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Biomedical subjects

R Dzúrik

Publications and source records attributed to R Dzúrik.

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

Enalapril in subantihypertensive dosage attenuates kidney proliferation and functional recovery in normotensive ablation nephropathy of the rat.

Most studies on the antiproliferative action of angiotensin converting enzyme inhibitors (ACEI) were performed in a rat hypertensive remnant kidney model with 5/6 kidney ablation which raised objections about the antihypertensive effect of ACEI and the influence of other antihypertensive drugs administered to remnant kidney control rats. To prevent these objections, a normotensive 4/6 remnant kidney model was elaborated and a subantihypertensive dosage of enalapril was used to evaluate its antiproliferative action. Subtotally nephrectomized rats (Nx) markedly increased the remnant kidney weight during a 4-week period and this rise was prevented by the treatment with enalapril (NxE) (Nx +297+/-35 mg vs. sham-operated +145+/-32 mg, p<0.001; NxE +154+/-35 mg vs. Nx p<0.001). While collagen concentration in the kidney cortex was not increased in sham-operated rats (Sham) in comparison with the control group (Ctrl) at the beginning of the study, the subsequent increase was significant in the Nx group and enalapril did not attenuate this increase (Sham 148+/-5 mg/100 g w.w. vs. Nx 164+/-2 mg/100 g w.w., p<0.01; NxE 161+/-4 mg/100 g w.w. vs. Sham p<0.05). The tubular protein/DNA ratio increase, which was significant in the Nx group, was inhibited by enalapril (Nx 26.2+/-10.5 vs. NxE 15.3+/-2.6, p<0.05). The protein/DNA ratio was much lower in glomeruli, with no significant changes in either the Nx or NxE groups. Serum urea concentrations were slightly higher in the Nx group than in the sham-operated group, but markedly elevated in the NxE group (Nx 10.71+/-0.76 mmol/l vs. Sham 6.10+/-0.33 mmol/l, p<0.001; NxE 28.9+/-2.6 mmol/l vs. Sham p<0.001). Creatinine concentrations in the Nx group were increased in comparison with the sham-operated group and markedly increased in the NxE group (Nx 63.7+/-3.56 micromol/l vs. Sham 37.2+/-2.84 micromol/l, p<0.001; NxE 107.0+/-5.2 micromol/l vs. Sham p<0.001). The clearance of creatinine was lower in the Nx group than in the sham-operated group and was markedly reduced in the NxE group (Nx 0.89+/-0.06 ml/min.g kidney wt. vs. Sham 1.05+/-0.16 ml/min x g kidney wt., p<0.01; NxE 0.58+/-0.029 ml/min x g kidney wt. vs. Sham, p<0.001). Enalapril improved proteinuria in comparison with the Nx group (NxE 5.6+/-0.6 mg/24 h vs. Nx 16.1+/-3.4 mg/24 h, p<0.05). Thus remnant kidney proliferation is substantial even in normotensive rats. It includes both proliferation and collagen accumulation with partial recovery of kidney weight and function, but is accompanied by enhanced proteinuria. Enalapril attenuates the proliferation and decreases proteinuria but prolongs kidney function recovery.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

[New perspectives of treatment of osteoporosis with thiazides].

Thiazides inhibit calcium and magnesium excretion, the basic substrates of bone mineralization. Clinical investigations pointed already previously to their effectiveness in the prevention and treatment of osteoporosis despite a relatively small effect on the balance. This aroused some distrust and prevented their acceptance among preparations with this indication. They were indicated mainly in patients with hypercalciuria. The results of recent research indicate however their direct inhibition of osteoclasts and in particular stimulation of osteoblasts. This confirms results of clinical investigations which could not be explained previously. It may be foreseen that within a short time thiazides will become an important member in the spectrum of drugs used for the treatment of osteoporosis.

Benzothiadiazines↗
PubMed1998

Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.

Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.

Aspirin↗
PubMed1998

Participation of P-dependent and P-independent glutaminases in rat kidney ammoniagenesis and their modulation by metabolic acidosis, hippurate and insulin.

The key regulatory enzymes of kidney ammoniagenesis appear to be P-dependent (PDG) and P-independent (PIG) glutaminases. While the participation of PDG has been satisfactorily elucidated, the significance of PIG remains doubtful. Rat kidney cortex slices synthesized ammonia even under basal conditions. Metabolic acidosis, hippurate and insulin stimulated ammonia production. Under basal conditions, PDG activity in kidney homogenate, was twice as high as PIG activity. Metabolic acidosis stimulated ammonia production by the stimulation of both PDG (100%) and PIG (57%) activities. Hippurate stimulated only PIG activity both under basal conditions (90%) and in metabolic acidosis (52%), while it inhibited PDG activity only insignificantly under basal conditions and markedly (53%) in metabolic acidosis. Insulin stimulated both PIG and PDG activities under basal conditions as well as in metabolic acidosis and potentiated the PIG stimulation by hippurate while it potentiated the hippurate inhibition of PDG both under basal conditions and in acidotic rats. In conclusion, both PDG and PIG participate in ammoniagenesis and are stimulated by metabolic acidosis and insulin. Hippurate stimulates PIG, while it inhibits PDG in metabolic acidosis and even after insulin administration. The effect of hippurate appears to be of physiological interest.

