Impact of the therapy by renin-angiotensin system targeting antihypertensive agents perindopril versus telmisartan on prothrombotic state in essential hypertension.

The aim of the study was to investigate the effect of therapy by perindopril or telmisartan on endothelial/platelet function and on coagulation/fibrinolysis in 20 and 16 hypertensive patients, respectively. The measurements were carried out before and after 1 month of therapy. Both systolic blood pressure and diastolic blood pressure were reduced (P<0.001) or normalized due to each therapy. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as indicators of endothelial dysfunction, plasma beta-thromboglobulin (betaTG), platelet factor 4 (PF4), soluble P-selectin (sPsel) and soluble glycoprotein V (sGpV) as indicators of in vivo platelet activation, plasminogen activator inhibitor type 1 (PAI-1) antigen and tissue type plasminogen activator (tPA) antigen as markers of fibrinolytic activity, soluble endothelial protein C receptor (sEPCR) as a new marker of hypercoagulation and fibrinogen level as a known risk factor for vascular changes were investigated. A decrease of plasma vWF, sPsel, sGpV, PAI-1 and tPA antigen level (P<0.05, respectively) after 1 month of therapy by perindopril was observed. On the other hand, a decrease of plasma sEPCR and fibrinogen level (P<0.05, respectively) after 1 month of therapy by telmisartan was found. We failed to find changes of plasma TM, betaTG and PF4 due to any therapy investigated. The additional beneficial 'antithrombotic' effects of the renin-angiotensin system targeting agents (vasculoprotective, anti-platelet and profibrinolytic effects of perindopril and anticoagulant/rheological effects of telmisartan) may be important in terms of the favourable role of antihypertensive drugs in cardiovascular morbidity.

[Complex therapy of chronic hepatic encephalopathy supplemented with probiotic: comparison of two studies]. / Komplexná liecba chronickej hepatálnej encefalopatie doplnená probiotikom. Porovnanie dvoch stúdií.

BACKGROUND: Several reports about usefulness of probiotics, including Enterococcus faecium in the treatment of chronic hepatic encephalopathy in patients with liver cirrhosis have been recently published. The results obtained by the administration of Enterococcus faecium M-74 + selenium will be evaluated and compared with those published by Loguercio et al. for Enterococcus faecium SF 68. METHODS AND RESULTS: Fifteen patients with liver cirrhosis, portal hypertension and chronic hepatic encephalopathy were treated, beside the standard therapy, also with one capsule of probiotic "Enterococcus faecium M-74 + Selenium" per day in three four-week periods, separated by two fortnight pauses. During the treatment, every patient was examined 9-times. The severity of chronic hepatic encephalopathy was evaluated with the aid of the portal systemic encephalopathy index, calculated from 5 parameters (mental stage, asterixis, number connecting test, blood ammonia, EEG). The indexes of initial and final values were compared. The time course of blood ammonia levels and that of results from number connecting test in either study were mutually compared on the basis of interval estimates of quadratic regression function. Significant improvement of the portal systemic encephalopathy index after the treatment was found: it decreased in average by 70% (55 to 85%, interval 95% confidence interval). The mental stage improved and the asterixis disappeared. The blood ammonia levels as well as the results from the number-connecting test after 8-9 weeks significantly approached the normal pattern. EEG findings improved and they were often normalised. Our starting blood ammonia levels (increased by 31% above norm) and results from the connecting test (increased by 60%) were significantly lower accordingly the Loguercio et al. (increased by 243 and 238%, respectively). During the treatment, the values in our study decreased by 25% and 30%, in the compared study by 50% and 70%. CONCLUSIONS: Our results proved the hypothetical favourable effect of probioticum Enterococcus faecium M-74 + Selenium on chronic hepatic encephalopathy. Interestingly, a markedly higher relative therapeutic effect has been achieved in more serious disorder in comparison with the less severe disorders in the present study.

