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At least 883 records · Page 49Linked to original sources
PubMed1992

Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic and laser Doppler flowmetric study using topical pharmacologic antagonists on irradiated skin.

Normal skin responds acutely to ultraviolet (UV) light exposure with complex inflammatory mechanisms. In the present study UVB irradiation ranging from subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96 mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti-inflammatory agents or vehicle control. The resultant change in erythema (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the UVB-induced vascular reactions in different and dose-dependent ways. Betamethasone-17-valerate and diphenhydramine were most effective at the 24 mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH) content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) > indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease = 21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%) > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2) and the decrease in OH was associated with an increased amount of deoxygenized hemoglobin (DOH). A similar slight venous dilatation was present at acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1981

Biosynthesis of porphyrins and heme from gamma, delta-dioxovalerate by intact hepatocytes.

The purpose of this study was to assess the ability of hepatocytes to synthesize porphyrins and heme from delta-aminolevulinic acid derived from gamma, delta-dioxovalerate and alanine. An alternate pathway for delta-aminolevulinic acid synthesis, in contrast to the condensation of succinate and glycine by delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] has been suggested. This has been supported by the isolation of gamma, delta-dioxovalerate transaminase from liver mitochondria (Varticovski, L., Kushner, J. P. & Burnham, B. F. (1980) J. Biol. Chem. 255, 3742-3747). Gamma, delta-dioxovalerate transaminase catalyzes the formation of delta-aminolevulinic acid by a transamination reaction involving gamma, delta-dioxovalerate and alanine. To assess the significance of this alternate route, we prepared suspensions of respiring rat hepatocytes, which were incubated with optimal concentrations of various additives and then analyzed spectrophotometrically for synthesized porphyrins. No porphyrin synthesis was detected in cell suspensions incubated with succinate(1 mM) and glycine (20 mM). Cell suspensions incubated with gamma, delta-dioxovalerate (0.5-1.0 mM) and alanine (20 mM) synthesized 0.19 nmol of porphyrin per 10(7) cells per 2 hr (SD, 0.057). Cell suspensions incubated with delta-aminolevulinic acid (0.1 mM) synthesized 1.26 nmol of porphyrin per 10(7) cells per 2 hr (range, 1.18-1.32). Incubations with chemically synthesized gamma, delta-dioxo[5-14C]valerate were followed by extraction and purification of porphyrin esters and heme. Liquid scintillation counting revealed radiolabel incorporation into both porphyrins and heme. These studies demonstrate significant tetrapyrrole synthesis by the gamma, delta-dioxovalerate transaminase reaction. That gamma, delta-dioxovalerate is an important precursor of heme in vivo must be considered.

Alanine↗
PubMed1985

Supplementation of dairy cow diets with ammonium salts of volatile fatty acids.

The objective was to determine the efficacy of a blend of ammonium salts of the volatile fatty acids, isobutyric, 2-methylbutyric, isovaleric, and valeric as a supplement to diets for dairy cows. Treatments of 0 (control) or 120 (supplemented) g/cow of the blend were fed daily from approximately 3 wk prepartum through a complete lactation. Five trials were conducted concurrently with a total of 116 multiparous Holstein cows. Dietary ingredients or combinations of ingredients differed in each of the trials. Diets contained either 1) corn gluten meal and urea, 2) soybean meal, or 3) cottonseed meal as the primary grain source of crude protein. The forage portion of the diets contained corn silage in combination with one or more of the following: alfalfa hay, alfalfa haylage, or wheat silage. Cows fed the supplement produced more milk and fat-corrected milk than the control cows for the 305-d lactation on four of the five diets, resulting in an average increase of 1.7 kg/d or 7%. Feed intake of cows on the supplemented diet was generally similar or lower than intake of the control cows throughout lactation, indicating that increased milk yield was associated with improved feed utilization. Percent milk fat was similar for cows on the supplemented diet, but fat yield was higher. Percent milk protein was lower for supplemented cows, but protein yield was about the same for both treatments because of higher milk yield. Health and reproduction were similar for all cows.

Animal Feed↗
PubMed1987

Activation of specific glutamate receptor subtypes increases C-fos proto-oncogene expression in primary cultures of neonatal rat cerebellar granule cells.

