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Biomedical subjects

G Paragh

Publications and source records attributed to G Paragh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Altered signal pathway in granulocytes from patients with hypercholesterolemia.

In the present study the signal transduction of the formyl-Met-Leu-Phe receptor was studied in granulocytes obtained from control subjects and patients with elevated low density lipoprotein levels. According to our results, 10 nm formyl-Met-Leu-Phe in control cells activates phospholipase C inducing a pronounced inositol phosphate production followed by a Ca(2+) signal from intracellular pools. The pertussis toxin-sensitive O(2)(-) generation and leukotriene synthesis were moderate. In contrast, in granulocytes from hypercholesterolemic patients, formyl-Met-Leu-Phe triggered an intensive pertussis toxin-insensitive oxidative burst and leukotriene synthesis. The inositol trisphosphate and Ca(2+) signals were decreased significantly in granulocytes of hypercholesterolemic patients and seem to be dependent on the extracellular Ca(2+) content. Furthermore, in the resting granulocytes of hypercholesterolemic patients the [Ca(2+)]i and the membrane-bound protein kinase C activity were higher than in controls, the time of normalization after the low Ca(2+) signal was delayed, while the membrane fluidity was decreased. Our results suggest that in these ex vivo experiments, the high level of circulating low density lipoprotein in patients can affect the membrane composition of granulocytes leading to altered signal transduction by the formyl-Met-Leu-Phe receptor, to altered Ca(2+) pump-activity, and protein kinase C translocation.

Calcium Signaling↗
PubMed1998

Altered postreceptor signal transduction of formyl-Met-Leu-Phe receptors in polymorphonuclear leukocytes of patients with non-insulin-dependent diabetes mellitus.

The signal transduction of the formyl-Met-Leu-Phe (FMLP) receptor in polymorphonuclear leukocytes (PMNLs) from patients with non-insulin-dependent diabetes mellitus (NIDDM) was compared to that of PMNLs obtained from healthy volunteers. According to our previous studies in this group of patients neither the decrease in insulin binding capacity nor the enhanced insulin-degrading enzyme activity was involved. In control PMNLs, 10 nM FMLP induced a pertussis toxin-sensitive increase in phosphatidyl inositol (PI) cleavage and a subsequent Ca2+ signaling from the intracellular pools. On the other hand, the FMLP-induced protein kinase C (PKC) activation and translocation into the membrane could not be detected in these cells via the measurement of 32P incorporation into histone. In contrast, in PMNLs of this special group of patients suffering from NIDDM the FMLP stimulus produced a significantly low increase in PI cleavage and Ca2+ signaling from the intracellular pools. Moreover, in resting PMNLs of these patients with NIDDM, not only the [Ca2+]i but also the membrane-bound PKC activity was found to be significantly increased. In addition, PKC translocation into the cell membrane of diabetic PMNLs could be further triggered with FMLP as judged by the measurement of 32P incorporation into histone. Based on these results, it appears that the signaling of FMLP receptors in PMNLs of some NIDDM patients may have an alternative pathway through Ca2+ influx from extracellular medium, arachidonic acid cascade, and PKC activation.

Arachidonic Acid↗
PubMed1998

The importance of obesity and hyperlipidaemia in patients with renal transplants.

The authors studied dyslipidaemia and "obesity" in 137 patients (87 males and 50 females) following cadaver renal transplantation with regard to the applied immunosuppressive treatment and the patients' hypertension. The most extreme dyslipidaemic values, the highest levels of total cholesterol, LDL and Apo were found 6 to 18 months after successful transplantation; these values were significantly higher in women than in men. While in the dialysis programme only 21.89% of the patients had BMI values higher than 25.1 kg/m2, after transplantation their proportion was 36.49%. In addition to hyperlipidaemia, hyperuricaemia was encountered in 39.42%, erythrocytosis in 8.76% and diabetes mellitus in 9.48%, respectively. In the group of patients treated only with Cyclosporine-A the incidence of hyperlipidaemia and hypertension was significantly lower than in those receiving a combination of either corticosteroids and Cyclosporine-A or corticosteroids, Cyclosporine-A and azathioprine. There was a close relationship between the unfavourable tendency of obesity and the measured hyperlipidaemia. On the other hand, the extent of proteinuria did not always have a positive correlation with the increase of BMI and body weight, the severity of hypertension and hyperlipidaemia. The authors emphasize the importance of a systematic control of the lipid levels, the significance of a diet with an adequate carbohydrate and lipid content, and the necessity of avoiding obesity by selecting the optimal immunosuppressive treatment.

