Antioxidant vitamin levels do not exhibit negative correlation with the extent of acute myocardial infarction

Serum levels of vitamin E (VE), beta-carotene (BC) and vitamin C (VC) were determined in 50 patients with the first acute myocardial infarction (AMI) before starting thrombolytical treatment. VE and BC were determined by HPLC, VC spectrophotometrically. The reperfused patients were divided according to vitamin concentrations into four groups. The lowest quartile was compared with the rest of the studied population (VE: group with high (H)>15.6 microM>group with low (L), BC: H>0.07 microM>L, VC: H>25 microM>L) in the following parameters: extent of myocardial damage (area under the curves of troponin I, CK-MB during 48 h), arrhythmia and congestive heart failure occurrence, size of ejection fraction, positivity of ventricular late potentials. No significant differences between groups H and L for either VE, BC or VC were found (P 0.05). As no correlation between serum concentrations of vitamins E, C and beta-carotene and the extent and clinical course of AMI was found, the actual vitamin concentrations may be important for prevention of ischemic heart a disease, but they do not play a decisive role in the acute phase of myocardial infarction in humans.     

Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumour necrosis factor alpha, lipid peroxidation and NO* are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2*-, H2O2 and OH* causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO* react with O2*- and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO and LPO in patients with WMS. METHODS: A group of 10 WMS patients (four males, six females; age, 26.5+/-19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3+/-18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO* levels were evaluated by Griess reaction. RESULTS: Mean levels of TNF-alpha (8.3+/-0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3+/-0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4+/-0.8 and 1.8+/-0.6 micromol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9+/-626.6 versus 5261.6+/-523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4+/-49.3 versus 713.4+/-55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7+/-42.0 versus 756.5+/-47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3+/-15.0 versus 131.4+/-19.7 U/g protein, p=0.0113). In addition, serum NO (NO*-2 + NO*-3) levels were also significantly (p = 0.0002) increased in WMS patients (54.4+/-5.7 versus 26.9+/-6.7 micromol/l). RBC-CAT levels were similar between groups (125.6+/-21.3 versus 131.0+/-21.5 k/g Hb, p = 0.8798). CONCLUSIONS: The elevated LPO, TNF-alpha and NO* with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.     

Relation of leptin and tumor necrosis factor alpha to body weight changes in patients with pulmonary tuberculosis

In this study we investigated whether leptin and TNFalpha levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients. 30 patients (8 females and 22 males) with active pulmonary tuberculosis formed the patient group, and 25 sex- and age-matched healthy subjects (8 females and 17 males) served as the control group. Body weight, body mass index (BMI) and serum leptin and plasma TNFalpha levels are measured before and in the sixth month of therapy in all patients. Before the initiation of therapy, BMI of the patients was significantly lower than BMI of the controls (20.2 +/- 1.6 vs. 25.2 +/- 2.7 kg/m(2), respectively; p < 0.05). After treatment, BMI of the patients increased significantly to 21.4 +/- 1.9 kg/m(2) (p < 0.05), but was still lower than that of the controls (p < 0.05). Pretreatment serum leptin (4.5 +/- 0.9 vs. 2.1 +/- 0.2 ng/ml, respectively; p < 0.05) and plasma TNFalpha (27.9 +/- 3.4 vs. 23.9 +/- 3.0 pg/ml, respectively; p < 0.05) levels of the patients were significantly higher than those of the controls. After treatment, serum leptin levels increased to 6.7 +/- 2.2 ng/ml, but this rise was not statistically significant (p > 0.05). Treatment did not result in any significant change in TNFalpha levels, either. Delta leptin was highly related to Delta BMI in patients with tuberculosis (r = 0.68, p = 0.02). In the pretreatment period, there was a significant correlation between leptin and TNFalpha levels in the whole patient group (r = 0.78, p < 0.001), and in female (r = 0.74, p < 0.001) and male patients separately (r = 0.74, p = 0.035). In conclusion, leptin and TNFalpha may be responsible for the weight loss in pulmonary tuberculosis patients, but their levels do not change with improvement in body weight with antituberculotic treatment.     