In primary cultures of rat cerebellar granule cells the activation of excitatory amino acid receptors by 1-glutamate enhances the steady state level of c-fos proto-oncogene messenger RNA. This effect is blocked by magnesium (1mM) as well as by the glutamate receptor antagonist 2-amino-5-phosphono-valerate (APV). Among the other excitatory amino acid agonists N-methyl-D-Aspartate (NMDA) and quisqualate also increased c-fos mRNA content, the latter however to a significantly lesser extent, while kainate failed to modify the basal level of c-fos expression. The addition of the muscarinic agonist carbachol or of the inhibitory neurotransmitter GABA did not affect the basal level of c-fos mRNA. This data demonstrate for the first time that activation of signal transduction at a specific excitatory amino acid receptor subtype can increase the steady state level of c-fos proto-oncogene mRNA in primary culture of cerebellar neurons.

Animals↗
PubMed1983

Net volatile fatty acid absorption in nonlactating holstein cows.

Net absorption of volatile fatty acids was measured in four nonlactating Holstein cows fed orchardgrass-clover silage ad libitum and 50 g trace mineralized salt daily. Cows ranged in age from 2 to 4 yr and in body weight from 326 to 525 kg. Portal blood flow and volatile fatty acid concentrations of portal and arterial plasma were determined at 30-min (three cows) or 90-min (one cow) intervals for about 12 h. Mean portal blood flow was 836 liters/h. Mean volatile fatty acid concentrations of portal plasma and differences of portal-arterial concentrations were (mM): acetate 2.00, .67; propionate .264, .228; isobutyrate .022, .017; n-butyrate .057, .038; 2-methylbutyrate .017, .014; 3-methylbutyrate .007, .005; and n-valerate .012, .008. Mean net volatile fatty acid absorption was 682 mmol/h. Acetate and propionate accounted for 91% of net volatile fatty acid absorption on a molar basis and 85% on an energy basis. Net energy absorbed as volatile fatty acid was 5.43 Mcal/cow per day, which was about 35% of calculated metabolizable energy intake. Portal blood flow was maximal 1.5 h postfeeding, and net volatile fatty acid absorption was maximal 2.5 h postfeeding.

Animals↗
PubMed1980

Cytotoxicity of pivalylphenylephrine and pivalic acid to corneal endothelium.

We examined the effects of topically applied pivalylphenylephrine (PPE) and pivalic acid (PA) on the corneal endothelium of rabbits and the direct effects of PPE and PA on monolayer cultures of bovine corneal endothelium. The PPE-treated corneas without epithelium significantly increased in thickness, whereas no change in thickness was observed in corneas with epithelium intact. The PA did not alter the thickness of corneas with or without epithelium. Although 0.001% PE had no noticeable effect in two hours, 0.01% PPE caused breakdown of intercellular junctions in cultured cells in five minutes. Higher concentrations of PPE caused the cells to detach from the culture dishes within 30 minutes of treatment. Only 1% PA caused cell elongation and loss of intercellular contact after 60 to 90 minutes of exposure; lower concentrations did not effect cultured cells.

Administration, Topical↗
PubMed1984

Influence of gemfibrozil and clofibrate on metabolism of cholesterol and plasma triglycerides in man.

Mechanisms for the hypolipidemic action of gemfibrozil were examined in seven patients with hypertriglyceridemia. In addition, seven hyperlipidemic patients were studied with and without clofibrate treatment to compare the mechanisms by which these two drugs lower plasma triglyceride levels. All patients were studied on a metabolic ward. The first month was a control period, followed by one month of either gemfibrozil or clofibrate therapy. During treatment with gemfibrozil, plasma total triglyceride levels decreased by an average of 51%, and triglyceride levels in very low-density lipoproteins (VLDLs) fell by 57%. Transport rates of VLDL triglyceride were determined by multicompartmental analysis following injection of tritiated glycerol as a precursor. Gemfibrozil decreased transport (production) of VLDL triglyceride by an average of 28% and increased the fractional catabolic rate (FCR) of VLDL triglyceride by 92%. Clofibrate reduced plasma total triglyceride values on an average of 32% and VLDL triglyceride values by 38%. In contrast to gemfibrozil, clofibrate did not change transport rates of VLDL triglyceride but increased the fractional catabolic rate of VLDL triglyceride by 35%. Gemfibrozil thus decreased production of VLDL triglyceride and enhanced its clearance, while clofibrate only increased clearance of VLDL triglyceride. On the average, plasma cholesterol levels did not fall during gemfibrozil treatment, but levels of cholesterol in high-density lipoproteins and in low-density lipoproteins increased by 31% and 11%, respectively. The drug produced a 30% increase in fecal excretion of neutral steroids and a 37% decrease in fecal excretion of bile acids. Outputs of total neutral steroids and net cholesterol balance thus remained unchanged.

Adult↗
PubMed1986

Early identification of isovaleric aciduria using photodiode array detection for liquid chromatographic profiling of urinary carboxylic acids.

