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At least 19 recordsLinked to original sources

PubMed1977

Cardiac lysosomal derangements in mouse heart after long-term exposure to nonmetabolizable sugars.

Hearts of late fetal mice were maintained in organ culture in the presence of 30-100 mM sucrose or mannitol. Activities of several lysosomal enzymes (cathepsin D, beta-acetylglucosaminidase, acid phosphatase) were increased by up to 30% after 18-24 hours and by up to 50% after 48-72 hours, as compared to enzyme activities in litter-matched hearts maintained in control medium or medium supplemented with equimolar urea. Simultaneously, the ratio of nonsedimentable to sedimentable enzyme activity was significantly increased, suggesting increased lysosomal fragility. Light and electron microsopic examination of the hearts revealed marked vacuolization in myocytic, interstitial, and endothelial cells. The vacuoles were limited by single membranes, often contained particulate or amorphous cellular debris resulting from autophagocytosis, and in cytochemical preparations frequently exhibited an electron-dense reaction product indicative of acid phosphatase activity. Hydrocortisone failed to prevent the marked lysosomal activation induced by the sugars. In conclusion, prolonged exposure to nonmetabolizable sugars induces severe lysosomal derangements with prominent autophagy, in fetal mouse heart maintained in organ culture.

Acetylglucosaminidase↗

PubMed2026

Early life sugar rationing and ageing related diseases, biological ageing and mortality.

Early-life nutrition may influence lifelong ageing, yet human evidence is scarce. Using Britain's postwar sugar rationing as a natural experiment, we examine its long-term effects in 64,809 United Kingdom Biobank participants. Exposure to sugar rationing during the first 1,000 days of life is associated with a 9% lower incidence of hallmark-related disease, with a hazard ratio of 0.91 and a 95% confidence interval of 0.88-0.94, and a 19% lower risk of all-cause mortality, with a hazard ratio of 0.81 and a 95% confidence interval of 0.69-0.93. Mediation analysis indicates that the survival association is statistically mediated, by approximately 60%, through differences in incident hallmark-related disease. Rationed individuals show 1.0-1.2-year younger biological ages across multiple clocks and lower organ ages, particularly in the lung, heart, and liver. Proteomic profiling identifies 47 altered proteins, with enrichment of adenosine monophosphate-activated protein kinase and longevity pathways and suppression of mechanistic target of rapamycin signaling. These findings are consistent with international recommendations to limit free or added sugars from the World Health Organization, United States Dietary Guidelines, and American Heart Association, and may inform policy discussions related to sugar taxation and infant food and marketing policies under the United Nations 2030 Agenda.

Humans↗

PubMed1977

Antigenic, chemical, and structural properties of cell walls of Histoplasma capsulatum yeast-form chemotypes 1 and 2 after serial enzymatic hydrolysis.

Cell walls of Histoplasma capsulatum yeast-form chemotypes 1 (chem 1) and 2 (chem 2) treated sequentially with several polysaccharolytic enzymes and Pronase yielded soluble, nondialyzable polysaccharides at each step, which were analyzed for monosaccharides, protein composition, and serological activity. Polysaccharide recovered after digestion of chem 1 walls with beta(1-->3)-glucanase contained glucose > mannose > glucosamine > galactose. This fraction (chem 1 betaG(1)) was analyzed by polyacrylamide gel electrophoresis and contained a component having an apparent molecular weight of 120,000. The chem 1 betaG(1) fraction was reactive in immunodiffusion (ID), producing an immune precipitate not identical to the H and M factors of histoplasmin. In a side-by-side ID comparison with extracts of chem 2, the chem 1 betaG(1) antigen contained an additional determinant not found in chem 2 extracts when tested with goat antiserum to H. capsulatum. Therefore, the chem 1 antigen gave preliminary ID evidence of antigenic group specificity. A chemical difference observed was the absence of glucosamine from chem 2 polysaccharide. In complement fixation (CF) tests, 9 of 17 sera from human histoplasmosis patients reacted with chem 1 betaG(1), but some cross-reactivity with sera of patients with other systemic mycoses occurred. The immunoelectrophoretic patterns of chem 1 wall-derived polysaccharides showed a marked shift in mobility after Pronase digestion, implying the presence of covalent peptides. The ultrastructural appearance and serological activity of intact walls and enzyme-resistant mural cores were also studied. The surface of the mural cores of both chemotypes was perforated and frayed. In shadow-cast preparations both fibrillar and globular areas persisted in the mural cores. The CF end point serum dilutions showed an increase after alpha- and beta-glucanase extractions of chem 2 walls and fourfold reduction after Pronase digestion. The mural cores of both chemotypes were still reactive in CF tests and retained some ability to bind fluorescent antibody. The chem 1 mural core reacted with specific fluorescein-labeled H. capsulatum antiglobulins produced by adsorption with Blastomyces dermatitidis, thus indicating at least partial retention of H. capsulatum-specific factors. The presence of galactose, mannose, and glucose was detected in the mural cores as well as enriched levels of amino sugar, despite exposure to chitinase.

