The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic acid-induced colitis in rats: an experimental study

The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrobenzene slfonic acid-induced colitis (TNBSIC) in rats. This study was carried out on 30 rats, divided in 3 groups: group 1: TNBSIC+ GH, group 2: TNBSIC, group 3: saline enema. Colitis was induced in male Sprague-Dawley rats (200 g-250 g) by intracolonic installation of 2, 4, 6-trinitrobenzene sulphonic acid in 50% ethanol. GH treatment has been started and continued throughout the study after inducing colitis. All rats were killed after 5 weeks and colonic segments were examined histopathologically. Microscopic and macroscopic damage scores were caulculated. Intestinal damage scores were found higher in Goups II when compared with treatment group (P < 0.05). There was no damage in group 3 as expected. Both macroscopic and microscopic scores were highest in group 2 (P < 0.05). The myloperoxidase activity was found lower comparing to group 2 (P < 0.05). In conclusion, growth hormone replacement had protective effects against colonic inflammation while reducing intestinal damage on TNB-induced colitis.     

Effect of tirofiban therapy on ST segment resolution and clinical outcomes in patients with ST segment elevated acute myocardial infarction undergoing primary angioplasty

BACKGROUND: In our study, we assessed the effect of glycoprotein (GP) IIb/IIIa receptor inhibition on microvascular flow after acute coronary occlusion using the early sum of ST segment resolution in electrocardiography. Platelets may play a major role in the dissociation of epicardial artery recanalization and tissue level reperfusion, referred to as the 'no-reflow phenomenon'. Therefore, GP IIb/IIIa receptor inhibition might improve myocardial reperfusion, distinct from its effects on epicardial patency. METHODS AND RESULTS: One hundred and fifteen patients (mean age 57.7 +/- 12.2 years, 96 males, 19 females) with < or = 12-hour acute ST segment elevation myocardial infarction who underwent successful primary percutaneous coronary intervention were retrospectively enrolled into the study. Patients were grouped according to whether they received tirofiban therapy or not. Clinical and electrocardiographic parameters were evaluated. The first sum of ST segment elevation amounts in millimeters was obtained immediately before angioplasty and the second 60 min after restoration of thrombolysis in myocardial infarction III flow. The difference between the two measurements was accepted as resolution of the sum of ST segment elevation and expressed as SigmaSTR. There were no significant differences between the groups regarding age, gender, cardiovascular risk factors, and laboratory parameters, duration from angina onset to the emergency unit, and from door to angioplasty. SigmaSTR was higher in patients who received tirofiban than in those who did not (7.2 +/- 2.8 and 4.2 +/- 2.6 mm, respectively; p < 0.001). There was a significant and positive correlation between GP IIb/IIIa inhibition and SigmaSTR (r = 0.336, p < 0.001), as well as between ejection fraction and SigmaSTR (r = 0.310, p < 0.001). GP IIb/IIIa inhibition was the only independent determinant of SigmaSTR in a multivariate linear regression model which contains 10 variables (p < 0.001). The incidence of in-hospital post-myocardial infarction refractory angina, reinfarction, and heart failure was significantly lower in the tirofiban group (p < 0.05, p < 0.05, and p < 0.05, respectively). Additionally, after 30 days, reinfarction and heart failure were lower in the tirofiban group (p < 0.05 and p < 0.05, respectively). CONCLUSIONS: It is well known that SigmaSTR determines microvascular perfusion. This study shows that GP IIb/IIIa inhibition with tirofiban is of value in preserving microvascular perfusion after restoring coronary thrombolysis in myocardial infarction III flow.     

A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue

The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.     

Left ventricular remodeling and aortic distensibility in elite power athletes

The aim of this study was to determine left ventricular (LV) morphology and aortic function in power athletes and to compare them with normal subjects. Thirty-two elite male wrestlers and 15 age-matched healthy male controls were included. All subjects underwent echocardiographic examination. Measurements included LV cavity dimension at systole and diastole, wall thickness, diastolic parameters, and aortic diameter, 3cm above aortic valve, at systole and diastole. Left ventricular mass and mass index were found to be higher in the athletes than in control subjects. The aortic distensibility index was found to be reduced in the athletes compared with controls (2.53 ± 0.91 vs 3.94 ± 1.77cm²dyne^–1 10^–6, P = 0.003), while the aortic stiffness index was significantly higher in the athletes than in controls (9.12 ± 3.23 vs 6.65 ± 2.35, P = 0.02). However, LV end-systolic wall stress was lower in the athletes than in controls. Furthermore, transmitral early (E) and late (A) peak velocity, peak velocity of the myocardial systolic wave (S _m), and early (E _m) and atrial (A _m) diastolic waves at the inferior wall were higher in the athletes than in controls. Reduced aortic distensibility in elite power athletes may be one of the cardiovascular adaptation factors which affect LV hypertrophy.     

