Differential expression of hypertension-associated microRNAs in the plasma of patients with white coat hypertension.

White coat hypertension (WCH) is a high cardiovascular risk condition, and a fundamental understanding of the cause and pathophysiology of the disorder is still lacking. Recent studies demonstrated that microRNAs (miRNAs) are involved in hypertension; however, the roles of miRNAs in WCH are not known. The expressions of selected 10 miRNAs were investigated independently in plasma samples from 30 hypertension (HT) patients, 30 WCH patients, and 30 normotensive (NT) subjects. MiR-21, miR-122, miR-637, and let-7e expression levels were significantly upregulated in the HT group compared with the NT groups (P = 0.017, P = 0.022, P = 0.048, and P = 0.013, respectively). MiR-122 and miR-637 expressions were also significantly upregulated in the WCH group compared with the NT group (P = 0.048 and P = 0.039, respectively). MiR-296-5p expression level was significantly downregulated in HT patients and upregulated in the WCH patients compared with the NT group (P = 0.049 and P = 0.039, respectively). Additionally, the ambulatory 24-hour and daytime systolic and diastolic blood pressures were negatively correlated with miR-296-5p. MiR-296 and miR-637 had area under the curve (AUC) values of 0.778 and 0.774, respectively, which demonstrates their sufficiency to distinguish WCH from NT individuals. MiR-296 and miR-637 had AUC values of 0.868 and 0.680, respectively, which shows their potential to distinguish WCH from HT individuals. We report for the first time a plasma miRNA profile for WCH patients and demonstrate a novel link between miRNA and WCH. These findings may reveal crucial insights into the development of WCH.

The effect of chronic long-term intermittent hypobaric hypoxia on bone mineral density in rats: role of nitric oxide.

Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.

Prevalence and characteristics of restless legs syndrome (RLS) in the elderly and the relation of serum ferritin levels with disease severity: hospital-based study from Istanbul, Turkey.

The RLS is an underdiagnosed condition, characterized by unpleasant sensations in the legs. Pathophysiological mechanisms may include iron deficiency as reflected by low serum ferritin levels and dopaminergic system dysfunction. The purpose of our study was to investigate the prevalence and characteristics of RLS in the elderly and the relation of serum ferritin levels with disease severity. Ambulatory 1012 (621 women, 391 men, mean age: 73.51 ± 7.12 years) consecutive patients above 65 years who admitted to our clinic for any reason were evaluated according to the International RLS Study Group (IRLSSG) criteria: 103 patients (74 women, 29 men, mean age: 72.43 ± 6.31) (10.18%) had RLS diagnosis. Only 9 of them had known RLS. The duration of symptoms was 4.80 ± 4.65 years and 27 patients (26.2%) had positive family history. The average of serum ferritin levels was 39.13 ± 23.74 ng/ml and 71 patients (68.9%) had serum ferritin levels ≤ 50 ng/ml. The disease severity was evaluated with IRLSSG rating scale. Patients were classified as severe-very severe group (n=49) and mild-moderate group (n=54). The ferritin levels of severe-very severe disease group were lower than those of mild-moderate disease group (26.01 ± 15.82 ng/ml versus 49.87 ± 23.24 ng/ml, p<0.001). Our data show that RLS is very common in the elderly and the disease is more severe in patients with lower ferritin levels.

Ezetimibe therapy and its influence on oxidative stress and fibrinolytic activity.

