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Biomedical subjects

Z Balogh

Publications and source records attributed to Z Balogh.

At least 37 records · Page 2Linked to original sources

Serum paraoxonase activity changes in uremic and kidney-transplanted patients.

Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36+/-30. 12 vs. control 188.05+/-58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5+/-35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7+/-54.8) and kidney-transplanted patients (144.5+/-32.7) when compared to controls (194.5+/-94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31. 62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.

Adult↗

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↗

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↗

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↗

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↗

[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↗

[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↗

[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↗

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↗

Predictive morphological findings in "zero-hour" biopsies of renal allografts.

"Zero-hour" biopsies of 65 donors have been performed since 1994. Donor kidneys were categorized into five groups based on the morphological findings in "zero-hour" biopsies. No morphological abnormalities were found in 38% of the cases (group 1). Arteriosclerosis was present in 31% of donor kidneys (group 2). Specific morphological alterations, i.e. acute tubular necrosis [21.5%], tubulointerstitial nephritis [6.2%] or glomerulonephritis [3.1%] were detectable in the cases remained (group 3-5). During an average of 336 posttransplant days clinical and histological follow up was performed (50 rebiopsies). Statistical data of mismatch (1.4-2.0), average of donor/recipient age (35-42 years), cold and warm ischaemic time (1290 and 66 min) were comparable in all groups. According to our observations: 1. higher creatinin was found in grafts with arteriosclerosis (group 2) (p < 0.05), 2. there were more non-viable grafts and longer period of delayed graft function in acute tubular necrosis (group 3), 3 higher creatinin, rejections with the need of rehemodialysis were observed in four cases of tubulointerstitial nephritis (TIN-group 4). Glomerulonephritis (GN-group 5) grafts had only delayed graft function, however these groups were few for statistical evaluation. Biopsy complication in 1/115 cases was found (rebiopsy induced kidney haemorrhage). In conclusion, "zero-hour" biopsies can be useful and safe tools to predict early graft function. Besides "zero-hour" biopsies help the histological interpretation of consecutive graft rebiopsies.

Adult↗

Effects of nitric oxide synthase inhibition on the hemodynamic changes in hyperdynamic endotoxemia.

In this study we compared the circulatory effects of the arginine analogue non-specific nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine (NNA), and the specific inducible NOS (iNOS) inhibitor S-methylisothiourea (SMT) and S-(2-aminoethyl)-isothiourea (AEST) in a hyperdynamic endotoxemic dog model. Mean arterial pressure (MAP), cardiac output (CO), and myocardial contractility (MC) were measured. A hyperdynamic circulatory response was elicited with a 2-h infusion of a total dose of 5.3 micrograms/kg E. coli endotoxin (ETX). NOS inhibitory treatment (2 mg/kg) was administrated from the 45th min of endotoxemia. ETX induced a hyperdynamic circulatory response, and a significant myocardial depression. NNA induced a prolonged, SMT a transient increase in MC, both drugs elevated MAP, but decreased CO. AEST significantly prolonged the elevation in CO, but did not affect MAP. Selective inhibition of the iNOS may be a beneficial in sepsis.

Animals↗

[Cytodiagnosis of Ewing sarcoma].

Pelvic Ewing's sarcomas were studied by fine needle aspiration biopsy in two young male patients. Local pain, subfebrility, high ESR had occurred in both cases. X ray examination showed osteolytic lesions in both patients. The differential diagnostic question was, are the lesions osteomyelitis or malignant tumors? Fine needle aspiration biopsies and cytological examinations were performed in order to determine the nature of the lesions. The aspirates consisted of monotonous population of small undifferentiated tumor cells. The nuclei were monomorph with small nucleoli and finely granular chromatin. The tumor cells contained large amounts of PAS positive diastase-digestible granular cytoplasmic glycogen. The aspirated material was examined by immunocytochemistry and electronmicroscopy in one of the cases. Both of these methods had diagnostic value in our patients in the detection of Ewing's sarcoma.

Adolescent↗

[Fatal myocardial lesion in systemic lupus erythematosus].

