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At least 1,333 records · Page 74Linked to original sources
PubMed2005

Impairment of VLDL secretion by medium-chain fatty acids in chicken primary hepatocytes is affected by the chain length.

To determine the effect of the chain length of medium-chain fatty acids (MCFAs) on VLDL secretion, the media of chicken hepatocyte cultures were supplemented with hexanoate (6:0), octanoate (8:0), decanoate (10:0), or dodecanoate (12:0). The supplementation of palmitate (16:0) or bovine serum albumin (BSA) alone in media was used as the positive control or the control, respectively. Palmitate significantly increased intracellular triacylglycerol (TG) accumulation and VLDL-TG, -cholesterol, and -apolipoprotein (apo)B secretion. On the other hand, the addition of hexanoate did not affect these variables relative to control cultures supplemented with BSA alone, whereas octanoate, decanoate, and dodecanoate decreased apoB secretion from the chicken hepatocytes. ApoB secretion from hepatocytes cultured with 1.0 mmol/L MCFA, in particular decanoate and dodecanoate, in the presence of 0.2 mmol/L palmitate was significantly lower than that obtained with 0.2 mmol/L palmitate alone. Decanoate at 0.25-1.0 mmol/L dose dependently reduced apoB mRNA expression compared with the control (BSA alone). The levels of 3-hydroxy-3-metylglutaryl-CoA reductase and apoA-I mRNA were significantly lower in cultures supplemented with hexanoate, octanoate, and decanoate than in cultures with dodecanoate and palmitate. These changes did not correspond to the reduction in VLDL-apoB secretion. We suggest that MCFAs with different chain lengths differentially affect apoB secretion and mRNA expression, with decanoate being the most effective at decreasing VLDL-apoB secretion by regulating apoB mRNA expression at the transcriptional level.

Animals↗
PubMed1976

Metabolism of N-nitrosohexamethyleneimine.

The metabolism of [2-14C]N-nitrosohexamethyleneimine in male MRC-Wistar rats was studied and some of the major urinary metabolites were identified. The extent of total oxidation to 14CO2 was 18.1% in 24 hours and radioactivity incorporation was observed in various tissues; that in the liver was the highest. Analysis of urine after 24 hours showed that 36.7% of the radioactivity administered was excreted by this route, with a minimum of 11 products present. Hexamethyleneimine (HX), epsilon-caprolactam, epsilon-aminocaproic acid, and 6-aminocaprohydroxamic acid were the identified metabolites. Of the remaining products, two appeared to result from HX metabolism and one was a glucuronide conjugate. No parent compound was found.

Aminocaproic Acid↗
PubMed2001

Reversal of methylation-mediated repression with short-chain fatty acids: evidence for an additional mechanism to histone deacetylation.

We have constructed a stable cell line, human embryonal kidney 293M+, containing a lacZ reporter gene controlled by an in vitro methylated hormone-responsive enhancer. Methylation of the enhancer-promoter abolishes lacZ expression controlled by ponasterone A (an analogue of ecdysone). Ponasterone A-induced expression is restored by the short-chain fatty acids valeric > butyric > propionic > acetic acid, but not by the histone deacetylase inhibitors trichostatin A and suberoylanilide hydroxamic acid (SAHA). lacZ expression is restored to levels approaching that from an unmethylated counterpart. Incubation with short-chain fatty acids alone does not promote demethylation of the lacZ promoter, however, some demethylation (30%) is observed when transcription is triggered by addition of ponasterone A. Similar levels of hyperacetylated histones H3 and H4 were observed in cells treated with short-chain fatty acids, trichostatin A or SAHA. In vivo DNase I footprinting indicates a more open chromatin structure at the promoter region for butyric acid-treated cells. A synergistic effect in reversing the methylation-mediated repression of the lacZ gene is obtained by combined treatments with the normally ineffective compounds trichostatin A and the short-chain fatty acid caproic acid. Our results suggest the existence of an alternative silencing mechanism to histone deacetylation in executing methylation-directed gene silencing.

Animals↗
PubMed1994

Metabolic effects of propionate, hexanoate and propionylcarnitine in normoxia, ischaemia and reperfusion. Does an anaplerotic substrate protect the ischaemic myocardium?

