Altered Ex Vivo Expression of Caspase 8, Caspase 9, and Bcl-2 Is Associated with T-Cell Hyporeactivity in Patients with Paracoccidioidomycosis

To better understand the T-cell hyporesponsiveness of patients with paracoccidioidomycosis, we tested the hypothesis that the T cells were committed to apoptosis. We show here that T cells of patients with paracoccidioidomycosis overexpress caspase 9 and caspase 8 but express low Bcl-2 levels and that interleukin-2 was unable to revert the hyporesponsiveness. These data suggest that the T cells would in vivo be driven to a tolerant state and apoptosis.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Education Level Explains Differences in Stroke Incidence among City Districts in Joinville, Brazil: A Three-Year Population-Based Study

Background: Current evidence suggests an inverse association between socioeconomic status and stroke incidence. Our aim was to measure the variation in incidence among different city districts (CD) and their association with socioeconomic variables. Methods: We prospectively ascertained all possible stroke cases occurring in the city of Joinville during the period 2005-2007. We determined the incidence for each of the 38 CD, age-adjusted to the population of Joinville. By linear regression analysis, we correlated incidence data with mean years of education (MYE) and mean income per month (MIPM). Results: Of the 1,734 stroke cases registered, 1,034 were first-ever strokes. In the study period, the crude incidence in Joinville was 69.5 per 100,000 (95% confidence interval, 65.3-73.9). The stroke incidence among CD ranged from 37.5 (22.2-64.6) to 151.0 per 100,000 (69.0-286.6). The stroke incidence was inversely correlated with years of education (r = -0.532; p<0.001). MYE and MIPM were strongly related (R = 0.958), resulting in exclusion of MIPM by collinearity. Conclusions: Years of education can explain a wide incidence variation among CD. These results may be useful to guide the allocation of resources in primary prevention policies. Copyright (C) 2011 S. Karger AG, Basel

Increased soluble TNF receptor 2 in antidepressant-free patients with late-life depression

Increased pro-inflammatory state has been implicated in the pathophysiology of major depressive disorder. The aim of this study was to determine serum levels of INF-alpha and soluble TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) in anti-depressant free depressed elderly patients as compared to healthy controls. Sixty-seven older adults (28 with major depression and 39 controls) were enrolled to this study. Participants were assessed by the SCID and diagnosis of major depressive episode was made according to the DSM-IV criteria. Serum INF-alpha, 5TNFR1 and sTNFR2 were determined by ELISA. Anti-depressant free patients with late-life depression showed an increased level of the sTNFR2 as compared to controls (p = 0.03). No significant differences were found in serum INF-alpha and sTNFR1 levels (p = 0.1 and p = 0.4, respectively). There was no correlation between serum levels of these inflammatory markers and the severity of depression. Our findings provide additional evidence of the involvement of abnormal pro-inflammatory state in late-life depression. (c) 2010 Elsevier Ltd. All rights reserved.

Inhibition of phospholipase A(2) increases Tau phosphorylation at Ser214 in embryonic rat hippocampal neurons

Background: Arachidonic acid is released from cellular membranes by the action of phospholipase A(2) (PLA(2)) and is implicated in microtubule-associated protein Tau phosphorylation. Tau hyperphosphorylation affects its ability to stabilize microtubules. Objective: To determine the effect of PLA(2) inhibition on the phosphorylation state of Tau phosphoepitopes in primary cultures of hippocampal neurons. Methods: 4 DIC neurons were incubated at different concentrations of methyl-arachidonylfluorophosphonate (MAFP), an irreversible inhibitor of cPLA(2) and iPLA(2). Changes on Tau phosphorylation were determined by Western blotting with a panel of anti-Tau antibodies (C-terminal, Ser199/202, Ser202/205, Ser396 and Ser214). Results: The Ser214 site was hyperphosphorylated upon MAFP treatment. Significant differences were observed with 10 mu M (p = 0.01), 50 mu M (p = 0.01) and 100 mu M (p = 0.05) of MAFP. Less-intense changes were found in other phosphoepitopes. Conclusion: The present findings indicate that the phosphorylation of Ser214 is regulated by c- and/or iPLA(2), whereas other phosphoepitopes primarily regulated by GKS3b were not affected. (C) 2009 Elsevier Ltd. All rights reserved.