[Bone changes in patients after partial gastric resection]. / Kostné zmeny u pacientov po parciálnej resekcii zalúdka.

Metabolic diseases of the bones may be a serious complication of gastrectomy. The pathogenesis of osseous changes is multifactorial. The most important causes include a reduced intake of dairy products, their fastened passage through the stomach and reduced calcium and vitamin D absorption. The objective of the work was to assess bone changes in patients after partial gastrectomy. From a total number of 261 patients with a minimal 10-year history of gastrectomy, in the investigation 31 patients were included (18 men and 13 women) who met the required criteria. The results were compared with a control group of 18 men and 13 women of equal age. The authors compared also groups of patients with the condition after surgery type Billroth I (8 patients) and Billroth II (23 patients). In all investigated subjects the authors examined the bone density in the area of the lumbar spine and neck of the femur and parameters of osteoresorption and osteoformation. The authors found a significant reduction of bone density in the area of the spine and neck of the femur (p < 0.001) and a significantly higher level of total alkaline phosphatase and intact parathormone in serum and N-terminal telopeptide collagen type I in urine (p < 0.001), as compared with the control group. The other parameters did not differ in the investigated groups. The authors did not find a statistically significant difference in the investigated parameters between patients after resection Billroth I and Billroth II. The results confirm the need of early diagnosis and treatment of bone changes in patients after partial gastrectomy.

Effect of the new centrally acting antihypertensive agent rilmenidine on endothelial and platelet function in essential hypertension.

The aim of the study was to investigate the effect of therapy by rilmenidine on endothelial and platelet function in 23 patients with the early stages of untreated essential hypertension. The measurements were carried out before therapy, after 1 week of placebo administration, after 1 week, after 1 month and after 3 months of therapy. After 1 week of therapy both systolic (SBP) and diastolic blood pressure (DBP) were reduced (P < 0.001) all over the study period. Plasma thrombomodulin (TM) and von Willebrand factor (vWF) as indicators of endothelial dysfunction, and plasma beta-thromboglobulin (betaTG) as an indicator of in vivo platelet activation, were investigated. Fibrinogen as a risk factor for vascular changes was also assayed. Platelet aggregation without stimulation (spontaneous, SPA) and induced by adrenaline (APA) was measured. A decrease of plasma vWF level after 1 month (P < 0.05) and after 3 months (P < 0.05) of therapy was observed. We failed to find any changes of plasma TM and fibrinogen level. A reduction of platelet aggregation was evident after 1 week (SPA and APA, P < 0.05, respectively) but mainly after 1 month (SPA P < 0.01, APA P < 0.05) and after 3 months of therapy (SPA and APA, P < 0.01, respectively). It was accompanied by a decrease of plasma betaTG level after 3 months of therapy (P < 0.05). The vasculoprotective and antiplatelet effect of rilmenidine may be important in terms of the favourable role of antihypertensive drugs in cardiovascular morbidity.

Thrombomodulin as a marker of endothelium damage in some clinical conditions.

Background: Thrombomodulin (TM) is a membrane glycoprotein in the vascular endothelium. It may be cleaved from endothelial cells and released into the circulation. The plasma TM level depends on the integrity of the endothelium and the clearance of the molecule. The physiological role of soluble TM forms is still unclear. The clinical significance of elevated levels of TM in various pathologic conditions is not well established yet. To analyze variations of plasma TM level in different clinical situations, its concentrations in patients with three groups of diseases were measured and compared with those in healthy subjects. Methods: Plasma samples from 23 patients at risk for development of vascular complications [essential hypertension (EH), stages 1 and 2], 31 patients with inflammatory bowel diseases [Crohn's disease (IBD), mostly in the active stage], and 19 patients with malignant tumors [gastric carcinoma (NEO)], were analyzed for soluble TM with an enzyme immunoassay kit. Results: In the group of patients with the early stages of EH and with non-active IBD, no significant changes were found in comparison to the healthy subjects. In the patients with active IBD and mainly with NEO, soluble TM was significantly increased (P<0.05 and P<0.001, respectively). Conclusions: Our TM levels failed to demonstrate increased endothelial damage in the early stage of EH. This suggests that TM is released into the plasma only by true endothelial cell damage during the development of vascular complications. Probably a certain degree of endothelial injury is necessary for an increase in plasma. In the active stage of IBD and in NEO, soluble TM appears to be derived not only from injured endothelial cells, but may also be proteolytically cleaved from membrane TM by proteases. There may also be increased synthesis of TM in activated and/or transformed cells.

