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At least 865 records · Page 48Linked to original sources
PubMed1980

Effects of branched-chain fatty acids on GABA-degradation and behavior: further evidence for a role of GABA in quasi-morphine abstinence behavior.

An increase in GABA-ergic activity has been implicated in the initiation of quasi-morphine abstinence behavior by di-n-propylacetate (DPA). Two structural analogues of DPA, namely, the branched-chain-fatty acid 2-methyl, 2-ethylcaproic acid and 2,2-dimethylvaleric acid have now been used to study this relationship between behavioral and biochemical effects. A correlation appeared to exist between the K1 of these compounds for succinic semi-aldehyde dehydrogenase, the second enzyme in the degradation of GABA, and the doses exerting a maximum effect on behavior. On the other hand concurrent inhibition of GABA-transaminase seemed to suppress the behavioral effects of the fatty acids. This apparent paradox can possibly be explained by supposing a different action of the fatty acids in distinct compartments of the brain, suggesting an important role for increased GABA-ergic activity in the neuronal compartment in the initiation of the quasi-morphine abstinence behavior.

4-Aminobutyrate Transaminase↗
PubMed1991

Physico-mechanical properties of degradable polymers used in medical applications: a comparative study.

The physico-mechanical properties of degradable polymers used for medical applications have been characterized. The following polymers were included in this study: three samples of poly(ortho esters) derived from 3,9-bis(ethylidene 2,4,8,10-tetraoxaspiro[5,5]undecane) and various ratios of 1,6-hexanediol and trans-cyclohexane dimethanol, poly(glycolic acid), six samples of poly(L-lactic acid) and poly(D,L-lactic acid) with mol wt from 21,000 to 550,000, poly(epsilon-caprolactone), poly(beta-hydroxybutyrate) and three copolymers of beta-hydroxybutyric acid and various amounts of hydroxyvaleric acid, one sample each of two different types of poly(anhydrides), poly(trimethylene carbonate) and two different poly(imino-carbonates). For each polymer, the thermal properties (glass transition temperature, crystallization, melting and decomposition points) were determined by differential scanning calorimetry and by thermogravimetric analysis. The tensile properties (Young's modulus, tensile strength and elongation at yield and break) were determined by tensile testing on an Instron stress-strain tester. The flexural storage modulus as a function of temperature was determined by dynamic mechanical analysis.

Anhydrides↗
PubMed1995

Protein modification by the degradation products of ascorbate: formation of a novel pyrrole from the Maillard reaction of L-threose with proteins.

Ascorbate (vitamin C) degradation products can undergo non-enzymatic glycation (Maillard reaction) with proteins to form highly crosslinked structures with brown pigmentation and characteristic fluorescence. Proteins in the body, especially the long-lived proteins develop similar changes during aging and diabetes. Several studies have shown excessive degradation of ascorbate in plasma in diabetes, and in ocular lens during aging and cataract formation. Recent studies have suggested that ascorbate degradation products-mediated glycation plays a role in lens pigmentation and cataract formation. However, the precise chemical nature of ascorbate-specific advanced glycation end-products are not known. Here, we report the purification and characterization of a glycation end-product derived from one of the major degradation products of ascorbate, L-threose. This compound was characterized to be 2-acetamido-6-(3-(1,2-dihydroxyethyl)-2-formyl-4-hydroxymethyl-1- pyrrolyl)hexanoic acid (formyl threosyl pyrrole or FTP) formed by the condensation of epsilon-amino group of lysine with two molecules of threose. Formation of FTP occurred rapidly in the incubation of threose and lysine and reached plateau level within a day. We have developed a sensitive assay for its quantification in proteins based on enzyme digestion followed by HPLC. Ribonuclease A and human lens crystallins incubated with L-threose showed time- and sugar concentration-dependent increases in FTP, reaching 8.2 and 2.48 nmol per mg protein, respectively after one week of incubation. Human plasma proteins showed a peak with identical retention time as that of purified FTP under two different HPLC conditions. FTP may be used as a sensitive marker to assess ascorbate-mediated protein glycation and modifications in aging and diabetes.