OBJECTIVE: The effect of ezetimibe on blood lipids, oxidative stress, and fibrinolytic activity in hyperlipidemic patients was investigated after three months of therapy. METHODS: Thirty hyperlipidemic patients were treated for twelve weeks with ezetimibe 10 mg/day. A healthy control group with matching age and gender was also included. Fasting blood glucose, lipid parameters, paraoxonase (PON1), protein carbonyl (PCO), oxidized LDL (oxLDL), 8-isoprostane (ISOPR), total antioxidant capacity (TAC) levels, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1), and PAI-1/t-PA levels were evaluated. RESULTS: Ezetimibe therapy for twelve weeks led to changes in lipid profile in accordance with the literature. Fibrinolytic activity parameters, PAI-1/tPA and tPA-1 decreased, whereas PAI-1 levels did not change significantly. Antioxidant parameters, serum PON1 activity, and TAC levels increased significantly compared with the basal values. Oxidant parameters, oxLDL, ISOPR, and PCO (which is an indicator of oxidative protein damage) decreased significantly after therapy. CONCLUSIONS: Ezetimibe therapy has beneficial effects on fibrinolytic activity and homeostasis between oxidant and antioxidant activity in hyperlipidemic patients This may be through lowering lipid levels or other mechanisms such as decreasing insulin resistance and the pleiotropic effects of the drug.

Nebivolol: more than a highly selective Beta blocker.

Although their specific mechanisms of action are incompletely understood, beta blockers are most likely lower blood pressure and provide target organ protection by several different mechanisms, including inhibition of renin-angiotensine system by decreasing renin release by the jugstaglomerular cells of the kidney, central inhibition of sympathetic nervous system outflow and slowing of heart rate with a decrease in cardiac output. These agents are widely recommended as important parts of antihypertensive regimens and as well as preferred therapies for patients at high risks of coronary heart disease, and including those with angina pectoris, myocardial infarction or heart failure. The third generation beta blockers are distinguished from the earlier class of beta blockers by their vasodilating activity. Labetalol, carvedilol and bucindolol appear to provide a vasodilation primarily through their blockade of alpha-1 rerceptors. Nebivolol is a lipophilic beta reseptor blocker of third generation with distinct beta-1 with selective and vasodilating properties. A number of experimental and human pharmological studies suggest that the vasodilatation is triggered via increasing vascular NO bioavailabilty which is a consequence of stimulation of NO release and antioxidant properties of this compound. The pharmocological profile is characterised by the significant antihypertensive effect as well as lowering of cardiac pre and after load. Nebivolol is well tolerated and does not appear to significantly influence glucose or plasma lipid metabolism. It is devoid of intrinsic sympathomimetic activity (ISA). This article will review patents, novel composition, pharmacology, haemodynamics, antihypertensive efficiency, metabolic effect and tolerability of nebivolol.

Course and prognosis of sarcoidosis in a referral setting in Turkey; analysis of 166 patients.

BACKGROUND: Clinical manifestations and prognosis of sarcoidosis are heterogenous and the prevalence varies depending on the country, area and race evaluated. Also the organs involved and courses of the disease differ greatly between countries, areas, races and individuals. AIMS: To investigate the sociodemographic characteristics, clinical presentation and symptoms and to determine the severity and prognosis of sarcoidosis in Turkey as a referral center. METHODS: Between January and July 2003 we retrospectively evaluated the outcome of the patients with sarcoidosis whose first clinical visits were between 1965 and 2003 in the multidisciplinary referral setting RS at Cerrahpasa Medical Faculty of the University of Istanbul. Data collected about each patient included sociodemographic characteristics, clinical presentation, symptoms, date of diagnosis, date and age of onset, method and stage of disease at the date of diagnosis and at the date of last evaluation; the mortality and survival rate were calculated. One hundred and sixty six consecutive patients whose first clinical visits were between 1965 and 2003 in the multidisciplinary RS at Cerrahpasa Medical Faculty were enrolled. We contacted every patient in our cohort by telephone calls or home visits. All those contacted were called back to outpatient clinic for a formal evaluation between June and September 2003. A formal physical examination and thorax radiography were performed in patients who came to the hospital. Their radiological stage, signs, symptoms and associated extrapulmonary manifestations were recorded. RESULTS: At the initial presentation, the mean age of diagnosis was 40.3 years. The 31-40 age group is the group with the highest number of patients. Coughing was the most frequent symptom and erythema nodosum was the most frequent sign in both sexes. Thirty eight percent of patients had extrathoracic involvement. The most frequent extrapulmonary site of involvement was skin. The mortality rate was 11.6% (10.8% in females and 13% in males). Comorbidity was 3% (5 females, 1 male). Females, youngs and patients without extrathoracic involvement had higher survival rates. CONCLUSION: Clinical characteristics, course and prognosis of sarcoidosis vary in different studies. The results may vary accordingly to ethnic, geographic, social and economic conditions.

