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Biomedical subjects

K Croft

Publications and source records attributed to K Croft.

13 recordsLinked to original sources
PubMed2002

P2Y receptor-induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat.

Extracellular nucleotides have been shown to induce vasodilatation of conductance arteries by release of the endothelium-derived hyperpolarizing factor (EDHF). As small resistance arteries are of greater importance for blood pressure regulation, a whole rat mesenteric arterial bed preparation was used in the present study when evaluating the physiological relevance for EDHF in mediating nucleotide dilatation. Dilatory responses were examined after pre-contraction with noradrenaline in the presence of 10 mM indomethacin. Adenosine-5'-O-thiodiphosphate (ADPbetaS), adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced vasodilatation (pEC50=6.5-7 and E(max)=40-70%), while uridine diphosphate (UDP) was ineffective. Endothelium-derived hyperpolarizing factor was studied in the presence of 0.5 mM Nvarpi-nitro-L-arginine (L-NOARG). ADPbetaS and UTP induced strong and potent EDHF-dilatations, while ATP only had a weak effect (E(max)=25%). After P2X1 receptor desensitization with 10 microM alphabeta-methylene-adenosine triphosphate, the ATP response was significantly increased (E(max)=65%). Putatively, this could be because of simultaneous activation of both endothelial P2Y receptors and P2X1 receptors on smooth muscle cells, which resulted in the release of EDHF and subsequent hyperpolarization, and depolarization, respectively. Nitric oxide (NO) was studied in the presence of 60 mM K+. ADPbetaS, ATP and UTP induced weak NO dilatations, suggesting a minor role for NO as compared with EDHF. In conclusion, extracellular nucleotides stimulate dilatation by activating P2Y(1) and P2Y(2)/P2Y(4) receptors, but not P2Y(6) receptors. The dilatory responses are mediated primarily by EDHF in the peripheral vascular bed.

Animals↗
PubMed2001

Identification and quantitation of unique fatty acid oxidation products in human atherosclerotic plaque using high-performance liquid chromatography.

Oxidation of lipoproteins, particularly low-density lipoprotein, is thought to play a major role in the development of atherosclerosis. We set out to identify and quantitate the major fatty acid oxidation products in human atherosclerotic plaque obtained from individuals undergoing carotid endarterectomy. Oxidized lipids were extracted from plaque homogenate under conditions to prevent artifactual oxidation. Identification and quantitation was performed using HPLC and GC-MS. High levels of hydroxyoctadecanoic acids (0.51 +/- 0.17 ng/microg of linoleic acid), 15-hydroxyeicosatetranoic acid (HETE) (0.66 +/- 0.24 ng/microg of arachidonic acid), and 11-HETE (0.84 +/- 0.24 ng/microg of arachidonic acid) were detected in all atherosclerotic plaques (n = 10). Low levels of 9-oxo-octadecanoic acid (oxoODE) (0.04 +/- 0.01 ng/microg of linoleic acid), were present in all samples, while 13-oxoODE (0.01 +/- 0.008 ng/microg of linoleic acid) was present in only 4 of the 10 plaque samples. Of interest was the identification of two previously unidentified compounds in atherosclerotic plaque, 11-oxo-eicosatetranoic acid in 9 of the 10 samples and 5,6-dihydroxyeicosatetranoic acid in 3 samples. Chiral analysis revealed that all the major compounds identified in this study are of a nonenzymatic origin. This study is the first to provide a convenient HPLC method to quantify all the products of both linoleic acid and arachidonic acid oxidation in human atherosclerotic plaque. The quantitation of lipid peroxidation products in plaque may be important given the potential biological activity of these compounds and their possible relationship to plaque pathogenesis and instability.

Aged↗
PubMed2001

Antiplasmodial and antioxidant isofuranonaphthoquinones from the roots of Bulbine capitata.