Aminocaproates↗
PubMed1982

Respiration and insulin release in mouse pancreatic islets. Effects of L-leucine and 2-ketoisocaproate in combination with D-glucose and L-glutamine.

In order to further evaluate the importance of B-cell metabolism for the stimulation of insulin release, respiration and insulin release were studied in mouse pancreatic islets. Leucine and 2-ketoisocaproate stimulated insulin release during an initial 1-h period, whereas there was no stimulation during two subsequent 1-h periods. This effect was in contrast to that of 16.7 mM glucose, which was a potent stimulator through all the 3 h. Furthermore, the presence of glucose (5.6 mM) or glutamine together with either leucine or 2-ketoisocaproate enhanced the insulin release and prolonged the stimulation. When the kinetics of islet respiration were studied both leucine and 2-ketoisocaproate exerted an initial stimulation on the O2 uptake which, however, was short-lived (less than 30 min). The presence of 5.6 mM glucose strongly delayed the respiratory retardation seen after the initial stimulation. Similarly, glutamine enhanced the leucine- and 2-ketoisocaproate-stimulated respiratory rates and prevented the respiratory retardation otherwise observed. Leucine (20 mM) and 2-ketoisocaproate (10 and 20 mM) stimulated the oxidation of glucose (5.6 mM). It is concluded that there is a strong correlation between respiratory stimulation and the enhancement of insulin release and that leucine and 2-ketoisocaproate depend on the presence of endogenous fuels for their ability to stimulate islet functions in vitro.

Animals↗
PubMed1984

Transport of 2-oxoisocaproate in isolated hepatocytes and liver mitochondria.

The transport of 2-oxoisocaproate into isolated hepatocytes and liver mitochondria of rat was studied using [U-14C]2-oxoisocaproate and the silicone oil filtration procedure. 2-Oxoisocaproate uptake by hepatocytes was composed of: rapid adsorption, unmediated diffusion and carrier-mediated transport. The carrier-mediated transport was strongly inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid and p-chloromercuribenzoate, was less sensitive to alpha-cyano-4-hydroxycinnamate and insensitive to p-chloromercuriphenylsulphonate. Other 2-oxo acids: pyruvate, 2-oxoisovalerate and 2-oxo-3-methylvalerate, were also inhibitory. The kinetic parameters of the carrier-mediated transport were Km 30.6 mM and Vmax 23.4 nmol/min per mg wet wt, at 37 degrees C. It is concluded that at its low, physiological, concentration, 2-oxoisocaproate penetrates the hepatocyte membrane mainly by unmediated diffusion. The uptake of 2-oxoisocaproate by isolated liver mitochondria was partly inhibited by alpha-cyano-4-hydroxycinnamate, the inhibitor of mitochondrial monocarboxylate carrier. The remaining uptake was linearly dependent on 2-oxoisocaproate concentration and represented unmediated diffusion. The carrier-mediated transport exhibited the following kinetic parameters: Km 0.47 mM, Vmax 1.0 nmol/min per mg protein at 6 degrees C; and Km 0.075 mM and Vmax about 8 nmol/min per mg protein at 37 degrees C.

Animals↗
PubMed1992

The developmental toxicity of 2-ethylhexanoic acid in Wistar rats.

