Aortic stiffness and left ventricular function in patients with differentiated thyroid cancer.

OBJECTIVE: The aim of this study was to investigate aortic stiffness and left ventricular (LV) systolic and diastolic function in patients with differentiated thyroid cancer (DTC) on thyroxine (L-T4) therapy and after L-T4 withdrawal to assess the cardiovascular impact of long-term subclinical hyperthyroidism and short-term overt hypothyroidism. METHODS: Twenty-four patients who had had total thyroidectomy and radioiodine ablation for differentiated thyroid cancer were studied on two occasions: on TSH suppressive L-T4 therapy (sTSH 0.24 ± 0.11 mU/L), and 4 weeks after L-T4 withdrawal (sTSH 89.82 ± 29.36 mU/L). Echocardiography was performed and thyroid function, serum thyroglobulin, lipid parameters, homocystine, C-reactive protein, fibrinogen and von Willebrand factor activity (vWF) were measured. Twenty-two healthy volunteers matched for age and sex served as euthyroid controls. RESULTS: Aortic stiffness was increased both in hypothyroidism (6.04 ± 2.88 cm(2)/dyn/10(3), p < 0.05) and subclinical hyperthyroidism (9.27 ± 4.81 cm(2)/dyn/10(3), p < 0.05) vs. controls (3.92 ± 1.84 cm(2)/dyn/10(3)). Subclinical hyperthyroidism had a more marked effect (p < 0.05). LV dimensions and ejection fractions were similar before and after L-T4 withdrawal. The E'/A' was higher in euthyroid controls (1.34 ± 1.02) as compared to both subclinical hyperthyroidism (1.0 ± 0.14, p < 0.05) and overt hypothyroidism (1.13 ± 0.98, p < 0.05). Change of aortic stiffness correlated with change of free-thyroxine (fT4), vWF and fibrinogen levels in a positive manner. CONCLUSION: Long-term thyrotropin-suppression therapy has continuous adverse effects on the arterial wall. The degree of TSH suppression in patients with DTC should be kept at the possible minimum, based on individually determined potential benefits and risks of treatment, especially in patients with cardiovascular co-morbidities.

Complement activation and its prognostic role in post-cardiac arrest patients.

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 °C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac arrest patients.

Evaluation of the thyroid function of healthy pregnant women by five different hormone assays.

A normal function of the thyroid gland during pregnancy is essential. Any change can affect both the pregnant woman and the fetus. Thyroid hormones play a crucial role in the brain development of the fetus, thus proper maternal free thyroid hormone levels are important especially during the first trimester. We compared the free thyroid hormone levels FT3 and FT4 in forty pregnant women with no thyroidal disease by five different assays available on the market. The blood samples were collected between the 8th and 22nd weeks of pregnancy. The correlation coefficient "r" between different assays was 0.908-0.975 for TSH, 0.676-0.892 for FT4 and 0.480-0.789 for FT3. These data show that the inter-assay results varied widely in the studied population. One reasonable explanation may be that during pregnancy the serum levels of the thyroid hormone binding proteins are altered and "free" hormone measurements by immunoassays are influenced by these alterations. Thus, the results may show higher or lower thyroid hormone values depending upon the assay used. Therefore, it is strongly suggested that every laboratory should establish its own pregnant reference ranges for the tests used for the evaluation of thyroid function, based on values of the population served.

Pressure dependence of Ce valence in CeRhIn5.

We have studied the Ce valence as a function of pressure in CeRhIn5 at 300 K and at 22 K using x-ray absorption spectroscopy in partial fluorescent yield mode. At room temperature, we found no detectable change in Ce valence greater than 0.01 up to a pressure of 5.5 GPa. At 22 K, the valence remains robust against pressure below 6 GPa, in contrast to the predicted valence crossover at P = 2.35 GPa. This work yields an upper limit for the change in Ce-valence and suggests that the critical valence fluctuation scenario, in its current form, is unlikely.

Role of histidyl residues in the binding of ligands to the porcine N-methyl-D-aspartate receptor.

