Insulin resistance and vitamin D deficiency in patients with chronic kidney disease stage 2-3.

Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range (>/=30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH)(2)D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease.

[Evaluation of the antihypertensive efficacy and tolerability of fixed very low-dose perindopril/indapamid combination in patients with mild to moderate hypertension. Results of a Czech and Slovak multicentric study]. / Fixní kombinace nízkých dávek perindoprilu a indapamidu v lécbe mírné az stredne tezké hypertenze. Výsledky ceské a slovenské multicentrické studie.

AIM OF THE STUDY: To evaluate the efficacy and tolerability of fixed, low-dose perindopril (2 mg) and indapamide (0.625 mg) combination in patients with mild to moderate hypertension. Secondary aim of the study was to assess the influence of this combination on basic echocardiographic parameters. GROUP OF PATIENTS AND METHODS: 112 patients (57% men, 43 women, mean age 52 +/- 13 years) with newly diagnosed mild to moderate hypertension, without left ventricular dysfunction. 55% of patients had at least one risk factor for coronary artery disease. The following parameters were studied: BMI, sitting and upright casual blood pressure, heart rate, main echocardiographic parameters and basal laboratory tests. RESULTS: Perindopril/indapamide treatment led already after 4 weeks to a significant blood (BP) reduction with most prominent BP differences at the end of the study (sitting BP 130 +/- 10/84 +/- 6 mm Hg vs. 153 +/- 10/97 +/- 5 mm Hg before the treatment). Normalisation of the BP was achieved in 76% of the hypertensives. Good response to treatment (decrease in systolic BP > or = 20 mm Hg and/or decrease in diastolic BP > or = 10 mm Hg) was reported in another 13% patients. Perindopril/indapamid treatment led to a significant decrease in interventricular thickness (10.7 vs. 10.2, P < 0.01) and to the improvement in the left ventricle diastolic function (E/A 1.06 vs. 1,14, P < 0.04). No significant changes in basal laboratory tests were reported during the study. Mild side effects were observed in a few patients. CONCLUSION: Fixed, low-dose perindopril/indapamide combination is a new and potent antihypertensive compound with very good tolerability without a negative influence on metabolic parameters. Perindopril/indapamide treatment resulted in the improvement of diastolic function and in the regression of the left ventricle mass.

[Treatment of postmenopausal osteoporosis with raloxifene]. / Liecba postenopauzálnej osteoporózy raloxifenom.

The authors present the results of the international multicentric clinical study (MORE--The Multiple Outcomes of Raloxifen Evaluation) of postmenopausal osteoporosis by raloxifen, participated by the authors. The evaluation of MORE indicated that raloxifen represents another further significant possibility of the treatment of postmenopausal osteoporosis by increasing bone density of vertebrae and femoral neck, and reducing the risk of vertebral fractures.

[The effect of monotherapy with ciprofibrate and in combination with acetylsalicylic acid on the spectrum of lipids, thromboxane and fibrinogen in patients with atherosclerosis and hyperlipoproteinemia]. / Vplyv ciprofibrátu v monoterapii a v kombinácii s acetylosalicylovou kyselinou na spektrum lipidov, tromboxán a fibrinogén u pacientov s manifestnou aterosklerózou a hyperlipoproteinémiou.

Ciprofibrate is one of the basic drugs used to lower risk values of lipid parameters and fibrinogen in atherosclerosis patients. Since antiaggregation treatment with acetylsalicylic acid is a complex part of obligatory therapy of these patients, the authors studied the influence of ciprofibrate on chosen lipid parameters, fibrinogen and thromboxane in monotherapy, and also in combination with acetylsalicylic acid (ASA) in patients with advanced atherosclerosis and hyperlipoproteinemia. In the first group of patients (A-C, n = 12) after one month of low-lipid diet acetylsalicylic acid in a dose of 100 mg was administered daily during a period of 2 months followed by addition of 100 mg of ciprofabrate daily during the next 2 months. In the second group of patients (C-A, n = 11) after one month of low-lipid diet the same drugs were administered but in opposite order. Ciprofibrate was most effective in lowering the levels of triacylglycerids (-41%) and VLDL-cholesterol (-34%), but effectively lowered also the values of total cholesterol and LDL-cholesterol. In both studied groups it led to mild increase of HDL-cholesterol levels. Simultaneous administration of ASA did not significantly influence its hypolipemic activity. Ciprofibrate also significantly lowered the level of fibrinogen (-17%). Increase of the total number of platelets by about 10% was not accompanied by changes of the values and production of thromboxane. Simultaneous administration of ASA caused more than 90% inhibition of thromboxane production in monotherapy and in combination with ciprofibrate. Ciprofibrate is an effective hypolipidemic agent, also lowering the level of fibrinogen. Its combination with ASA is adequate, safe and without negative interaction influencing treatment. (Tab. 6, Fig. 1, Ref. 16.)