[Bone changes in ulcerative colitis]. / Kostné zmeny pri ulceratívnej kolitíde.

One of the complications of ulcerative colitis with frequent relapses is mineral deficiency (potassium, calcium, magnesium and phosphorus). The objective of the present work is to examine the bone density and laboratory parameters of bone metabolism in 25 patients with a medium severe and severe form of ulcerative colitis. In patients with ulcerative colitis a significantly reduced bone density was found in the era of neck of the femur (p < 0.05), a a non-significantly reduction of the bone density in the era of the lumbar vertebrae and an elevated level of osteocalcin (p < 0.05). These findings indicate a higher prevalence of bone changes in patients with ulcerative colitis. Early detection of bone changes makes adequate prevention and treatment of bone complications possible.

[Endogenous levels of somatostatin, C-peptide and insulin in acute pancreatitis]. / Endogénne hladiny somatostatínu, C-peptidu a inzulínu pri akútnej pankreatitíde.

The authors compared in seven patients with acute pancreatitis the levels of endogenous somatostatin, insulin and C-peptide to assess their mutual correlation and relation to the development of the disease and serum amalyse levels. The results were compared with values recorded in 11 healthy volunteers. The levels of endogenous somatostatin were in patients with acute pancreatitis significantly higher (p < 0.05) than in the control group. The authors found an inverse relationship between the somatostatin and amylase level (correlation coefficient 0.75). They did not observe a significant correlation between somatostatin and insulin levels nor between somatostatin and C-peptide levels. The elevated somatostatin level may be due to the counteregulatory reaction during secretion, stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).

[Diurnal changes in blood pressure, albuminuria and urinary excretion of retinol-binding protein in type I diabetics]. / Diurnálne zmeny krvného tlaku, albuminúria a exkrécia proteínu viazúceho retinol mocom u diabetikov I. typu.

We studied 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), 16-h daytime and 8-h nighttime urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20 type 1 diabetic patients (group 1) with normoalbuminuria (UAE < 20 micrograms/min) and 20 type 1 diabetic patients (group 2) with microalbuminuria and low proteinuria (UAE 20-500 micrograms/min). The groups were comparable in age, diabetes duration and actual glycaemic control. Daytime and nighttime SBP and DBP were higher in group 2 compared to group 1 (p < 0.01). Nighttime decrease in SBP and DBP correlated with nighttime decrease in UAE in group 2 (p < 0.05, p < 0.001). There was no correlation between BP and actual glycemic control in either group. Daytime UAE was found in group 2 by 20% higher than nighttime UAE. We found higher daytime and nighttime URBP in group 2 compared to group 1 (p < 0.05). We conclude, that microalbuminuric and low-proteinuric patients had elevated BP and nighttime decrease in BP correlated with nighttime decrease in UAE but not with actual glycemic control. Increased URBP in these patients suggests impaired proximal renal tubular function in early stages of diabetic nephropathy.

[Cortisol and diseases of the gastrointestinal tract]. / Kortizol a niektoré ochorenia gastrointestinálneho traktu.