Possible involvement of histidyl residues in the binding of ligands to ionotropic glutamate receptors and to modulatory sites on the N-methyl-D-aspartate (NMDA) receptor was assessed in porcine cortical synaptic plasma membranes after covalent modification with diethyl pyrocarbonate (DEPC). Binding of [3H]glutamate to the NMDA sites was enhanced but to the 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate receptors unaffected by 1 and 5 mM DEPC. Binding of 3-[(R)-carboxypiperazin-4-yl]-[1,2-(3)H]propyl-1-phosphonate ([3H]CPP) was reduced in a dose-dependent manner by DEPC and the activation of binding by 1-hydroxy-3-amino-2-pyrrolidone (HA-966) blocked by 10 mM DEPC. DEPC reduced the strychnine-insensitive binding of [3H]glycine and the glycine- and glutamate-activated binding of [3H]dizocilpine. Protection experiments indicated that histidyl residues are directly involved in the binding of glycine (but not HA-966) and allosterically modulate the binding of glutamate, CPP and dizocilpine. The results corroborate the existence of agonist- and antagonist-preferring sites or conformational states of the NMDA receptors.

Ligand binding to porcine ionotropic glutamate receptors with chemically modified arginyl residues.

The involvement of arginyl residues in the binding of ligands to different ionotropic glutamate receptors, to the modulatory glycine site in the N-methyl-D-aspartate (NMDA) receptor and to the NMDA-governed ionophore was assessed with porcine cortical synaptic membranes. The arginyl residues were covalently modified with phenylglyoxal. The binding and protection experiments showed that arginine residue(s) are directly involved in the binding of ligands to the agonist sites of all ionotropic glutamate receptors and to the modulatory glycine site but not to the ion channel in the NMDA receptor complex.

[Epidemiology of hypertension in adolescence and factors influencing blood pressure]. / A serdülókori hypertonia epidemiológiája és a vérnyomást befolyásoló tényezók.

The authors summarize the determining and influencing factors of adolescent hypertension. An overview of the definition and prevalence of hypertension in adolescence is given and the predictive role of the adolescent hypertension on the incidence of adult cardiovascular diseases is pointed out. According to the previous literature data, adult hypertension is more frequent in those people who have had hypertension in their adolescence. There are no widely used, population-based nomograms of adolescent hypertensives available. According to the opinion of the authors, a population-based hypertension screening program would help in delineating the factors influencing adolescent blood pressure, and the most frequent risk factors for hypertension in Hungary. With the follow-up and appropriate treatment of the hypertensives the reduction of target-organ damages may be possible.

Improved endothelial function and lipid profile compensate for impaired hemostatic and inflammatory status in iatrogenic chronic subclinical hyperthyroidism of thyroid cancer patients on L-t4 therapy.

OBJECTIVE: We aimed to compare the changes of endothelial function and haemostatic, inflammatory and metabolic parameters of short-term iatrogenic hypothyroidism to the characteristics of subclinical hyperthyroidism in patients with differentiated thyroid cancer. DESIGN: Twenty four women (mean age 42.4+/-8.1 years) had undergone total thyroidectomy and radioiodine ablation in treatment for differentiated thyroid cancer. We measured serum thyroglobulin, thyroid function, plasma levels of lipid parameters, homocystine, C-reactive protein, fibrinogen, von Willebrandt factor activity (vWF), nitric oxide, as well as flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation of the brachial artery during iatrogenic hypothyroidism (TSH 89.82+/-29.36 mU/L) and again in the same patients during subclinical hyperthyroidism secondary to exogenous levothyroxine administration (TSH 0.24+/-0.11 mU/L). RESULTS: In hypothyroidism, FMD was markedly lower than in subclinical hyperthyroidism (6.79+/-4.44 vs. 14.37+/-8.33%, p<0.005). Total cholesterol (7.34+/-1.23 vs. 4.75+/-1.14 mmol/L, p<0.001), LDL-cholesterol (4.55+/-1.10 vs. 2.70+/-0.89 mmol/L, p<0.005) and homocystine (12.95+/-4.49 vs. 9.62+/-2.29 micromol/L, p<0.005) were significantly higher in hypothyroidism. There was no difference in nitroglycerin-mediated vasodilatation, blood pressure, serum triglyceride and HDL-cholesterol levels according to thyroid function. Fibrinogen (3.23+/-0.50 vs. 4.01+/-0.84 g/L, p<0.005), vWF (90.09+/-25.92 vs.130.63+/-29.97%, p<0.001), C-reactive protein (4.39+/-5.16 vs. 5.55+/-5.15 mg/L, p<0.001) and plasma nitric oxide (24.56+/-6.71 vs. 32.34+/-7.0 micromol/L, <0.005) values were significantly lower in hypothyroidism. FMD correlated in a positive manner with fibrinogen, vWF and nitrogen oxide. CONCLUSIONS: Chronic subclinical hyperthyroidism was associated with improved endothelial function and lipid profile, while haemostatic and inflammatory parameters were impaired. The two opposite mechanisms may well compensate for each other at the level of the vessel wall.