[Hypertension in pregnancy]. / Hypertenzia v gravidite.

Hypertensive disorders are the most common medical complications of pregnancy and are an important cause of maternal and perinatal morbidity and mortality. The author presents a review on Hypertension in pregnancy from the point of view of classification, diagnosis and treatment. According to JNC 6 and WHO/ISH recommendations hypertensive disorders of pregnancy can be divided into three categories: 1. chronic hypertension, 2. transient hypertension, 3. preeclampsia; preeclampsia superimposed on chronic hypertension. (Tab. 3, Ref. 23.)

[Celiprolol improves glucose metabolism in essential hypertension]. / Celiprolol zlepsuje metabolizmus glukózy pri esenciálnej hypertenzii.

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.

[24-hour effectiveness and tolerance of perindopril (Prestarium), an ACE inhibitor, in the treatment of mild to moderate hypertension. A 1-year Czech and Slovak study]. / 24hodinová úcinnost a snásenlivost inhibitoru ACE perindoprilu (Prestarium) v lécbe mírné az stredne tezké hypertenze. Jednorocní ceská a slovenská studie.

This one-year open study conducted in two centres investigated the 24-hour effectiveness of the ACE inhibitor perindopril in the treatment of 31 patients with mild or moderate hypertension. The investigation evaluated the so-called "through" effect, i.e. the effect of the drug at the end of the 24-hour dosage period. Monotherapy with perindopril (4 mg or 8 mg administered once a day) led to normalization of the diastolic pressure to values lower than 90 mmHg in 48% of the patients, and a combination of perindopril with hydrochlorothiazide produced this effect in another 38% of patients. Treatment thus was able to normalize the diastolic blood pressure in 86% of patients. The mean decline of systolic pressure in a recumbent position was 17.6 mmHg and 13 mmHg for diastolic pressure assessed in a recumbent position 24 hours after ingestion of the drug. The reduction of blood pressure achieved after three months treatment persisted for the whole year. In 93% of the patients the diastolic pressure was at the end of one year lower than 95 mmHg. The drug was very well tolerated and in none of the patients the treatment had to be discontinued because of undesirable side-effects. Perindopril is a significant contribution to the spectrum of drugs used in the treatment of hypertension because of its 24-hour effectiveness and very good tolerance.

[Prevention of progression in nephropathies]. / Prevencia progresie nefropatií.

Intermittent dialysis is excessively expensive and pretentious psychologically and socially. As a result the research is concentrated on the prevention of kidney disease progression. Preventive measures: a) Protein restriction forms the basis of nonpharmacologic measures. b) Consequent antihypertensive therapy, with the aim to decrease blood pressure < 17.5/11.25 kPa (140/90 Torr), is the most effective prevention. The basic drugs are ACEI eventually in combination with Ca antagonists. They even reverse kidney disease progression in early phases. c) Antiaggregation therapy prevents the formation of fibrin deposits in glomeruli and the thrombogenesis. d) Insulin resistance correction prevents the development of glomerulosclerosis and atherosclerosis. e) Antihyperlipemic therapy is required only in a small number of patients. f) Correction of mineral balance prevents or corrects osteodystrophy. These measures could decrease kidney disease progression and the entrance of patients into intermittent dialysis by 10-20% and a further decrease to 50% is expected to be reached until the year 2000. (Fig. 3, Tab. 3, Ref. 43.).

Effects of angiotensin-converting enzyme inhibitors on glucose and lipid metabolism in essential hypertension.

Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma glucose and insulin levels, as well as total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before and after the 8- to 12-week treatment. Minor differences in the blood pressure (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors studied; only lisinopril improved glucose tolerance significantly; blood lipids were not changed by any drug. The entire patient population showed only a slight reduction in 1-h postload glucose after treatment. More obvious improvement in glucose tolerance was evident in hypertensive patients who were glucose intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup also showed a slight but not significant increase in HDL-cholesterol and a decrease in triglycerides levels. Only a slight change or no change in plasma glucose, insulin, and lipid values was noted in hypertensive patients with normal glucose tolerance (NGT) and insulin sensitivity. These favorable effects were expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide was added. The results indicate that a lack of stratification of hypertensive patients with regard to glucose tolerance or insulin sensitivity could be a confounding factor in evaluation of metabolic effects of ACE inhibitors.

[Diuretics in the treatment of hypertension]. / Diuretiká v liecbe hypertenzie.