Elevated homocysteine levels in patients with slow coronary flow: relationship with Helicobacter pylori infection

BACKGROUND AND OBJECTIVE: Elevation of plasma homocysteine (Hcy) level has been implicated in the pathogenesis of slow coronary flow (SCF) as it can severely disturb vascular endothelial function. Helicobacter pylori chronically infect the human stomach and causes malabsorption of vitamin B(12) and folate in food, leading ultimately to an increase in circulating Hcy levels. METHODS: Forty-three patients with angiographically proven SCF (group I) were enrolled in this study; 43 cases with normal coronary flow pattern (group II) served as controls. Fasting plasma levels of Hcy, vitamin B(12), and folate were measured in all subjects. Presence of H. pylori infection was defined as positive 14 C urea breath test. Coronary flow patterns for each major epicardial coronary artery were determined with the Thrombolysis in Myocardial Infarction (TIMI) frame count method. RESULTS: Mean TIMI frame count was 46.3 +/- 8.7 in group I and 24.3 +/- 2.9 in Group II (p = .0001). Vitamin B(12) levels were similar, whereas folate levels were dramatically reduced in group I compared to group II (13.2 +/- 4.3 vs. 17.1 +/- 5.2, p = .0001). Plasma Hcy levels were significantly higher in group I compared to group II (13.4 +/- 5.6 vs. 7.9 +/- 2.5, p = .0001) as was the prevalence of H. pylori infection (90.7% in group I vs. 58.1% in group II, p = .001). Hcy levels were elevated (11.7 +/- 5.3 vs. 7.5 +/- 2.7, p = .0001) and folate levels were reduced (13.9 +/- 4.7 vs. 18.6 +/- 4.9, p = .0001) in patients with H. pylori infection, while vitamin B(12) levels were similar in patients with and without H. pylori infection. Correlation analysis revealed a significant negative correlation between plasma folate and Hcy levels and also between folate levels and mean TIMI frame counts (r = -.33, p = .002 vs. r = -.33, p = .003). Moreover, there was a significant positive correlation between plasma Hcy levels and mean TIMI frame counts (r = .66, p = .0001). In addition, the folate level was the only significant determinant of the variance of Hcy in multiple regression analysis (r = -.21, p = .03). CONCLUSION: Our data showed that plasma folate levels were decreased and plasma Hcy levels were increased in patients with SCF compared to controls. Also, the prevalence of H. pylori infection was increased in patients with SCF. These findings suggest that elevated levels of plasma Hcy, possibly caused by H. pylori infection, and/or a possible disturbance in its metabolism may play a role in the pathogenesis of SCF.     

Selenium in the treatment of autoimmune thyroiditis

We recently conducted a prospective, placebo-controlled clinical study, where we could demonstrate, that a substitution of 200 microg sodium selenite for three months in patients with autoimmune thyroiditis reduced thyroid peroxidase antibody (TPO-Ab) concentrations significantly. Forty-seven patients from the initially 70 patients agreed to participate in a follow-up cross-over study for further six months. One group (n = 13), which initially received selenium continued to take 200 microg sodium selenite (Se-Se), one group stopped taking selenium (Se-0) ( n = 9), another group which received placebo started to take 200 microg selenium (n = 14) (Plac-Se) and the last group was without selenium substitution (Plac-0) (n = 11). TPO-Ab concentrations were measured at beginning and the end of the study. In the Se-Se group, the TPO-Ab concentrations further significantly p = 0.004) decreased from 625 +/- 470 U/ml to 354 +/- 321 U/ml, in the Se-0 group the TPO-Ab concentrations increased significantly p = 0.017) from 450 +/- 335 to 708 +/- 313 U/ml. In the placebo group, the TPO-Ab concentrations in those patients who were followed without selenium substitution were unchanged (1351 +/- 940 vs. 1724 +/- 1112 U/ml, p = 0.555). In contrast, the patients who received 200 microg sodium selenite after placebo, the TPO-Ab concentrations decreased significantly (p = 0.029) from 1182 +/- 723 to 643 +/- 477 U/ml.     

Role of ventilation strategy on perfluorochemical evaporation from the lungs.

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.     

Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy

BACKGROUND/AIM: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. METHODS: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. RESULTS: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 +/- 119.5 vs. 350.1 +/- 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 +/- 78.2 vs. 368.2 +/- 122.5 ng/ml, p = 0.03) and in the controls (430.3 +/- 78.2 vs. 350.1 +/- 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 +/- 129.2 vs. 427.2 +/- 113.7 ng/ml and 368.2 +/- 122.5 vs. 350.1 +/- 90.2 ng/ml, respectively). CONCLUSIONS: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.     