Prevalence of cardiovascular risk factors of the smokers and non-smokers in the city of Debrecen, Hungary.

The aim of our study was to compare the major cardiovascular disease (CVD) risk factors of smokers and non-smokers. Risk screening of CVD was estimated by a questionnaire, via interview. Random samples of 20 000 inhabitants of Debrecen, Hungary, aged 30-65 y, took part in the study. 19 922 questionnaires were considered appropriate for further evaluation. 32.2% of the participants (n=6410) were smokers, whose data were compared to those of the 68.8% of non-smokers (n=13 512). There were more male smokers than female (39.3% vs 27.7%), (P<0.001). 36.5% of males and 58.9% of females had not previously smoked regularly (P<0.001). 24.2% of males and only 13.3% of females were able to stop smoking (P<0.001). 8.7% of the participants smoked more than 20 cigarettes per day (14.8% of males, 5.0% of females), (P<0.001). Smokers were younger, with a mean age of 43.4 y vs 47.1 y for non-smokers (P<0.01). The ex-smokers and non-smokers had a higher body mass index than light, moderate and heavy smokers (26. 75+/-4.1 kg/m2 and 26.09+/-4.3 kg/m2 vs 24.87+/-3.9 kg/m2 and 24. 89+/-4.2 kg/m2 and 25.32+/-4.3 kg/m2, respectively), (P<0.001). The results of the last measured blood pressures did not differ between the two groups. 94.8% of smokers and 93.6% of non-smokers did not perform any regular leisure time exercises (P<0.01). 39.8% of smokers regularly ate fatty food, in comparison to 28.0% of non-smokers (P<0.001). 30.6% of smokers vs 28.6% of non-smokers were factory workers while 69.4% of smokers vs 71.4% of non-smokers did sedentary jobs (P<0.001). 2.3% of smokers vs 0.9% of non-smokers admitted regular consumption of alcohol (P<0.001). Amongst the parents and brothers/sisters of smokers the prevalence of heart attack was higher 19.7% vs 18.7%, than for those of non-smokers (P<0. 05). We observed an accumulation of cardiovascular risk factors in the case of smokers, which indicates the higher susceptibility of smokers to CVD.

Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors.

A study was made of the effects of reduced (GSH) and oxidized (GSSG) glutathione on the Na(+)-independent and N-methyl-D-aspartate (NMDA) displaceable bindings of glutamate, on the binding of kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ligand of the brain NMDA receptor-ionophore complex: glycine, dizocilpine (MK-801) and (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP). GSH and GSSG strongly inhibited the binding of glutamate, CPP and AMPA, kainate and glycine binding being less affected. Both peptides enhanced the binding of dizocilpine in a time- and concentration-dependent manner. This activatory effect was not additive to that of saturating concentrations of glutamate or glutamate plus glycine. The activation of dizocilpine binding by GSH and GSSG was prevented by the competitive NMDA and glycine antagonists DL-2-amino-5-phosphonovalerate and 7-chlorokynurenate. GSH and GSSG may be endogenous ligands of AMPA and NMDA receptors, binding preferably to the glutamate recognition site via their gamma-glutamyl moieties. In addition to this, at millimolar concentrations they may regulate the redox state of the NMDA receptor-ionophore complex.

