There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic ...infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Subcostal scars may increase the risk of healing complications in abdominoplasty. The authors evaluated the use of thermography as a potential tool for patient selection and surgery planning to avoid ...complications and improve abdominoplasty outcomes. Two candidates for abdominoplasty procedures who presented with extensive subcostal scars were submitted to an infrared thermography protocol at all phases of the procedure: preoperative, intraoperative, and postoperative at 1 and 6 months. The preoperative thermography for both patients revealed near-normal abdominal wall perfusion. The thermograms captured intraoperatively during flap elevation did not show perfusion deficits on the upper abdominal flap. At 1 month and 6 months postoperative, dynamic thermography for both patients showed normal to near-normal perfusion. The procedures had a complication-free course with a good aesthetic result. Plastic surgeons may be reluctant to perform a full abdominoplasty in patients with a previous subcostal incision. In this preliminary analysis, we raise the potential usefulness of thermography for patients with recent subcostal scars and/or important comorbidities as a strategy for adequate patient and technique selection, avoiding possible complications. Future studies, with an increased number of patients and adequate statistical analysis, may allow us to validate the utility of thermography in these cases and reassure that the presence of previous extensive subcostal scars may not be a contraindication for a full abdominoplasty, especially if they are not recent.
Abstract Objectives Pachydermoperiostosis is a rare clinical entity characterized by skin thickening of the forehead, eyelids, and hands, digital clubbing, and periostosis. Two genes have been ...associated, HPGD and recently SLCO2A1. We present a detailed clinical and genetic description of an African pachydermoperiostosis patient with a SLCO2A1 mutation. Methods Standard clinical and laboratory evaluation was carried out. Genetic screening was done with PCR followed by direct sequencing. We discuss the clinical features and known mutations of previously reported cases identified through a PubMed literature review. Results The clinical findings showed special features, including exuberant knee effusions and an extraordinary good response on surgery of the blepharoptosis. We found a splice site mutation in the SLCO2A1 gene in homozygous form: c.940+1G>A. This mutation was previously reported only in 1 Chinese and 3 Japanese cases and was considered as a founder mutation in Japan. Beside our case, only one other patient in the literature carried this mutation in homozygous condition, but with different main clinical symptoms. Conclusions Our case demonstrates phenotypic heterogeneity of PDP even between homozygous carriers of the same mutation, suggesting further modifiers. Besides, it shows that this rare SLCO2A1 mutation is not exclusively present in East-Asia, but can occur in various ethnicities, with different origin, thus the incidence is probably underestimated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: The addition of ezetimibe to statin therapy has been reported to result in increased efficacy for reduction of LDL-C levels and achievement of lipid targets, compared with monotherapy.
...Objective: This study was designed to demonstrate the noninferiority of therapy with fixed-dose rosuvastatin plus ezetimibe formulations versus fixed dose simvastatin and ezetimibe formulations for reduction of LDL-C levels in Brazilian patients with hypercholesterolemia or mixed dyslipidemia.
Methods: Phase III, multicenter, randomized, parallel, open-label, noninferiority study that included male and female participants (aged 21–80 years) with hypercholesterolemia or mixed dyslipidemia. After a 1-week screening period with washout of lipid-lowering medications when needed, patients were treated with simvastatin 20 mg/d for 5 weeks. Participants with LDL-C levels ≥100 mg/dL after the initial treatment were submitted to a 1-week washout period, and then randomized 1:1 to receive either combined rosuvastatin 10 mg + ezetimibe 10 mg (R/E) or simvastatin 20 mg + ezetimibe 10 mg (S/E) for 4 weeks and, if they still did not achieve the stipulated target, doses were readjusted to rosuvastatin 20 mg + ezetimibe 10 mg or simvastatin 40 mg + ezetimibe 10 mg, respectively, for 4 weeks.
Results: One hundred twenty-nine participants were enrolled, including 66 in R/E and 63 in S/E. At the end of simvastatin 20 mg treatment period, mean LDL-C values were 124.79 mg/dL and 121.27 mg/dL for participants randomized to R/E and S/E arms, respectively. After 4 weeks of R/E 10 mg + 10 mg or S/E 20 mg + 10 mg combined treatments, adjusted mean LDL-C values were 74.21 mg/dL and 85.58 mg/dL, respectively (P = 0.0005), and after 9 weeks, with dose adjustment to R/E 20 mg + 10 mg in 6 patients and to S/E 40 mg +10 mg in 19 patients, LDL-C adjusted mean values were 75.29 mg/dL and 86.62 mg/dL, respectively (P = 0.0006). There was a statistically significant difference between the association R/E and S/E (P = 0.0013) in percentage change of LDL-C after 9 weeks of combined treatments. The adjusted mean difference was estimated at –10.32% (95% CI, –16.94% to –3.70%). The LDL-C <100 mg/dL target was achieved in a significantly greater proportion of participants at week 4 in the R/E compared with the S/E arm (84.8% vs 68.2%; P = .0257), and at week 9, the proportion was 81.2% versus 73.0%, respectively (P = 0.23). LDLC <70 mg/dL was achieved at a significantly greater proportion in the R/E arm, both at week 4 (45.4% vs 15.9%; P = 0.003) and week 9 (40.9% vs 15.9%; P = 0.0017). A statistically significant difference at week 9 (P = 0.0106) was observed in fasting blood glucose in the R/E arm, but the overall incidence of adverse events was not significantly different between groups.
