together with suppression of fibrogenic gene expression, suggesting that prolonged treatment may further enhance antifibrotic efficacy. Mechanistically, GR-7 effectively inhibited microbial BSH activity in vivo, leading to reduced cecal unconjugated primary and secondary bile acids-including deoxycholic acid and lithocholic acid, which was associated with improved gut barrier integrity and reduced hepatic inflammation. In parallel, BSH inhibition reprogrammed hepatic bile acid metabolism toward activation of the alternative CYP27A1-mediated synthesis pathway, accompanied by reduced food intake, thereby contributing to improved hepatic lipid accumulation. Furthermore, late-stage high-dose treatment selectively remodeled the hepatic immune landscape rather than fully restoring homeostasis, highlighting immune recalibration as a key component of therapeutic response. Together, these findings identify microbial BSH inhibition as a promising microbiome-targeted therapeutic strategy for MASH.

Gut microbiome↗

PubMed2003

Women s perception about food properties in a tertiary care hospital.

OBJECTIVE: To understand the existing food beliefs regarding hot, cold and badi (gas-producing) properties of different food items and also to assess whether there is any relationship with education of women and these beliefs. DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: Community Health Center (CHC), The Aga Khan University Hospital, Karachi from July to September 2000. SUBJECTS AND METHODS: Four hundred adult female respondents, who came to CHC as a patient or as an attendant, were interviewed after taking verbal consent. A self-administered pre-coded and pre-tested questionnaire was filled by the respondent. Descriptive frequencies and cross tabulation were computed to assess the existing food beliefs. Chi-square test was used to assess the association between education level of women and belief regarding these food items. RESULTS: More than three-fourth of respondents were literate. The percentages of respondents saying that certain foods were hot, cold and badi were 71%, 55% and 80% respectively. Meat, either beef or mutton, fish, egg, chicken, was perceived as hot by majority of the respondents. Majority of vegetables was perceived as cold foods in our study. The other foods like rice, yogurt, banana, watermelon, milk and cold drink were also thought to be cold by many of the respondents. Cabbage, cauliflower, potato, rice, gram and mash pulses (chane and mash-ki-dal) were highly rated as badi foods. Level of education of women didn t show any statistically significant difference in keeping beliefs regarding hot, cold and badi properties of food items. CONCLUSION: A significant concept of different properties of food exists in our culture. We recommend future studies to explore scientific basis for classifying hot, cold or badi foods and also to look into its impact on health by their restriction based on their beliefs.

Adult↗

PubMed2002

Degradation of apple cell wall material by commercial enzyme preparations.

The action of commercial enzyme preparations on the release of cell wall constituents from alcohol-insoluble substance prepared from apples without skins and cores as well as their influence on the water binding of remaining residues is described as a model for the enzymatic cell wall destruction during production of liquid fruit products. Besides 'normal' enzyme concentrations adapted from the usual industrial dosage, 'tenfold' enzyme concentrations were applied. Dependent on enzyme spectrum and activities, concentrations of dietary fibre, e.g., pectin, increased in the soluble fractions using conditions of enzymatic 'mash treatment'. A further release of these cell wall constituents occurred when cellulase containing enzyme preparations were used under conditions of 'pomace treatment', especially with the 'tenfold' enzyme dosage. The partial enzymatic degradation of the cell wall material is connected with a decrease in water binding of the remaining residues during both simulated mash treatment of pomace treatment. Alcohol-insoluble substance from apples is a suitable model for the determination of complex enzymatic actions of enzyme preparations containing pectolytic, hemicellulolytic, and/or cellulolytic activities under standardised conditions.

Cell Wall↗

PubMed1995

Simultaneous raw starch hydrolysis and ethanol fermentation by glucoamylase from Rhizoctonia solani and Saccharomyces cerevisiae.