The effect of 3-weeks stationary cardiac rehabilitation on plasma lipids level in 444 patients with coronary heart disease

The aim of this study was to investigate the effect of 3-weeks stationary cardiac rehabilitation on plasma lipids level in patients with CHD. The study included 444 consecutive patients (364 male and 80 female, mean age 58 +/- 9 year) with CHD who underwent 3-weeks stationary cardiac rehabilitation. Patients were divided into groups depending on their baseline levels of cholesterol and medication therapy: patients with normal (< 5 mmol/L, group I, 129 patients) and elevate plasma level of Total cholesterol (> 5 mmol/L, group II, 315 patients) and subgroups Ia and IIa (with statin in therapy), Ib and IIb (without statin in therapy). After 3-weeks cardiac rehabilitation, the levels of Total cholesterol 5.75 +/- 1.34 vs. 5.17 +/- 1.08 mmol/l; p < 0.001, triglycerides 2.04 +/- 1.33 vs. 1.81 +/- 1.06 mmol/L; p = 0.004, LDL-cholesterol 3.77 +/- 1.14 vs. 3.21 +/- 0.96 mmol/L; p < 0.001 were significantly lower while the level of HDL-cholesterol 0.94 +/- 0.28 vs. 0.99 +/- 0.27 mmol/L; p = 0.008 were significantly higher in comparison with the baseline values. Furthermore, we found significant changes in lipid profile at the end of rehabilitation in each group of patients compared with the baseline values. There were no significant differences in plasma lipids level between group of patients with or without statin in therapy at the end of rehabilitation. The results of this study suggest that moderate regular physical activity and diet alone or in combination with hypolipidemic drugs already after 3 weeks have a favourable effect on plasma lipids level and should be propagate in the prevention of CHD.     

Ventilatory and gas exchange kinetics during exercise in chronic airways obstruction

The influence of chronic obstructive pulmonary disease (COPD) on exercise ventilatory and gas exchange kinetics was assessed in nine patients with stable airway obstruction (forced expired volume at 1 s = 1.1 +/- 0.33 liters) and compared with that in six normal men. Minute ventilation (VE), CO2 output (VCO2), and O2 uptake (VO2) were determined breath-by-breath at rest and after the onset of constant-load subanaerobic threshold exercise. The initial increase in VE, VCO2, and VO2 from rest (phase I), the subsequent slow exponential rise (phase II), and the steady-state (phase III) responses were analyzed. The COPD group had a significantly smaller phase I increase in VE (3.4 +/- 0.89 vs. 6.8 +/- 1.05 liters/min), VCO2 (0.10 +/- 0.03 vs. 0.22 +/- 0.03 liters/min), VO2 (0.10 +/- 0.03 vs. 0.24 +/- 0.04 liters/min), heart rate (HR) (6 +/- 0.9 vs. 16 +/- 1.4 beats/min), and O2 pulse (0.93 +/- 0.21 vs. 2.2 +/- 0.45 ml/beat) than the controls. Phase I increase in VE was significantly correlated with phase I increase in VO2 (r = 0.88) and HR (r = 0.78) in the COPD group. Most patients also had markedly slower phase II kinetics, i.e., longer time constants (tau) for VE (87 +/- 7 vs. 65 +/- 2 s), VCO2 (79 +/- 6 vs. 63 +/- 3 s), and VO2 (56 +/- 5 vs. 39 +/- 2 s) and longer half times for HR (68 +/- 9 vs. 32 +/- 2 s) and O2 pulse (42 +/- 3 vs. 31 +/- 2 s) compared with controls. However, tau VO2/tau VE and tau VCO2/tau VE were similar in both groups. The significant correlations of the phase I VE increase with HR and VO2 are consistent with the concept that the immediate exercise hyperpnea has a cardiodynamic basis. The slow ventilatory kinetics during phase II in the COPD group appeared to be more closely related to a slowed cardiovascular response rather than to any index of respiratory function. O2 breathing did not affect the phase I increase in VE but did slow phase II kinetics in most subjects. This confirms that the role attributed to the carotid bodies in ventilatory control during exercise in normal subjects also operates in patients with COPD.     

Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK

There is a close association between hyperglycemia and increased risk of mortality after acute myocardial infarction (AMI). However, whether acute hyperglycemia exacerbates myocardial ischemia/reperfusion (MI/R) injury remains unclear. We observed the effects of acute hyperglycemia on MI/R injury and on the cardioprotective effect of glucose-insulin-potassium (GIK). Male rats were subjected to 30 min of myocardial ischemia and 6 h of reperfusion. Rats were randomly received one of the following treatments (at 4 ml.kg(-1).h(-1) iv): Vehicle, GIK (GIK during reperfusion; glucose: 200g/l, insulin: 60 U/l, KCL: 60 mmol/l), HG (high glucose during ischemia; glucose:500 g/l), GIK + HG (HG during I and GIK during R) or GIK + wortmannin (GIK during R and wortmannin 15 min before R). Blood glucose, plasma insulin concentration and left ventricular pressure (LVP) were monitored throughout the experiments. Hyperglycemia during ischemia not only significantly increased myocardial apoptosis (23.6 +/- 1.7% vs. 18.8 +/- 1.4%, P < 0.05 vs. vehicle), increased infarct size (IS) (45.6 +/- 3.0% vs. 37.6 +/- 2.0%, P < 0.05 vs. vehicle), decreased Akt and GSK-3beta phosphorylations (0.5 +/- 0.2 and 0.6 +/- 0.1% fold of vehicle, respectively, P < 0.05 vs. vehicle) following MI/R, but almost completely blocked the cardioprotective effect afforded by GIK, as evidenced by significantly increased apoptotic index (19.1 +/- 2.0 vs. 10.3 +/- 1.2%, P < 0.01 vs. GIK), increased myocardial IS (39.2 +/- 2.8 vs. 27.2 +/- 2.1%, P < 0.01 vs. GIK), decreased Akt phosphorylation (1.1 +/- 0.1 vs. 1.7 +/- 0.2%, P < 0.01 vs. GIK) and GSK-3beta phosphorylation (1.4 +/- 0.2 vs. 2.3 +/- 0.2%, P < 0.05 vs. GIK). Hyperglycemia significantly exacerbates MI/R injury and blocks the cardioprotective effect afforded by GIK, which is, at least in part, due to hyperglycemia-induced decrease of myocardial Akt activation.     

Demonstration of a dawn phenomenon in normal adolescents

To ascertain whether the dawn phenomenon occurs in normal adolescents and, if so, to determine its mechanism, we measured nocturnal plasma glucose, insulin, glucagon, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH) levels between 01.00 and 08.00 h in 10 healthy adolescents. The prehepatic insulin secretion rate was calculated based on C peptide levels. The metabolic clearance rate of insulin (MCRI) was calculated as the ratio of mean insulin secretion rate to mean insulin concentration. There was no change in plasma glucose, insulin, and glucagon between 01.00-04.00 and 05.00-08.00 h (paired t test). The MCRI was higher at 05.00-08.00 h compared to 01.00-04.00 h (9.30 +/- 1.50 vs. 4.87 +/- 1.11 ml.kg-1.min-1; p = 0.008). The prehepatic insulin secretion increased at 05.00-08.00 h relative to 01.00-04.00 h (1.1 +/- 0.2 vs. 0.6 +/- 0.1 pmol.kg-1.min-1; p = 0.013). Similarly, cortisol and ACTH levels were higher at 05.00-08.00 versus 01.00-04.00 h (323 +/- 33 vs. 102 +/- 22 nmol/l, p less than 0.001; 3.6 +/- 0.5 vs. 1.8 +/- 0.4 pmol/l, p = 0.006, respectively). Growth hormone was higher at 01.00-04.00 versus 05.00-08.00 h (7.6 +/- 1.2 and 3.0 +/- 0.9 microgram/l; p = 0.019). ACTH correlated with MCRI (r = 0.66; p = 0.002) and prehepatic insulin secretion (r = 0.75; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

An evaluation of ventilation in dystrophic Syrian hamsters

Ventilatory responses of 10 control and 10 dystrophic male hamsters to air, hypercapnia, and hypoxia were evaluated at four ages (40, 70, 100, and 140 days). Tidal volume (VT), frequency (f), minute ventilation (VE) as well as inspiratory and expiratory time of awake animals were measured with a plethysmograph. There was a small increase of VT in both groups with age. Although there was no change of f in the control group with age, there was a progressive decrease in f (means +/- SE: 92 +/- 8, 97 +/- 9, 74.5 +/- 10, and 68 +/- 8 breaths/min) in the dystrophic group. Consequently VE on air decreased in the dystrophic group. Both groups showed similar responses to hypoxia (13 and 10% O2) and hypercapnia (3, 5, and 8% CO2) at 40 days. By 70 days the hypercapnic, but not hypoxic, response of the dystrophic animals was significantly decreased compared with that of the control group (at 8% CO2, VE = 47.4 +/- 4.1 vs. 75.7 +/- 7.6 ml/min, P less than 0.01). At both 100 and 140 days the response of the dystrophic group to CO2 was flat; i.e., the slope VE vs. fractional concentration of inspired CO2 was close to zero, and the hypoxic responses were greatly diminished. Because hamsters increase VE in response to CO2 primarily by increasing VT, the data suggest that dystrophic hamsters are unable to increase VT at a very early age, presumably due to muscle weakness. The normal response of hamsters to hypoxia, which is primarily to increase f, appears to be maintained for a longer time.     

Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, +/-dP/dt max, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 micromol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% +/- 6.4% vs. 35.0% +/- 6.1%, +dP/dt max recovered to 80.9% +/- 4.2% vs. 43.0% +/- 6.4%, and -dP/dt max recovered to 87.4% +/- 7.3% vs. 53.8% +/- 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 +/- 0.2 vs. 4.0 +/- 0.4, respectively; p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (K ATP) blocker (10 micromol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mumol/L NaHS. These findings provide the first evidence that H2S increases the open probability of K ATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.     

Plasma fibronectin levels in patients with glomerular proteinuria

Plasma fibronectin concentration was measured by means of rocket immunoelectrophoresis in 20 cases of glomerular proteinuria of various origins, and correlated with urinary protein loss, serum albumin, cholesterol and plasma alpha 1 antitrypsin and alpha 2 macroglobulin. Plasma fibronectin was significantly increased in the patient's group as compared to the controls (1.91 +/- 0.659 U/ml, 1.01 +/- 0.193 U/ml respectively, p less than 0.001) and correlated with cholesterolaemia (r = 0.662, p less than 0.001). Increased plasma fibronectin may be an additional risk factor for thrombotic tendency in NS.     

Changes in plasma angiotensin-converting enzyme activity and noradrenaline responses to long-term nitric oxide inhibition vary depending on their basal values in chickens

In this study, we investigated the effects of N(omega)-nitro-L-arginine (L-NNA) on arterial blood pressure (BP), plasma noradrenaline (NA) and adrenaline (A) levels and angiotensin-converting enzyme (ACE) activity. L-NNA was applied with tap water (1 mg/ml) from the 3rd to the 8th week of age (group L-NNA1). In Experiment 1, long-term L-NNA application increased BP compared to the control group (group C1) (L-NNA1 = 131.4 +/- 6.3, n = 6; C1 = 82.7 +/- 4.7 mm Hg, n = 7) but decreased plasma noradrenaline and adrenaline levels and ACE activity (NA levels: C1 = 15.5 +/- 0.8, n = 7; L-NNA1 = 8.6 +/- 0.5 ng/ml, n = 7; A levels: C1 = 15.5 +/- 0.8, n = 7; L-NNA1 = 6.0 +/- 0.5 ng/ml, n = 7; ACE activities: C1 = 87.3 +/- 3.1, n = 6; L-NNA1 = 46.2 +/- 1.9 U/l, n = 5). On the other hand, in Experiment 2 (carried out under the same conditions and in age-matched chickens), blood pressure, plasma noradrenaline levels and ACE activity were found to differ in the control group (C2) (BP = 141.4 +/- 15.5 mm Hg, n = 7; NA = 1.1 +/- 0.4 ng/ml, n = 7; ACE = 57.2 +/- 5.3 U/l, n = 7) as compared to C1, while plasma adrenaline levels were similar. In this series, long-term L-NNA application (group L-NNA2) did not change the BP, but surprisingly increased noradrenaline and ACE values (values of L-NNA2: BP = 165.7 +/- 15.6 mm Hg, n = 7; NA = 9.3 +/- 1.3 ng/ml, n = 8; ACE = 149.4 +/- 16 U/l, n = 8) while decreasing plasma adrenaline levels. L-arginine addition to L-NNA treatment completely reversed plasma noradrenaline and ACE activity values. These results indicate the modulatory activity of an L-arginine-NO pathway on adrenaline release as well as on the renin-angiotensin system in chickens.     

Leptin in type 2 diabetic or myotonic dystrophic women.