Adolescent↗
PubMed1998

Specific and scavenger low-density lipoprotein receptors involved in the disturbed lipid metabolism of patients with non-insulin-dependent diabetes mellitus are independent of obesity.

Comparative studies were performed on monocyte-derived macrophages (MDMs), prepared by a 72-hour incubation of blood monocytes obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM) and age-matched obese and non-obese controls. The MDMs, after a 72-hour culturing, expressed both specific and scavenger low-density lipoprotein (LDL) receptors on their surfaces. To study the binding capacity of both receptor types, [125I]LDL and [125I] acetylated LDL (acLDL) were applied to cells and the labeled ligands were then monitored to estimate the rate of intracellular degradations. The LDL-induced inhibition of endogenous cholesterol synthesis and the acLDL-triggered apolipoprotein (apo) E secretion were also studied, as the biological marker of receptor activation. The results indicate that the binding capacities of both specific and scavenger LDL receptors were not reduced in MDMs of diabetic patients. However, the intracellular degradation after LDL incorporation was decreased. The LDL-induced inhibition of cholesterol synthesis and the acLDL-transmitted apo E secretion were also found to be decreased in the MDMs of patients with NIDDM as compared with the obese and non-obese control groups. The NIDDM-induced impaired signal transduction of both specific and scavenger LDL receptors suggests an unclarified functional alteration of both receptor structures.

Acetates↗
PubMed1998

The serum paraoxonase activity in patients with chronic renal failure and hyperlipidemia.

Human serum paraoxonase is physically associated with an apolipoprotein (Apo-A1) and clusterin-containing high-density lipoprotein (HDL) and prevents low-density lipoprotein from lipid peroxidation. The aim of our study was to determine whether paraoxonase activity or phenotype is altered in patients with chronic renal failure and in hyperlipidemic subjects without renal insufficiency and to compare the values with those of healthy controls. We investigated the serum paraoxonase activity and polymorphism in 119 hemodialyzed uremic patients, 107 patients with primary hyperlipoproteinemia, and in 110 healthy control subjects. The serum paraoxonase activity was significantly decreased both in hyperlipidemic (p < 0.01) and uremic patients (p < 0.001) as compared with controls. On comparison, the serum paraoxonase activity was significantly lower (p < 0.001) in uremic than in hyperlipoproteinemic patients. The HDL and Apo-A1 levels were as follows: uremic < hyperlipidemic < control. To assess whether the observed reduction in paraoxonase activity was due to HDL and Apo-A1 level decreases, we standardized the enzyme activity for HDL and Apo-A1 concentrations. We found that the standardized paraoxonase activity (paraoxonase/HDL ratio) was also lower in the uremic patients (103.3 +/- 69.5) as compared with hyperlipidemic patients (137.64 +/- 81.0) and controls (194.45 +/- 94.45). The standardized values for Apo-A1 showed a similar tendency: paraoxonase/Apo-A1 ratio in uremic patients 89.64 +/- 47.8, in hyperlipidemic patients 128.12 +/- 69.83, and in controls 161.40 +/- 47.35. The phenotypic distribution of paraoxonase (AA, AB, BB) did not change significantly in the patient groups. These results suggest that HDL concentration and phenotypic distribution of paraoxonase may not be the only determining factors, but that other as yet undetermined factors could be involved in the enzyme activity changes.

Adult↗
PubMed1998

Heterogeneous signal pathways through TSH receptors in porcine thyroid cells following stimulation with Graves' immunoglobulin G.

OBJECTIVE: We compared different signal transduction pathways through thyroid stimulating hormone receptor (TSH-R) in porcine thyroid cells (PTC) following stimulation with thyroid stimulating hormone (TSH) and 11 thyroid stimulating immunoglobulin samples (TSI) obtained from patients with Graves' disease. DESIGN: Following stimulation with TSI, the level of inositol trisphosphate (IP3) and [Ca2+]i, as well as the membrane bound protein kinase C (PKC) activity and the intensity of the arachidonic acid (AA) cascade, were determined in PTC. RESULTS: Seven out of eleven TSI samples activated PTC through IP3 generation, elevated [Ca2+]i from the intracellular pools, exhibited verapamil-insensitive membrane-bound PKC activation, and enhanced release of [14C]AA derivates (however, one of the samples was also able to take up Ca2+ from the extracellular space). Four out of eleven TSI samples did not activate the phospholipase C (PLC) system in which case the Ca2+ signal occurred only in the presence of extracellular Ca2+, the membrane bound PKC activation was verapamil sensitive, and in two of these four TSI samples, the AA release was extremely high. CONCLUSIONS: The simultaneous examination of the majority of the known signal pathways using TSI samples showed that TSI samples from different patients activate thyroid cells through different pathways. Their effects differ from that of TSH and, to a certain extent, from each other. The results give a certain new insight into the intracellular mechanisms exerted by TSI.