Antigens, Fungal↗

PubMed1978

Studies on the interaction between protein A and immunoglobulin G. I. Effect of protein A on the functional activity of IgG.

Staphylococcal protein (A (PA) and IgG anti-Forssman immunoglobulin formed complexes that behaved functionally like IgM in their ability to lyse sheep erythrocytes (E) in the presence of whole guinea pig complement (GPC) and to fix purified guinea pig C1. Concanavalin A, a plant lectin that inhibited IgM but not IgG hemolytic activity, inhibited the hemolytic activity of IgG-protein A complexes that behaved like IgM but had no effect on complexes that behaved functionally like IgG. Since Con A is known to bind specifically to glucose and mannose residues, our results suggested that the interaction of protein A with the Fc region of IgG led to exposure of sugar moieties that may participate in complement (C) binding. The production of IgM-like complexes depended on the ratio of protein A to IgG and the empirical formula of these IgM-like complexes was found to be [(IgG)2PA]n. As the ratio of PA to IgG was increased, the resulting complexes tended to behave functionally like IgG but with reduced hemolytic activity and C1 fixing ability. Furthermore, the binding of C1 to EIgG was inhibited by PA and the binding of PA to EIgG was inhibited by C1 indicating that the binding sites for C1 and PA were located near each other or were identical. Our results offer a reasonable explanation for the reported effects of PA or mixtures of PA and IgG in vitro and in vivo.

Animals↗

PubMed1979

The stimulus-secretion coupling of glucose-induced insulin release. XXXV. The links between metabolic and cationic events.

When isolated rat islets were exposed to glucose, the concentrations of NADH and NADPH, and the NADH/NAD+ and NADPH/NADP+ ratios were increased. The dose-response curve resembled that characterising the glucose-induced secondary rise in 45Ca efflux, displaying a sigmoidal pattern with a half-maximal value at glucose 7.5 mmol/l. The glucose-induced increase in NAD(P)H was detectable within 1 min of exposure to the sugar. Except for the fall in ATP concentration and ATP/ADP ratio found at very low glucose concentrations (zero to 1.7 mmol/l) no effect of glucose (2.8-27.8 mmol/l) upon the steady-state concentration of adenine nucleotides was observed. However, a stepwise increase in glucose concentration provoked a dramatic and transient fall in the ATP concentration, followed by a sustained increase in both O2 consumption and oxidation of exogenous + endogenous nutrients. This may be essential to meet the energy requirements in the stimulated B-cell. Although no significant effect of glucose upon intracellular pH was detected by the 5,5-dimethyloxazolidine-2,4-dione method, the net release of H+ was markedly increased by glucose, with a hyperbolic dose-response curve (half-maximal response at glucose 2.9 mmol/l) similar to that characterising the glucose-induced initial fall in 45Ca efflux. It is proposed that the generation of both NAD(P)H and H+ participates in the coupling of glucose metabolism to distal events in the secretory sequence, especially the ionophoretic process of Ca2+ inward and outward transport, and that changes in these parameters occur in concert with an increased turn-over rate of high-energy phosphate intermediates.

Adenine Nucleotides↗

PubMed1979

Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells.

In contrast with newly isolated cells or early primary cultures, synovial cell lines in standardised growth conditions assume a rather uniform fibroblast-like appearance. However, 2 distinct variations in the cytological pattern can be induced at this stage. The first is characterised primarily by increased numbers of small phase-dense organelles that show the distinctive fluorescence of lysosomes after supravital staining, and are interspersed with vacuoles. The associated functional changes include increased enzyme activity and decreased net synthesis of hyaluronic acid. This variation can be induced by exposure to indigestible neutral sugars, adenosine, or its 5' nucleotides. The second variation consists of a striking reorganisation of cytoplasm by condensation into dense ridges or a dendritic network of processes. It is accompanied by increased hyaluronic acid secretion and is induced by agents that enhance intracellular activity of cyclic adenosine monophosphate, such as dibutyryl cyclic adenosine monophosphate and cholera enterotoxin. It appears possible to direct differentiation in synovial cell lines to correspond at least in part with the presumed functions of the different cell types in the parent tissue. The 2 patterns may be useful markers to correlate with other aspects of synovial cell function in vitro.

