Organic aciduria associated with isovaleric acidemia.
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The lipid lowering drug Gemfibrozil significantly increased the levels of HDL-apoproteins, apoA-I and apoA-II in a group of 20 Swedish hyperlipemic males who were given 1200 mg daily of the drug for 8 weeks and thereafter submitted to a 4 weeks placebo period. It strikingly increased serum reserve cholesterol in binding capacity (SRCBC). No change was observed in "free" apoA-I or inthe level of Lp(a) lipoprotein. The results suggest that the effect of Gemfibrozil on HDL, may be particularly striking on a subclass (or on subclasses) of HDL responsible for most of SRCBC. The findings suggest that Gemfibrozil may become a useful drug for hyperlipidemic people, if its safety in pharmacological doses can be established.
Three patients are described with different forms of isovaleric acidemia: a girl with the neonatal form and two brothers with an intermittent form. In all three patients the biochemical aspects are identical: Considerable amounts of metabolites of isovaleric acid, especially isovalerylglycine, are secreted with the urine. In the patients' cultured fibroblasts leucine oxydation is greatly depressed. The clinical presentation of the younger brother prompted to a direct search for a metabolic defect. After diagnosing an isovaleric acidemia in the younger brother, investigations on the presence of the same defect were performed in the elder brother too, though he did not show clinical symptoms. As a result, also isovaleric acidemia was found. It is concluded that sibs of patients with a proven inborn error of metabolism have to be studied too for the presence of the same defect. In all patients, especially in the girl with the neonatal form of isovaleric acidemia diet therapy had a beneficial effect on the further course of the disease.
Severe pancytopenia developed in two infants with isovaleric acidemia. Previous reports indicate these hematologic abnormalities are a leading cause of death in affected infants. Our findings suggest that the pancytopenia may be due to arrested maturation of hematopoietic precursors. Prompt transfusion of appropriate blood components prevented complications due to the hematologic abnormalities.
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Four naturally occurring main forms of rumen dystonia of alimentary origin were observed in cattle: acidotic conditions; microflora inactivity; acidosis, and alkalosis. The following disturbances in the metabolism of carbohydrates, protein and energy were observed: 1. Acidotic conditions in rumen--ruminal pH, total and protein nitrogen decreased, whereas the total amount of VFA and the reduction activity of bacteria increased. 2. Inactivity of rumen microflora--significant changes of pH of rumen fluid were not observed, but the total number and activity of infusoria decreased. Fermentation of glucose, digestibility of cellulose, and reduction activity of bacteria decreased, whereas the amount of non-protein nitrogen increased. 3. Acidosis--ruminal pH, reduction activity of bacteria, and total number of VFA decreased. The percentage ratio between VFA changed--acetic acid concentration decreased, the concentration of valeric and caproic acids increased. The amount of total and non-protein nitrogen increased. 4. Alkalosis--ruminal pH increased, reduction activity of bacteria, fermentation of glucose, and concentration of VFA decreased. The amount of total and non-protein nitrogen increased. This investigation of different forms of rumen dystonia of alimentary origin is believed to be useful for the development of more effective treating methods and measures.
Twenty-two women, oophorectomized in connection with surgical treatment for cervical carcinoma in clinical stage IB or IIA, were given ORG OD14 [(7 alpha,17 alpha)17-hydroxy-7-methyl-19-norpregn-5-(10)20-yn-3-one; 2.5 mg/day], a placebo, and estradiol valerate (2 mg/day), six weeks each, in a double blind, cross-over study. ORG OD14 is a synthetic steroid for continuous treatment of climacteric symptoms which in traditional bioassays has been shown to have weak estrogenic and progestogenic as well as very weak androgenic-anabolic properties. The aim of this study was to evaluate its effects on serum lecithin as well as on the relative fatty acid composition of serum lecithin and serum cholesterol ester. In serum lecithin, OD14 induced an increase in palmitic acid and a decrease in stearic acid, effects typical of 17-C-alkylated steroids, compared to both placebo and estradiol valerate. Furthermore, there was an increase in linoleic acid and a decrease in both arachidonic and dihomo-gamma-linolenic acid after OD14 administration. This decrease is interpreted as an inhibitory action of the steroid on the mechanisms of elongation and desaturation of linoleic acid and is considered to be an androgenic influence. The relative decrease is further accentuated by the decrease in total serum lecithin induced by OD14. Since these fatty acids are the major precursors for prostaglandin synthesis, these findings might have relevance in that context.
