A new silent germline mutation of the TSH receptor: coexpression in a hyperthyroid family member with a second activating somatic mutation.

BACKGROUND: Up to date, three thyroid-stimulating hormone receptor (TSHR) germline variants have been reported for which no functional consequences have been detected by in vitro characterizations. However, familial nonautoimmune hyperthyroidism and hot nodules are clearly associated with constitutively activating TSHR germline mutations. We describe a family with a new TSHR germline mutation that is associated with euthyroidism in 13 family members and hyperthyroidism in 1 family member. METHODS: Mutation analysis of the TSHR gene was performed by denaturing gradient gel electrophoresis. TSHR constructs were characterized by determination of cell surface expression, 3'-5'-cyclic adenosine monophosphate (cAMP) accumulation, and constitutive cAMP activity. RESULTS: A novel TSHR germline mutation (N372T) was found in a man who presented with thyrotoxicosis. The mutation was also detected in 13 family members, all of whom were euthyroid. Interestingly, an additional constitutively active somatic mutation (S281N) was identified on the second parental TSHR allele of the hyperthyroid index patient. Linear regression analysis showed a lack of constitutive activity for N372T. Moreover, coexpression studies of N372T with S281N did not reveal any evidence for a functional influence of N372T on the constitutively active mutation (CAM). CONCLUSIONS: N372T is unlikely to cause altered thyroid function. This is consistent with the finding that only the index patient with the additional somatic mutation S281N was hyperthyroid.     

The effects of rosiglitazone and metformin on inflammation and endothelial dysfunction in patients with type 2 diabetes mellitus

Diabetic patients have a markedly increased risk of cardiovascular disease compared with non-diabetics. Two drug groups today target insulin resistance; biguanides and thiazolidinediones. In addition, these may have other effects on cardiovascular risk factors. The aim of this study was to evaluate the effects of metformin and rosiglitazone on non-traditional cardiovascular risk factors. Forty type 2 diabetic patients were randomized into metformin and rosiglitazone groups. After receiving the optimal doses, the patients were monitored for 12 weeks. Biochemical parameters, lipid parameters, CRP, insulin, c-peptide, and HbA1c levels were analyzed. VWF, PAI-1, ICAM-1, TNF-α, IL-6, E-selectin, and fibrinogen levels were measured in order to assess coagulation status and endothelial dysfunction. In the metformin group, body mass index, PPG, HbA1c, IL-6, ICAM-1, and TNF-α levels were significantly decreased after 12 weeks compared with the basal levels. IL-6 levels decreased from 75 pg/ml ± 20 to 42 pg/ml ± 9 (P 0.023) and TNF- α levels from 61 pg/ml ± 31 to 39 pg/ml ± 10 (P 0.018). In the rosiglitazone group, FPG, PPG, HbA1c, insulin, HOMA-IR, IL-6, and TNF-α levels decreased significantly after 12 weeks compared with the basal levels. IL-6 levels decreased from 78 pg/ml ± 21 to 41 pg/ml ± 9 (P 0.028) and TNF-α levels from 62 pg/ml ± 19 to 37 pg/ml ± 10 (P 0.012). At the end of the study, no significant differences were determined between groups. Insulin resistance and type 2 diabetes are strongly associated with low grade inflammation. Both metformin and rosiglitazone were effective in controlling inflammatory markers in addition to metabolic parameters.     

Protective effect of β-glucan on lung injury after cecal ligation and puncture in rats

Objective Understanding the biological mediators involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations targeting treatment based on these mediators. This study investigated whether macrophage activator -glucan has a protective effect on acute lung injury in an experimental model of sepsis.Design and setting Experimental study in an experimental research center.Materials 30 rats randomized into three groups (sham, sepsis, and -glucan).Interventions Cecal ligation and puncture were performed in the -glucan and sepsis groups. The -glucan group was given a single intraperitoneal dose of -glucan (4 mg/kg) following cecal ligation.Measurements and results Rats treated with -glucan had fewer circulating neutrophils, more blood monocytes, and higher serum interleukin 6 levels than septic animals. The percentages of neutrophils and lymphocytes from the bronchoalveolar lavage fluid and the myeloperoxidase activity measured in the lung tissue were lower in the -glucan group than in the sepsis group. Less alveolar hemorrhage and neutrophil infiltration were observed in lungs from animals in the -glucan group in the septic groups.Conclusions In this rat model of intra-abdominal sepsis -glucan treatment partially protected against secondary lung injury, decreased lung hemorrhages, and lung neutrophilia. These results suggest that -glucan protects against sepsis-associated lung damage.     