Acidosis↗
PubMed1998

[The TEAM study--a study of the effectiveness and tolerance of treatment of essential hypertension with a fixed combination of trandolapril and verapamil].

The TEAM trial investigated the effectiveness and tolerance of a fixed combination of the ACE inhibitor and calcium channel blocker (2 mg trandolapril and 180 mg verapamil retard) (preparation Tarka) in an open multicentre prospective study of treatment of moderately severe hypertension (diastolic pressure at the end of the two-week wash-out period 100-115 mm Hg). The trial comprised 163 patients who were treated first for four weeks by a monotherapy with 2 mg trandolapril. After these four weeks patients who attained normal blood pressure proceeded with trandolapril treatment. Hypertensive patients who did not attain normal diastolic pressure levels were treated for another four weeks by a fixed combination of trandolapril and verapamil SR. After four weeks of treatment with trandolapril 62 patients of 163 (37%) had a diastolic blood pressure of less than 90 mm Hg. The fixed combination of trandolapril and verapamil SR reduced the diastolic blood pressure to less than 90 mm Hg in 71.6% of the patients resistant to treatment with 2 mg trandolapril and in another 15.6% of patients it reduced the diastolic blood pressure by 10 mm Hg or more. After two months of treatment 60 patients had a normal blood pressure due to trandolapril (37%) and another 73 patients (45%) treated by a combination of trandolapril and verapamil SR, i.e. a total of 133 patients (82%) who originally suffered from moderately severe hypertension, attained a normal diastolic blood pressure. The mean decrease of diastolic pressure after two months of treatment was 19.5 mm Hg in "non-respondents" to trandolapril monotherapy and 23.6 mm Hg in "respondents". The mean decrease of systolic pressure in "non-respondents" and "respondents" after trandolapril treatment was 19.5 mm Hg and 35.0 mm Hg resp. The fixed combination of trandolapril and verapamil was not only effective but was associated with a minimum of undesirable effects. The incidence of headaches declined significantly. The combination of the above preparations is useful also because both preparations have a cardio- and nephroprotective effect and do not affect the lipid and carbohydrate metabolism. Treatment with a fixed combination of trandolapril and verapamil SR is indicated in moderately severe hypertension not responding to monotherapy, in particular when associated with diabetes, hyperlipoproteinaemia, ischaemic heart disease or left ventricular hypertrophy.

Adult↗
PubMed1998

[Celiprolol improves glucose metabolism in essential hypertension].

The authors investigated in 18 patients with essential hypertension the action of celiprolol (usually in combination with a diuretic) on the glucose and lipid metabolism in an open three-month trial. They evaluated the glucose, insulin and C-peptide concentration during an oral glucose tolerance test (oGTT) and the serum lipid concentration before and after treatment. It was revealed: 1. There are no significant changes in the glucose, insulin and C-peptide concentrations on fasting, 2. There is a significant reduction of the blood sugar level during the second hour of oGTT after treatment, 3. A significant reduction of glucose and C-peptide during the 1st and 2nd hour of oGTT after treatment in the sub-group with a poor glucose tolerance/insulin sensitivity, 4. There are no differences between the mentioned variables in hypertonic patients with a normal glucose metabolism, 5. There are no significant changes in values of total cholesterol, HDL-, LDL and VLDL-cholesterol and triacylglycerols. Celiprolol can exert in combination with diuretics also a favourable effect on the glucose tolerance/insulin sensitivity in patients with essential hypertension and metabolic syndrome.

Adrenergic beta-Antagonists↗
PubMed1997

Dietary protein restriction in combination with angiotensin converting enzyme inhibitor improves insulin resistance in patients with chronic renal disease.