Bone metabolism in ovariectomized rats with induced hyperthyroidism: the effect of estrogen replacement.

We aimed to investigate whether or not the estrogen is playing any role in the effect of thyroid hormones on bone metabolism. The rats were divided into five groups. In the first group L-thyroxine-induced hyperthyroid rats were ovariectomized (OVX) while the OVX rats were administered L-thyroxine in the second group. 17beta-Estradiol (E2) was replaced in OVX rats in Group III. L-thyroxine and E2 were simultaneously administered to OVX rats in Group IV. The fifth group received sham operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)alpha, calcium (Ca), phosphorous (P), parathyroid [corrected] hormone (PTH), alkaline phosphatase (t-ALP), bone-specific alkaline phosphatase (b-ALP) and E2. The levels of cytokines, t-ALP and b-ALP increased but PTH decreased, while there was no change in Ca and P levels in L-thyroxine-administrated rats. However, the levels of cytokines, Ca, P, PTH, t-ALP and b-ALP did not change in L-thyroxine-administered OVX rats. In OVX rats, the cytokines, t-ALP and b-ALP increased while Ca, P remained the same, but PTH decreased. L-thyroxine administration to OVX rats did not change the cytokines, Ca, P, PTH, t-ALP and b-ALP levels. The replacement of E2 in OVX rats decreased the cytokines, t-ALP and b-ALP values, increased PTH levels while there was no change in Ca and P. L-thyroxine and E2 administration to OVX rats increased the cytokines, t-ALP and b-ALP levels and decreased PTH, but Ca and P remained the same. In sham-operated rats, there was no change in all parameters compared to initial values. This study suggests that estrogen may play a role in the effects of thyroid hormones on bone metabolism.

White coat hypertension: cardiovascular outcome. Is it necessary to treat?

The clinical significance of white coat hypertension (WCH) that characterized by an elevated office but a normal ambulatory blood pressure remains uncertain. The prevalance and prognosis change according to the cut-off points described and it has been thought as a prehypertensive state. After the identification of WCH, target organ damage should be assessed and future cardiovascular mortality and morbidity should be evaluated in comparison with normotensives (NTives) and sustained hypertensives (SHTives). Due to the existance of target organ damage and high cardiovascular risk, treatment should be applied. The cross sectional studies showed that the risk of adverse events with WCH lies somewhere between the risk of NTives and SHTives patients whereas it appears to be more benign than sustained hypertension (SH) and has an equal prognosis with nornotension (NT) for any given length of follow-up in longitudinal studies. Endothelium has been found to take an important role in the pathogenesis of hypertension and atherosclerosis. It may be the cause of the high clinical blood pressure in WCH and/or may lead a poor cardiovascular prognosis such as atherosclerosis or even may progress to SH. Several studies found that endothelial dysfunction is a marker of development of atherosclerosis. The majority of studies evaluating endothelial function indicate that endothelial dysfunction is more prevalent in WCH than in NT, but it is either equal or worse in SH as compared to WCH. Nitric oxide (NO) is a free radical considered to be the major endothelium-derived relaxing facto r and the factors reducing the activity and/or expression of the endothelial nitric oxide synthase [e (NOS)] such as asymmetric dimethyl arginine (ADMA), the endogenously produced competitive inhibitor of e(NOS), and homocystein were investigated. Oxidized low-density lipoprotein (oxLDL) plays an important role in endothelial dysfunction...

Hyperhomocysteinemia: an additional risk factor in white coat hypertension.