Right ventricular myocardial performance index and exercise capacity in athletes

Right ventricular function is important for exercise capacity in athletes. The aim of this study was to investigate the effects of habitual exercise training on right ventricular global function. Fifty-two male athletes (25 runners, 27 wrestlers) and 43 age-matched sedentary male subjects were studied. All subjects in the study underwent an echocardiography examination and cardiopulmonary exercise test. Maximal oxygen consumption, right ventricular cavity diameters, and diastolic parameters were higher in the athletes than in controls. However, the right ventricular myocardial performance index was lower in athletes compared with controls. Therefore, the right ventricular myocardial performance index showed a negative correlation with maximal oxygen consumption (r = −0.61; P < 0.001). The right ventricular myocardial performance index may reflect changes in right ventricular function and exercise capacity in athletes.     

The relation between joint erosion and generalized osteoporosis and disease activity in patients with rheumatoid arthritis

The aim of this study is to investigate the correlation between joint erosion and osteoporosis in patients with rheumatoid arthritis (RA). Fifty-one patients with RA were included for the study. Hand radiograms of all patients were evaluated by the Larsen modified Sharp and carpometacarpal ratio methods. Bone mineral density (BMD) measurements were performed at the femur, lumbar, and forearm regions. Disease activity was assessed clinically by the health assessment questionnaire (HAQ), visual analog scale, erythrocyte sedimentation rate, C-reactive protein (CRP), and the rheumatoid factor (RF). There was no statistically significant difference in terms of the BMD values at L1-4 between the patients with RA and the control group. The BMD measurements at the right forearm and the right hip were statistically significantly lower in the patient group. For radiological scoring, hand radiograms were evaluated by three different methods. There was a significant correlation between the duration of disease and the radiological evaluation methods. HAQ scores, Larsen and Sharp methods 1/3 distal and mid-distal (MID), and BMD measurements of the forearm were correlated. Moreover, 1/3 distal, MID, and ultra-distal BMD showed significant correlations with CRP levels. Radiogram continues to have an important role in determining and following-up the joint erosion seen in patients with RA. However, we believe that as establishing periarticular osteoporosis in the early term by performing BMD measurements on the forearm is correlated with disease activity, it may be useful in the early diagnosis of RA and its objective results will be efficient in predicting the progression of disease     

Oxidative protein damage in type I diabetic patients with and without complications

To examine the influence of oxidative stress on oxidative protein damage, we studied 47 Type I diabetic patients with and without complications. We determined plasma protein carbonyl, plasma protein thiol and nitrotyrosine levels as markers of oxidative protein damage, plasma lipid hydroperoxide levels as markers of oxidative stress, and plasma total thiol, plasma nonprotein thiol, erythrocyte glutathione, plasma ceruloplasmin, transferrin and total iron binding capacity as markers of free radical scavenging. There were no significant differences in nitrotyrosine, total plasma thiol, protein thiol, and erythrocyte glutathione levels between diabetic patients with complications and without complications. However, plasma protein carbonyl, lipid hydroperoxide, and nonprotein thiol levels were significantly increased in diabetic patients with complications compared with diabetic patients without complications. Although redox status of plasma is impaired in diabetic patients, we suppose these significantly different markers reflect enhanced oxidative protein damage in diabetic patients with complications.     

