49 research outputs found
Antithyroid drugs in Graves’ hyperthyroidism: differences between “block and replace” and “titration” regimes in frequency of euthyroidism and Graves’ orbitopathy during treatment
No full textPurpose: Whereas antithyroid drugs (ATD) are the preferred treatment modality for Graves’ hyperthyroidism (GH), there is still controversy about the optimal regimen for delivering ATD. To evaluate whether ‘Block and Replace’ (B + R) and ‘Titration’ (T) regimes are equivalent in terms of frequency of euthyroidism and Graves’ Orbitopathy (GO) during ATD therapy. Methods: A prospective multicentre observational cohort study of 344 patients with GH but no GO at baseline. Patients were treated with ATD for 18 months according to B + R or T regimen in line with their institution’s policy. Results: Baseline characteristics were similar in both groups. In the treatment period between 6 and 18 months thyrotropin (TSH) slightly increased in both groups, but TSH was on average 0.59 mU/L (95% CI 0.27–0.85) lower in the B + R group at all time points (p = 0.026). Serum free thyroxine (FT4) remained stable during the same interval, with a tendency to higher values in the B + R group. The point-prevalence of euthyroidism (TSH and FT4 within their reference ranges) increased with longer duration of ATD in both groups; it was always higher in the T group than in the B + R group: 48 and 24%, respectively, at 6 months, 81 and 58% at 12 months, and 87 and 63% at 18 months (p < 0.002). There were no significant differences between the B + R and T regimens with respect to the fall in thyrotropin binding inhibiting immunoglobulins (TBII) or thyroid peroxidase antibodies (TPO-Ab). GO developed in 15.9% of all patients: 9.1 and 17.8% in B + R group and T group, respectively, (p = 0.096). GO was mild in 13% and moderate-to-severe in 2%. Conclusion: The prevalence of biochemical euthyroidism during treatment with antithyroid drugs is higher during T compared to B + R regimen. De novo development of GO did not differ significantly between the two regimens, although it tended to be higher in the T group. Whether one regimen is clinically more advantageous than the other remains unclear
Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes
No full textAIMS: Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low-density lipoprotein (LDL) size and all seven subclasses, as well as the 'atherogenic-lipoprotein phenotype'[ALP, e.g. concomitant presence of elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol and increased small, dense LDL]. METHODS: In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation. RESULTS: Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL-I (P = 0.0074) and increased LDL-IVA (P = 0.0146) and -IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL-I and positively with LDL-IVA and -IVB (all P < 0.05). ALP due to high HDL-cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107). CONCLUSIONS: Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end-points in these women remains to be determined by future prospective studies
Vedolizumab versus Adalimumab for moderate-to-severe ulcerative colitis
No full textBackgroundBiologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.MethodsIn a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of <= 2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.ResultsA total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P=0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years.ConclusionsIn this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.
MOESM1 of Dietary-phytochemical mediated reversion of cancer-specific splicing inhibits Warburg effect in head and neck cancer
No full textAdditional file 1: Fig. S1. PKM protein expression and DNA methylation in HNC patients(a-c) PKM2 expression in HNC tumor samples extracted from (a) Cromer Head-Neck, (b) Toruner Head-Neck and (c) Ye Head-Neck cancer analyzed by using Oncomine database. (d-e) shows the stage-wise expression of BORIS in (d) Ye Head-Neck and (e) Slebos Head-Neck cancer analyzed by using Oncomine database. (f) Western blot showing the protein level of PKM2, PKM1, and BORIS in paired normal and tumor tissue of HNC patients, GAPDH act as a loading control. (g) MeDIP in paired normal and tumor tissue of HNC patients samples and qRT-PCR of PKM exon 9 and exon 11 region, relative to input and control IgG (n = 4). (h-i) ChIP in paired normal and tumor tissue of HNC patients, (i) using RNA Pol II and (h) BORIS antibody and qRT-PCR with indicated exonic primers relative to input and control IgG(n = 3). Graphs show mean values ± SD. P-value calculated using two-tailed Student’s t-test, * P < 0.05, ** P < 0.01, *** P < 0.001, ns = non-significant
Anti-TNF treatments in Crohn's disease and improvement in work productivity and quality of life: an observational study from Turkey
No full textVisfatin reduces gap junction mediated cell-to-cell communication in proximal tubule-derived epithelial cells
No full textBackground/Aims: In the current study we examined if the adipocytokine, visfatin, alters connexinmediated
intercellular communication in proximal tubule-derived epithelial cells.