It has been suggested that propionyl-L-carnitine administration to ischaemic hearts facilitates the restoration of cardiac function upon reperfusion, but it is still a matter of dispute whether its effect is conveyed via the metabolic effect of the propionyl moiety, the carnitine moiety or other mechanisms involving membrane receptor interactions. The metabolism of propionylcarnitine involves the formation of succinyl-CoA, which causes an increase in the total amount of tricarboxylic acid cycle intermediates. According to the current paradigm, anaplerosis ensures rapid restoration of tricarboxylic acid cycle activity during reperfusion. To evaluate the contribution of anaplerosis to the protective effect of propionylcarnitine during ischaemia and reperfusion, isolated rat hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 5 mM glucose+insulin (12 IU per litre), to which 1 mM propionate, 0.8 mM hexanoate or 1 mM propionylcarnitine were added. Global 20 or 24 min no-flow ischaemia was followed by 10 min reperfusion. The flavoprotein redox state, myoglobin oxygenation, oxygen consumption and mechanical functioning of the heart were recorded and metabolites determined in freeze-trapped tissue. In parallel experiments, the cellular energy state was studied with phosphorus nuclear magnetic resonance spectrometry. The addition of 1 mM propionylcarnitine failed to cause an anaplerotic effect, but did bring about an oxidation of flavins, probably due to citrate synthase inhibition. Propionate showed similar but stronger effects and a marked anaplerosis, but still failed to improve the recovery of the heart upon reperfusion. The addition of hexanoate caused marked anaplerosis upon reperfusion and flavin reduction. The results failed to demonstrate that propionylcarnitine had any beneficial effect on the ischaemic myocardium.

Animals↗
PubMed1988

First trimester bleeding in clinical IVF pregnancies.

First trimester bleeding has been investigated in 72 pregnant women undergoing in-vitro fertilization and embryo transfer and was compared to 70 pregnant patients in whom ovulation was induced, in addition to 70 spontaneous pregnancies. Abortion rates did not differ significantly between the first two groups but were significantly higher in comparison to normal pregnancies. Furthermore, among IVF pregnancies that continued, a high incidence of first trimester bleeding occurred (P less than 0.01). This complication was mainly related to luteal insufficiency and multiple pregnancies, whereas hyperstimulation was the major risk factor for bleeding in pregnancies arising from HMG-induced ovulation. Other currently unknown, aetiological factors for first trimester bleeding in IVF pregnancies remain to be investigated.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed2005

Effects of di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites on fatty acid homeostasis regulating proteins in rat placental HRP-1 trophoblast cells.

Di-(2-ethylhexyl)-phthalate (DEHP) is a widely used plasticizer and ubiquitous environmental contaminant. The potential health hazards, including teratogenicity, from exposure to DEHP may be related to the role of DEHP or its metabolites in the trans-activation of peroxisome proliferator-activated receptors (PPARs). Fetal essential fatty acid (EFA) homeostasis is controlled by directional transfer across the placenta through a highly regulated process, including PPAR activation. Using HRP-1 rat trophoblastic cells, the effects of DEHP and two of its metabolites, mono-(2-ethylhexyl)-phthalate (MEHP) and 2-ethylhexanoic acid (EHA), on the mRNA and protein expression of the three known PPAR isoforms (alpha, beta, and gamma), fatty acid transport protein 1 (FATP1), plasma membrane fatty acid binding protein (FABPpm), and the heart cytoplasmic fatty acid binding protein (HFABP) were investigated. This study also investigated the functional effects of exposure on the uptake and transport of six long chain fatty acids (LCFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), linoleic acid (LA), alpha-linolenic acid (ALA), oleic acid (OA), and stearic acid (SA). In the presence of DEHP, MEHP, and EHA, the expression of PPARalpha, PPARgamma, FATP1, and HFABP were up-regulated in a dose- and time- dependent manner, while PPARbeta and FABPpm demonstrated variable expression. The uptake rates of EFAs (AA, DHA, LA, ALA) increased significantly upon exposure, and the transport of AA (omega-6) and DHA (omega-3) were directionally induced. These results suggest that DEHP, MEHP, and EHA can influence EFA transfer across HRP-1 cells, implying that these compounds may alter placental EFA homeostasis and potentially result in abnormal fetal development.

Animals↗
PubMed1989

Calcium uptake by bovine epididymal spermatozoa is regulated by the redox state of the mitochondrial pyridine nucleotides.