The roots of B. capitata yielded the new compounds 5,8-dihydroxy-1-tigloylmethylnaphtho[2,3-c]furan-4,9-dione, 1-acetoxymethyl-8-hydroxynaphtho[2,3-c]furan-4,9-dione, and 1-acetoxymethyl-5,8-dihydroxynaphtho[2,3-c]furan-4,9-dione, in addition to the known compounds chrysophanol, 10,10'-chrysophanol bianthrone, 8-hydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-hydroxymethylnaphtho[2,3-c]furan-4,9-dione, and 8-hydroxy-5-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione, or 5-hydroxy-8-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione. The new as well as the known isofuranonaphthoquinones showed antioxidant and weak antiplasmodial activities.

Animals↗
PubMed2001

Study of plasma factors associated with neutrophil activation and lipid peroxidation in preeclampsia.

Neutrophil activation occurs in women with preeclampsia and is resolved after delivery. The present study examined whether circulating factors in plasma of women with preeclampsia caused neutrophil activation and lipid peroxidation. Twenty-one women with proteinuric preeclampsia were matched for age and gestational age with 19 normal pregnant women. Plasma was collected from all subjects before delivery and at 6 weeks postpartum and incubated with autologous white-cell buffy coat collected at the postpartum visit. Neutrophil activation was assessed by level of CD11b and CD18 expression after incubation with autologous antepartum or postpartum plasma. Lipid peroxidation was assessed by measurement of F(2)-isoprostanes in plasma, plasma-white cell incubates, and urine. Neutrophil CD11b and CD18 expression was not differentially altered by incubation with plasma from either women with preeclampsia or normal pregnant women and was similar between groups when incubation was performed with plasma collected after delivery. In preeclampsia, plasma F(2)-isoprostanes were significantly increased before and after delivery compared with controls. Plasma F(2)-isoprostanes were increased 2-fold after incubation of plasma with buffy coat, but preeclamptic women had higher levels compared with those of controls when either pregnant or postpartum plasma was used. In pregnant preeclamptics, plasma F(2)-isoprostanes were positively correlated with lymphocyte count. Six weeks after delivery, plasma F(2)-isoprostanes in the preeclamptic women were significantly positively associated with lymphocyte count and cholesterol and negatively associated with albumin. In conclusion, the present study does not suggest that a stable circulating factor causes neutrophil activation in preeclampsia. However, lipid peroxidation is elevated before and after delivery in women with preeclampsia, which suggests that these women may have an underlying predisposition to increased oxidative stress that may be driven by or contribute to a persistent low-grade inflammatory response.

Adult↗
PubMed2000

Inhibition of lipoprotein oxidation by prenylated xanthones derived from mangostin.

Oxidative damage is thought to play a critical role in cardiovascular and other chronic diseases. This has led to considerable interest in the antioxidant activity of dietary compounds. Flavonoids have received the most attention and much is known about the structural requirements for antioxidant activity. However, little is known about the antioxidant activity of other plant derived phenolic compounds such as the xanthones. We have previously shown that the prenylated xanthone, mangostin, can inhibit the oxidation of low density lipoprotein. In order to examine the effects of structure modification on antioxidant activity of this class of compound we have prepared a number of derivatives of mangostin and tested antioxidant activity in an isolated LDL and plasma assay. The results of this study show that structural modification of mangostin can have a profound effect on antioxidant activity. Derivatisation of the C-3 and C-6 hydroxyl groups with either methyl, acetate, propane diol or nitrile substantially reduces antioxidant activity. In contrast, derivatisation of C-3 and C-6 with aminoethyl derivatives enhanced antioxidant activity, which may be related to changes in solubility. Cyclisation of the prenyl chains had little influence on antioxidant activity.

Antioxidants↗
PubMed1998

Alcohol-related diols cause acute insulin resistance in vivo.