Relationship between arterial stiffness and myocardial damage in patients with newly diagnosed essential hypertension

BackgroundArterial stiffness increases in hypertensive individuals. Arterial stiffness is associated with impairment of systolic and diastolic myocardial function in hypertension (HT). However, the relationship between arterial stiffness and serum heart-type fatty acid-binding protein (H-FABP) levels, a sensitive marker of myocardial damage, has not been previously examined in patients with HT. We investigate the relationship between serum H-FABP levels and arterial stiffness in patients with newly diagnosed HT.MethodsWe studied 46 (48.5 +/- 10.6, years) never-treated patients with HT and age-matched control group of 40 (47 +/- 8.6, years) normotensive individuals. H-FABP levels were determined in all subjects. We evaluated arterial stiffness and wave reflections of study population, using applanation tonometry (Sphygmocor). Carotid-femoral pulse wave velocity (PWV) was measured as indices of elastic-type, aortic stiffness. The heart rate-corrected augmentation index (AIx@75) was estimated as a marker of wave reflections.ResultsCarotid-femoral PWV (10.5 +/- 2.2 vs. 8.7 +/- 1.6, m/s, P = 0.0001) and AIx@75 (22.7 +/- 9.5 vs. 15 +/- 11, %, P = 0.001) were significantly higher in patients with HT than control group. H-FABP levels were increased in hypertensive patients compared with control group (21.1 +/- 14.8 vs. 12.9 +/- 8.5, ng/ml, P = 0.002). In multiple linear regression analysis, we found that the body mass index (beta = 0.42, P = 0.0001) and carotid-femoral PWV (beta = 0.23, P = 0.03) were significant determinants of H-FABP levels.ConclusionArterial stiffness is associated with serum H-FABP levels, a sensitive marker of myocardial damage, in patients with newly diagnosed HT.American Journal of Hypertension (2008). doi 10.1038/ajh.2008.235American Journal of Hypertension (2008); 21, 9, 989-993. doi 10.1038/ajh.2008.235.     

Two possible cases of Trichosporon infections in bone-marrow-transplanted children: the first case of T. japonicum isolated from clinical specimens

Trichosporon spp. are emerging as opportunistic agents that cause systemic diseases in immunocompromised hosts. Trichosporonosis carries a poor prognosis in neutropenic patients. Trichosporon japonicum was isolated from the air and named by Sugita et al. Here we present the first case of T. japonicum isolated from a clinical specimen. Two cases of acute myeloid leukemia who had Trichosporon isolates are discussed because of their rarity and growing importance. T. asahii was isolated from the throat, feces and urine of the first patient. T. japonicum was isolated from the sputum of the second patient. Both cases produced high MICs to itraconazole, and low MICs to fluconazole and voriconazole. In virulance factor investigations there was (++) biofilm formation in T. japonicum but not in T. asahii. Conventional mycological studies were not adequate for the identification of the isolate at the species level. In our second case as in the first one, the isolate was identified as T. asahii with 99.9% accuracy by API 20C AUX. Although two T. asahii isolates from the same patient yielded identical typing profiles by arbitrary primed-PCR, the isolates of the two different patients showed different arbitrary primed-PCR typing profiles. However, the genetic identification of the other patient's strain gave the result of T. japonicum.     

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.     

Effects of inspiratory muscle training in patients with heart failure

Aim

To investigate the effects of inspiratory muscle training (IMT) on functional capacity and balance, respiratory and peripheral muscle strength, pulmonary function, dyspnea, fatigue, depression, and quality of life in heart failure patients.

Methods

A prospective, randomized controlled, double-blinded study. Thirty patients with heart failure (NYHA II-III, LVEF<40%) were included. Sixteen patients received IMT at 40% of maximal inspiratory pressure (MIP), and 14 patients received sham therapy (15% of MIP) for 6 weeks. Functional capacity and balance, respiratory muscle strength, quadriceps femoris muscle strength, pulmonary function, dyspnea, fatigue, quality of life, and depression were evaluated.

Results

Functional capacity and balance, respiratory and peripheral muscle strength, dyspnea, depression were significantly improved in the treatment group compared with controls; quality of life and fatigue were similarly improved within groups (p < 0.05). Functional capacity (418.59 ± 123.32 to 478.56 ± 131.58 m, p < 0.001), respiratory (MIP = 62.00 ± 33.57 to 97.13 ± 32.63 cmH₂O, p < 0.001) and quadriceps femoris muscle strength (240.91 ± 106.08 to 301.82 ± 111.86 N, p < 0.001), FEV₁%, FVC% and PEF%, functional balance (52.73 ± 3.15 to 54.25 ± 2.34, p < 0.001), functional dyspnea (2.27 ± 0.88 to 1.07 ± 0.79, p < 0.001), depression (11.47 ± 7.50 to 3.20 ± 4.09, p < 0.001), quality of life, fatigue (42.73 ± 11.75 to 29.07 ± 13.96, p < 0.001) were significantly improved in the treatment group. Respiratory muscle strength (MIP = 78.64 ± 35.95 to 90.86 ± 30.23 cmH₂O, p = 0.001), FVC%, depression (14.36 ± 9.04 to 9.50 ± 10.42, p = 0.011), quality of life and fatigue (42.86 ± 12.67 to 32.93 ± 15.87, p = 0.008) were significantly improved in the control group.

Conclusion

The IMT improves functional capacity and balance, respiratory and peripheral muscle strength; decreases depression and dyspnea perception in patients with heart failure. IMT should be included effectively in pulmonary rehabilitation programs.     

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.     

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.