Immature caput epididymal sperm accumulate calcium from exogenous sources at a rate 2- to 4-fold greater than mature caudal sperm. Calcium accumulation by these cells, however, is maximal in the presence of lactate as external substrate. This stimulation of calcium uptake by optimum levels of lactate (0.8-1.0 mM) is about 5-fold in caput and 2-fold in caudal sperm compared to values observed with glucose as substrate. Calcium accumulation by intact sperm is almost entirely mitochondrial as evidenced by the inhibition of uptake by rotenone, antimycin, and ruthenium red. The differences in the ability of the various substrates in sustaining calcium uptake appeared to be related to their ability to generate NADH (nicotinamide adenine dinucleotide). Previous reports have documented that mitochondrial calcium accumulation in several somatic cells is regulated by the oxidation state of mitochondrial NADH. A similar situation obtains for bovine epididymal sperm since calcium uptake sustained by site III oxidation of ascorbate in the presence of tetramethyl phenylenediamine and rotenone was also stimulated by NADH-producing substrates, including lactate, and inhibited by substrates generating NAD+ (nicotinamide adenine dinucleotide, oxidized form). Further, calcium uptake by digitonin-permeabilized sperm in the presence of succinate was stimulated when NADH oxidation was inhibited by rotenone. The compounds alpha-keto butyric, valeric, and caproic acids, which generate NAD+, inhibited the maximal calcium uptake observed in the presence of succinate and rotenone, and the hydroxy acids lactate and beta-hydroxybutyrate reversed this inhibition. These results document the regulation of sperm calcium accumulation by the physiological substrate lactate, emphasize the importance of mitochondria in the accumulation of calcium by bovine epididymal sperm, and suggest that the mitochondrial location of the isozyme LDH-X in mammalian sperm may be involved in the regulation of calcium accumulation.

3-Hydroxybutyric Acid↗
PubMed2001

The effects of peripheral administration of a novel selective antagonist for prostaglandin E receptor subtype EP(1), ONO-8711, in a rat model of postoperative pain.

UNLABELLED: Mechanically evoked pain, also known as incident pain, induced by coughing or deep breathing after surgery leads to potentially devastating consequences. It is generally thought that the prostaglandin receptor- (especially, the receptor for prostaglandin E(2), EP receptor) mediated sensitization of sensory nerve fibers is a key contributor to the generation of hyperalgesia. We examined whether a peripherally administered novel selective EP(1) antagonist, ONO-8711, would be a potential analgesic for incision-induced mechanical hyperalgesia. We used a rat model of postoperative pain introduced by Brennan et al. (1). Withdrawal thresholds to punctate stimulation and response frequencies to nonpunctate mechanical stimulation were determined by using von Frey filaments applied adjacent to the wound and directly to the incision site of the hind paw, respectively. Mechanical hyperalgesia to punctate and nonpunctate stimuli was observed 2 and 24 h after the incision. ONO-8711 (2, 10, or 50 microg) or saline was administered subcutaneously into the hind paw on the ipsilateral side to the incision. ONO-8711 significantly (P < 0.01) increased the withdrawal thresholds to punctate mechanical stimulation and significantly (P < 0.01) decreased the response frequencies to nonpunctate mechanical stimulation in a dose- and time-dependent manner 2 and 24 h after the incision. We conclude that EP(1) receptor-mediated sensitization of sensory nerve fibers may contribute to the generation of mechanical hyperalgesia produced by incisional surgery, and that the EP(1) receptor antagonist ONO-8711 may be an option for treatment of postoperative pain, especially incident pain. IMPLICATIONS: The peripheral administration of an antagonist for EP(1) receptor that is a subtype of prostaglandin E receptors can inhibit the mechanical hyperalgesia induced by a surgical incision.

Animals↗
PubMed2001

A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve constriction.

UNLABELLED: Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent mechanical hyperalgesia and allodynia. CCI is widely known as a model of neuropathic pain, and many studies using this model have been reported. Recently, c-fos has been used as a neural marker of pain, and various studies have assessed the relationship between hyperalgesia and c-fos expression in the lumbar spinal cord. In this study, we examined the role of a prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) in a rat CCI model. EP1 receptor antagonist (EP1-ra) oral administration from day 8 to day 14 significantly reduced hyperalgesia and allodynia in the three pain tests on day 15. EP1-ra treatment from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V-X compared with saline treatment. A single dose of EP1-ra treatment on day 8 significantly reduced hyperalgesia and allodynia at 1 h and 2 h after administration, but the efficacy was not observed at 24 h. We conclude that EP1-ra treatment may be useful for hyperalgesia and allodynia and that EP1 receptor mechanisms are involved in the maintenance of c-fos gene expression induced by nerve injury. IMPLICATIONS: We examined whether a prostaglandin E2 receptor subtype EP1 receptor antagonist abrogates neuropathic pain induced by chronic constriction injury model in rats. The EP1 receptor antagonist significantly reduced hyperalgesia, allodynia, and c-fos positive cells. These findings suggested that EP1 receptor antagonists may have a role in treatment of neuropathic pain.

Animals↗
PubMed2002

The effects of intrathecal administration of an antagonist for prostaglandin E receptor subtype EP(1) on mechanical and thermal hyperalgesia in a rat model of postoperative pain.