Cortisol is the hormone reacting to endogenous and exogenous stress. An important role is ascribed to stress in the genesis and development of malignant and inflammatory diseases of the GIT. The authors examined in their investigation the 24-hour secretion of cortisol in patients with gastric affections, polyps of the large bowel and compared them mutually and with groups of patients with ulcerative colitis and healthy probands. In all investigated groups a 24-hour rhythm of cortisol secretion was confirmed. The only significant difference between the investigated groups was a lower 24-hour amplitude in patients with ulcerative colitis, as compared with healthy probands. The results do not suggest a significant role of cortisol in the development of premalignant diseases of the GIT.

[Serum gastrin and somatostatin in diseases of the stomach]. / Sérový gastrín a somatostatín u ochorení zalúdka.

Gastrin and somatostatin are enterohormones which influence several physiological processes in the gastrointestinal tract. Gastrin has a pro-malignant and pro-ulcerogenic effect, while somatostatin deficiency has a similar effect. The authors examined in their investigation the 24-hour secretion of both hormones in patients with gastric ulcer and atypical gastric conditions. They revealed a significant difference in the 24-hour somatostatin level which was higher in patients with atypical gastric conditions (p < 0.05). The finding may suggest a more intense reaction of somatostatin to malignant than to non-malignant disease. In the other compared parameters no statistically significant difference was revealed.

Circadian rhythmicity and cross correlation of plasma gastrin, cortisol and somatostatin levels in ulcerative colitis patients and healthy subjects.

Gastrin, somatostatin and cortisol circadian (24 hours) rhythmicity was confirmed in healthy subjects. Gastrin and cortisol circadian rhythmicity was studied and also established in patients with ulcerative colitis (UC). UC patients were found to have a lower 24-hour amplitude of plasma cortisol and a shorter acrophase of plasma gastrin. Gastrin correlated positively with somatostatin and negatively with cortisol.

Effect of the exercise test on albuminuria, blood pressure and blood glucose in type I (insulin-dependent) diabetic patients.

Twenty-nine male type I diabetic patients (age range 16-46 years) and thirteen healthy men (age range 18-43 years) were exercised on a cycling ergometer at 75 W and 100 W after having achieved a steady state of water diuresis. Diabetic patients were subdivided into Group A (n = 19, resting urinary albumin excretion rate - UAER less than or equal to 16 micrograms/min) and Group B (n = 10, 16 less than resting UAER less than 126 micrograms/min). The groups were comparable in weight, serum creatinine, duration of diabetes and glycosylated hemoglobin. Group B showed the highest elevation of UAER at the work load of 100 W, with no correlation between increase in UAER and increase in systolic blood pressure (SBP) at both work loads. The only correlation between these parameters was found in Group A at the work load of 100 W (p less than 0.05). No correlation was found between exercise UAER and actual blood glucose in either group. The difference in UAER between healthy subjects and Group B patients (p less than 0.001) remained on the same level during exercise as at rest, but the difference between Group A and Group B (p less than 0.001) decreased with increasing work load (p less than 0.05). The highest exercise-induced systolic and diastolic blood pressure (DBP) was found in Group B, although there was no difference between the diabetic groups in pre-exercise blood pressure and in mean SBP and DBP from previous outpatient check-ups. Blood glucose did not change significantly during exercise in either diabetic group. Working capacity of diabetic patients was lower than that of healthy subjects. The test revealed some diabetic patients with strong elevation of UAER and with abnormally raised systolic and diastolic BP during exercise. The value of the findings reported is to be clarified in a further longitudinal study.

The effect of small doses of guanfacine (Estulic Sandoz) on the lipid levels and catecholamine excretion in patients with essential hypertension.

During three-month therapy with small doses of guanfacine (Estulic Sandoz) that were sufficient to control blood pressure in patients with stage II essential hypertension and led to a decrease in excretion of noradrenaline and vanillylmandelic acid, the authors found a decrease in the level of blood cholesterol in patients with hyperlipidaemia. There was no adverse effect on the levels of triglycerides, beta, pre-beta and alpha lipoproteins. The authors conclude that Estulic therapy is indicated in patients who, in addition to essential hypertension, have hyperlipidaemia.