Prognostic usefulness of IL-6 and VEGF for the occurrence of changes in coronary arteries of patients with stable angina and implanted stents.

AIM: The aim of this study was to determine the prognostic significance of interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) in patients with chronic coronary artery disease treated who underwent percutaneous coronary intervention with stent implantation, for assessing the risk of restenosis and the occurrence of de novo lesions. PATIENTS AND METHODS: 498 patients with stable angina were examined during 18 months. 50 patients with significant (> 70%) stenosis of one coronary artery, eligible for the implantation of one stent, were enrolled to the study. Il-6 and VEGF level was measured using ELISA immunoassays during the initial coronary angiography with simultaneous angioplasty and stent implantation and 4 weeks after stent implantation. Coronary angiography was carried out 8-12 months after stent implantation. RESULTS: Statistically significant increase in IL-6 (from 4.02 ± 4.40 to 10.90 ± 8.23) and VEGF (from 310.13 ± 50.90 to 392.32 ± 106.84) level was observed 4 weeks after stent implantation in the group with restenosis. CONCLUSIONS: Increased levels of IL-6 and VEGF in the peripheral blood of patients with chronic stable angina pectoris, measured 4 weeks after coronary angioplasty with stent implantation, may indicate an increased risk of angiographic restenosis and de novo coronary artery lesions.

Supplementation with L-arginine favorably influences plasminogen activator inhibitor type 1 concentration in obese patients. A randomized, double blind trial.

BACKGROUND: Elevated plasminogen activator inhibitor type 1 (PAI 1) plays an important role in the pathogenesis of excess blood coagulability in obese patients. L-arginine supplementation has shown to be associated with enhanced cardiovascular and metabolic health. The aim of the study was to assess the effect of L-arginine supplementation on PAI 1 concentration and to evaluate the relation to changes in nitric oxide (NO) plasma level, insulin sensitivity (M value), and total antioxidant status (TAS) in obese patients. MATERIAL/SUBJECTS AND METHODS: A randomized, double-blind, placebo-controlled study was conducted from March 2010 to June 2011. Eightyeight obese patients were randomly assigned to receive either 9 g of L-arginine or placebo daily for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed, and PAI 1, NO, TAS levels were assessed. Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique. RESULTS: We found that 6-month L-arginine supplementation resulted in significant decrease of PAI 1. Significant increase of NO, TAS, and insulin sensitivity level were noticed. In a group of patients treated with L-arginine, negative correlation between a change of insulin sensitivity value and a change of PAI 1 concentration was found. CONCLUSIONS: The present findings demonstrate favorable influence of L-arginine supplementation on PAI 1 concentration in obese patients. Beneficial influence is related to insulin sensitivity improvement. The potential therapeutic role of L-arginine administration in patients with obesity needs further investigation.

Effect of 3-month L-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity.

BACKGROUND: The role of tumor necrosis factor alpha (TNF-alpha), one of the adipose tissue products, in the pathogenesis of insulin resistance is well-documented. Many recent studies have shown beneficial influence of L-arginine supplementation on cardiovascular system. However, molecular mechanisms of its positive actions are not fully elucidated. AIM: The aim of the study was to evaluate the influence of L-arginine supplementation on tumor necrosis factor alpha, insulin resistance and selected anthropometric and biochemical parameters in patients with visceral obesity. PATIENTS AND METHODS: 60 patients with visceral obesity were randomly assigned to either receive 9 g of L-arginine or placebo for 3 months. 20 healthy lean subjects were used as control. Selected anthropometrical measurements and blood biochemical analyses were performed at baseline and after 3-months. TNF-alpha and its soluble receptor 2 (sTNFR2) were assessed in both treated groups. Insulin resistance in the participants was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol. RESULTS: The concentration of insulin, TNF-a and sTNFR2 and HOMA-IR level in both obese groups significantly exceeded these observed in the control. Basal TNF-alpha and sTNFR2 concentrations were positively correlated with basal body mass index (BMI), waist circumference, percent of body fat and HOMA-IR. We found that 3-month L-arginine supplementation resulted in significant decrease of HOMA-IR and insulin concentration. Only insignificant tendency to decrease of TNF-alpha and sTNFR2 was observed. CONCLUSIONS: Our results confirm TNF-alpha role in the complex pathogenesis of insulin resistance in patients with visceral obesity. 3-months L-arginine supplementation in a dose of 9 g improves insulin sensitivity in patients with visceral obesity with no impact on tumor necrosis factor alpha concentration.

The effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities.