The developmental toxicity of 2-ethylhexanoic acid (2-EHA), a wood preservative and a mammalian metabolite of di-(2-ethylhexyl) phthalate was examined in Wistar rats (20-21 pregnant females/dose). Mated animals were exposed to 2-EHA in their drinking water at doses of 100, 300, or 600 mg/kg/day on Days 6-19 of gestation. Control animals received vehicle water. The fetuses were examined (on Gestational Day 20) for external, visceral, and skeletal malformations and variations. 2-EHA was marginally toxic to the dams at 600 mg/kg, but not at lower doses, since the mean near term body weight was reduced by 11%. This dose level was also slightly fetotoxic as indicated by a 5 to 8% decrease in the mean fetal body weight both in males and females. No treatment-related effects were observed in the number of implantations or live fetuses. At doses of 100 mg/kg and above, 2-EHA caused skeletal malformations (clubfoot, absence of fibula, polydactyly), while the development of visceral tissues was less affected. The number of affected fetuses increased in a dose-dependent way (4.9, 8.9, and 15.3% of treated offspring at 100, 300, and 600 mg/kg/day, respectively, vs 2.4% control). These results indicate that 2-EHA is teratogenic in rats already at doses which are not yet maternally toxic. The skeleton appears to be the main target of 2-EHA in developing rats.

Abnormalities, Drug-Induced↗
PubMed1986

Growth patterns and hormonal sensitivity of primary tumor, abdominal metastasis and ascitic fluid from human epithelial ovarian carcinomas in the tumor colony-forming assay.

The human tumor colony forming assay was used to evaluate the response of ovarian carcinoma cells from primary tumors, ascitic fluids and metastasis to hormonal treatment. In 12/35 patients a sufficient colony formation (greater than 30 colonies/dish) was obtained in order to perform a simultaneous drug testing. The plating efficiency of the metastatic samples (0.12%) was significantly higher (P less than 0.053) than those from the primary tumor (0.076%) or those that were derived from the ascitic fluid (0.082%). Colonies from the metastatic tissues could be evaluated 2-4 days earlier than those from primary tumors. These discrepancies may be due to a heterogeneity in the clonable tumor cell compartment of primary tumor and metastasis. The antiproliferative properties of the antiestrogen tamoxifen and the progestin gestoneron were studied. In 9/12 cases a significant, dose-dependent reduction of colony formation (greater than 70-90% of the controls) was observed after continuous exposure to 1 mumole tamoxifen. No correlation between the dose response and the content of steroid receptors was found. Even estrogen receptor negative tumor samples showed a maximal antiproliferative effect of tamoxifen.

Abdominal Neoplasms↗
PubMed1994

An assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a limited population study.

The plasticizer di-2-(ethylhexyl) adipate (DEHA), which may be present in food-contact films, can migrate into certain foodstuffs. Results from plasticizer migration studies into food have enabled an indirect estimate of the maximum daily dietary intake of DEHA. A previous study of the metabolism and pharmacokinetics of DEHA in humans identified the urinary metabolite 2-ethylhexanoic acid (EHA) as a useful marker metabolite for assessing DEHA intake. The present study was designed to investigate urinary EHA concentrations following a controlled dose of DEHA presented with food, and to assess the average daily intake of DEHA in a limited population survey. The urinary elimination profile of EHA, following a dose of DEHA in food, showed that in order to extrapolate DEHA intake from EHA measurements, a 24-hr urine sample was required. In the survey the elimination of EHA was determined in 24-hr urine samples in 112 individuals from five different geographical locations in the UK. No restrictions were placed on age or gender. Estimates of daily intake of DEHA show a skewed distribution with a median value of 2.7 mg. This is similar to an estimated maximum daily intake of 8.2 mg/day, derived using an indirect method by the UK Ministry of Agriculture, Fisheries and Food.

Adipates↗
PubMed1987

Bacterial tests as indicators for the detoxification of the mycotoxin penicillic acid by ammonia treatment.

The detoxification of penicillic acid by reaction with ammonia was examined by means of a polymerase assay using two strains of Escherichia coli (pol A+ and pol A-1) and a recombination assay using two strains of Bacillus subtilis (rec+ and rec-). A 100-fold surplus of ammonia added to penicillic acid abolished the cytotoxic and genotoxic effects of penicillic acid towards the bacteria under the test conditions. The study presents the possibility of detoxifying mycotoxins in feeds by ammonia treatment and demonstrates the suitability of bacterial assays as indicators for mycotoxins.

Ammonia↗
PubMed1978

Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content.

The insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.

Animals↗