Adult↗
PubMed1997

[Biologic effect of LDL binding and intracellular degradation in monocytes from patients with hypercholesterolemia].

The granulocytes from elderly patients were investigated, in previous studies, with FMLP and it was found that the postreceptor signal, the inositol phosphate production and inositol phosphate dependent calcium signal were markedly reduced. It was observed that the 125I LDL binding was slightly reduced while the intracellular degradation of the LDL and endogenous cholesterol synthesis inhibitory effect was significantly decreased on monocytes of patients with non insulin dependent diabetes mellitus. It was suggested that of in patients suffering from NIDDM with hypercholesterolemia the LDL receptor numbers of monocytes are close to normal, while the post receptor signal transmission is damaged. In this study the monocytes from 12 patients with hypercholesterolemia were investigated before and after LDL treatment and were compared to the 11 age-matched healthy volunteer control patients. The cells were stimulated with LDL and chemotactic peptide FMLP. The postreceptor signal mechanism in monocytes was investigated. According to the results the inositol phosphate level of the patient group decreased independently from the stimulus. The LDL induced IP3 and Ca2+ level elevation was PT resistant both in the control and in the patients group.

Aged↗
PubMed1997

[Abnormal function of lipoprotein receptors in the monocytes of hypercholesteremic patients].

The familial hypercholesterinemia (HCh) is as a genetically determined disorder. The genetical damage and functional abnormalities of the LDL receptors lead to familial Hch. The LDL plays an important role in cholesterol metabolism. They carry cholesterol which metabolizes through specific and scavenger LDL receptors. The ApoB100 particle of LDL binds to the receptors, internalizated, and digested, and the remaining free cholesterol regulates the intracellular cholesterol synthesis. It inhibits the key enzyme, HMG-CoA reductase and decreases the LDL receptor synthesis and increases cholesterol esterification. These mechanism can prevent the cholesterol accumulation of the cells. The aim of the present study was to clarify the activity and number of the LDL receptor, to study the LDL binding and degradation and to evaluate how the intracellular cholesterol can regulate the synthesis in patients with HCh. 58 pts with HCh and their monocytes were investigated, because the monocyte derived macrophages contained both specific and scavenger receptors. Monocytes of the pts were compared to the healthy individual controls. From the results it could be recognized--that the decreased binding to the specific LDL receptors only at 6 pts cholesterol synthesis was elevated in HCh pts group, while the synthesis inhibition induced by 50 micrograms LDL was decreased. The presented experimental results suggested that the decreased binding ability to LDL receptors is a rare cause of cholesterol abnormalities, while during the intracellular degradation process more metabolic steps can be damaged in patients with HCh.

Cholesterol↗
PubMed1997

[Granulocyte function and lipid peroxidation in untreated patients with hyperlipoproteinemia].

The fatty acid composition in free fatty acid and phospholipid fraction of plasma in untreated mildly hyperlipidemic patients were determined. The general trend was an increase in saturation in both free and phospholipid fractions of plasma in patients compared with that of healthy controls. Furthermore, arachidonic acid, precursor of formation of prostaglandins and leukotrienes was detected in significantly lower amount in plasma of mildly and untreated hyperlipidemic patients. These fatty acid abnormalities were connected with the increased lipidperoxidation in plasma lipids and in both resting and stimulated granulocytes.

Adult↗
PubMed1997

[Lipoprotein (a) studies in thyroid diseases].