INTRODUCTION: Numerous studies indicate hyperglycemia and oxidative stress as factors responsible for endothelium dysfunction and the following development of angiopathy. Increased production of free radicals by vascular endothelium causes disturbance in production and/or decreases bioaccessibility of nitric oxide (NO). It has been suggested that L-arginine supplementation is a reasonable method to increase endothelium NO production and lower free radicals formation. There is a growing number of evidence showing that dietary supplementation of arginine reverses endothelial dysfunction associated with major cardiovascular risk factors and ameliorates many common cardiovascular disorders. OBJECTIVE: The aim of the study was to evaluate the potential influence of two-months oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status (TAS). MATERIALS AND METHODS: 38 patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II and coexisting type 2 diabetes and 12 healthy volunteers as control group were studied. All patients were treated with oral L-arginine (3 x 2 g/day) for two months. Fasting glucose, HbAlc, nitric oxide and total antioxidant status (TAS) were measured before and after the study. RESULTS: Fasting glucose and HbAlc did not change significantly after L-arginine treatment. Statistically significant increase in NO concentration and TAS level was found. CONCLUSIONS: Oral two-month supplementation with L-arginine (3 x 2 g/day) had no effect on fasting glucose and HbA1 level in diabetic patients with atherosclerotic peripheral arterial disease of lower extremities at Fontaine's stage II. The supplementation of L-arginine led to substantial increase in NO concentration and TAS level in these patients, suggesting its indirect antioxidative effect.

Supplementation with L-arginine does not influence arterial blood pressure in healthy people: a randomized, double blind, trial.

BACKGROUND AND OBJECTIVES: It cannot be excluded that supplementation with L-arginine, by improving function of endothelium and hypotensive effect, can be advantegeous in prevention of cardiovascular diseases in healthy people. However, reports about hypotensive effect of L-arginine in healthy people are unclear. Moreover, no research including ambulatory blood pressure measurement (ABPM) has been conducted so far. Therefore, the aim of our study was to show if 4-week supplementation of healthy people with L-arginine influences blood pressure measured with ABPM. MATERIALS AND METHODS: The study was carried out on 19 healthy people randomized to 6 g/24-hour, 12 g/24-hours of L-arginine or placebo. ABPM was carried out 4 times: before randomization, after 2 and 4 weeks of supplementation and 2 weeks after finishing supplementation. RESULTS: It was found that 4 weeks of supplementation of healthy people with L-arginine (6 or 12 g/24-hour) led to nonsignificant decrease of systolic and diastolic blood pressure; the decrease was greater during night. CONCLUSION: These findings showed that supplementation with L-arginine is not necessarily advantageous in healthy people.

Influence of L-arginine on the nitric oxide concentration and level of oxidative stress during ischemia-reperfusion injury in a rat model.

OBJECTIVE: This study aimed at evaluating whether supplementation of L-arginine in the course of ischemia and reperfusion syndrome after acute, experimental ischemia of the hind legs of the rat, could influence nitric oxide (NO) concentration and selected biochemical parameters concentration related to the oxidative stress. MATERIAL AND METHODS: The study included 64 male Wistar rats. The animals were divided into four groups: Group I = control, Group II = placebo, Group III = L-arginine (500 mg/kg body mass/day for 5 days, p.o.), Group IV = L-arginine and nonspecific nitric oxide synthase (NOS) inhibitor - N(G)-Nitro-L-arginine-methyl ester (L-NAME) (75 micromol/ rat/day for 5 days, p.o.). Each group was further divided into subgroups: 1 = animals not subjected to ischemia and reperfusion, 2 = animals underwent 4-hour ischemia and subsequent reperfusion. Animals from Subgroup 2 were anesthetized and submitted to acute tourniquet ischemia of the hind limb. Blood samples were collected from all anesthetized rats by puncturing the right ventricle to assess total antioxidant status, lipids' peroxide concentration and nitric oxide concentration before ischemia and at 4th hour of ischemia and at 30th, 60th or 120th minute of reperfusion. RESULTS: We found that administration of L-arginine to rats resulted in significant increase of NO, level of total antioxidant status (TAS), and decrease of lipid' peroxide concentration when compared to the control and placebo groups. All these laboratory changes were progressing along with lengthening of reperfusion time. Simultaneous application of L-NAME led to reversal of phenomena caused by L-arginine. CONCLUSIONS: The present results suggest that L-arginine may protect tissues and organs against ischemia-reperfusion injury. The potential therapeutic role of L-arginine administration in prevention and treatment of ischemia-reperfusion syndrome consequences needs further investigation in humans.

Plasma homocysteine is a determinant of tissue necrosis factor-alpha in hypertensive patients.