T he relationship between enthesitis indices and disease activity parameters in patients with ankylosing spondylitis

In this study, patients with ankylosing spondylitis (AS) were assessed both by patient and physician using two enthesitis indices and the relationship between these indices and disease activity parameters was investigated. The study involved 100 AS patients. The patients were evaluated with 10-cm visual analog scale (VAS) for spinal pain (VAS-S), peripheral joint pain (VAS-P), global assessment of patient, and global assessment of doctor. In the laboratory evaluations, the erythrocyte sedimentation rates (ESR) and serum C-reactive protein levels of the patients were determined. Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index, and Bath AS radiology index were calculated. The severity of enthesitis was evaluated according to Mander enthesitis index (MEI) and Maastricht ankylosing spondylitis enthesitis score applied by both the patient (MASES-P) him/herself and the physician (MASES-D). There was a correlation between BASDAI and BASFI as well as MEI, MASES-D, and MASES-P indices (r = 0.447, r = 0.342, r = 0.663, r = 0.530, r = 0.464, and r = 0.435, respectively). No correlation between the laboratory parameters and enthesitis indices were detected. In multiple linear regression analysis, BASFI, VAS-S, and female gender (41.3%) were the best predictors of MEI-D, whereas BASFI, VAS-S, female gender, and ESR (32.5%) were the best predictors for MASES-D and BASFI (18.9%) was the best predictor of MASES-P. The assessment of simple and easily applicable MASES score by a patient may be expected to help the physician in clinical practice. When the disease activity of the patients with AS are evaluated, both BASDAI, the clinical importance of which has been confirmed in numerous studies and which is recommended by ASAS, and BASFI, which is valued by patients, should be considered.     

Pyoderma gangrenosum and exacerbation of psoriasis resulting from pegylated interferon alpha and ribavirin treatment of chronic hepatitis C

Interferon therapy is the cornerstone of chronic hepatitis C treatment. Side effects of interferon include possible triggering or exacerbation of immune diseases in consequence of immunomodulatory effects. We describe the unique case, in which pyoderma gangrenosum and exacerbation of psoriasis were developed 8 weeks after pegylated interferon alpha 2a and ribavirin therapy in a 45-year-old woman. The therapy had to be stopped on account of pyoderma gangrenosum and exacerbation of psoriasis in spite of a biochemical response to the therapy for hepatitis C. The evolution was favorable after stopping treatment. Therefore, we propose this would suggest a possible autoimmune mechanism for the development of pyoderma gangrenosum and exacerbation of psoriasis with pegylated interferon therapy. A susceptible patient, who has an autoimmune disease before interferon therapy, had to be informed that interferons may induce de novo or exacerbate existing immune diseases by immunomodulatory actions. To the best of our knowledge, this is the first case report of pyoderma gangrenosum and psoriasis that resulted from pegylated interferon alpha 2a and ribavirin treatment of chronic hepatitis C.     

Metabolic syndrome and vaspin in patients with bipolar disorder

Metabolic disorders and abnormal levels of circulating adipokines have been reported in patients with bipolar disorder (BD). The aim of this study was to investigate the differences in the correlations of vaspin plasma levels and metabolic parameters between two groups: patients with BD and mentally healthy persons. We measured plasma levels of vaspin, metabolic parameters, and metabolic syndrome (MS) in 101 patients with BD and 90 healthy control (HC) subjects. Patients with BD were evaluated with the Young Mania Rating Scale (YMRS) to assess manic symptoms and the Hamilton Depression Scale (HDS) to assess depressive symptoms. The Global Assessment of Functioning (GAF) was used to evaluate the general functions of the patients. Body mass index (BMI), weight, waist circumference (WC), fasting glucose, and triglyceride levels of the study group were statistically higher than those of the healthy controls (p = 0.001, p < 0.001, p < 0.001, p = 0.027, and p = 0.001 respectively). Plasma levels of vaspin were 0.978 ng/ml in patients with BD and 0.292 in the HC group (p < 0.001). Our study revealed associations between metabolic parameters/metabolic syndrome and vaspin plasma concentrations in patients with BD. Vaspin can play a specific role in the pathogenesis of metabolic disorders in these subjects and can be a specific indicator substance in BD.