PM(2.5) and PM(10): The influence of sugarcane burning on potential cancer risk

In Brazil, sugarcane fields are often burned to facilitate manual harvesting, and this burning causes environmental pollution from the large amounts of soot released into the atmosphere. This material contains numerous organic compounds such as PAHs. In this study, the concentrations of PAHs in two particulate-matter fractions (PM(2.5) and PM(10)) in the city of Araraquara (SE Brazil, with around 200,000 inhabitants and surrounded by sugarcane plantations) were determined during the sugarcane harvest (HV) and non-harvest (NHV) seasons in 2008 and 2009. The sampling strategy included four campaigns, with 60 samples in the NHV season and 220 samples in the HV season. The PM(2.5) and PM(10) fractions were collected using a dichotomous sampler (10 L min(-1), 24 h) with Teflon (TM) filters. The filter sets were extracted (ultrasonic bath with hexane/acetone (1:1 v/v)) and analyzed by HPLC/Fluorescence. The median concentration for total PAHs (PM(2.5) in 2009) was 0.99 ng m(-3) (NHV) and 3.3 ng m(-3) (HV). In the HV season, the total concentration of carcinogenic PAHs (benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(a)pyrene) was 5 times higher than in the NHV season. B(a)P median concentrations were 0.017 ng m(-3) and 0.12 ng m(-3) for the NHV and HV seasons, respectively. The potential cancer risk associated with exposure through inhalation of these compounds was estimated based on the benzo[a]pyrene toxic equivalence (BaP(eq)), where the overall toxicity of a PAR mixture is defined by the concentration of each compound multiplied by its relative toxic equivalence factor (TEF). BaP(eq) median (2008 and 2009 years) ranged between 0.65 and 1.0 ng m(-3) and 1.2-1.4 ng m(-3) for the NHV and HV seasons, respectively. Considering that the maximum permissible BaPeq in ambient air is 1 ng m(-3), related to the increased carcinogenic risk, our data suggest that the level of human exposure to PAHs in cities surrounded by sugarcane crops where the burning process is used is cause for concern. (C) 2010 Published by Elsevier Ltd.

Neither Molecular Diversity of the Envelope, Immunosuppression Status, Nor Proviral Load Causes Indeterminate HTLV Western Blot Profiles in Samples From Human T-Cell Lymphotropic Virus Type 2 (HTLV-2)-Infected Individuals

Although human T-cell lymphotropic virus type 2 (HTLV-2) is considered of low pathogenicity, serological diagnosis is important for counseling and monitoring. The confirmatory tests most used are Western blot (WB) and PCR. However, in high-risk populations, about 50% of the indeterminate WB were HTLV-2 positives by PCR. The insensitivity of the WB might be due to the use of recombinant proteins of strains that do not circulate in our country. Another possibility may be a high level of immunosuppression, which could lead to low production of virus, resulting in low stimulation of antibody. We found one mutation, proline to serine in the envelope region in the position 184, presented at least 1/3 of the samples, independent the indeterminate WB profile. In conclusion, we found no correlation of immune state, HTLV-2 proviral load, or env diversity in the K55 region and WB indeterminate results. We believe that the only WB kit available in the market is probably more accurate to detect HTLV-1 antibodies, and some improvement for HTLV-2 detection should be done in the future, especially among high-risk population. J. Med. Virol. 82:837-842,2010. (C) 2010 Wiley-Liss, Inc.

Effect of Femtosecond Laser Energy Level on Corneal Stromal Cell Death and Inflammation