Insulin resistance (IR) and secondary hyperinsulinaemia are major risk factors of atherosclerosis and probably also of related glomerulosclerosis. Angiotensin converting enzyme inhibitors (ACEI), while improving IR in essential hypertension, do not improve it in patients with chronic renal disease. Thus, the combination of ACEI and low protein diet was evaluated. Thirty-eight patients with various kidney diseases and mild to moderate impairment of kidney function were included in the study. Thirteen of them suffered from IR. Their dietary protein intake was decreased from > or = 1.0 g/kg/d to 0.6-0.7 g/kg/d. Moreover, they were treated by ACEI enalapril at dosages of 2-10 mg/d depending on the absence/presence and severity of hypertension. The patients were followed for 8 months. No clinically relevant kidney disease progression (KDP) was found. IR patients improved remarkably. IR was examined by the oral glucose tolerance test and glucose, insulin and C-peptide determinations. Their increased plasma triglyceride, VLDL concentrations and proteinuria decreased, HDL concentration increased. Acid-base balance and anaemia did not change. It is concluded that protein restriction in combination with ACEI treatment improve IR and the associated dyslipoproteinaemia and proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Modulators and mediators of kidney disease progression: new targets of prevention and treatment.

BACKGROUND: Hemodynamic (i.e. hyperfiltration) and metabolic (i.e. insulin resistance) changes are the targets of the present preventive measures of kidney disease progression. New horizons of molecular nephrology have extended the possibilities in the proliferation research. OBJECTIVES: To review evidence on the significance of proliferative processes and the possibilities of interfering with proliferation. METHODS: A review of experimental and clinical studies elucidating the significance of thromboxane, platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) for the proliferation and kidney disease progression. RESULTS: Proliferation participates in the development and progression of glomerulosclerosis and interstitial fibrosis. A number of growth factors and cytokines trigger and accelerate the progression of kidney diseases. A number of PDGF antagonists (i.e. simvastatin, heparin, trapidil, tertatol and low protein diet) attenuate the kidney disease progression. CONCLUSIONS: Even the present knowledge enables to improve further the kidney disease treatment schedules. (Tab. 3, Ref. 22.)

Disease Progression↗
PubMed1996

Inhibition of glucose uptake by 5-hydroxyindoleacetic acid in the isolated rat soleus muscle.

Accumulated end-products were identified to participate in the late development of glucose intolerance and insulin resistance (IR) in patients with chronic renal insufficiency. The possible pathophysiological role of accumulated 5-hydroxy-indoleacetic acid (5HIAA) in the genesis of IR was investigated employing an in vitro animal model. 5HIAA inhibited the basal glucose uptake in isolated rat soleus muscle with intact membrane with A50 = 1.25 mumol/l, and Emax = 88.6%. 5HIAA significantly inhibited the insulin, and tolbutamide stimulated glucose uptake. In Ca and Mg depletion 5HIAA showed a partially additive inhibitory effect, while nonadditive inhibitory activity was observed in the case of K+ excess. It is concluded that 5HIAA is a metabolically active end-product interfering with glucose uptake in muscle at an insulin postreceptor level, and its effect is related to Ca modulation in the insulin regulatory cascade.

Animals↗
PubMed1996

[Diuretics in the treatment of hypertension].

Diuretics are basic antihypertensives indicated in essential and secondary hypertension. Their pharmacodynamics is well known, their therapeutic spectrum is wide, their tolerance is excellent, the cost/benefit is lowest among all contemporary antihypertensives and after re-evaluation of the safety of small doses, diuretics have come to their revival.

Diuretics↗
PubMed1996

[Pharmacodynamics of angiotensin-converting enzyme inhibitors].

ACEI form a group of antihypertensives which inhibit the angiotensin II (A II) production and thus not only reduce the blood pressure but exert also a positive metabolic and antiproliferative effect (A II is a proliferative hormone). They are therefore indicated nowadays in the treatment of essential and secondary hypertension, left-ventricular hypertrophy, chronic heart failure, acute myocardial infarction, insulin resistance and other disorders. Despite intensive studies we still do not know many, in particular mediated effects, of ACEI but these drugs have become one of the key groups in therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[A protein-restricted diet combined with ACE inhibitors does not improve insulin sensitivity in renal hypertension].

Hypertension is one of the most important accelerating factors for progression of nephropathies. Its prevalence is about 35% in patients with nephropathies, even in minor or medium severe functional impairment. This is evidence that it is essential to select an optimal therapeutic regimen as soon as possible. A group of 38 patients (14 hypertensive patients) with a minor or medium severe functional impairment were included in a controlled trial. The patients were served a low-protein diet--0.6-0.7 g/kg/day and 2-10mg enalapril/day divided into two doses. The amount of enalapril depended on the blood pressure and enalapril was given also to normotensive patients. The investigation lasted 8 months. In the course of 8 months the authors did not reveal progression of the renal disease, as apparent from results of assessment of the creatinine level and clearance, assessment of uric acid and urea. The authors did not find deterioration of metabolic acidosis, nor of nephrogenic anaemia. Hypertensive patients had a tendency to deteriorating of insulin sensitivity while in normotensive patients a decline of triacylglycerols, VLDL and rise of HDL was recorded. The total cholesterol and LDL cholesterol level did not change. The authors conclude that the combination of a low-protein diet with ACEI in hypertensive and normotensive patients with mild to medium severe functional disorders inhibits the progression of nephropathies, but in hypertensive patients it does not prevent deterioration of insulin sensitivity.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Prevention and therapy of atherosclerosis].