This study evaluated three white-rot basidiomycetes for their potential to improve the ruminal degradation of wheat straw. Pleurotus ostreatus (PO), Pleurotus ostreatus-mutant (PO-M) and Trametes gibbosa (TG) were incubated on wheat straw for 30 days at 28 degrees C. Neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein and in vitro dry matter digestibility (IVDMD) were determined. The results demonstrated increasing crude protein and ash contents (%) in the fungi-treated straws. The IVDMD values were also increased. Compared to untreated wheat straw (UWS), the NDF and ADF contents were reduced in fungi-treated straw (TWS). Out of the three fractions-hemicellulose, cellulose and lignin-hemicellulose showed the largest proportionate loss and lignin the smallest in all three fungi-treated straws. TWS with Pleurotus ostreatus (TWS-PO), Pleurotus ostreatus-mutant (TWS-PO-M) and Trametes gibbosa (TWS-TG) together with barley (80:20%) were used as the experimental diets in the artificial rumen. UWS with barley (80:20%) served as the control diet. The results revealed significantly higher IVDMD values, NDF, ADF and cellulose digestibilities (%) with the experimental diets. The production of propionic acid decreased, n-butyric, n-valeric and isovaleric acids (mmol/day-1) increased and the volatile fatty acid (VFA) production expressed in mol VFAs.kg-1 digested dry matter decreased in experimental diets. The total microbial production also decreased at fermentation in the experimental diets.
Knowledge of the fermentation pattern of D-tagatose is important for the assessment of energy value and compliance of D-tagatose. In vitro fermentation experiments with pig intestinal contents and bacteria harvested from the gastrointestinal tract of pigs were used to investigate the degradation of D-tagatose and the formation of fermentation products. Two groups of eight pigs were fed either a control diet containing 150 g/kg sucrose or a diet which had 100 g/kg of the sucrose replaced by D-tagatose. After 18 d the pigs were killed and the gastrointestinal contents collected for in vitro studies. No microbial fermentation of D-tagatose occurred in the stomach or in the small intestine, whereas the sugar was fermented in the cecum and colon. Formate, acetate, propionate, butyrate, valerate, caproate and some heptanoate were produced by the microbial fermentation of D-tagatose by gut microbiota. Hydrogen and methane were also produced. The population of D-tagatose-degrading bacteria in fecal samples and the capacity of bacteria from the hindgut to degrade D-tagatose were higher in the pigs adapted to D-tagatose compared with unadapted pigs. In unadapted pigs, the major fermentation product from D-tagatose was acetic acid. Much more butyric and valeric acids were produced from D-tagatose by bacterial slurries of tagatose-adapted pigs compared with unadapted pigs; this was especially the case for samples from the colon. We conclude that D-tagatose is not fermented in the upper gastrointestinal tract, and the ability of the large intestinal microbiota to ferment D-tagatose is dependent on adaptation.
A method was developed to analyze and quantify volatile fatty acids (VFA) such as acetic, propionic, butyric, isobutyric, valeric and isovaleric acids in biological specimens. To obtain good sample transfer into the chromatographic system an organic solvent had to be used together with an aqueous milieu, thus improving wetting properties of the liquid sample plug introduced into the column. Sample preparation was carried out under alkaline conditions in order to exclude or minimize sample losses due to sample transfer during the extraction and work-up procedure. A cold on-column injection was applied to avoid irregular discrimination of the various acids due to sample splitting and an automatic injection technique was used to accommodate the large number of samples generated from biological origin. Connection of a pre-column of wide internal diameter (0.53 mm) to the analytical column (0.32 m) was optimized and adapted to the nature of the injection solvent mixture consisting of acetonitrile, water and hydrochloric acid. To obtain well-separated and correctly quantifiable gas chromatographic peaks, it was essential to perform the chromatography under acidic aqueous conditions. Standard resolution conditions and response factors were evaluated. The chromatographic results of applying this method to biological specimens from both rats and humans are provided.
The investigation of a patient blood sample showing a discrepancy between cell grouping and serum confirmation demonstrated a serum agglutinin which reacted with all red blood cells tested when exposed to EDTA. This reaction was 4+ macroscopic at room temperature, 2+ macroscopic with hemolysis at 37 degrees C in albumin, and 1+ macroscopic in the anti-human globulin phase. Agglutination was abolished following dithiothreitol treatment of the patient's serum or following saline washing of the EDTA-exposed test cells. The agglutination reaction was not limited to EDTA, but could be produced with polycarboxylic acids (citrate, L-tartrate, succinate) and monocarboxylic acids (acetate, lactate, propionate, valerate, butyrate). Non-carboxylic acids and low molecular weight ketones or alcohols failed in the agglutination reaction. This study reports an additional example of an IgM "EDTA dependent agglutinin" and demonstrates the dependence on carboxyl groups for its agglutinating activity.