BACKGROUND: Insulin resistance is an important determinant of circulating leptin concentrations in humans, but its independent contribution on plasma leptin levels are controversial. In the present study, we characterized plasma leptin levels and their regulation in women with 2 different insulin resistance states: type 2 diabetes and myotonic dystrophy disease, and in controls. MATERIAL AND METHODS: We studied 3 groups of women: 21 type 2 diabetic patients, 20 myotonic dystrophic patients and a control group of 20 normoglycemic subjects, matched in age and body mass index. Body composition, fasting glucose and insulin, IGF-I, IGF-binding protein-3 and leptin were studied. Body composition was measured using a bioelectrical impedance analyser. Insulin sensitivity (in percentage) was modeled according to a computer-based homeostasis model assessment model. Data are expressed in mean +/- SEM. RESULTS: In both groups of patients, glucose concentrations were higher in type 2 diabetic patients than in myotonic dystrophic patients, and insulin concentrations and insulin sensitivity were similar in the 2 groups of patients (82.4 +/- 18.6% in type 2 diabetic patients vs. 69.7 +/- 9.7% in myotonic dystrophic patients, p = 0.2) and lower than in controls. Serum leptin and leptin/fat mass ratio were higher in myotonic dystrophic patients than in type 2 diabetic patients (30 +/- 4.9 ng/ml vs. 17.7 +/- 2.6 ng/ml, p = 0.03 and 2.32 +/- 0.69 ng/ml/kg vs. 1.07 +/- 0.2 ng/ml/kg, p = 0.02, respectively) or those found in controls. In type 2 diabetic patients, leptin concentrations were correlated with body mass index and body fat, and in myotonic dystrophic patients leptin concentrations were correlated with age, body mass index, fasting insulin and lower insulin sensitivity, whereas leptin concentrations were not correlated with body fat. CONCLUSIONS: These findings suggest that leptin concentrations and regulation in myotonic dystrophic patients are different from type 2 diabetes.     

Intracerebroventricular infusion of hypertonic NaCl increases urinary CGMP in healthy and cirrhotic rats

Implication of serum atrial natriuretic peptide (ANP) and endothelin-1 (ET1) in the central nervous system (CNS)-induced natriuresis and hypertension respectively, was investigated in healthy and cirrhotic rats. Both healthy and nonascitic CCl(4)-induced cirrhotic rats under pentobarbital anesthesia received either normotonic (140 mmol/L) or hypertonic (320 mmol/L) NaCl artificial cerebrospinal fluid into the CNS lateral ventricle at a rate of 8.3 microl/min for 120 min. A sham operated group, but not centrally infused, served as matched control. Hypertonic NaCl solution significantly increased mean arterial pressure (MAP) similarly in both healthy (n = 5) ((MAP: 16 mm Hg, 13%) and cirrhotic rats (n = 6) ((MAP: 20 mm Hg, 15%) (ANOVA, p <.001) although the latter showed a slower increment. Under hypertonic NaCl infusion, natriuresis was also significantly increased in a similar manner in both healthy (U (Na) V: baseline: 0.38 +/- 0.22 micromol/min x 100 g; experiment: 2.36 +/- 0.90 micromol/min x 100 g; mean +/- SD) and cirrhotic rats (0.69 +/- 0.48 vs. 3.16 +/- 0.87; p <.001). By contrast, central hypertonic NaCl solutions did not show a significant modification of serum ANP in neither healthy (62 +/- 18 fmol/ml vs. 51 +/- 17 fmol/ml) nor cirrhotic rats (126 +/- 61 vs. 115 +/- 30). Likewise, ET-1 was not significantly modified under central hypertonic NaCl infusion in neither healthy (352 +/- 46 pg/ml vs. 344 +/- 39 pg/ml) nor cirrhotic rats (287 +/- 58 vs. 277 +/- 61). Despite no modification in serum ANP, there was a significant increment in urinary excretion of cGMP under central hypertonic NaCl infusions in bo th healthy (6.8 +/- 4.1 pmol/min x 100 g vs. 13.0 +/- 6.5 pmol/min x 100 g; p <.05) and cirrhotic rats (8.6 +/- 1.7 vs. 11.1 +/- 1.3; p <.05). Our data indicate the preservation of the mechanisms of central natriuresis in a model of non-ascitic CCl(4 )-induced cirrhosis in rats. An increment in urinary cGMP could potentially be implicated in the natriuretic response obtained by intracerebroventricular hypertonic NaCl stimulus in both healthy and cirrhotic rats. The lack of modification of serum ANP and ET-1 does not appear to support a systemic implication of these peptides in the natriuretic and hypertensive responses respectively induced by this manoeuvre.