Epidemiological studies suggest that alcohol consumption is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Alcoholism is known to be associated with increased plasma levels of two novel diols, 2,3-butanediol and 1,2-propanediol, metabolites known to impair insulin action in isolated adipocytes. This study examines whether 2,3-butanediol and 1,2-propanediol have the capacity to impair insulin action acutely in vivo in the rat. Using the euglycemic-hyperinsulinemic clamp, it is shown that the two diols reduce whole-body glucose utilization (by approximately 30%), with the onset of insulin resistance in vivo occurring at plasma concentrations of 2,3-butanediol (33 micromol/L) at least one order of magnitude (P < .001) lower than 1,2-propanediol (432 micromol/L). Tracer methodologies using [U-14C]glucose and 2-deoxy[1-(3)H]glucose indicate that the reduction in whole-body glucose utilization is accompanied by a reduction in glucose uptake and glycogen synthesis in the skeletal muscle and heart. The association between elevated plasma diol levels and insulin resistance demonstrated in this report raises the question of whether there is a link between the high plasma diol levels in alcohol abusers and their increased susceptibility to NIDDM.

Alcoholism↗
PubMed1995

Increased blood pressure and changes in membrane lipids associated with chronic ethanol treatment of rats.

1. Changes in membrane fluidity have been proposed to contribute to the pathogenesis of ethanol-induced hypertension possibly through changes in membrane lipid patterns, but reports are inconsistent. 2. In a controlled trial we documented ethanol-induced changes in blood pressure and composition of membrane lipids in ethanol-fed rats. 3. Systolic blood pressure increased significantly in the ethanol-treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (-1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not differ significantly between ethanol-fed and control rats. Phospholipids of aorta, red cells and kidney showed a significant decrease in the polyunsaturated to saturated fatty acid ratio, while membrane phospholipids from the heart showed a significant increase in the polyunsaturated to saturated fatty acid ratio with ethanol treatment. 4. In univariate regression blood pressure was significantly negatively related to levels of arachidonic acid in the kidney (P = 0.0013) and to linoleic acid in the aorta (P = 0.0341) and red cells (P = 0.0289). Blood pressure was not significantly related to fatty acids in the heart nor to membrane cholesterol or phospholipids. 5. Differences in fatty acid composition of phospholipids between controls and ethanol-fed rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved in ethanol-induced hypertension.

Animals↗
PubMed1995

Mangostin inhibits the oxidative modification of human low density lipoprotein.

The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50 microM as monitored by the formation of conjugated dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 100 microM mangostin. We observed an inhibition of TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50 microM mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin (100 microM) significantly inhibited the consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in this in vitro system.

Amidines↗
PubMed1994

Fatty acid and amino acid composition in haruan as a potential role in wound healing.

1. Two species of snakehead fish are available in Sabah, i.e. Channa striatus and Channa melanosoma, and are commonly known as haruan. Haruan is consumed by many Malaysians to induce healing after a clinical operations. However, there is no scientific evidence as yet to substantiate the claim, and so it was decided to analyse the biochemical composition in haruan to determine which compounds may have a possible role or potential in wound healing. 2. Samples (midline fillet) of both species were extracted separately in hexane for the qualitative analysis of fatty acids by a gas chromatography, Hewlett-Packard 5890A, using a 10 meter superox 11 column (Alltech) at temperature between 190 and 245 degrees C. Peak areas were calculated automatically using Hewlett-Packard 3393A computing integrator. Subsequently, the amino acid composition was analysed using a precolumn derivatization reverse phase HPLC waters PICO-TAG system. 3. Haruan is found to contain unusually high arachidonic acid (AA) but almost no eicosapentaenoic acid (EPA). AA which is a precursor of prostaglandin may initiate blood clotting and be responsible for growth. Haruan also contains all the essential amino acids for wound healing, particularly glycine which is the most important component of human skin collagen. Therefore, haruan contained all the basic biochemical requirements for wound healing.

Amino Acids↗
PubMed1983

Influence of dietary polyunsaturated fatty acids on renal & aortic prostaglandin synthesis in 1 kidney 1 clip Goldblatt hypertensive rats.