The association between homocysteine and sustained hypertension (HT) has been studied. The aim of this study was to assess homocysteine levels in white coat hypertension (WCH) as an indicator of increased risk in the development of cardiovascular diseases. WCH was defined as clinical hypertension and a daytime ambulatory blood pressure of < 135/85 mmHg. Plasma levels of homocysteine were determined in patients with WCH, hypertension, and normotension (NT). The study group included 100 subjects, 33 with WCH (16 males, 17 females) aged 49.1 +/- 1.9; 35 sustained hypertensives (17 males,18 females) aged 48.5 +/- 1.7 and 32 normotensive control subjects (15 males, 17 females) aged 48.8 +/- 2.2. The subjects were matched for age, gender, and body mass index. Patients with a smoking habit, dyslipidemia, or diabetes mellitus were not included in the study. Homocysteine levels were analyzed by ELISA. Plasma homocysteine levels were significantly higher in the WCH group compared to the controls (12.32 +/- 1.07 versus 5.35 +/- 1.38 micromol/L; P < 0.001) and the WCH group had significantly lower homocysteine values than the hypertensives (19.03 +/- 0.76 micromol/L P < 0.001). Total cholesterol and tri-glycerides were not different among the groups. There were no statistically significant differences in urinary albumin excretion (UAE) or creatinine clearance between the three groups. Hypertensive retinopathy was observed in the WCH group, but was less severe and less frequent compared to HTs. LVMI was greater in the WCH group compared to the NTs, but significantly less than HTs. The data demonstrate that WCH is associated with high levels of homocysteine. The increase in homocysteine level in WCH is not as high as in SHT. Since an elevated plasma homocysteine level is a strong risk factor for coronary artery disease and there was target organ damage in our WCH group, we conclude that WCH should not be considered to be an innocent trait.

The role of nitric oxide on bone metabolism in ovariectomized rats following chronic ethanol intake.

This experimental study was designed to examine the effect of nitric oxide (NO) on bone metabolism in ovariectomized rats following chronic ethanol treatment. Chronic ethanol intake was produced by gradual substitution (within 3 weeks) of tap water in diet with 5,10,15 and finally 20% of ethanol. Thereafter, the rats were maintained under these conditions for a duration of 4 months. The rats were divided into two groups. The first group received sham operation (SHAM) and the rats in Group II were ovariectomized (OVX). Five weeks after the SHAM and ovariectomy, the rats were treated with ethanol for 4 months. After this period of ethanol administration, the NOS inhibitor N(W)-nitro-L-arginine methyl ester (L-NAME) was given for three weeks along with ethanol to the same rats. Serum interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, NO, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), 25 HydroxyvitaminD3 [25(OH)D3], alkaline phosphatase (ALP), bone alkaline phosphatase (b-ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), gamma-glutamyltransferase (GGT) levels were measured in different stages of the experiment. IL-1beta, IL-6, TNFalpha and NO levels increased after ethanol administration in SHAM and OVX rats. The decrease in serum Ca was significant while the changes in P, PTH and 25 (OH)D3 levels were not. ALP and b-ALP levels were significantly decreased; ALT, AST and GGT levels were significantly increased. In ovariectomized and SHAM rats, administration of L-NAME together with ethanol, produced a significant increase in IL-1beta, IL-6 and TNFalpha levels. In this group, Ca and P levels were significantly increased, PTH and 25 (OH)D3 levels were significantly decreased. Also, there was a significant decrease in ALT, AST, ALP, b-ALP, and GGT levels. NO increase due to alcohol intake may function as a protective mechanism preventing bone resorption in cases of estrogen insufficiency.

Potential effects of L-NAME on alcohol-induced oxidative stress.