Chronic sub-clinical inflammation observed in hypertension plays a prominent role in the progression of atherosclerosis. Accumulating evidence suggests that homocysteine (Hcy) can cause inflammation. The aim of this study was to compare the predictive utility of Hcy and lipid measures as determinants of inflammation in hypertensive patients. We studied a group of 100 patients (45.0+/-12.2 years old) with essential hypertension and a control group of 40 healthy volunteers (44.0+/-8.7 years old). We found that plasma total Hcy (tHcy), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and C-reactive protein (CRP) were significantly higher in hypertensive patients compared with the control group. The subgroup of hypertensive patients with obesity had higher levels of TNF-alpha (p<0.001), IL-6 (p<0.01), and tHcy (p=0.063), compared with the subgroup of hypertensive patients without obesity. The subgroup of patients with a history of myocardial infarction or stroke had significantly higher levels of tHcy, TNF-alpha, IL-6, and CRP compared to patients with a negative history of vascular events. In the group of hypertensive patients, a strong positive correlation between tHcy and TNF-alpha was observed (r=0.48; p<0.001). In contrast, no correlation was observed between TNF-alpha and any of the lipid measures. In multivariate regression analysis tHcy, but not lipids, was an independent predictor of TNF-alpha. In conclusion, our findings show that plasma tHcy is a determinant of TNF-alpha in hypertension and that obesity or a history of vascular events aggravates inflammation in patients with hypertension. A positive correlation between Hcy and TNF-alpha suggests a mechanism underlying the pro-atherogenic properties of Hcy.

Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus.

OBJECTIVE: Leukocyte migration to the subendothelial space is considered crucial in the initiation of atherosclerosis. There is increasing evidence that overexpression of chemokine receptors contribute to this process. CCR5 is one of the receptors present on peripheral T lymphocytes, monocytes and macrophages. We decided to evaluate the expression of CCR5 on monocytes and macrophages in peripheral blood and selected inflammatory markers in patients with type 2 diabetes mellitus before and after the initiation of insulin therapy. MATERIAL AND METHODS: A total of 10 patients with newly diagnosed type 2 diabetes and 6 healthy control subjects were studied. Assessment of CCR5 expression on the surface of monocytes and macrophages in peripheral blood was performed using flow cytometry before the initiation of insulin therapy and after 5-week treatment. Serum concentrations of RANTES, TNF-alpha, IL-6 and hsCRP were assessed. RESULTS: When compared to control subjects, we observed higher densities of CCR5 on the surface of peripheral blood monocytes and macrophages and higher concentrations of RANTES, TNF-alpha, IL-6 and hsCRP before insulin therapy. After 5-week insulin therapy, there was a significant decrease in the expression of CCR5 on the surface of these cells and a significant fall in serum levels of RANTES, IL-6, TNF-alpha and hsCRP. CONCLUSIONS: Type 2 diabetes leads to an increase in the inflammatory process, and insulin therapy inhibits the early stages of this process.

[Digoxin as a cause of chromatopsia and depression in a patient with heart failure and hyperthyroidism]. / Digoksyna przyczyna objawów barwnego widzenia oraz depresji u chorego z niewydolnoscia serca i nadczynnoscia tarczycy.

67 year old patient with chronic heart failure and persistent atrial fibrillation had overdosed glycosides for several months. The symptoms of gastrointestinal system and nervous system appeared after long term therapy with toxic doses of glycosides. Originally depression was diagnosed based on the central nervous system disturbances. Even though overdose of glycosides was diagnosed the blood serum glycoside level was within the therapeutic limits. Based on the precise analysis of the data, it was concluded that the reason for normal blood serum glycoside level in this case was coexisting hyperthyreosis.

[The system of drug side effects monitoring in the cardiological wards of the University Hospital No. 1 in Poznan. 6-year observation]. / System wewnetrznego monitorowania dzialan niepozadanych leków w oddzialach kardiologicznych Panstwowego Szpitala Klinicznego nr 1 w Poznaniu. Obserwacje 6-letnie.

According to the guidelines from the Polish Ministry of Health, it is necessary to develop in Poland a system for supervising the safety of pharmacotherapy. Within the framework of this system a crucial role has been allocated to the Regional Centres for Monitoring of Side Effects of Drugs, affiliated to University Schools of Medicine. As there is no established routine for reporting side effects of drugs in Poland by medical professionals, the only way to obtain the data on drugs side effects was to prepare the system for internal monitoring of side effects of drugs in three clinical cardiology wards of the Institute of Cardiology at the University Hospital No. 1 in Poznan. During the 6-year follow up, 208 cases were registered and classified according to the type of the side effect (A, B, C, D) and according to the division into pharmacological groups. Most of the reported side effects belonged to the type A (67.8%), and, subsequently, type C (23.6%), type D (6.2%), type B (2.4%). The presented analysis allowed only for identifying the side effects. For the assessment of incidence and the range of occurrence of these side effects it is necessary to work out an effective, multicenter system for monitoring side effects of drugs in Poland.