A comprehensive anaerobic leachate treatment in batch reactors was conducted for 9 months. Activities of two main bacterial groups, sulfidogens and methanogens were observed with monitoring parameters as chemical oxygen demand (COD), total gas production, pH, alkalinity, dissolved sulfide and volatile suspended solids/total suspended solids (VSS/TSS). Leachate contained high concentrations of volatile fatty acids. Some competition between microbial species was observed. COD was applied at a range of 1100-8200 mg/L at a slowly increasing rate over time. COD removal was mostly above 80%, dissolved sulfide was produced at a range of 100-450 mg/L in the first weeks, proving high sulfidogenic activity and making 40-50% of COD removal. Methanogenesis seemed under stress and improved after several weeks with increasing COD load whereas hydrogen sulfide (HS-) production leveled off around 100 mg/L, making 4-8% COD removal by sulfidogens. Then, 40-70% of overall COD removal was achieved by methanogens. Volatile fatty acids (VFA) except acetic acid (propionic, isobutyric, butyric, isovaleric, valeric, caproic and heptanoic acids) were readily degraded and found near detection limit on gas chromatographic runs, accordingly VFA-oxidizing bacteria were assumed to be highly active and tolerant to sulfide levels encountered in our study, also with hydrogenotrophic groups providing favorable conditions for the process. pH was the key parameter to determine the degree of inhibition from sulfurous species. Alkalinity was produced proportionally with COD applied as a result of VFA degradation. Overall system performance was good and optimum pH was 7.8-8.2 at which inhibition due to unionized VFA was eliminated.
Modifications in dietary fatty acid intake might lead to a modification in membrane phospholipid fatty acid composition. The purpose of this study was to investigate relationship between different type of oil consumption and leukocyte membrane phospholipid composition. This study was carried out in subjects utilizing butter (n = 15), margarine (n = 15), fluid oil (n = 15) and mixed types of oils (n = 15) in total 60 subjects. Leukocytes were separated from total blood by dextran sedimentation method. Membrane lipids and proteins were isolated following the cell disruption. Fatty acids of membrane phospholipids were isolated by hydrolysation with phospholipase B under ultrasonic dismembranator. Free fatty acids were identified with gas chromatography at chloroform phase. The results obtained were compared with data obtained by chromatograms of the standards. Results more prominent values of arachidic, dihomo-gamma-linolenic and palmitoleic acids were found in butter-or mixed oil-user groups; eicosadienoic, eicosamonoenoic, dihomo-gamma-linolenic and behenic acids in fluid oil heptanoic, valeric, eicosadienoic and linolenic acids in margarine groups. The fatty acid composition of mixed oil; was similar to butter, while other two oils were so different. From this study, it was concluded that the type of oil consumption might have an influence on phospholipid components of plasma membranes.
The effect of short-chain aliphatic acids on [3H]deoxythymidine incorporation into DNA was studied in human mitogen-stimulated lymphocytes. Butyric acid at 1-2 mM level was strongly inhibitory; however, its hydroxy or amino derivatives were ineffective. Valeric and propionic acids were less inhibitory. Formic, acetic, and hexanoic acids did not have any inhibitory effect. The effect of butyrate persisted in washed lymphocytes for 24-48 hr depending on the concentration used and the time of its addition into the incubation medium. The inhibitory effects of butyrate, valerate, and propionate on deoxythymidine and amino acid incorporation into DNA and protein were also found in human leukocytes in myelocytic and lymphocytic leukemias.
Glucocorticoids were injected sc into rat foetuses through the uterine wall on day 19 of intrauterine development; two days later the foetuses were removed and their adrenal glands were weighed. Some betamethasone derivatives produced marked adrenal hypertrophy in the foetuses. Structural characteristics of the effective compounds were 17alpha-esterification and 16beta-methylation. 9alpha-Halogenation and 21-esterification of glucocorticoids were not essential for producing the hypertrophy. Propionic acid at the C-17 position was more effective than valeric and acetic acids in producing the hypertrophy. The effect of betamethasone 17, 21-dipropionate was dose-responsive and prevented by simultaneous administration of betamethasone 21-disodium phosphate. Results obtained with decapitated or encephalectomized foetuses suggested that the hypertrophy produced was not due to a direct action of the glucocorticoids on the adrenal gland, but mediated by the hypothalamo-pituitary system.
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