To study the influence of dietary modification on prostaglandin synthesis and on blood pressure regulation, the effects of dietary enrichment with linolenic or linoleic acid was compared with standard rat chow in 3 groups of 13 rats before and after renal artery constriction and contralateral nephrectomy. Before renal artery constriction 4 weeks supplementation with 40 en% linseed oil (53% linolenic acid) increased renal linolenic acid, decreased arachidonic acid, and suppressed synthesis of 6-keto-PGF1 alpha and PGE2 by renal homogenates (33% and 38% respectively, p less than 0.01) compared with standard diet. Rats fed on 40 en % sunflower seed oil (63% linoleic acid) increased renal prostaglandin synthesis (p less than 0.05) compared with linseed oil, but not compared with standard diet. Seven weeks after renal artery constriction renal and aortic 6-keto-PGF1 alpha and PGE2 were suppressed 30% to 50% (p less than 0.05) by linseed oil supplements compared with sunflower seed oil and standard diets. In the sunflower seed oil group aortic 6-keto-PGF1 alpha correlated (r = 0.75, p less than 0.02) with final systolic blood pressure. Final systolic blood pressures were similar in linseed oil (152.9 mm Hg +/- se 3.3, sunflower oil (155.1 +/- se 6.6) and standard diet group (159.0 +/- se 4.2). Thus dietary linseed oil suppressed renal and aortic prostaglandin synthesis but did not accentuate renal hypertension, and linoleic acid supplementation did not protect against 1 kidney 1 clip renal hypertension.

Animals↗
PubMed1978

Young children's knowledge about visual perception: hiding objects from others.

Children of ages 2 1/2, 3, and 3 1/2 years were tested for their understanding of object hiding, believed to reflect an early developmental level of knowledge about visual perception. Even the youngest subjects could nonegocentrically hide an object by placing it on the opposite side of a screen from another person, even though placing it there necessarily left it unhidden from themselves. In contrast, there was a significant increase with age in the ability to achieve the same physical end state by placing the screen between the other person and the object. Most subjects at each age level correctly indicated that the other person could see the object when the experimenter interposed the screen between the child and the object but that the other person could not see the object when she placed the screen between the other person and the object. These and other recent findings indicate that children of this age can be both nonegocentric and skillful at estimating what other people do and do not see under various viewing conditions.

Age Factors↗
PubMedDate not supplied

Platelet-activating factor biosynthesis in rat vascular smooth muscle cells.

The ability of platelet-activating factor (PAF) receptor antagonists to protect rats from the cardiovascular collapse induced by large doses of endothelin 1 led us to examine the capacity of rat cultured vascular smooth muscle cells to produce PAF and also to evaluate its potential functional roles in this cell type. Adenosine triphosphate and the vasoactive peptides, endothelin 1, angiotensin II, and arginine vasopressin, each elicited an increase in the PAF level in extracts of rat cultured vascular smooth muscle cells as determined by bioassay. PAF was not detectable (above 20 fmol/mg protein) in the supernatants of these cells. The identity of the bioactivity as PAF was confirmed by GC/MS which indicated that more than 80% of the PAF was 1-O-hexadecyl-2-acetyl-3-sn-glyceryl-phosphorylcholine. Exogenous PAF (100 nM) elicited increases in intracellular calcium that were inhibited by WEB 2086 (10 microM). Endothelin 1, at a concentration which stimulated PAF synthesis, (1 nM), elicited increases in intracellular calcium levels that were not inhibited by WEB 2086 (10 microM). Thus, endogenous PAF is unlikely to be involved in the endothelin-1-induced calcium increases. Although WEB 2086 (3-100 microM) inhibited concentration dependently fetal calf serum (10% v/v) induced [3H]-thymidine incorporation, reaching a maximum effect at 30 microM of 40-50% reduction, in parallel experiments WEB 2086 had no effect on serum-induced increases in cell numbers. We conclude that PAF is produced and retained by cultured rat vascular smooth muscle and that it is unlikely to contribute to the signaling of increases in intracellular calcium or proliferation.

Adenosine Triphosphate↗