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Biomedical subjects

A Hornych

Publications and source records attributed to A Hornych.

At least 19 recordsLinked to original sources
PubMed2002

The effect of gamma-linolenic acid on plasma and membrane lipids and renal prostaglandin synthesis in older subjects.

UNLABELLED: Senescence is associated with a decreased activity of enzyme delta-6 desaturase, which converts linoleic acid to gamma-linolenic acid. This enzymatic defect may alter the composition of plasma and membrane lipids, and influences the biosynthesis of renal prostaglandins. Exogenous supplementation of GLA during 3 months increases the plasma level of dihomo-gamma-linolenic acid (p < 0.002), and to a smaller degree, the level in erythrocyte membrane lipids. This treatment was associated with a beneficial reduction of cardiovascular risk factors (arterial hypertension, total cholesterol, apolipoprotein B, HDL-cholesterol, apolipoprotein A-I) and the renal function has become stable reached. Epogam treatment also increased the biosynthesis of renal prostaglandins, especially that of prostaglandin E2, which has a vasodilatory effect on vessel walls and reduces the elevated blood pressure. CONCLUSION: Dietary supplementation of essential fatty acids such as gamma-linolenic acid to old subjects has beneficial effect on their health condition. (Tab. 6, Fig. 5, Ref. 37.)

Aged↗
PubMed2000

[Microabluminuria in arterial hypertension. Measurement, variables, interpretation, recommendations].

Permanent hypertension is frequently associated with increased glomerular permeability to albumin at an early stage, indicating renal involvement and endothelial dysfunction. The definition of microalbuminuria is an urinary albumin excretion of 30-300 mg/24 hrs, confirmed on two occasions over a 3 month period. It may also be expressed in microgram/min, m/l or mg/mmol of creatinine. Radio-immunological, immunonephelometric methods and Elisa are specific and the most sensitive methods of measurement. There is a large intra-individual variability (25-60%) making it essential to repeat measurements always by the same technique. The prevalence of microalbuminuria is 5-8% in the general population and 6-24% in hypertensive patients. When present, it is a marker of increased cardiovascular risk. Clinical recommendations suggest adaptation of urinary collection according to the context: screening, diagnosis or clinical research. It is always necessary to start by dip-stick detection of proteinuria, haematuria or urinary infection. Clinical research requires repeated measurement of 24 hour microalbuminuria, sometimes divided into two periods of day and night, often associated with ambulatory blood pressure recordings and renal function tests. Studies of the effects of anti-hypertensive drugs on microalbuminuria could provide better evaluation. In conclusion, measurement of microalbuminuria remains a tool of clinical research allowing an assessment of cardiovascular and renal risk of hypertensive patients.

Albuminuria↗
PubMed1999

[Microalbuminuria and arterial hypertension].

UNLABELLED: IMPACT OF HYPERTENSION ON THE KIDNEY: Permanent uncontrolled hypertension affects target organs, particularly the kidney. Infraclinical renal dysfunction can be detected by early measurements of microalbuminuria which is an expression of the increased glomerular permeability related to increased arterial pressure, endothelial dysfunction and hormonal factors. Trace albumin can be detected in the urine of normal subjects. Although the amount of albumin in the urine increases with exercise, output should not exceed 20 mg/24 h. DEFINITIONS: Microalbuminuria is defined as urinary excretion of albumin in the 30-300 mg/24 h or 20-200 micrograms/min range. Due to the wide variability, tests should be repeated 2 or 3 times to confirm the persistent nature of the microalbuminuria. In hypertensive patients, microalbuminuria can be reversible if blood pressure levels are normalized. Urinary secretion of albumin above 300 mg/24 h is considered to be a macroalbuminuria expressing a more severe renal condition. INCIDENCE: The incidence of microalbuminuria in patients with borderline hypertension is 12-15%, in those with mild or moderate hypertension, it is 15-30%, and in those with severe hypertension, the percentages exceed 50%. RISKS: Albuminuria is positively correlated with blood pressure levels measured in inpatients; the correlation is even tighter with ambulatory recordings. Microalbuminuria is a risk factor for cardiovascular disease and for the development of nephroangiosclerosis. It should be searched for in all patients with persistently high blood pressure. Monitoring urine albumin is an effective tool for assessing the efficacy of an antihypertensive treatment and is useful for preventing renal damage.