Methods: The effects of visfatin (10-200ng/mL) on cell viability and cytotoxicity in HK2-cells were
assessed by MTT, crystal violet and lactate dehydrogenase assays. Western blot analysis was used to
confirm expression of Cx26, Cx40 and Cx43. The effect of visfatin (10-200ng/mL) on TGF-β1
secretion was confirmed by ELISA, and the effects of both TGF-β1 (2-10ng/mL) and visfatin (10-
200ng/mL) on connexin expression were assessed by western blot. Functional intercellular
communication was determined using transfer of Lucifer Yellow and paired-whole cell patch clamp
electrophysiology.
Results: In low glucose (5mM), visfatin (10-200ng/mL) did not affect membrane integrity,
cytotoxicity or cell viability at 48hrs, but did evoke a concentration-dependent reduction in Cx26 and
Cx43 expression. The expression of Cx40 was unaffected. At 48hrs, visfatin (10-200ng/mL)
increased the secretion of TGF-β1 and the visfatin-evoked changes in connexin expression were
mimicked by exogenous application of the pro-fibrotic cytokine (2-10ng/ml). Visfatin reduced dye
transfer between coupled cells and decreased functional conductance, with levels falling by 63% as
compared to control. Although input resistance was increased following visfatin treatment by 166%,
the change was not significant as compared to control. The effects of visfatin on Cx-expression and
cell-coupling were blocked in the presence of a TGF-β1 specific neutralizing antibody.
Conclusions: The adipocytokine visfatin selectively evoked a non-toxic reduction in connexin
expression in HK2-cells. The loss in gap-junction associated proteins was mirrored by a loss in
functional conductance between coupled cells. Visfatin increased TGF-β secretion and the pattern of
change for connexins expression was mimicked by exogenous application of TGF-β1. The effect of
visfatin on Cx-expression and dye transfer were negated in the presence of a TGF-β1 neutralising
antibody. These data suggest that visfatin reduces connexin-mediated intercellular communication in
proximal tubule-derived epithelial cells via a TGF-β dependent pathway
Anti-TNF treatments in Crohn's disease and improvement in work productivity and quality of life: an observational study from Turkey
No full text[Abstract Not Available
Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome
No full textIs our recommendation to quit smoking considered in patients with Graves’ Disease and Graves’ Orbitopathy?
No full textSERUM OMENTIN-1 LEVELS AND ENDOTHELIAL DYSFUNCTION IN OBESITY
No full textIntroduction. Our aim was to investigate the relationship between serum
omentin-1 levels and endothelial dysfunction in obese patients.
Material and Methods. We evaluated 50 obese patients, and age/gender
matched 45 healthy non-obese subjects as controls. Oral glucose
tolerance test, lipid parameters, uric acid levels, homeostatic model
assessment insulin resistance (HOMA-IR) index, serum omentin-1 levels
and flow mediated dilatation (FMD) \% were measured in all subjects.
Body compositions were analyzed with bioelectrical impedance method
using a Tanita Body Composition Analyzer and ViScan.
Results. Serum omentin-1 levels were found significantly lower in obese
population compared to the control subjects. FMD response was
significantly decreased in obese population. There was a significant
positive correlation between serum omentin-1 levels and FMD response
(r=0.359, p<0.001). Serum omentin-1 levels were negatively correlated
with body mass index (BMI), waist circumference, total fat percentage,
visceral fat, fasting insulin and HOMA-IR index.
Conclusion. Lower serum omentin-1 levels and decreased FMD response may
be an early marker of endothelial dysfunction in obese patients