High lipoprotein (a) levels have been established as a risk factor for atherosclerosis. The physiological and pathological function of lipoprotein (a) and the effect of other factors of lipoprotein (a) plasma concentrations are not well known. The role of thyroid hormones concerning Lp(a) plasma concentrations are not fully cleared. The Lp(a) levels are genetically determined, relatively stable, while the thyroid hormones react differently. 30 hyperthyroid and 29 hypothyroid patients were studied. The thyroid status and lipid parameters were investigated. A significant correlation was observed between the cholesterol, triglyceride, LDL-cholesterol, Apolipoprotein B and the thyroid hormone levels. The HDL-cholesterol and Apolipoprotein A correlated inversely with the thyroid hormone levels. Data obtained on the Lp(a) and thyroid hormone was in contrast with those of other studies. Hyperthyroid patients were increased Lp(a) concentrations as compared those of euthyroid subjects. In severe thyreotoxicosis (especially with high levels of antithyroid antibodies) elevated Lp(a) plasma concentrations were found. In hypothyroid patients the high levels of Lp(a) were measured as described in previous studies. Authors concluded that further studies are needed to investigate this phenomenon.

Apolipoproteins A↗
PubMed1997

[In vitro study of endothelium-dependent relaxation and contraction of human atherosclerotic femoral artery].

According to present knowledge, altered arterial reactivity associated with hypertension, atherosclerosis and hypercholesterolemia is related to impaired release of endothelial derived relaxing factor (EDRF). Impaired relaxation followed by enhanced vasoconstriction leads to a well known clinical entities such as unstable angina, acut myocardial infarction. Impairment of EDRF may also account for smooth muscle cell proliferation and migration. Aim of present study was to examine the endothelial dependent response during in vitro conditions in human femoral arteries taken from bypass operation and leg amputation. Examining the contractility, the effect was modulated with nifedipin, EDTA and pertussis toxin, respectively. Endothelium dependent relaxation to acethylcholin and histamine were markedly diminished, while those to calcium ionophore were maintained throughout the study. These results suggest that at least two or more receptor-coupled system may be involved in generation of EDRF. However, direct relaxation of femoral artery to nitrovasodilatators (nitroglycerine) were comparable between control and atherosclerotic artery. Another striking change in atherosclerotic artery was the increased sensitivity to the vasoconstrictions. To eluciadate to exact biochemical mechanism underlying the endothelial dysfunction may help to develop a new vasodilatator drug.

Arteriosclerosis↗
PubMed1997

[Intracellular signal transmission of low density lipoprotein receptors in human monocytes].

The authors found that in human monocytes administered low density lipoprotein in doses of 50 micrograms had optimal inhibition of endogenous cholesterol synthesis which measured by [14C] acetate incorporation. There was not effect of pertussis toxin and phorbol myristate acetate on the inhibiton of endogenous cholesterol synthesis, whereas calcium channel blocker verapamil and phospholipase A2-inhibitor chloroquine decreased it. In contrast, the protein kinase C-stimulant phorbol myristate acetate alone had effects as LDL, but the protein kinase C-inhibitor H-7 had antagonist effect against LDL. Inositol phosphate generation was induced by administration of LDL in doses of 50 micrograms, which was pertussis toxin insensitive. The calcium signal was not also pertussis toxin sensitive, while occurred an intensive protein kinase C activation by administration of LDL. In signal transduction of monocytes activated by LDL may be an important role of the opening of calcium channels and activation of two enzymes, such as phospholipase A2 and protein kinase C.

Calcium Channel Blockers↗
PubMed1997

[Lipid lowering treatment in secondary prevention following myocardial infarct].

1081 patients treated with myocardial infarction between 1990-1995 were investigated retrospectively, 652 (60.3%) of the patients were male and 429 (39.7%) were female. 154 (14.2%) patients had an early, while 927 (85.5%) patients had late myocardial infarction. Of the patients with early myocardial infarction 52.3% were smokers, 45.2% had positive family history for ischaemic heart disease or acute myocardial infarction. The lipid parameters were analysed in detail, because 83.3% of the patients were hyperlipoproteinaemic. The mean cholesterol level was 6.91 +/- 1.2 mmol/l, the HDL-C level was 1.19 +/- 0.38 mmol/l, the triglyceride level was 2.66 +/- 1.8 mmol/l, the LDL-C level was 4.71 +/- 1.2 mmol/l. The serum LDL-C and the HDL-C levels of the patients with early myocardial infarction were compared to the desirable levels suggested for secondary prevention. Only 7.2% of the male patients had a cholesterol level below 5.2 mmol/l, while all female patients cholesterol levels were above 5.2 mmol/l. Of the male patients 53.6%, while 78.6% of females had lower triglyceride levels than 2.3 mmol/l 78,6% of the male patients had higher protective HDL-C level in the optimal range (> 1.1 mmol/l). 12.5 percent of the male patients had an LDL-C level lower than the value targeted by secondary prevention (3.0 mmol/l), while all of the female patients LDL-C levels were higher. The authors emphasize the importance of secondary prevention and a more widespread use of lipid lowering treatment for patients after acute myocardial infarction.