Crude glucoamylase preparation from Rhizoctonia solani was used to saccharify raw and cooked starch. Various concentrations of potato starch and wheat flour from 10-40%, w/v were used for mashing but 30% was found to be the optimal and economical. The saccharified mash yielded 5.89%, v/v ethanol in a simultaneous saccharification and fermentation process using a yeast strain Saccharomyces cerevisiae (SC-39) at 35 degrees C for 4 days. Removal of inhibitory substances from the fermenting broth through dialysis caused considerable increase in ethanol production.

Ethanol↗

PubMed2005

Differential properties of dentate gyrus and CA1 neural precursors.

In the present article we investigated the properties of CA1 and dentate gyrus cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in situ was investigated by rating the number of cells incorporating BrdU after kainate-induced seizures. CA1 precursors displayed a greater proliferation capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1 expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In animals pretreated with the antimitotic azacytidine, the capacity of kainate to enhance the proliferation was higher in CA1 than in the dentate gyrus. Differences in intrinsic progenitor cell activity could underlie these different expansion capacities. Thus, we compared the renewal- expansion and multipotency of dentate gyrus and CA1 precursors isolated in vitro. We found that the dissected CA1 region, including the periventricular zone, is enriched in neurosphere-forming cells (presumed stem cells), which respond to either EGF or FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus neurospheres mostly produced glial cells. The analysis of the effects of EGF on organotypic cultures of hippocampal slices depicted similar features: BrdU and Nestin immunoreactivities increased after EGF treatment in CA1 but not in the dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like than granule cell precursors, which may represent a more restricted precursor cell.

Analysis of Variance↗

PubMed1994

The expression pattern of two zebrafish achaete-scute homolog (ash) genes is altered in the embryonic brain of the cyclops mutant.

Two achaete-scute homolog sequences, Zash-1a and Zash-1b, were isolated from a zebrafish embryonic cDNA library. The Zash-1a cDNA encodes a protein very similar to rat Mash-1 and Xenopus Xash-1, with over 94% identity in the C-terminal three-fourths of all three polypeptides. The Zash-1b cDNA encodes a more distantly related protein, with 80% identity of amino acids to Mash-1 in this part of the sequence. At 24 hr, the Zash-1a transcripts are found in the hindbrain in two bilaterally symmetrical lines of cells which mark the boundary between the alar and basal plates and in rhombomere 1 in ventral cells near the floorplate. The gene is also expressed in particular regions of the telencephalon and diencephalon, in the epiphysis, the ventral tegmentum, the neural retina, and in specific cells in the spinal cord. Zash-1b transcripts are found in the hindbrain in segmentally arranged fan-like groups of cells which are located close to the anterior and posterior boundaries of each of rhombomeres 2-6 and in ventral cells close to the floor plate of most rhombomeres. The gene is also expressed at sites distinct from cells expressing Zash-1a in the tegmentum, diencephalon, telencephalon, and spinal cord. In the mutant cyclops, Zash-1a transcripts are absent from the ventral region of the tegmentum and in the ventral cells of rhombomere 1, while more dorsal expression regions are unaffected. The effects of the mutation on Zash-1b expression, however, are more complex. In the hindbrain, the ventral expression zone of this gene is absent, the more dorsal segmented expression is disorganized, and ectopic expression in the alar plate is observed. A dramatic ectopic expression is also observed in the anterior tegmentum. The cyclops gene, therefore, has both positive and negative effects on the CNS of the wild-type embryo: it is required for activation of both Zash-1a and -1b in particular ventral cells, but it also restricts the expression of Zash-1b in other ventral cells and in some dorsal regions. Zash-1a and -1b gene probes will be extremely useful in the analysis of additional mutations affecting development of the central nervous system in zebrafish embryos.

Animals↗

PubMed1988

Fenfluramine disrupts the behavioural satiety sequence in rats.