The 190 nm high performance liquid chromatographic photodiode array profiling of the urinary carboxylic acids of the first urine of a newborn affected with isovaleric aciduria afforded an abnormal peak at 27.8 min. This peak was greatly increased in the carboxylic acid profiling of the 14 h urine sample from the same infant. Isolation of this peak by fraction collecting; solvent extraction of the eluent; trimethylsilyl derivatization of the residue and gas chromatographic/mass spectrometric analysis identified the compound as isovalerylglycine. Correlation of the 190 nm absorbance of isovalerylglycine (y) with concentration (x) afforded a least squares curve: y = 476.4x-13.72 (r = 0.99); run-to-run variation 6.92%; day-to-day variation 8.88% with a minimum detectable concentration of 25 micrograms/ml.

Carboxylic Acids↗
PubMedDate not supplied

Quantitative microscopy comparison of peroxisome proliferation by the lipid-regulating agent gemfibrozil in several species.

Peroxisome proliferation, a well-documented subcellular reaction which follows the administration of hypolipidemic agents, has been well studied in rodents. However, quantitative studies of this phenomenon in other species of laboratory animals are not readily available even though these species are commonly used as predictors of tolerance or safety in humans. The quantitative stereologic studies reported here compared the effects of the new hypolipidemic agent gemfibrozil on hepatic peroxisomes of monkeys, dogs, hamsters and rats of both sexes under several treatment schedules. Gemfibrozil was administered to rats at 300 mg per kg per day for 1 year in the diet; to hamsters at 400 mg per kg per day for 2 weeks by diet admixture; to dogs at 300 mg per kg per day in gelatin capsules for 1 year; and to monkeys at 300 mg per kg day for 3 months by gavage. These dose levels were selected on the basis of tolerance from preliminary studies in each species. At the end of each experimental interval, liver samples were processed for quantitative microscopy. Peroxisomes from male rats were enlarged and the number of peroxisomes per cell were increased 7-fold over controls, resulting in a 20-fold increased peroxisome volume per cell. Statistically, significant increases also occurred in female rats and the difference between treated and controls was 3-fold for both number and volume of peroxisomes per cytoplasmic unit volume. In hamsters, peroxisomes were proliferated and were of significantly smaller size to the extent that the volume of cytoplasm occupied by peroxisomes was not significantly changed. In dogs, the number of peroxisomes per cell was increased and the volume fraction was significantly increased in females only. The number of peroxisomes in young monkeys did not change after treatment, and the peroxisome volume was decreased in males and increased in females. Aged monkeys had increased number of peroxisomes per hepatocyte with increased volume fraction. These results indicate significant differences in the magnitude and direction of peroxisome changes, reflecting species-dependent organelle response to hypolipidemic agents. The order of susceptibility of peroxisome proliferation in laboratory animals is dog less than monkey less than hamster less than rat.

Age Factors↗
PubMed2006

Nutritional therapy improves function and complements corticosteroid intervention in mdx mice.

Corticosteroid therapy for Duchenne muscular dystrophy is effective but associated with long-term side effects. To determine the potential therapeutic benefit from four nutritional compounds (creatine monohydrate, conjugated linoleic acid, alpha-lipoic acid, and beta-hydroxy-beta-methylbutyrate) alone, in combination, and with corticosteroids (prednisolone), we evaluated the effects on several variables in exercising mdx mice. Outcome measures included grip strength, rotarod performance, serum creatine kinase levels, muscle metabolites, internalized myonuclei, and retroperitoneal fat pad weight. In isolation, each nutritional treatment showed some benefit, with the combination therapy showing the most consistent benefits. Prednisolone and the combination therapy together provided the most consistent evidence of efficacy; increased peak grip strength (P < 0.05), decreased grip strength fatigue (P < 0.05), decreased number of internalized myonuclei (P < 0.01), and smaller retroperitoneal fat pad stores (P < 0.001). This study provided evidence for therapeutic benefit from a four-compound combination therapy alone, and in conjunction with corticosteroids in the mdx model of DMD.

Animals↗
PubMed1975

Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets.

In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-keto-isovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to l-leucine, l-norleucine or l-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids.

Amino Acids↗
PubMed1979

Tetrapyrrole biosynthesis from 4,5-dioxovaleric acid in rhodopseudomonas spheroides.

Prophyrin biosynthesis from 4,5-dioxovaleric acid was studied in cell suspensions of R. spheroides. The experiments show that 4,5-dioxovaleric acid is a far precursor of porphyrins through delta amino laevulinic acid formation in a transmination reaction involving also l-alanine. It differs radically from the classical delta aminolaevulinic acid synthesis using glycine and succinyl CoA as substrates.

Alanine↗