AIM: Nitric oxide (NO) is a highly reactive oxidant synthesized from L-arginine by nitric oxide synthase (NOS). NO may cause injury through the generation of potent radicals. Nw- nitro-L-arginine methyl ester (L-NAME) is a non-selective inhibitor of NOS. We aimed to evaluate whether L-NAME treatment had protective effects against oxidative stress in rats intragastrically fed with ethanol during a 4 wk-period. METHODS: Thirty-six male Wistar rats were divided into 3 equal groups: group 1 (control group-isocaloric dextrose was given), group 2 (6 g/kg.d ethanol-induced group) and group 3 (both ethanol 6 g/kg.d and L-NAME 500 mg/L in drinking water-given group). Animals were sacrificed at the end of 4 wk-experimental period, and intracardiac blood and liver tissues were obtained. Biochemical measurements were performed both in plasma and in homogenized liver tissues. Alanine amino transferase (ALT), aspartate amino transferase (AST), malondialdehyde (MDA), NO, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels were measured by spectrophotometry. RESULTS: ALT and AST in group 2 (62 U/L and 128 U/L, respectively) were higher than those in group 1 (24 U/L and 38 U/L) and group 3 (37 U/L and 81 U/L) (P<0.001 for both). Plasma and tissue levels of MDA in group 2 (4.66 micromol/L and 0.55 nmol/mg protein) were higher than in group 1 (2.65 micromol/L and 0.34 nmol/mg protein) and group 3 (3.43 micromol/L and 0.36 nmol/mg protein) (P<0.001 for both). Plasma and liver tissue levels of NO in group 2 (54.67 micromol/L and 586.50 nmol/mg protein) were higher than in group 1 (34.67 micromol/L and 435.33 nmol/mg protein) and group 3 (27.50 micromol/L and 412.75 nmol/mg protein) (P<0.001 for both). Plasma and liver tissue SOD activities in group 2 (15.25 U/mL and 5.38 U/ mg protein, respectively) were lower than in group 1 (20.00 U/mL and 8.13 U/ mg protein) and group 3 (19.00 U/mL and 6.93 U/ mg protein) (P<0.001 for both). Plasma and liver tissue CAT activities in group 2 (145 U/mL and 37 U/ mg protein, respectively) were lower than in group 1 (176 U/mL and 73 U/mg protein) and group 3 (167 U/mL and 61 U/mg protein) (P<0.001 for both). Meanwhile, erythrocytes and liver tissue levels of GSH in group 2 (4.12 mg/g Hb and 5.38 nmol/mg protein, respectively) were lower than in group 1 (5.52 mg/g Hb and 4.49 nmol/mg protein) and group 3 (5.64 mg/g Hb and 4.18 nmol/mg protein) (P<0.001 for both). CONCLUSION: Our findings show that L-NAME may produce a restorative effect on ethanol-induced liver damage via decreasing oxidative stress and increasing antioxidant status.

The role of peripheral chemoreceptor activity on the respiratory responses to hypoxia and hypercapnia in anaesthetised rabbits with induced hypothyroidism.

The purpose of this study was to investigate the role of peripheral chemoreceptor activity on the hypoxic and hypercapnic ventilatory drives in rabbits with induced hypothyroidism. Experiments were carried out in control and hypothyroid rabbits. Hypothyroidism was induced by an administration of an iodide-blocker, methimazole in food (75 mg/100 g food) for ten weeks. At the end of the tenth week, triiodothyronine (T3) and thyroxine (T4) levels significantly decreased (P<0.001) while thyroid stimulating hormone (TSH) increased (P<0.001). Tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) and systemic arterial blood pressure (BP) were recorded during the breathing of the normoxic, hypoxic (8% O2-92% N2) and hypercapnic (6% CO2-Air) gas mixtures, in the anaesthetised rabbits of both groups. At the end of each experimental phase, PaO2, PaCO2, and pHa were measured. The same experimental procedure was repeated after peripheral chemoreceptor denervation in both groups. VT significantly decreased in some of the rabbits with hypothyroidism during the breathing of the hypoxic gas mixture (nonresponsive subgroup) (P<0.05). After chemodenervation, a decrease in VT was observed in this nonresponsive subgroup during normoxia (P<0.05). The percent decrease in VT in nonresponsive subgroup of hypothyroid rabbits after chemodenervation was lower than that of the chemodenervated control animals (P<0.01). When these rabbits with hypothyroidism were allowed to breath the hypercapnic gas mixtures, increases in VT and VE were not significant. In conclusion, although there is a decrease in peripheral chemoreceptor activity in hypothyroidism, it does not seem to be the only cause of decrease in ventilatory drive during hypoxia and hypercapnia.