PURPOSE: To analyze the effects of variations in femtosecond laser energy level on corneal stromal cell death. and inflammatory cell influx following flap creation in a rabbit model. METHODS: Eighteen rabbits were stratified in three different groups according to level of energy applied for flap creation (six animals per group). Three different energy levels were chosen for both the lamellar and side cut; 2.7 mu J (high energy), 1.6 mu J (intermediate energy), and 0.5 mu J (low energy) with a 60 kHz, model II, femtosecond laser (IntraLase). The opposite eye of each rabbit served as a control. At the 24-hour time point after surgery, all rabbits were euthanized and the comeoscleral rims were analyzed for the levels of cell death and inflammatory cell influx with the terminal uridine deoxynucleotidyl transferase dUTP-nick end labeling (TUNEL) assay and immunocytochemistry for monocyte marker CD11b, respectively. RESULTS: The high energy group (31.9 +/- 7.1 [standard error of mean (SEM) 2.9]) had significantly more TUNEL positive cells in the central flap compared to the intermediate (22.2 +/- 1.9 [SEM 0.8], P=.004), low (17.9 +/- 4.0 [SEM 1.6], P <= .001), and control eye (0.06 +/- 0.02 [SEM 0.009], P <= .001) groups. The intermediate and low energy groups also had significantly more TUNEL positive cells than the control groups (P <= .001). The difference between the intermediate and low energy levels was not significant (P=.56). The mean for CD11b-positive cells/400x field at the flap edge was 26.1 +/- 29.3 (SEM 11.9), 5.8 +/- 4.1 (SEM 1.6), 1.6 +/- 4.1 (SEM 1.6), and 0.005 +/- 0.01 (SEM 0.005) for high energy, intermediate energy, low energy, and control groups, respectively. Only the intermediate energy group showed statistically more inflammatory cells than control eyes (P = .015), most likely due to variability between eyes. CONCLUSIONS: Higher energy levels trigger greater cell death when the femtosecond laser is used to create corneal flaps: Greater corneal inflammatory cell infiltration is observed with higher femtosecond laser energy levels. [J Refract Surg. 2009;25:869-874.] doi:10.3928/1081597X-20090917-08

Factors Related to the Selection of Surgical Versus Percutaneous Revascularization in Diabetic Patients With Multivessel Coronary Artery Disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) Trial

Objectives We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. Background Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. Methods In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. Results Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >= 70% (OR: 2.86), proximal left anterior descending stenosis >= 50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >= 65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). Conclusions The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305) (J Am Coll Cardiol Intv 2009;2:384-92) (C) 2009 by the American College of Cardiology Foundation

Nomograms of fetal thyroid measurements estimated by 2-dimensional sonography

Purpose. To build nomograms of fetal thyroid circumference (FTC), fetal thyroid area (FTA), and fetal thyroid transverse diameter (FTTD) throughout gestational age (GA). Method. Between January 2006 and July 2006, FTC, FTA, and FTTD were measured once in 196 normal fetuses examined at a GA of 22-35 weeks. Inclusion criteria were a healthy mother with normal maternal thyrotropin level during pregnancy, a singleton pregnancy with normal fetal morphology on sonography, and GA confirmed via first-trimester sonographic examination. Results. Mean FTC, FTA, and FTTD ranged from 3.21 cm, 0.58 cm(2), and 1.19 cm at 22 weeks to 5.11 cm, 1.69 cm(2), and 1.89 cm at 35 weeks, respectively. Linear regression analysis yielded the following formulas for FTC, FTA, and FTTD according to GA: FTC (cm) = 0.146 X GA (weeks); FTA (cm(2)) = -1.289 + 0.085 X GA (weeks); FTTD (cm) = 0.054 X GA (weeks). The following logarithmic formulas were obtained for the expected fetal thyroid measurements according to estimated fetal weight (FW): FTC (cm) = -4.791 + 1.265 X logN FW; FTA (cm(2)) = -1.676 + 0.455 X logN FW; and FTTD (cm) = 0.399 + 0.001 X logN FW. Conclusion. We describe new nomograms of fetal thyroid measurements throughout gestation that may be useful in case of thyroid dysfunction. (C) 2008 Wiley Periodicals, Inc.

Effects of low level laser therapy (808 nm) on physical strength training in humans

Recent studies have investigated whether low level laser therapy (LLLT) can optimize human muscle performance in physical exercise. This study tested the effect of LLLT on muscle performance in physical strength training in humans compared with strength training only. The study involved 36 men (20.8 +/- 2.2 years old), clinically healthy, with a beginner and/or moderate physical activity training pattern. The subjects were randomly distributed into three groups: TLG (training with LLLT), TG (training only) and CG (control). The training for TG and TLG subjects involved the leg-press exercise with a load equal to 80% of one repetition maximum (1RM) in the leg-press test over 12 consecutive weeks. The LLLT was applied to the quadriceps muscle of both lower limbs of the TLG subjects immediately after the end of each training session. Using an infrared laser device (808 nm) with six diodes of 60 mW each a total energy of 50.4 J of LLLT was administered over 140 s. Muscle strength was assessed using the 1RM leg-press test and the isokinetic dynamometer test. The muscle volume of the thigh of the dominant limb was assessed by thigh perimetry. The TLG subjects showed an increase of 55% in the 1RM leg-press test, which was significantly higher than the increases in the TG subjects (26%, P = 0.033) and in the CG subjects (0.27%, P < 0.001). The TLG was the only group to show an increase in muscle performance in the isokinetic dynamometry test compared with baseline. The increases in thigh perimeter in the TLG subjects and TG subjects were not significantly different (4.52% and 2.75%, respectively; P = 0.775). Strength training associated with LLLT can increase muscle performance compared with strength training only.