Conclusions: Rosuvastatin and ezetimibe fixed dose combination in both 10 mg/10 mg and 20 mg/10 mg doses, respectively, provided significantly lower levels of LDL-C compared with simvastatin and ezetimibe in doses of 20 mg/10 mg and 40 mg/10 mg, respectively. The fixed-dose combinations were both effective and well tolerated in this Brazilian study population. ClinicalTrials.gov identifier: NCT01420549. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Methods Twenty-four patients (14 male 10 female) 30,8 year-old average with severe AD,allergic respiratory disease and high levels of IgE (>2000 UI/L) not responding to conventional therapies were ...proposed for omalizumab treatment.They were evaluated for SCORAD index and daily/rescue medication before,during and after treatment.Omalizumab was administrated subcutaneously at doses range from 150 to 600 mg every 2 weeks for 19,6 months average treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background: Nebicapone is a reversible catechol-O-methyltransferase (COMT) inhibitor. Coadministration of a COMT inhibitor with levodopa and a dopa-decarboxylase inhibitor (carbidopa or ...benserazide) increases levodopa exposure and its therapeutic effect. Objectives: The primary objective of this study was to investigate the effect of nebicapone (50, 100, and 200 mg), compared with placebo, on levodopa pharmacokinetics when coadministered with a single dose of controlled-release levodopa 100 mg/benserazide 25 mg. The secondary objectives were to investigate the effect of nebicapone on the erythrocyte-soluble COMT (S-COMT) activity and on the plasma levels of the levodopa 3- O -methylated metabolite (3- O -methyldopa 3-OMD). Nebicapone's tolerability was also assessed. Methods: This was a single-center, Phase I, doubleblind, randomized, placebo-controlled, 4-way crossover study conducted in healthy adult volunteers. Each of the 4 single-dose treatment periods was separated by a washout period of ≥5 days. During the different treatment periods, subjects received a single dose of controlled-release levodopa 100 mg/benserazide 25 mg concomitantly with nebicapone 50, 100, and 200 mg or placebo. Plasma concentrations of nebicapone, levodopa, and 3-OMD were determined by HPLC. Blood samples (7 mL) for determination of plasma concentrations of levodopa, 3-OMD, and 2258 nebicapone, as well as for the assay of S-COMT activity, were collected in potassium EDTA test tubes at the following times: predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours postdose. S-COMT activity was assessed as the amount of metanephrine formed by the action of S-COMT on an epinephrine substrate. Spontaneously reported clinical adverse events (AEs) were recorded throughout the study. Results: Sixteen subjects (8 females, 8 males; mean SD age, 26.13 6.29 years; weight, 69.4 12.4 kg; body mass index, 24.0 3.0 kg/m2 ) completed the 4 treatment periods and had data available for pharmacokinetic and pharmacodynamic analyses. Compared with placebo, levodopa Cmax increased 25%, 30%, and 34%, and AUC increased 14%, 37%, and 42% after administration of nebicapone 50, 100, and 200 mg, respectively. After administration of nebicapone 50, 100, and 200 mg, 3-OMD Cmax decreased 44%, 57%, and 58%, and 3-OMD AUC0–∞ decreased 33%, 37%, and 45%, respectively, compared with placebo. Extent of exposure to levodopa, as assessed by using AUC0−t , increased with all doses of nebicapone in relationship to placebo, but the difference did not reach statistical significance. This may be related to a relatively high inter-subject variability: %CVs ranged from 48.0% with nebicapone 100 mg to 66.8% with placebo. Maximum S-COMT inhibition by nebicapone occurred at ~1.5 hours postdose and ranged from 57% with nebicapone 50 mg to 74% with nebicapone 200 mg. There was an inverse correlation between plasma concentrations of nebicapone and S-COMT activity; Tmax of nebicapone plasma concentrations and time to occurrence of the maximum inhibition of S-COMT activity appeared to correlate. Nineteen AEs were reported; 8 were assessed by the investigator as possibly related to treatment. All AEs were mild in severity. There were no serious AEs or discontinuations due to AEs. No abnormalities in liver enzyme levels were found. Conclusions: When administered concomitantly with a single dose of controlled-release levodopa 100 mg/benserazide 25 mg, single doses of nebicapone 50, 100, and 200 mg were well tolerated in these healthy adult volunteers, and dose dependently inhibited S-COMT activity and reduced 3-OMD formation compared with placebo. However, there was no significant difference in levodopa bioavailability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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