Previous studies have shown that when hungry rats are fed to satiety, the offset of eating is followed by a short period of activity superseded by resting behaviour. Observations of rats consuming wet mash or sucrose confirmed this "behavioural satiety sequence" and showed that the duration of resting was related to the intake of calories rather than of bulk. Fenfluramine reduced the consumption of sucrose and wet mash, but at anorectic and subanorectic doses, fenfluramine also suppressed resting behaviour; the effects of dl- and d-fenfluramine were qualitatively similar. It is argued that the suppression of resting behaviour by fenfluramine is incompatible with an enhancement of satiety.

Animals↗

PubMed1978

[Demonstration of early local vital reactions by combination of morphological investigation methods (author's transl)].

In extension of earlier Scanning Electron Microscopical findings on local vital reaction, we initially tried conventional microscopic histology. By standard staining methods--generally used in demonstrating fibrins (Ladew IG, PTAH, PAS etc.) fresh fibrinous mashing was hardly demonstrable. Tryptophan reaction as per Adams brought positive results. By modifying Scanning Electron Microscopic preparation techniques, the surface transverse striation could be shown. For dissolution of the complex morphological structural patterns on the wound surface, Transmission Electron Microscopy was used. Identification of fibrinous filaments was done by their interior transverse striation. Mashing of shaped structure components of the blood in vital and post mortal injuries should be more closely analyzed. Advantages and disadvantages of Scanning and Transmission Electron Microscopic techniques are discussed in view of forensic problems and a tentative judgement passed.

Animals↗

PubMed1997

Is there any possibility of detecting the use of genetic engineering in processed foods?

To elucidate if there is any possibility to identify highly processed foods as produced through genetic engineering, beer, soya bean oil, processed tomato (ketch-up, paste, pizza tomatoes, peeled tomatoes, soup) and potato (french fries, crisps, mashed potatoes, flour, starch, fried potatoes) products as well as an enzyme preparation (Natuphos) were investigated by PCR. In pizza tomatoes, peeled tomatoes, french fries, fried potatoes, potato flour and potato crisps DNA suitable for PCR was found. Therefore, it is possible to identify these products as produced through genetic engineering. Such an identification is impossible in certain beers (pilsener, export, Nutfield lyte), soya bean oil, tomato soup, potato starch, mashed potatoes and Natuphos since PCR-analysis gave no indication of the presence of DNA in these products. As it was shown by adding Escherichia coli DNA the used method is, in principle, capable of detecting specifically small amounts of DNA in such products.

DNA Primers↗

PubMed2002

5-HT1B receptors modulate components of satiety in the rat: behavioural and pharmacological analyses of the selective serotonin1B agonist CP-94,253.

RATIONALE: 5-HT(1B) receptors are thought to be one of the receptor subtypes that mediate the inhibitory control of serotonin on food intake and satiety. OBJECTIVE: To use the selective 5-HT(1B) receptor agonist, CP-94,253 as a probe of 5-HT(1B) receptor function in feeding behaviour, and to confirm the pharmacological selectivity of CP-94,253-induced hypophagia with a range of antagonists. METHODS: Dose-response functions for CP-94,253 (0, 1.25, 2.5, 5.0 mg/kg; IP) were determined in animals consuming wet mash in a 40-min test session during which time-sampled behavioural observations were collected to evaluate satiety sequences. A meal patterning study was carried out in a separate group of rats. The 5-HT(1A) antagonist WAY 100,635 (0, 1.0, 3.0 mg/kg; SC), the 5-HT(1B/1D)antagonist GR 127,935 (0, 3 mg/kg; IP), and the 5-HT(1B) antagonist SB 224289 (0, 2.5, 5.0 mg/kg; IP) were used to confirm that 5-HT(1B) receptor subtypes were responsible for the action of CP-94,253 on feeding behaviour. RESULTS: CP-94,253 (2.5 mg/kg) reduced food intake and preserved the satiety sequence in animals consuming a diet of mash. GR 127,935 (3.0 mg/kg) and SB 224289 (2.5 mg/kg), but not WAY 100,635, attenuated the hypophagic effect of the 5-HT(1B) agonist, and returned the changes in satiety sequence to control patterns. Meal patterning analyses indicated that CP-94,253 (2.5 mg/kg) reduced food intake through a decrease in meal size and duration in the absence of any alteration in the rate of eating. A hypodipsic action of CP-94,253 was also observed (2.5 and 5.0 mg/kg). CONCLUSION: These findings imply that 5-HT(1B) receptors regulate discrete elements of satiety. We discuss the potential role of 5-HT(1B) agonists for the treatment of obesity.