UNLABELLED: Despite substantial advances in understanding acute pain mechanisms and in the treatment of pain, postoperative pain, especially mechanically evoked pain (incident pain), is generally not effectively treated. Tissue injury and inflammation increase the release of prostaglandin E(2) in the spinal cord, contributing to the development of hyperalgesia. We designed the present study to determine whether the intrathecal administration of an antagonist for prostaglandin E(2) receptor subtype EP(1), ONO-8711, has an analgesic effect on incision-induced mechanical and thermal hyperalgesia. A 1-cm longitudinal skin incision was made in the plantar aspect of the rat foot. The withdrawal threshold to mechanical stimulation and the withdrawal latency to thermal stimulation applied adjacent to the wound of the hindpaw were investigated. Both mechanical and thermal hyperalgesia were observed at 2 h and 24 h after the incision had been made. ONO-8711 (50, 80, 100 micro g) or saline was administered intrathecally. ONO-8711 significantly increased the withdrawal thresholds to mechanical stimulation, but not to thermal stimulation, in a dose- and time-dependent manner. We conclude that EP(1) receptor-mediated sensitization of the spinal dorsal horn may contribute to the generation of mechanical, but not thermal, hyperalgesia and that an EP(1) receptor antagonist administered intrathecally is a potential analgesic for postoperative pain, especially mechanically evoked pain (incident pain). IMPLICATIONS: We examined the effects of an intrathecally administered selective EP(1) receptor antagonist on mechanical and thermal hyperalgesia in a postoperative pain model. The intrathecal EP(1) receptor antagonist inhibited the mechanical, but not thermal, hyperalgesia, indicating the potential for an EP(1) receptor antagonist to be used as an analgesic for postoperative pain, especially incident pain.

Animals↗
PubMed2002

Role of prostaglandin receptor EP1 in the spinal dorsal horn in carrageenan-induced inflammatory pain.

BACKGROUND: Prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the generation of hyperalgesia caused by inflammation. The current study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the development and maintenance of inflammatory pain, using behavioral, microdialysis, and intracellular calcium ion concentration ([Ca2+]i) assays. METHODS: Inflammation was induced by an injection of carrageenan into the plantar surface of the rat hind paw. The effects of inflammation were evaluated at the time points of 3 h (early phase) and 15 h (late phase) after carrageenan injection. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated. The effect of an intrathecally administered selective EP1 antagonist, ONO-8711, on the carrageenan-induced hyperalgesia was examined. Using a spinal microdialysis method, PGE2 concentration in the spinal dorsal horn was measured. In [Ca2+]i assays, we measured [Ca2+]i in the spinal dorsal horn in transverse spinal slices and examined the effects of pretreatment with ONO-8711. Sensitivities of the changes in [Ca2+]i to PGE2 perfusion were also assessed. RESULTS: Mechanical hyperalgesia and paw edema were observed in both the early and late phases. The hyperalgesia was inhibited by intrathecal ONO-8711 in the late, but not early, phase. The concentration of PGE2 in the spinal dorsal horn increased in the late phase. The [Ca2+]i in the dorsal horn increased on the ipsilateral side to the inflammation in the late, but not early phase. This increase was suppressed by the pretreatment with ONO-8711. Magnitude of the increase in [Ca2+]i on the ipsilateral side in response to PGE2 perfusion was greater in the late phase than in the early phase. CONCLUSION: The results suggested that activation of spinal EP1 receptors was crucial in the carrageenan-induced mechanical hyperalgesia in the late phase. It seems that some of the mechanisms underlying inflammation-induced plastic changes are mediated by time-dependent increase in PGE2 concentration, activation of EP1 receptors, and increase in [Ca2+]i in the spinal dorsal horn.

Animals↗
PubMed1999

Specific determination of plasmin inhibitor activity in plasma: documentation of specificity of manual and automated procedures.

Recently, a chromogenic kit for determination of plasmin inhibitor activity, Coamatic Plasmin Inhibitor, has been developed with the aim to increase specificity and to allow application to a wide range of automates. The highly sensitive plasmin substrate S-2403 is used and, to further improve specificity, a low level of plasmin and a short incubation time is utilized as well as the incorporation of methylamine to quench alpha2-macroglobulin activity. The Coamatic Plasmin Inhibitor kit has been evaluated regarding specificity and compared with six commercially available plasmin inhibitor (also denoted alpha2-antiplasmin) kits and with the manual Immediate Plasmin Inhibition Test (IPIT) method, the reference method within the framework of the European Concerted Action against Thrombosis and Disabilities. Analysis of plasmin inhibitor deficient plasma with Coamatic Plasmin Inhibitor resulted in activities below 5% for all instrument applications, whereas all other commercial kits displayed unexpectedly higher values for this plasma (16-35%). There was a good agreement between the Coamatic Plasmin Inhibitor method and the IPIT method for all tested instrument applications; slope =0.80-1.02 and r = 0.92-0.97. No interference was detected from alpha2-macroglobulin, lysine, unfractionated and low-molecular weight heparin, and epsilon-amino caproic acid or from the non-plasminogen binding form of plasmin inhibitor.

Adult↗