Interference of S-alkyl derivatives of glutathione with brain ionotropic glutamate receptors.

The effects of glutathione, glutathione sulfonate and S-alkyl derivatives of glutathione on the binding of glutamate and selective ligands of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA receptors were studied with mouse synaptic membranes. The effects of glutathione and its analogues on 45Ca2+ influx were also estimated in cultured rat cerebellar granule cells. Reduced and oxidized glutathione, glutathione sulfonate, S-methyl-, -ethyl-, -propyl-, -butyl- and -pentylglutathione inhibited the Na+-independent binding of L-[3H]glutamate. They strongly inhibited also the binding of (S)-2-amino-3-hydroxy-5-[3H]methyl-4-isoxazolepropionate [3H]AMPA (IC50 values: 0.8-15.9 microM). S-Alkylation of glutathione rendered the derivatives unable to inhibit [3H]kainate binding. The NMDA-sensitive binding of L-[3H]glutamate and the binding of 3-[(R)-2-carboxypiperazin-4-yl][1,2-(3)H]propyl-1-phosphonate ([3H]CPP, a competitive antagonist at NMDA sites) were inhibited by the peptides at micromolar concentrations. The strychnine-insensitive binding of the NMDA coagonist [3H]glycine was attenuated only by oxidized glutathione and glutathione sulfonate. All peptides slightly enhanced the use-dependent binding of [3H]dizocilpine (MK-801) to the NMDA-gated ionophores. This effect was additive with the effect of glycine but not with that of saturating concentrations of glutamate or glutamate plus glycine. The glutamate- and NMDA-evoked influx of 45Ca2+ into cerebellar granule cells was inhibited by the S-alkyl derivatives of glutathione. We conclude that besides glutathione the endogenous S-methylglutathione and glutathione sulfonate and the synthetic S-alkyl derivatives of glutathione act as ligands of the AMPA and NMDA receptors. In the NMDA receptor-ionophore these glutathione analogues bind preferably to the glutamate recognition site via their gamma-glutamyl moieties.

The epidemiology of hypertension and its associated risk factors in the city of Debrecen, Hungary.

The purpose of this work was to estimate the prevalence of hypertension and cardiovascular risk factors and its association with sociodemographic, behavioural and lifestyle characteristics among the adult population of the city of Debrecen, Hungary.A cross-sectional study was conducted in 1996. Amongst 21 800 inhabitants aged 30-65 y risk screening for cardiovascular disease (CVD) was estimated by a questionnaire that included sociodemographic, lifestyle characteristics, family history of CVD and results of self-reported data of body weight, height and blood pressure. Of the total of 19 961 surveyed sample, 37.02% were considered to be hypertensive, 53.73% were overweight, 32.18% were current smokers and 58.85% were physically inactive. Hypertensives were older than normotensives (50.81+/-9.01 vs 44.78+/-8.97 y, P<0.001). The prevalence of various risk factors amongst hypertensives as compared to normotensives were overweight (68.49 vs 45.06%, P<0.0001), current smoking (28.38 vs 34.41%, P<0.0001), physical inactivity (64.78 vs 55.36%, P<0.001), and high alcohol consumption (1.91 vs 1.06%, P<0.01). Of the hypertensives 37.11% were on drug therapy. Of those on therapy, only 17.03% had normal blood pressure. Being overweight and having low physical activity was positively associated with hypertension (OR=2.25, CI=2.11-2.40) and (OR=1.26, CI=1.15-1.38). Manual work, a family history of CVD, low education, and the male gender were also associated with hypertension and more CVD risk factors. These findings illustrate a very high prevalence of hypertension and CVD risk factors in Debrecen, indicating the importance of the need for more effective prevention programmes and control of hypertension in Hungary.