The authors present the case of a 47-year old female patient. She suffered from a moderate activity SLE for two years. The outcome of SLE was changed by an ulcer because of leg injury, which was repeatedly infected. Severe polyarthritis, leucopenia, thrombocytopenia, clinical signs of vasculitis and in the last two months fever, high ESR, and pericarditis appeared. The angina pectoris, the cardiac decompensation, the electrocardiogram, the echocardiogram was suspect to diffuse myocardial lesion. Cardiac decompensation caused the death of the patient. Besides the activation of her autoimmune disease, infection was suspect in the patient taken immunosuppressive and steroid drugs, though it could not be verified. Autopsy verified besides the recent necrosis of heart without reaction, and multifocal myocardial abscess, which appeared possible in the terminal phase.

Abscess↗

[Effect of acipimox on diabetes mellitus-associated hyperlipoproteinemia].

The authors give summary on the pathogenesis of hyperlipoproteinaemia in patients with diabetes mellitus. They investigated the effects of acid nicotinic derivate acipimox on lipid metabolism in these patients. They treated with acipimox 15 patients who suffered from non-insulin-dependent diabetes mellitus, as well as II/B, IV type hyperlipoproteinaemia by Fredrickson. They investigated the effect of acipimox on the lipoprotein content and quality in the sera and uric acid and carbohydrate metabolism. The authors found decreased cholesterol, triglyceride, apolipoprotein-B, glycosilated haemoglobin, glucose and uric acid levels in the sera and they found that the atherogenic index decreased too. During the treatment they could not recognise a change in the low-density lipoprotein level of the sera while the high density lipoprotein and apo-A1 level increased.

Adult↗

[Molecular genetic, laboratory and clinical study of serum amyloid P].

Studying the gene polymorphism of serum amyloid P a common constituent of amyloid deposits two restriction fragment length polymorphism patterns were found among Hungarian rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus (SLE) patients and healthy controls. Although no direct connection between DNA polymorphism and the frequency of amyloidosis in three patient groups was found, a marked predominance of the heterozygosity in all studied groups has been described. Authors found close correlation between the serum levels of SAP and CRP in juvenile rheumatoid arthritis, but failed to find the same correlation in SLE and healthy controls. Moreover, the serum level of CRP of heterozygous patients were significantly higher than that of homozygous patients within the juvenile rheumatoid arthritis patient groups.

Amyloid↗

Interleukin 6 levels in synovial fluids of patients with different arthritides: correlation with local IgM rheumatoid factor and systemic acute phase protein production.

Interleukin 6 (IL-6), a multifunctional cytokine particularly active in regulation of the acute phase response, governs the terminal maturation of B lymphocytes and participates in early activation of T cells. IL-6 levels of synovial fluids of 153 patients with different arthritides were measured by a simple sandwich enzyme immunoassay. Highest IL-6 concentrations were detected in patients with rheumatoid arthritis (RA), particularly in those characterized by very active general symptoms and severe joint pain. High IL-6 levels were detected in patients with juvenile RA with polyarticular onset of disease and in gout. Corresponding to the suggested in vivo relevance of IL-6, dose correlation of IL-6 levels with the synovial IgM rheumatoid factor accumulation was demonstrated. The rate of the correlation between synovial IL-6 level and concentration of serum C-reactive protein in RA was inversely proportional to the dose of steroid treatment in patients with RA.

Arthritis↗

Juvenile psoriatic arthritis.

Among 664 juvenile chronic arthritis patients cared for in the Outpatient Clinic of the Pediatric Rheumatology Unit of the National Institute of Rheumatology and Physiotherapy 11 were found with juvenile psoriatic arthritis, and their data regarding skin, joint, ophthalmological, laboratory and radiological manifestations were analysed. These patients were categorised according to the four subgroups suggested by Truckenbrodt et al. Considering that the occurrence of the disease is rare, the small number of patients investigated in this study can provide additional data to the study of Truckenbrodt. The higher number of patients with JPA thus studied can give more information for a multicentric evaluation.

Adolescent↗

[Recurrent juvenile pancreatitis in dermatomyositis].

The authors present the case history of an 11-year-old girl who suffered from the rarely occurring grave juvenile dermatomyositis associated with recurring pancreatitis. Factors which may cause pancreatitis: juvenile dermatomyositis as underlying disease, steroid-, cytostatic- and thiazide diuretic treatment are analysed.

Adrenal Cortex Hormones↗