Diuretics are one of the basic groups of antihypertensive drugs. They have also certain limitations and undesirable effects which are better defined than in other more recently developed antihypertensives. Undesirable effects can be prevented by early combination of saluretics with K+ sparing diuretics or other antihypertensive drugs and by prevention of metabolic disorders (in particular insulin resistance and dyslipoproteinaemia) and by prescription of small doses. Only prospective intervention studies will show whether the advantages of other groups of antihypertensives, as compared with diuretics, will influence the prognosis of patients with essential hypertension in a substantial way. Several studies along these lines are under way.

[Treatment of hypertension in kidney diseases]. / Lécba hypertenze u ledvinových chorob.

The authors review recent therapeutic procedures in arterial hypertension associated with renal disease. Treatment of hypertension is comprehensive, it comprises non-medicamentous procedures, pharmacotherapy and in some affections also interventional and surgical therapy. Effective reduction of the blood pressure to values < or = 140/90 mmHg unequivocally retards progression of renal disease, the development of nephrosclerosis and delays the development of renal insufficiency. In medicamentous treatment of nephrogenic hypertension a wide range of conventional antihypertensive drugs is used. Their selection and dosage must be adapted to the type of the basic renal disease and the reduction of renal functions. Recently the demand has been raised that the antihypertensive drugs used should possess in addition to the blood pressure lowering effect also an additive renoprotective effect ensuing above all from diminished intraglomerular hypertension and undesirable hyperfiltration, a changed permeability of capillary membranes due to reduction of microalbuminuria and proteinuria or restriction of proliferation procedures. These demands are met by the angiotensin I-converting enzyme (ACEI) inhibitor. If the correct dosage is used, ACEI are, due to their excellent antihypertensive action, absence of undesirable metabolic sequelae and significant renoprotective effect, drugs of the first line in nephrogenic hypertension. The authors use above all ACEI with a long-term effect, i.e. those without a SH group in the molecule. Very small doses (e.g. 2.5 mg Enalapril per day) reduce microalbuminuria and proteinuria and retard progression of nephrosclerosis also in nephropathies without systemic hypertension, e.g. in diabetic glomerulosclerosis. The renoprotective effect is manifested more markedly in initial stages of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[24-hour effect and tolerance for perindopril (Prestarium) in mild and moderate essential hypertension]. / 24hodinová úcinnost a tolerance perindoprilu (Prestarium) u mírné az stredne tezké esenciální hypertenze.

A multicentre investigation of antihypertensive treatment by perindopril was conducted in three centres of Czechoslovakia. The investigation comprised 51 patients with mild to moderate essential hypertension (diastolic pressure 95-115 mmHg) who were taking perindopril for a period of three months, the initial dose being 4 mg (1 tablet per day). If the blood pressure did not drop to normal levels (dBP < 90 mmHg), the dose was increased to 8 mg after 1 month and if after 2 months of treatment the blood pressure did not reach normal levels, a thiazide diuretic was added. The antihypertensive effectiveness was assessed 24 hours after ingestion of the drug. The blood pressure declined significantly already after the first month of monotherapy with perindopril. It declined then significantly up to the end of the 3rd month of treatment. The systolic blood pressure declined by 9.4 mmHg after the first month of monotherapy with perindopril and by 15.9 mmHg after 3 months of treatment. The diastolic blood pressure declined by 8.1 mmHg after one month of monotherapy and by 12.4 mmHg at the end of three-month treatment. The clinical and biological tolerance was excellent and only one patient discontinued treatment for reasons not related to the administered drug. Twenty-four hour monitoring of the blood pressure also proved the favourable effect of perindopril.

Metabolic effects of enalapril in the treatment of essential hypertension.

In an open two-month study with an initial placebo period, the effect of enalapril on glucose tolerance, insulin (IRI) sensitivity and lipid profile was evaluated in 20 patients with mild to moderate essential hypertension. The following results were obtained: 1. Enalapril produced a favourable effect of blood pressure both in monotherapy and if combined with a diuretic. 2. Therapy did not lead to significant differences in blood glucose, IRI or IRI/glucose increase at 1 or 2 hours of oral glucose tolerance test either in patients with monotherapy or combination therapy, and with normal or disturbed glucose tolerance, respectively. 3. Serum lipids (total and HDL-cholesterol and triglycerides) did not change significantly in any group of patients.

Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension.

Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism).

Platelet-activating effect of low-density lipoprotein and its reversal by isradipine.

The effect of the calcium antagonist isradipine on platelet aggregation (induced ex vivo by serotonin and low-density lipoprotein [LDL]) was studied in 17 nonsmoking patients with essential hypertension. Platelet aggregation was measured after a four-week placebo period, and after four and 12 weeks of treatment with isradipine. Both the serotonin-induced and the LDL plus serotonin-induced platelet aggregation were significantly decreased after four weeks of isradipine treatment compared with placebo. The amplifying effect of LDL on the serotonin-induced aggregation was significant both after placebo and after active treatment with isradipine. A further decrease in platelet aggregation induced by LDL plus serotonin was observed after 12 weeks of isradipine treatment so that no amplification of serotonin-induced aggregation by LDL could be detected. In conclusion, it appears that treatment with isradipine restores the impaired platelet response to serotonin and LDL in hypertensive patients. The inhibition of this response may represent a cellular mechanism of thrombovascular protection.