Adult↗
PubMed1998

The effect of high density lipoprotein subfractions on endothelial eicosanoid secretion.

Epidemiological, clinical, and experimental studies have demonstrated that high density lipoproteins (HDL) are protective against atherosclerosis. However, the respective influence of two main HDL subfractions (HDL2 and HDL3) on atherosclerosis process is not yet clear. The present study was designed to determine, which HDL subfraction was antiatherogenic in terms of eicosanoid release by human umbilical vein endothelial cells (HUVEC). Endothelial cells were incubated for 4 hours with HDL2 or HDL3 and prostaglandins 6-keto-PGF1alpha, thromboxane B2 and prostaglandin E2 were measured by RIA in culture supernatant. HDL2 has a dose dependent stimulatory effect on 6-keto-PGF1alpha release without stimulatory effect on thromboxane B2 secretion. The 6-keto-PGF1alpha/thromboxane B2 ratio increased progressively from 1.65 to 4.65 for 0.39 to 6.25 mg HDL protein/ml. The pattern of prostanoid secretion under influence of HDL3 showed a predominant response in 6-keto-PGF1alpha and TxB2 release. As regards PGE2, both HDL subfractions stimulated considerably secretion of this prostanoid in a dose dependent manner. In terms of PGI2/TxA2 balance the better antiatherogenic effect was observed with HDL2 subfraction.

Cells, Cultured↗
PubMed1998

[Atherogenic and anti-atherogenic plasma lipoproteins modulate secretion of prostanoids by endothelial cells in vitro].

The authors present the evidence of atherogenic properties of VLDL and LDL potentiation on the model of endothelial cells-human umbilical vein endothelial cells, by preferable stimulation of the endothelial cell to thromboxane A1 production at in vitro conditions by atherogenic lipoproteins. The vasoconstrictive, thrombogenic and atherogenic effects of TXA2 are exerted on the vessel in this way. The ratio prostacycline/thromboxane, decisive for the maintenance of vascular homeostasis, is less than 1, this means the beneficial effect of prostacycline can not be applied. Protective, antiatherogenic effect of HDL and its subfractions HDL2 and HDL3/predominantly through their function in the reverse cholesterol transport from the periphery to the liver, antioxidative influence on LDL, as far as antiaggregation and fibrinolytic effects of HDL/is multiplied by the fact that HDL preferably stimulates the secretion of prostacycline by the endothelial cell. The ratio prostacycline/thromboxane A2 is higher than 1, that means beneficial vasodilative, antiaggregation and antiatherogenic effect of prostacycline on the vessel wall predominate. Quantitative evaluation of antiatherogenic effects of HDL subfractions (HDL2 and HDL3) revealed more significant antiatherogenic effect in HDL2 subfraction-in the sense of prostacycline secretion stimulation and exertion of its beneficial effects on the vessel. (Fig. 5, Ref. 33.)

Arteriosclerosis↗
PubMed1996

Effects of OKY-046 and nifedipine in cyclosporine-induced renal dysfunction in rats.