Leukocytoclastic vasculitis and renal cell carcinoma.

The association of leukocytoclastic vasculitis and renal cell carcinoma has been rarely documented. We report a patient who presented with leukocytoclastic vasculitis involving the skin and was diagnosed later as renal cell carcinoma. After the nephron-sparing surgery, the vasculitic lesions disappeared. We also briefly review cases of vasculitis and renal neoplasms.

Effects of osteoporotic cytokines in ovary-intact and ovariectomised rats with induced hyperthyroidism; is skeletal responsiveness to thyroid hormone altered in estrogen deficiency?

This experimental study was designed to examine the effects of hyperthyroidism on osteoporotic cytokines such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in the physiological concentrations and in the deficiency of estrogen. We investigated the effects of thyroid hormones on cytokines and bone metabolism in L-thyroxine induced ovary-intact and ovariectomised rats, as levels of cytokines were increased in hyperthyroidism. The rats were divided into three groups. In the first group, L-thyroxine-induced hyperthyroid rats were ovariectomised (OVX), while the OVX rats were administered L-thyroxine in the second group. The third group received sham-operation. Blood samples taken from the tail vein of rats were analyzed for plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (b-ALP). L-thyroxine administration increased the cytokines, ALP and b-ALP and decreased PTH, while there was no change in Ca and P. However, the ovariectomy of these rats did not change the levels of cytokines, Ca, P, PTH, ALP, and b-ALP. In ovariectomised rats, the cytokines, ALP and b-ALP increased but not Ca and P conversely, PTH decreased. L-thyroxine administration to ovariectomised rats did not change the levels of cytokines, Ca, P, PTH, ALP and b-ALP. In sham-operated rats there was no change in any of the parameters compared with initial values. Thyroid hormones may not be effective on bone metabolism in estrogen deficiency.

Adult intussusception due to inverted Meckel's diverticulum: laparoscopic approach.

Nowadays, laparoscopy appears to be an attractive alternative to conventional surgery in the management of small bowel obstruction. Adult intussusception is an unusual cause of intestinal obstruction, and a wide range of pathologic conditions can result with intussusception. In this report, we present a very rare case of intussusception secondary to inverted Meckel's diverticulum in an adult who underwent laparoscopic surgery. The diagnostic modalities and surgical management of intussusception are discussed.

Erdheim-Chester disease: a rare cause of paraplegia.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. It is characterized by osteosclerosis of the metaphyseal regions of long bones and several extraskeletal manifestations. Clinically, it ranges from an asymptomatic focal process to systemic disease with life-threatening visceral involvement. Until now, only two cases of Erdheim-Chester disease with paraparesis have been reported. Herein we report the first case of Erdheim-Chester disease with the clinical manifestation of paraplegia. Our patient also had diabetes insipidus, pleural and pericardial effusion, retro-orbital and cavernous sinus masses, fibrotic changes in the retroperitoneal, perirenal, and periaortic areas, and epidural space-occupying lesions. We want to emphasize that ECD may be a very rare cause of paraplegia.