[Evaluation of noradrenaline and atrial natriuretic hormone concentration in blood serum of pharmacologically untreated patients with chronic heart failure]. / Ocena stezenia noradrenaliny i przedsionkowego hormonu natriuretycznego w surowicy krwi u nieleczonych farmakologicznie chorych na przewlekla niewydolnosc serca.

Heart failure is a condition of increased neurohormonal stimulation the level of which is affected by both the rate of clinical advancement of the disease and by the manner of its treatment. Hence the work of determining the level of the neuroendocrine activation of the plasma within the range of the adrenergic system and of the atrial natriuretic hormone in not pharmacologically treated patients with mild and moderate heart failure. Consistently investigated were the concentrations of noradrenaline and of the atrial natriuretic hormone in 9 patients (mean age 66.3 years) and the results of the determinations were compared with data of the age approximate group of healthy persons. Then shown, too, could be the concentration increase of noradrenaline and of the atrial natriuretic hormone (both comparisons p < 0.001) over the values that are found in healthy people.

The level of plasma neuroendocrine activity and the concentration of digoxin in the serum of patients with mild chronic heart failure.

The concentrations of adrenaline, noradrenaline, dopamine, aldosterone, the atrial natriuretic hormone, and plasma renin activity were investigated in 50 patients with mild chronic heart failure. The patients received oral digoxin chronically in a daily dose of 0.125 mg. On the basis of the estimate of the dosing of digoxin these patients were divided into two groups: the first with therapeutic and the second with subtherapeutic concentrations of digoxin in serum. The therapeutic concentration of digoxin in serum was found in 23 patients (46%), while subtherapeutic levels were found in 27 patients (54%). The concentrations of noradrenaline, dopamine, the renin activity of plasma, aldosterone and the atrial natriuretic hormone in the blood serum in the group of patients in whom the presence of subtherapeutic concentrations of digoxin was found, did not differ essentially from the concentration that was observed in the group with therapeutic concentrations. Only the concentration of adrenaline was higher (p < 0.05) in the group of patients with therapeutic concentrations of digoxin. The above results reveal that the neuroendocrine activity of plasma (except for the concentration of adrenaline) is alike in both ranges of digoxin concentrations in serum.

The acetylation and oxidation phenotypes in insulin-dependent diabetes mellitus.

Polymorphism of the acetylation and oxidation phenotypes in patients with IDDM was evaluated. A greater statistically significant number of fast acetylators in IDDM was found.

[Assessment of gentamicin dosage in patients before planned surgical operation]. / Ocena dawkowania gentamycyny u chorych przed planowanym zabiegiem chirurgicznym.

The study included 18 patients, whom before planned surgical operation administered preventively gentamicin in the dose 3 x 80 mg/24 h i.m. After 24 hours the venous blood was taken before administration of the next dose of the drug and the concentration of gentamicin was determined by FPIA method. The subtherapeutic level of the drug was found in 15 patients (83%), therapeutic level - in 2 patients (11%) and toxic level in 1 patient (6%). It seems, that in patients after surgical operation, in whom after the prophylactic administration the treatment of gentamicin is continued, it is necessary the monitoring of the concentration of this antibiotic.

[Biochemical evaluation of digoxin dosage in patients with heart failure]. / Biochemiczna ocena dawkowania digoksyny u chorych z niewydolnoscia serca.

The investigations were carried out in 56 patients aged 54 to 84 years, treated with a supporting dosage 0.25 mg of digoxin because of chronical insufficiency of the heart, according to the NYHA classification II and III degree, in whom the functions of liver and kidneys have not been ascertained. A fourfold determination of digoxin concentrations in the blood was established in the time of distribution balance. From among the examined patients three groups were separated: receiving the drug chronically at 8.00 a.m. (group A), receiving it at 8.00 p.m. (group B) and group C, for which the sacral method was used. Depending on medical indications the patients received during the examination other drugs. In group C the therapy was limited to diuretic drugs. In no clinical symptoms of digitalism could be observed. Subtherapeutic levels of digoxin (< 0.8 ng/ml) were found in the three groups on an average in 50% of the patients. The high percentage of patients with nontherapeutic concentration in blood serum confirms once more, that treatment with digoxin without checking their concentration in the serum does not give the certainty of suitable dosage. The results of the studies show that the optimalization of digoxin therapy from the point of pharmacological view should be based on a penetrating estimation of the whole of the clinical image, the checking of the image with the help of the concentration determinations of the drug.