Cyclosporine (CsA) (37.4 mumol/kg per day for 7 days) treated female Wistar rats exhibited significantly decreased creatinine clearance (Ccr) and body weight loss (BWL), but had neither proteinuria (PU) nor alteration in their urine volume (V). Light microscopic (LM) sections of rat kidneys showed that all kidneys were affected by lesions, mainly diffuse vacuolization. These changes were associated with decreased urinary excretion ratios of 6-ketoprostaglandin F1 alpha to thromboxane B2 (6kPGF1 alpha/TXB2) and prostaglandin E2 to TXB2 (PGE2/TXB2). When OKY-046, a TXA2-synthetase inhibitor or nifedipine (NFD), a calcium channel blocker and an antagonist of endotheline (ET), were administered in addition to CsA, they restored Ccr and increased urine V but they did not prevent BWL. LM sections showed that only 5 or 7 out of 9 kidneys of animals were affected, respectively. These changes were associated with prevention of the diminished ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 mainly in the OKY-046 treated animals. In conclusion, our results suggest that inhibitors of TXA2 or antagonists and/or inhibitors of endothelin play a protective role in the development of the dysfunction induced by CsA. However, the protection observed using OKY-046 and NFD did not reach that obtained by evening primrose oil (EPO) or Ketanserine (KTS), substances which prevented the fall of Ccr and BWL. Furthermore, with these protective agents only 5 out of 9 kidneys were affected and the lesions were of minor importance.

Animals↗
PubMed1996

Biocompatibility of haemodialysis membranes: haemodialysis-related leukotriene B4 and C4 generation. France.

UNLABELLED: The aim of our study was (1) to verify whether haemodialysis (HD) with cuprophane (CUP) and polyacrylonitrile (PAN) membranes is associated with the release of vasoactive leukotriene (LT) C4 and chemotactic LTB4 and (2) to analyse the respective roles of lipoxygenase and cyclo-oxygenase metabolites of arachidonic acid in membrane bio-incompatibility. The investigation was performed in 10 uremic patients using hollow-fibre dialysers and dialysed successively, in random order, with CUP and PAN membranes. The arterial and venous (from dialyser) blood was sampled for the measurement of biochemical parameters, plasma LTC4, LTB4 and prostaglandins (PG) 6-keto-F1 alpha, E2, F2 alpha and thromboxane B2 before and after 15, 30 and 240 min of HD. Eicosanoids were measured by RIA after prior extraction and HPLC separation. RESULTS: CUP HD was associated with a marked early leukopenia and a delayed decrease in blood pO2. Simultaneously, plasma LTB4 and LTC4 increased significantly in arterial blood after 30 min of HD and in venous blood at the end of session of 240 min. Cyclo-oxygenase metabolites increased as well, but nonsignificantly, with a maximum at the end of HD. PAN HD did not significantly change white blood cell count, pO2, or plasma eicosanoid levels. CONCLUSION: CUP membranes stimulate the release of proinflammatory and vasoactive LTB4 and LTC4. PAN membrane haemodialysis is without such side effects. The release of LTs may be an additional valuable marker of membrane bioincompatibility.

Acrylic Resins↗
PubMed1995

Renal and endocrine effects of flosulide, after single and repeated administration to healthy volunteers.

UNLABELLED: Two double-blind, placebo-controlled, balanced cross-over studies were carried out successively in 8 male normotensive volunteers to investigate the acute and chronic effects of two doses of a novel non-steroidal anti-inflammatory drug flosulide (5 mg b.d. and 25 mg b.d.), on the renin-angiotensin-aldosterone system, linking this to changes in the urinary excretion of prostaglandins. Plasma renin and aldosterone were determined on Days 2 and 9, with the subject supine, after 1 h of rest in the sitting position following 1 h of walking, and 3 h after oral intake of 40 mg furosemide, also in the sitting position. Twenty-four hour urine samples were collected on Days 1 and 8 for the measurement of the electrolytes, aldosterone pH1 and the urinary prostaglandins PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TxB2. RESULTS: After the first day of treatment with 25 mg b.d. flosulide, the increase in body weight was close to significance (0.86 vs -0.08 kg with placebo). A dose- and time-dependent decrease in both active and inactive plasma renin were observed, whereas the fall in plasma and urinary aldosterone was statistically significant only after the higher dose of flosulide. These changes in the renin-angiotensin-aldosterone system were observed in the absence of oedema. Two out of eight volunteers experienced a strong and immediate reduction in the excretion of prostaglandins but overall the two doses tested did not produce a statistically significant inhibition in renal prostaglandins, especially following repeated dosing. The inhibitory effect of flosulide on renal prostaglandin synthesis was found to be less pronounced after repeated treatment, as documented on Day 9 by the lower inhibition of 6-keto-PGF1 alpha and TxB2. CONCLUSION: These two studies in normal volunteers, in spite of some methodological limitations, were helpful in order to select doses of flosulide which should be effective and safe in patients during Phase II trials, by examining the inhibitory effect of the drug on renin synthesis and renal prostaglandin synthesis.