Osteoporotic cytokines and bone metabolism on rats with induced hyperthyroidism; changes as a result of reversal to euthyroidism.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Raised levels of serum osteoporotic cytokines, such as interleukin (IL) -1beta, IL-6 and tumor necrosis factor (TNF)-alpha have been demonstrated previously in hyperthyroidism. These elevations are controversial and it is difficult to differentiate the contribution of thyroid hormones to the elevation of cytokines from that of the autoimmune inflammation in Graves' disease (GD) and follicular cell damage in thyroiditis. Therefore, we investigated the effect of thyroid hormones on serum IL-1beta, IL-6, TNF-alpha levels and bone metabolism on L-thyroxine induced hyperthyroid rats and changes in cytokine levels and bone metabolism on the same rats after reversal to euthyroidism. Rats were treated with L-thyroxine for 5 weeks (0.4 mg/ 100 g food). Plasma T3, T4, TSH and serum IL-1beta, IL-6, TNFalpha, Calcium (Ca), phosphorous (P), parathyroid hormone (PTH), alkaline phosphatase (ALP), bone alkaline phosphatase (B-ALP) levels were measured and differential leucocyte counts were made initially, at the 5th week of the experiment (hyperthyroid state) and 5 weeks after quitting the administration of L-thyroxine (euthyroid state). Significant rises in serum IL-1beta, IL-6 and TNFalpha were noted in hyperthyroidism (P < 0.001). In euthyroid state, IL-15, IL-6 and TNFalpha decreased significantly, but IL-beta and TNFalpha were significantly higher than the baseline values (P < 0.05) while IL-6 levels turned back to the baseline values. Plasma T3 and T4 levels were significantly correlated with serum cytokines in hyperthyroid state while there was no correlation in euthyroid states. Ca and P levels did not differ significantly while PTH levels declined significantly in the hyperthyroid state (P < 0.05). After the reversal to the euthyroidism, there was no significant change in Ca, P and PTH levels. ALP and B-ALP increased significantly in hyperthyroidism (P < 0.001, P < 0.01) and they did not decrease in euthyroid state. The lymphocyte number and ratio in differentials increased significantly in the hyperthyroid state (P < 0.001). In euthyroidism they decreased significantly (P < 0.001) but it was significantly higher than the baseline value (P < 0.05). Our findings showed that the deleterious effect on bone metabolism in hyperthyroidism might be mediated by cytokines and the increased bone turnover in hyperthyroidism failed to decrease despite euthyroidism.

Effects of low and high doses of atorvastatin on arterial compliance.

At the beginning of atherosclerosis before evidence of morphological lesions or plaques, vascular distensibility or arterial compliance decreased gradually. This endothelial dysfunction is regarded as an early feature of atherosclerosis. In a randomized, double-blind study design, group 1 (12 patients; 7 males, 5 females) with serum LDL-C levels higher than 170 mg/dL and without any other risk factor for atherosclerosis received three months of 20 mg/day atorvastatin treatment while group 11 (8 males, 4 females) with the same characteristics received 80 mg/day. Baseline and posttreatment serum lipid fractions and arterial compliance were measured. Arterial compliance was measured noninvasively in the left common carotid artery with color Doppler ultrasound. Atorvastatin reduced total cholesterol (TC), LDL-C, and triglyceride levels by 32% (P < 0.001), 40.8% (P < 0.001), and 19% (P < 0.001), respectively, and increased HDL-C by 6.9%, (P = 0.002) in the first group. In the second group these reductions were 38.5% (P < 0.001), 46.2% (P < 0.001), and 26.78% (P < 0.001), respectively, and the increase in HDL was 7.8% (P = 0.03). It was observed that the decrease in serum TC, LDL-C and triglyceride levels were significantly higher in the second group than the first group. With atorvastatin, the distensibility coefficient (DC) and compliance coefficient (CC) increased from 18.7 +/- 3.4 to 21.3 +/- 2.9 10(-3) x kPa(-1) (P < 0.001) and from 0.69 +/- 0.05 to 0.77 +/- 0.03 mm2 x kPa(-1) (P < 0.001) in the first group while they changed from 18.3 +/- 3.6 to 21.9 +/- 3.0 10(-3) x kPa(-1) (P < 0.001) and from 0.70 +/- 0.04 to 0.81 +/- 0.01 mm2 x kPa(-1) (P < 0.001) respectively, in the second group. DC and CC increased in both groups, but the differences between the groups were not significant. High doses of atorvastatin reduce blood lipid levels more than conventional doses, however, the change in compliance is not dose-dependent. As endothelial dysfunction is regarded as an early feature of atherosclerosis, there would be no need to administer aggressive doses in a patient without any risk factors other than hyperlipidemia.