Animals↗

PubMed2006

Mycotoxins in poultry feed in Kuwait.

A survey was conducted at a poultry feed production unit in Kuwait for mycotoxin contamination in the samples of yellow maize, soybean meal, wheat bran used as raw material and the poultry feed prepared for broiler starter, broiler finisher, and layer mash. Individual aflatoxins were determined by high-pressure liquid chromatography after immunoaffinity column purification. Repeated analysis revealed average aflatoxin concentration in maize at 0.27 ppb (range 0 to 1.69 ppb), soybean meal at 0.20 ppb (range 0 to 1.27 ppb), wheat bran at 0.15 ppb (range 0 to 1.07 ppb), prepared poultry feed for broiler starter at 0.48 ppb (range 0 to 3.26 ppb), broiler finisher at 0.39 ppb (range 0 to 1.05 ppb), and layer mash at 0.21 ppb (range 0 to 1.30 ppb). Other mycotoxins (ochratoxin, fumonisin, deoxynivalenol (DON), and zearalenone), were detected by quantitative enzyme-linked immunosorbent assay. The average levels of ochratoxin A ranged from 4.6 to 9.6 ppb, fumonisin from 1.4 to 3.2 ppm, DON from 0.17 to 0.29 ppm, and zearalenone from 46.4 to 67.6 ppb in various commodities and prepared feed samples. The study revealed the coexistence of determined mycotoxins, although their concentrations in general were found to be lower than the permissible levels, wherever defined, for the poultry feed.

Animal Feed↗

PubMed2005

The importance of aeration strategy in fuel alcohol fermentations contaminated with Dekkera/Brettanomyces yeasts.

Whole corn mash fermentations infected with industrially-isolated Brettanomyces yeasts were not affected even when viable Brettanomyces yeasts out-numbered Saccharomyces yeasts tenfold at the onset of fermentation. Therefore, aeration, a parameter that is pivotal to the physiology of Dekkera/Brettanomyces yeasts, was investigated in mixed culture fermentations. Results suggest that aeration strategy plays a significant role in Dekkera/Brettanomyces-mediated inhibition of fuel alcohol fermentations. Although growth of Saccharomyces cerevisiae was not impeded, mixed culture fermentations aerated at rates of > or =20 ml air l(-1) mash min(-1) showed decreased ethanol yields and an accumulation of acetic acid. The importance of aeration was examined further in combination with organic acid(s). Growth of Saccharomyces occurred more rapidly than growth of Brettanomyces yeasts in all conditions. The combination of 0.075% (w/v) acetic acid and contamination with Brettanomyces TK 1404W did not negatively impact the final ethanol yield under fermentative conditions. Aeration, however, did prove to be detrimental to final ethanol yields. With the inclusion of aeration in the control condition (no organic acid stress) and in each fermentation containing organic acid(s), the final ethanol yields were decreased. It was therefore concluded that aeration strategy is the key parameter in regards to the negative effects observed in fuel alcohol fermentations infected with Dekkera/Brettanomyces yeasts.

Acetic Acid↗

PubMed2007

Contribution of the fermenting yeast strain to ethyl carbamate generation in stone fruit spirits.