Adult↗
PubMed1995

Effect of ketanserine in cyclosporine-induced renal dysfunction in rats.

Cyclosporine (CsA)-treated female Wistar rats, in dose of 37.5 microM (45 mg)/kg/day for 7 days, exhibited significantly decreased creatinine clearance (Ccr), and provoked body weight loss (BWL), which is consistent with the development of nephrotoxicity (NT). Urine volume (V) did not change and proteinuria (PU) was not provoked. These changes were associated with significantly diminished ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 excretions. Light-microscopic (LM) sections of rat kidneys showed that all kidneys were affected but the lesions (mainly diffuse vacuolization) were reversible. When CsA-treated animals were pretreated with ketanserine (KTS), which antagonizes (a) the direct vasoconstrictor effect of serotonin (5-HT), and (b) the amplifying effects of 5-HT on other vasoactive substances (such as noradrenaline (NA), alpha 1-receptors, histamine, H2 receptors, and prostaglandin F2 alpha), Ccr and urine volume significantly increased, BWL was partially prevented and the ratios of urinary PGE2/TXB2 and 6kPGF1 alpha/TXB2 excretions were significantly enhanced. LM sections showed that only 5 of 9 rats were affected but the lesions were of less importance. These observations indicate that the NT induced by CsA in our studies was mediated by 5-HT, a potent vasoconstrictor agent, and by the metabolites of arachidonic acid. However, other vasoactive agents and additional mechanisms could also be implicated.

Animals↗
PubMed1995

Normal human polyspecific immunoglobulin G (intravenous immunoglobulin) modulates endothelial cell function in vitro.

We have analysed the in-vitro effect of pooled normal polyspecific immunoglobulin G (IVIg) and F(ab')2 fragments of IVIg on the secretion of prostacyclin (PGI2), thromboxane A2 (TxA2), and endothelin from cultured human umbilical vein endothelial cells. The stable metabolites, 6-keto-PGF1 alpha and TxB2, as well as endothelin, were measured by radioimmunoassay after extraction from the culture supernatants. IVIg inhibited TxB2 and endothelin secretion in a dose-dependent manner, but not that of 6-keto-PGF1 alpha. Therefore the ratio of 6-keto-PGF1 alpha/TxB2 increased (+600%). The effect of F(ab')2 fragments prepared from IVIg was similar to that observed with IVIg, indicating that the effect of IVIg was mediated by the variable region of immunoglobulin. The results suggest that part of the effects of IVIg in inflammatory vasculitis may be due to a modification of the PGI2/TxA2 ratio and inhibition of endothelin secretion, and that natural IgG antibodies may participate in the homeostatic process of endothelium under physiological conditions.

Cells, Cultured↗
PubMed1992

Prostaglandins and systolic blood pressure, but not angiotensin II, independently affect atrial natriuretic peptide levels in man.