Adult↗
PubMed1997

Relative abundance of some free fatty acids in plasma of uremic patients: relationship between fatty acids, lipid parameters, and diseases.

The unesterified fatty acid patterns in plasma of predialytic (PHD) and hemodialysis (HD) patients were determined. The HD patients were divided into three groups: (1) HD without cardiovascular disease (HD-norm); (2) HD with cardiomyopathy (HD-CAD), and (3) HD with hyperlipidemia (HD-hyp). The relative abundance of saturated fatty acids (SFAs) was greater in the plasma of HD-norm and HD-CAD patients (73.3 and 70.0%, respectively) than that in controls (62.6%), and the relative abundance of monounsaturated fatty acids (MUFAs) was significantly greater in the plasma of HD-hyp patients than that in controls (38.9 vs. 21.6%, p < 0.01). In all HD patients the relative concentration of polyunsaturated fatty acids (PUFAs) was lower than in controls. There were no significant differences in the fatty acid patterns of PHD patients. In conclusion, the relative abundance of SFAs and MUFAs in plasma of HD patients is associated with their concomitant lipid disorders and cardiomyopathy, while the low relative abundance of PUFAs was common in all HD patients.

Cardiomyopathy, Dilated↗
PubMed1997

Treatment possibility of hypercholesterolaemia associated with hypertriglyceridaemia.

Thirty patients were investigated with hyperlipoproteinaemia, 15 patients with non-insulin dependent diabetes mellitus (NIDDM) and 15 with primary hyperlipoproteinaemia. The patients took 250 mg acipimox (5-metyl-pyrazine-carboxylic acid 4-oxide) 3 times per day for 2 months. Serum examinations were performed before and after 1 and 2 months of acipimox administration. After treatment the cholesterol and triglyceride levels decreased in both groups. Patients with NIDDM had 11% increase of high density lipoprotein-cholesterol (HDL-C) level at the end of the first, and 18% increase at the end of the second month, while patients with primary hyperlipoproteinaemia did not change significantly. The low density lipoprotein (LDL) level did not change significantly in either groups of patients. The apolipoprotein A 1 (apo A 1) levels increased significantly during the second month of acipimox administration. Uric acid levels decreased in both groups, but significant change could be detected mainly in the NIDDM group. Serum glucose level did not change in the non-diabetic patients, while it decreased significantly in the NIDDM group.

Apolipoprotein A-I↗
PubMed1996

Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

Adenoma↗
PubMed1995

[Cilazapril replacing captopril in the therapy of medium-severe essential hypertension].

Authors performed an open, crossover, multicenter study of oral cilazapril versus previous captopril treatment in mild to moderate hypertension. The treatment of the 100 outpatients on daily three or four times captopril was found ineffective, or in some cases side effects or non compliance necessitated a switch to a once daily dose of cilazapril. Reasons of ineffectivity were compliance problems in 76% of the patients during long term captopril therapy. Blood pressure decreased from 163.28 +/- 14.5/97.5 +/- 9.35 mmHg on captopril therapy to 136.67 +/- 12/83.49 +/- 7.77 mmHg at the end of a 12 week cilazapril treatment (p < 0.001). 80 patients received cilazapril monotherapy (with doses of 2.5 mg in 54 cases, 5 mg in 18 patients). 7.5 mg in 4 cases, 1 and 1.25 mg in 2 patients. In 20 patients an adjunctive diuretic was also added, while the cilazapril treatment was ineffective in 3 patients. In respect of the global evaluation and scoring of cilazapril versus captopril therapy, a clear and statistically significant improvement could be demonstrated in efficacy, tolerability and compliance after a 12 week cilazapril treatment. The 24 hour ambulatory blood pressure measurement performed in 13 patients also verified a decrease in blood pressure achieved by cilazapril therapy. Authors conclude that in case of ineffectivity of three or four times daily captopril treatment (caused most likely by non-compliance), a switch to a once daily dose drug like cilazapril is indicated.

Administration, Oral↗