Fermented fruit and beverages frequently contain ethyl carbamate (EC), a potentially carcinogenic compound that can be formed by the reaction of urea with ethanol. Both are produced by the yeast Saccharomyces cerevisiae with ethanol as the major end product of hexose fermentation and urea as a by-product in arginine catabolism. In spirit production, EC can also be derived from cyanide introduced by stone fruit. To determine the relative contribution of yeast metabolism to EC production, we genetically engineered a diploid laboratory strain to reduce the arginase activity, thus blocking the pathway to urea production. For this purpose, strains with either a heterozygous CAR1/car1 deletion or a homozygous defect (car1/car1) were constructed. These strains were compared to the parental wild type and to an industrial yeast strain in cherry mash fermentations and spirit production. The strain with the homozygous car1 deletion showed a significant reduction of EC in the final spirits in comparison to the non-engineered controls. Nevertheless, using this strain for fermentation of stoneless cherry mashes did not completely impede EC formation. This indicates another, as yet unidentified, source for this compound.

Arginase↗

PubMed2005

Comparison of wild-type and UV-mutant beta-glucanase-producing strains of Talaromyces emersonii with potential in brewing applications.

A screen of 46 UV-mutant strains of the moderately thermophilic fungus Talaromyces emersonii yielded two mutants (TC2, TC5) that displayed gross morphological differences to the parent strain and enhanced activity against mixed linkage cereal beta-glucans. Activity against beta-(1, 3)(1, 4)-D: -glucan from barley (BBGase) was measured during growth of the mutant and wild-type strains on a variety of carbon sources, ranging from solka floc to crude cereal fractions. In liquid culture, TC2 and TC5 secreted 1.2- to 8.6-fold more BBGase than the parent strain and markedly less beta-glucosidase (exo-activity); enzyme levels were dependent on the carbon source. Cellulose induced high BBGase. However, beet pulp, wheat bran, carob and tea-leaves were cheap and effective inducers. T. emersonii wild-type, TC2 and TC5 crude enzyme preparations achieved similar end-points during the hydrolysis of commercial barley beta-glucan (13.0-16.9%), but were more active against crude beta-glucan from barley (16.0-24.2% hydrolysis). The products of hydrolysis were quantified by high-performance anion-exchange chromatography. Mash trials indicated that enzyme preparations from all three organisms effected a significant reduction in wort viscosity and residual mash beta-glucan. Finally, TC2 and TC5 produce more efficient beta-glucan-depolymerizing enzymes; and wheat bran and solka floc can be used to provide inexpensive and potent enzyme cocktails with potential in brewing applications.

Beer↗

PubMed1996

Hyperphagia induced by direct administration of midazolam into the parabrachial nucleus of the rat.

Benzodiazepine receptor agonists increase food intake in many different species, yet there has been little investigation of the central site of actions of these drugs on ingestive behaviour. In the present experiments, direct administration of the benzodiazepine receptor agonist midazolam (3-30 micrograms/microliter) into the parabrachial nucleus of the pons significantly increased the consumption of a wet mash diet and a 3% sucrose solution in adult non-deprived rats. The hyperphagic response was blocked by pre-treatment with the selective benzodiazepine receptor antagonist flumazenil. Injection of midazolam into the parabrachial nucleus had no effect on locomotor activity, despite the fact that in the same animals an increase in mash intake was observed following intra-parabrachial midazolam. These data suggest that benzodiazepine receptors located in the parabrachial nucleus may be an important site of action for the effects of benzodiazepines specifically on ingestive behaviour.

Analysis of Variance↗

PubMed1983

Anti-proliferative effect of pyridinolcarbamate and of aspirin in the early stages of atherogenesis in swine.