Atherosclerosis is a complex progressive process with high morbidity and frequent dramatic mortality. The experience from the developed countries justifies the effectiveness of atherosclerosis prevention. The combination of nonpharmacologic, antiaggregatory and antihyperlipemic prevention reaches currently the effectiveness of surgical intervention, with the exception of sudden events. On the other hand the surgical intervention does not restore the process of atherosclerosis and requires the same secondary prevention if the long term prognosis is to be improved. The review presents the guidelines on nonpharmacologic, antihyperlipemic (up to the combination of statin with fibrates) and the antiaggregatory prevention with the initial dose of ASA being 200 mg and a long term dose being > or = 30 mg of ASA/d treatment. (Tab. 4, Fig. 3, Ref. 25.)

Arteriosclerosis↗
PubMed1996

[The role of thromboxane in the pathogenesis of nephropathies].

Impaired haemostasis, in particular aggregation in renal disease stimulated research of its prevention and treatment. The achieved results are a significant contribution not only to theoretical research but also to its application in nephrological practice. The submitted review presents specific features of nephrological patients ensuing from overproduction of prostaglandins, in particular thromboxane, by renal cells, focused on glomeruli where mesangial and epithelial cells participate in prostaglandin production and where thromboxane is associated with hyperfiltrations, proliferation, aggregation and other processes damaging glomeruli.

Animals↗
PubMed1996

A highly sensitive HPLC method for the simultaneous determination of acetylsalicylic, salicylic and salicyluric acids in biologic fluids: pharmacokinetic, metabolic and monitoring implications.

A number of methods have been developed for the determination of acetylsalicylic acid (ASA, aspirin). However, they are not sensitive enough for the simultaneous determination of ASA and its major metabolites salicylic (SA) and salicyluric (SUA) acids at the low dosage schedules (30-100 mg ASA/d). The HPLC method with UV detection described here fulfills these requirements. The calibration curves were linear at the range 0.18-10 mumol/l. Coefficients of variation were 3.9% for SUA, 7.89% for ASA and 5.88% for SA. The recovery of ASA, SA and SUA was between 90-105%. ASA administered in doses of 30-400 mg was rapidly absorbed from gastrointestinal tract and deacetylated, forming the dominant plasma metabolite SA. SA was eliminated to about 60% by conjugation with glycine and therefore SUA was a dominant metabolite in urine. ASA was never found in urine at the low-dose ASA treatment. For this reason, SUA, but not ASA, can be determined in urine and may be used for monitoring patient compliance.

Adult↗
PubMed1996

[The role of platelet-derived growth factor in progression of nephropathy].

The platelet growth factor (PDGF) is a potent proliferative factor which stimulates the proliferation of the kidneys in particular of mesangial cells and moreover by stimulating the production of the transforming growth factor beta (TGF-beta) it stimulates also proliferation of the mesangium, glomerulosclerosis and obviously also interstitial fibrosis. By these mechanisms it participates in the progression of experimental and human nephropathies. Production of PDGF can be suppressed by a low protein diet, heparin, acetylsalicylic acid, dipyridamol, and some new antagonists are being developed. These findings were assembled in experimental investigations and must be confirmed in clinical trials.

Animals↗
PubMed1995

The prevalence of insulin resistance in kidney disease patients before the development of renal failure.

Patients with advanced renal failure suffer from almost constant insulin resistance (IR) which is a major risk factor of atherosclerosis and very probably also of glomerulosclerosis. However, data on IR in kidney disease patients with mild-to-moderate kidney function decrease are lacking. A group of 52 patients with various kidney diseases and decreased kidney function of different degree but not with advanced renal failure was evaluated. Almost half of them suffered from IR though they did not differ from insulin-sensitive patients in age, sex, prevalence of various kidney diseases, hypertension, clearance of endogenous creatinine, serum creatinine, urea, uric acid, hippurate or pseudouridine concentrations. They did not differ in the prevalence and degree of metabolic acidosis or in the concentration of plasma and total and free magnesium in erythrocytes. They were just slightly more obese and their serum TG and VLDL concentrations were increased and HDL concentration decreased. It is concluded that IR and dyslipoproteinemia develop in the early stages of kidney diseases and could participate in kidney disease progression since the beginning of kidney disease. It is suggested that early treatment of these alterations could decrease the progression of kidney disease more effectively than their treatment in advanced stages.

Acidosis↗