Serotonin and platelet activation during treatment with isradipine.

The effect of the calcium antagonist isradipine on serotonin metabolism and platelet aggregation was studied in 17 patients with essential hypertension. Platelet serotonin content, plasma serotonin, 5-hydroxyindoleacetic acid levels, and platelet aggregation [induced ex vivo by serotonin and low-density lipoprotein (LDL)] were measured after a 4-week placebo period and after 12 weeks of oral treatment with isradipine. Isradipine treatment significantly inhibited platelet aggregation induced by LDL and serotonin; the amplifying effect of LDL on serotonin-induced aggregation seen with placebo was not observed after 12 weeks of treatment with isradipine. Platelet serotonin content increased significantly during isradipine treatment; this increase was inversely related to the pretreatment content of serotonin in platelets. The results indicate that treatment with isradipine restores the impaired handling of platelet serotonin as well as the platelet response to serotonin and LDL in hypertensive patients. This effect of isradipine may be regarded as one of the cellular mechanisms of thrombovascular protection and may be of clinical significance in terms of platelet and vessel wall interaction.

A high-performance liquid chromatographic method for the determination of stobadin pharmacokinetics in serum.

A high-performance liquid chromatographic method was developed to determine stobadin pharmacokinetics in dog and man. The relative bioavailability of stobadin dipalmitate compared with dihydrochloride was 46.4 per cent in dog. In man peak serum concentrations ranged from 12 to 289 ng ml-1 after a single oral dose of stobadin dipalmitate (0.79 to 2.5 mgkg-1).

Acute effect of urapidil on peripheral serotonin metabolism.

In a cross-over study, the effect of 25 mg urapidil infusion (U, Ebrantil 25, Byk-Gulden, FRG) on serotonin (5HT) metabolism and platelet aggregation (PA) was compared with the effect of placebo (P) in 7 patients with essential hypertension. No changes in 5HT and 5-hydroxyindolacetic acid (5HIAA) plasma levels and platelet 5HT content were observed. PA induced ex vivo by ADP decreased significantly. 5HIAA urinary excretion and fractional excretion (FE) increased, while 5HT renal metabolism changed only moderately. No changes in adrenaline and noradrenaline excretion were observed. In in vitro studies, U in therapeutic levels decreased ADP-induced PA and completely inhibited 5HT-induced PA (platelets of healthy volunteers). It is suggested that U has a direct antiaggregatory effect through 5HT2 receptors of platelets.

Low-density lipoprotein amplifies the platelet response to serotonin in human plasma.

The effect of low-density lipoprotein, serotonin and low-density lipoprotein plus serotonin on platelet aggregation (measured ex vivo in plasma) was studied in 28 normotensive subjects (15 non-smokers, 13 smokers) and 15 previously untreated non-smoking patients with essential hypertension. Low-density lipoprotein alone had no platelet-activating effect. Serotonin-induced platelet aggregation was enhanced by low-density lipoprotein in both the normotensive and the hypertensive subjects. The platelet response to low-density lipoprotein plus serotonin was higher in the smokers than in the non-smokers; it was also higher in the hypertensive patients than in the normotensive controls. We conclude that low-density lipoprotein activates platelets in plasma via an interaction with a serotonergic mechanism. Low-density lipoprotein amplifies the serotonin-induced platelet aggregation (normally reversible), making it irreversible. A higher platelet response to low-density lipoprotein plus serotonin in patients with essential hypertension may be of pathophysiological relevance in respect to the thrombovascular lesions accompanying hypertension and/or atherosclerosis.

[Bopindolol does not affect normal glucose and lipid metabolism in hypertensive patients]. / Bopindolol neovplyvnuje normálny metabolizmus glukózy a lipidov u hypertonikov.

The authors administered to ten patients with mild to medium severe hypertension and with a normal glucose tolerance and serum lipid spectrum bopindolol in amounts of 0.5 to 2 mg/day in the course of 12 months. They revealed: a) bopindolol reduced effectively the blood pressure with a maximum decline already during the first month, b) It reduced significantly the heart rate, c) it did not cause deterioration of the glucose tolerance and did not interfere with the response of immunoreactive insulin (IRI) after a glucose load, d) it did not influence significantly the levels of lipoprotein cholesterol, total cholesterol, VLDL cholesterol, HDL cholesterol; within the reference range a slight increase of LDL cholesterol was recorded during the 12th month; e) it did not influence the concentration of triglycerides, apolipoprotein A1 and apolipoprotein B.