Acetylglucosaminidase↗

PubMed2026

Sugar rationing during the first 1000 days and early onset cancer: a natural experiment.

BACKGROUND: The "first 1000 days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. OBJECTIVES: We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces risk of early onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. METHODS: We analyzed 63,819 United Kingdom Biobank participants born between October 1951 and March 1956, spanning the end of United Kingdom sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy with those unexposed. Early onset cancer incidence (≤50 y) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. RESULTS: Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early life sugar restriction significantly reduced early onset cancer risk (HR: 0.66; 95% confidence interval: 0.53, 0.81; P < 0.001). A dose-response relationship was observed, with peak protection in individuals exposed for ≤24 mo postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. CONCLUSIONS: Restricting sugar intake during the first 1000 days is associated with a reduced risk of early onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early life dietary guidelines against the rising burden of early onset cancer.

Humans↗

PubMed1978

Inhibition of protein degradation in mouse hearts by agents that cause lysosomal dysfunction.

Although the heart contains lysosomes, it has been uncertain whether these organelles and their proteolytic enzymes can play an important role in cardiac protein degradation. Recent studies have demonstrated that fetal mouse hearts in organ culture sustain selective derangements in lysosomal structure and function during exposure to chloroquine or nonmetabolizable sugars. Accordingly, we tested the effects of these agents on cardiac proteolysis under controlled conditions in vitro using two techniques (measurement of loss of radioactivity from trichoroacetic acid-precipitable protein after prelabeling with tritiated phenylalanine and measurement of loss of cold phenylalanine after blockade of protein synthesis with cycloheximide). Chloroquine (0.1 mM) reduced the average rate of protein breakdown in hearts of matched littermates from 45%/24 hours to 32%/24 hours (P less than 0.01) and decreased the release of cold phenylalanine by 31 +/- 5% (0.108 vs 0.075 nmol/mg per hour, P less than 0.01). Exposure to 100 mM sucrose for 24-48 hours reduced the rate of breakdown from 44%/24 hours to 33%/24 hours (P less than 0.01) and decreased the release of cold phenylalanine by 35 +/- 9% (0.092 vs. 0.060 nmol/mg per hour, P less than 0.01). The results suggest that interference with lysosomal function in cultured fetal mouse hearts causes a significant reduction in the cardiac capacity to degrade proteins.

Amino Acids↗

PubMed1977

The effect 3,5,3'-triiodo-L-thyronine on the kinetic parameters of sugar transport in cultured chick embryo heart cells.

The effect of 3,5,3'-triiodo-L-thyronine (T3; 10(-8)M) on sugar transport was studied in cultured chick embryo heart cells. T3 did not increase the uptake of L-glucose, a sugar which enters the cell by simple diffusion. The effect of T3 on the kinetic parameters of the uptake of both 3-0-methyl-D-glucose (3-OMET) and 2-deoxy-D-glucose (2-DOG) was studied after 6 and 24 h exposure to T3. T3 had no effect on the Km for either sugar. T3 increased the Vmax for the first 6 h or exposure for 3-OMET, a sugar which is only transported, and increased the Vmax after 6 and 24 h for 2-DOG, a sugar both transported and phosphorylated. T3 also increased the relative phosphorylation of 2-DOG within the cells in the period between 6 and 24 h. The data show a biphasic effect of T3 on sugar accumulation, an early effect on transport along and a later effect on phosphorylation as well.

Animals↗

PubMedDate not supplied

[Nervous tissue glycoproteins normally and under the action of oxygen under pressure].

Salt-soluble proteins of great hemispheres of rats, intact and those subjected to the effect of hyperbarooxigenation, were separated by DEAE-cellulose chromatography into 10 heterogenous fractions, each of them containing 5-12 subfractions. The content of glucosamine and sialic acid was determined in each of the isolated fractions. Changes in the degree of heterogeneity and in total content of protein in the fractions as well as variations in the content of carbohydrate components in the chromatographic fractions are observed under the effect of hyperoxia.

Amino Sugars↗

PubMedDate not supplied

[Effect of chronic exposure to carbon monoxide on the biochemical composition of human blood].