1. Two hours after a single dose of indomethacin (INDO), plasma renin activity (PRA) and atrial natriuretic peptide (ANP) levels decreased, which is consistent with an effect of lowering prostaglandins (PG). 2. After 48 h of INDO, PRA remained low but ANP had increased, which is consistent with the known effect of prostaglandin inhibitors to cause sodium retention, with a resulting volume expansion. 3. Infusions of angiotension II (AII), which raises diastolic blood pressure (BP) 20 mmHg or more, consistently raised ANP levels. The ANP response to AII infusion was reduced 48 h after INDO, which is consistent with an important role for PG in AII-stimulated ANP release. 4. After PG were blocked with INDO, the stimulating effect of AII on ANP at doses that increased diastolic BP less than 20 mmHg was insignificant, whereas before INDO it was significant. 5. In dose-response studies, INDO increased the systolic BP response but decreased the ANP response to AII, which is consistent with a direct effect of PG on ANP that is independent of systolic BP. 6. Prostaglandins and BP are important in the ANP response to AII infusion in normal subjects, but AII itself appears to have little direct effect on ANP.

Adult↗
PubMed1991

Plasma prostaglandins, leukotrienes and thromboxane in acute high altitude hypoxia.

To explore the hypothesis that acute exposure to altitude hypoxia and acute mountain sickness (AMS) are associated with the release of vasoactive eicosanoids, 10 adult subjects were studied at sea-level and after 1-8 days (H1-H8) of exposure to an altitude of 4350 m (Observatoire Vallot). Plasma concentrations of 6 eicosanoids were determined in peripheral venous blood samples by radioimmunoassay after extraction with cooled ethanol and chromatographic separation by HPLC. All subjects experienced symptoms of AMS. Maximal clinical scores were observed at H1 or H2. Symptoms were no longer noted at H8. Hypoxia induced a very large increase in plasma concentration of most eicosanoids; thromboxane B2 (TxB2) and leukotriene B4 (LTB4) were maximum at H1 and H2 (about 5 times the normoxic value); prostaglandins PGE2, 6-keto-PGF1 alpha and PGF2 alpha were maximum at H3 or H4 (about 2.5-5 times of normoxic value). All eicosanoids returned almost to normoxic values by H8. Vasoconstricting mediators were released mostly at the initial phase (H1, H2), vasodilating mediators becoming predominant thereafter (H3, H4). The time pattern of appearance in blood of mediators acting on vascular permeability was strikingly parallel to the clinical score of AMS. In conclusion, exposure to acute hypoxia induced a large increase in plasma concentration of eicosanoids, the variation with time of which is compatible with a hydrostatic-permeability hypothesis of AMS pathophysiology.

Adult↗
PubMed1991

The influence of age on renal prostaglandin synthesis in man.

The purpose of our study was to determine influence of age on renal prostaglandin (PG) synthesis in man. Urinary prostaglandins 6-Keto-PGF1 alpha, TxB2, PGE2 and PGF2 alpha were measured in 45 normotensive subjects aged from 20-95 years. Urinary 6-Keto-PGF1 alpha excretion, reflecting mainly renal cortical prostacyclin synthesis, decreased significantly with age, while urinary TxB2 showed the opposite development. The ratio of urinary 6-Keto-PGF1 alpha/TxB2 decreased with age. PGE2 excretion was preserved in old subjects probably because the age-dependent decrease in renal function concerns mainly the cortex and spares the medulla. PGF2 alpha synthesis was least influenced by age. This age-dependent decrease in renal prostacyclin synthesis may play a role in the renal alterations of the elderly.

Adult↗
PubMed1991

The syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate: is there a deficiency in vasodilator prostaglandins?

1. In Gordon's syndrome (GS; a syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate), excessive proximal sodium reabsorption leads to suppression of renin and aldosterone, hyperkalaemia and hyperchloraemic acidosis. 2. Low urinary levels of vasodilator prostaglandins (PG) have been reported in GS, suggesting renal hypoprostaglandinism as a pathophysiological mechanism. 3. In four cases of GS, levels of vasodilator prostaglandins PGE2 and 6-keto-PGF1 alpha were low. 4. In one case of GS, low PGE2 levels were normalized by dietary salt restriction or diuretic therapy.

Adult↗