When young swine are fed a suitable hyperlipidemic (HL) diet the number of cells in intimal cell masses (ICM) of large and medium-sized arteries begins to increase in number; by 90 days on the diet the cell increase is several-fold compared to no significant increase in cell numbers in ICM of mash-fed controls. The objective of the current study was to see if the cell increase associated with the HL diet could be reduced by pyridinolcarbamate or aspirin. Arteries studied were the abdominal aorta and the coronaries; time on HL diet was 90 days. Both drugs resulted in significant reductions in the increases in cells in ICM associated with the HL diet in both of the arterial beds that were studied. The reduction was most prominent in the abdominal aorta where the increase in ICM cells in the untreated HL diet-fed swine was from an average of 242 +/- 50 cells per cross-section in the mash-fed controls to 1925 +/- 556; in the pyridinolcarbamate-treated swine the increase was only to 641 +/- 214 and in the aspirin-treated group to 770 +/- 146.

Animals↗

PubMed1985

Endothelial cell labeling indices in swine aortas in relation to intimal cell mass-derived atherosclerotic lesions.

In the swine abdominal aorta, most atherosclerotic lesions arise from naturally occurring collections of intimal cells called intimal cell masses. The main objective of this study was to determine if the tritiated thymidine labeling index of endothelial cells lying over intimal cell masses was greater than that of endothelial cells not over intimal cell masses. A higher endothelial cell labeling index over intimal cell masses would indicate possibly a greater turnover in the area. Such a finding would suggest possible transient but repeated breaks in the endothelial cell barrier that might contribute to the initiation of the atherosclerotic lesion in intimal cell masses. In 2 groups of mash-fed swine, 2 and 11 months old, no differences were found in labeling indices of endothelial cells lying over or not over intimal cell masses. It appears that the initiation of atherosclerosis in swine abdominal aorta is not dependent upon pre-existing altered endothelial cell kinetics as measured by tritiated thymidine labeling indices. The labeling index of cells within the intimal cell mass was significantly higher than in the media; this also is obviously not dependent upon an increased labeling index of the covering endothelial cells. Another group of swine were killed at 11 months of age after receiving a hyperlipidemic diet for 270 days. The labeling index of endothelial cells over atherosclerotic lesions was significantly higher than the labeling index of endothelial cells not over lesions in these swine, and also significantly higher than that of endothelial cells over intimal cell masses in the 11-month old mash-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1985

Intimal cell mass-derived atherosclerotic lesions in the abdominal aorta of hyperlipidemic swine. Part 1. Cell of origin, cell divisions and cell losses in first 90 days on diet.

Atherosclerotic lesions may originate and develop in a variety of ways. In this study we are focusing our attention on atherosclerotic lesions arising in normally occurring intimal cell masses (ICM) in the abdominal aortas of hyperlipidemic (HL) swine. Times chosen for study were 0, 14, 49 and 90 days on HL diet; mash-fed swine were used as controls. Total numbers of cells in the ICM of HL and mash swine were similar at 14 and 49 days; by 90 days the number of cells had increased dramatically in the HL swine to 8-fold greater than control values. Changes present at 49 days and thus preceding increase in cell numbers included extensive intracellular lipid accumulation with by count nearly half of the ICM cells involved and elevated tritiated thymidine labeling indices (LI) 4-fold greater than control. Differential cell counts by transmission electron microscopy were made on the ICM lesions in the HL swine at 49 and 90 days. More than 95% of all cells were smooth muscle cells (SMC), with relatively few monocytes being present. Calculations from the LI and total cell counts showed that the entire increase in cell numbers could be accounted for by divisions among the resident SMC in the ICM. Further calculations suggested that cell losses (deaths) from the ICM were minimal. Scanning electron microscopy studies reported elsewhere revealed no loss of endothelial integrity. The results suggest: (1) that the lesions arise by stimulation of the resident SMC in the ICM to hyperplastic activity, (2) that the role of monocytes in the early development of these lesions is minimal if any, (3) that in view of the intact endothelium platelets are not likely to play an important role, (4) that ICM cell death is not a major factor, (5) that the most likely candidate for the cell growth stimulatory role (? mitogen) is some component(s) of the excess lipid that accumulates in the ICM.

Animals↗