Protein, lipid and carbohydrate metabolism of men was investigated during their prolonged exposure to a closed atmosphere containing carbon monoxide at a concentration of 20-10 mg/m3. A 30-day exposure of test subjects to carbon monoxide at a concentration of 20-15 mg/m3 caused an increase of albumin, beta-globulins, total lipids, cholesterol, beta-lipoproteins in the serum and a decrease of the sugar concentration in the blood. A 90-day exposure of test subjects to carbon monoxide at a concentration of 10 mg/m3 did not bring about significant changes in the above parameters. The provocative test for glucose tolerance showed no changes in the glycaemic regulation.

Adult↗

PubMedDate not supplied

[Changes in the sugar content in the blood of dogs during 6 years of chronic gamma irradiation].

The paper presents the results of a many-year investigation of the sugar content in dogs irradiated with total doses of 125, 370, 720, 750, 1130 rad. During the first year the sugar content tended to increase and later to decrease. Irradiated and untreated animals showed different reactions to additional loads (running, thermal exposure, acute irradiation). The differences included the direction and level of changes in the sugar content. There was no correlation between the changes and the dose rate. The changes returned to normal after termination of the exposure.

Animals↗

PubMed1975

Fungal growth and acid production during fermentation and refermentation of organic acid treated corn silages.

Chopped corn (35% dry matter) treated with either propionic, formic, 60% propionic plus 40% formic, or 80% propionic plus 20% acetic acids at 0, .5, 1, and 2%, was placed in polyethylene bags inside metal drums, and evacuated. During fermentation silages were sampled and temperatures determined. On day 40 of fermentation silages were placed in open containers at 25 C and were sampled during refermentation. All samples were analyzed for volatile and lactic acids, pH, and number and type of fungi. Lactate fermentation was totally inhibited at 2% addition of all acids, but formic acid was more effective than propionic acid at .5 and 1%. Acerate production was equally depressed by both propionic and formic additions. Heating, growth of fungi, and days until spoilage were delayed by all acid additions during refermentation, with propionic more effectivethan formic. The large increases in lactate and acetate of treated silages during refermentation reflect a protection of soluble sugars during fermentation and subsequent use by microbes after exposure to air. Silages treated with more than 1%propionic (as propionic or a mixture) did not increase in fungal colonies during refermentation. At initiation of fermentation yeasts werehigher than other fungi but decreases by day 40. During refermentation, yeasts again grew. Geotrichum comprised 35% on day 40 of refermentation but was lower at other times. Aspergillus proliferated during refermentation and few Penicillium were detected.

Acetates↗

PubMed1977

Changes in tissue glycogen stores of rats under acute and chronic hypoxia and their relationship to hypoxia tolerance.

Rats were exposed to simulated altitudes of 3658 m, 4877 m, and 7620 m, for 5 h/d for 30 d at an ambient temperature of 28 degrees C. Blood sugar and tissue glycogen levels were measured--after acute exposure and chronic exposure while either fed ad lib or fasted for 24 h--in liver, kidney, brain, heart, lungs, and skeletal muscles. Glycogen levels were decreased significantly in several tissues under chronic hypoxia in fed animals. In the animals which were fasted 24 h before sacrifice after their 1 month altitude exposure, there was a significant glycogen increase in livers but no change in other tissues. In fasted, acute-exposed animals, glycogen decreased in hearts while in other tissues its levels were unchanged. Hyperglycemia invariably accompanied all conditions of altitude exposures (in fed, fasted, acute, or chronic exposed). Glucose injected i.p. to fed rats as single doses of 20 g/kg body weight 3 h before sacrifice resulted in significantly increased glycogen in all tissues except brain. These glucose injected rats had highly increased resistance to hypoxic stress.

Altitude Sickness↗

PubMed1977

Glycosylation of hemoglobin S by reducing sugars and its effect on gelation.

The binding of various reducing mono- and disaccharides to hemoglobin S has been measured both before and after treatment of the sugar-protein adducts with NaBH4. Incubation of 0.3 M solutions of D-glucose, D-galactose, D-maltose, and lactose, with 2% hemoglobin for 2 h at 37 degrees C, pH 7.2, leads to the incorporation of 1.1, 1.8, 1.8, and 3.3 mol of sugar, respectively, into 1 mol of hemoglobin tetramer (either A or S). Exposure of these aldose-protein adducts to NaBH4 for an additional hour at 10 degrees C increases the binding to 2.0, 3.3, 2.5, and 4.1 mol per mol tetramer, as would be expected if Schiff base linkages were involved in this protein modification reaction. The data suggest a stereochemical requirement for enhanced binding. The dependence of the pre-reduction binding of glucose on the sugar concentration, and on the oxygenation state of hemoglobin has also been examined. Glycosylation of hemoglobin significantly increases the minimum gelling concentration of the deoxy conformation, as measured by sedimentation equilibrium ultracentrifugation. Of the sugar derivatives of hemoglobin S examined by this method, those modified by D-galactose or lactose have minimum gelling concentrations (in the absence of 2,3-diphosphoglycerate) which are comparable to, or greater than, that of fully carbamylated hemoglobinS.

Carbohydrates↗

PubMed2024

Sulfonamide-induced DNA hypomethylation disturbed sugar metabolism in rice (Oryza sativa L.).

DNA methylation is well-accepted as a bridge to unravel the complex interplay between genome and environmental exposures, and its alteration regulated the cellular metabolic responses towards pollutants. However, the mechanism underlying site-specific aberrant DNA methylation and metabolic disorders under pollutant stresses remained elusive. Herein, the multilevel omics interferences of sulfonamides (i.e., sulfadiazine and sulfamerazine), a group of antibiotics pervasive in farmland soils, towards rice in 14 days of 1 mg/L hydroponic exposure were systematically evaluated. Metabolome and transcriptome analyses showed that 57.1-71.4 % of mono- and disaccharides were accumulated, and the differentially expressed genes were involved in the promotion of sugar hydrolysis, as well as the detoxification of sulfonamides. Most differentially methylated regions (DMRs) were hypomethylated ones (accounting for 87-95 %), and 92 % of which were located in the CHH context (H = A, C, or T base). KEGG enrichment analysis revealed that CHH-DMRs in the promoter regions were enriched in sugar metabolism. To reveal the significant hypomethylation of CHH, multi-spectroscopic and thermodynamic approaches, combined with molecular simulation were conducted to investigate the molecular interaction between sulfonamides and DNA in different sequence contexts, and the result demonstrated that sulfonamides would insert into the minor grooves of DNA, and exhibited a stronger affinity with the CHH contexts of DNA compared to CG or CHG contexts. Computational modeling of DNA 3D structures further confirmed that the binding led to a pitch increase of 0.1 Å and a 3.8° decrease in the twist angle of DNA in the CHH context. This specific interaction and the downregulation of methyltransferase CMT2 (log2FC = -4.04) inhibited the DNA methylation. These results indicated that DNA methylation-based assessment was useful for metabolic toxicity prediction and health risk assessment.

DNA Methylation↗

PubMed1977

Mutation of an inosine-producing strain of Bacillus subtilis to DL-methionine sulfoxide resistance for guanosine production.

An inosine-producing strain of Bacillus subtilis was mutated to resistance against the antagonist of glutamine, DL-methionine sulfoxide. Among the mutants derived, guanosine producers were observed frequently. The best strain, 14119, produced 9.6 g of guanosine per liter at a weight yield of 12% from consumed sugar. Inosine production decreased concomitantly. When resistance was increased further by exposure to higher doses of DL-methionine sulfoxide, another strain, AG169, was obtained that did not excrete inosine but produced increased amounts of xanthosine. In these strains, the specific activity of 5'-nucleotidase was lower and that of inosine 5'-monophosphate (IMP) dehydrogenase was higher than the parent strain. It is speculated that the metabolic flow from IMP to xanthosine 5'-monophosphate proceeds more smoothly than that from IMP to inosine and yields more xanthosine and guanosine.

Bacillus subtilis↗

PubMed1977

Acute and repetitive human exposure to isobutane.

Eight adult volunteers of both sexes were exposed to isobutane in a controlled-environment chamber for the purpose of monitoring their physiological responses to a series of gas concentrations ranging from 250 to 1,000 ppm. First, the response to exposure periods of 1 min, 2 min, 1 h, 2 h, and 8 h were studied. There being no untoward responses to these acute exposures, the eight volunteers were exposed repetitively to isobutane at concentrations of 500 ppm, 1, 2 or 8 h per day, five days per week for two weeks. Then exposures to two mixtures of isobutane and propane for 1, 2 or 8 h per day for two days were studied. During the investigation all subjects were kept under comprehensive medical surveillance. No untoward subjective responses or abnormal physiological responses occurred during or following these exposures. Special emphasis was placed on evaluating the cardiac and pulmonary response to these exposures through the use of continuous ECG telemetry and serial computerized spirometric measurements. The following serial laboratory studies were unaltered by the exposures: complete blood count, urinalysis, serum alkaline phosphatase, SGOT, LDH, serum bilirubin, blood sugar, serum calcium, serum phosphorus, BUN, spontaneous electroencephalogram, visual evoked response, a battery of cognitive tests, and an ACTH stimulation test.

Adrenal Cortex↗