Tension band wire fixation for valgus osteotomies of the proximal femur: A biomechanical study of three configurations of fixation

Background. A variety of techniques can be used to achieve stabilization of femoral valgus osteotomies in children, but what is lacking is a versatile fixation system that associates stability and versatility at different ages and for different degrees of deformity. Methods. Mechanical tests of three configurations used to fix femoral valgus osteotomies, based oil the tension band wire principle, were carried out. A 30 degrees wedge valgus osteotomy was performed at the subtrochanteric level in 60 swine femurs and fixed with three different systems. In Group 1, two Kirschner wires (K wire) were introduced from the tip of the greater trochanter to the medial cortex, crossing the osteotomy. A flexible steel wire was anchored to the K wires into holes in the lateral cortex and tightened to form a tension band. The same setup was used in Group 2, but two additional smooth K wires were inserted into the lateral surface of the greater trochanter and driven to the femoral head with the distal extremities bent and tied around tile bone shaft. In Group 3, the fixation was similar to that in Group 2, but tile ascending K wires were introduced below the osteotomy level, crossing the osteotonly. Mechanical tests in bending-compression and torsion were used to access the stability. Findings. The torsional relative stiffness was 116% greater for Group 3 (0.27 N m/degree) and no significant difference was found between Group 1 (0.10 N m/degree) and Group 2 (0.12 N m/degree). The average torque was 103% higher for Group 3 (1.86 N m). Stiffness in bending-compression was significantly higher in Group 3 (508 x 10(3) N/m) than in Group 1 (211 x 10(3) N/m) and Group 2 (219 x 10(3) N/m). Interpretation. Fixation as used in Group 3 was significantly more stable, both in torsion and bending-compression tests, than tile other two techniques. (c) 2007 Elsevier Ltd. All rights reserved.

Effects of changing blood viscosity and heart rate on vena contracta width as evaluated by color Doppler flow mapping. An in vitro study with a pulsatile flow model

Background: There is only limited knowledge on how the quantification of valvular regurgitation by color Doppler is affected by changing blood viscosity. This study was designed to evaluate the effect of changing blood viscosity on the vena contracta width using an in vitro model of valvular insufficiency capable of providing ample variation in the rate and stroke volume. Methods: We constructed a pulsatile flow model filled with human blood at varying hematocrit (15%, 35%, and 55%) and corresponding blood viscosity (blood/water viscosity: 2.6, 4.8, 9.1) levels in which jets were driven through a known orifice (7 mm(2)) into a 110 mL compliant receiving chamber (compliance: 2.2 mL/mmHg) by a pulsatile pump. In addition, we used variable pump stroke volumes (5, 7.5, and 10 mL) and rates (40, 60, and 80 ppm). Vena contracta region was imaged using a 3.5 MHz transducer. Pressure and volume in the flow model were kept constant during each experimental condition, as well as ultrasound settings. Results: Blood viscosity variation in the experimental range did not induce significant changes in vena contracta dimensions. Also, vena contracta width did not change from normal to low hematocrit and viscosity levels. A very modest increase only in vena contracta dimension was observed at very high level of blood viscosity when hematocrit was set to 55% . Pump rate, in the evaluated range, did not influence vena contracta width. These results in controlled experimental settings suggest that the vena contracta is an accurate quantitative method for quantifying valvular regurgitation even when this condition is associated with anemia, a frequent finding in patients with valvular heart disease.

Effect of low-dose combined oral contraceptive on aerobic capacity and anaerobic threshold level in active and sedentary young women

Background: The purpose of this study was to evaluate the effect of long-term use of oral contraceptives (DC) containing 0.20 mg of ethinylestradiol (EE) combined with 0.15 mg of gestodene (GEST) on the peak aerobic capacity and at the anaerobic threshold (AT) level in active and sedentary young women. Study Design: Eighty-eight women (23 +/- 2.1 years old) were divided into four groups active-OC (G1), active-NOC (G2), sedentary-OC (G3) and sedentary-NOC (G4) and were submitted to a continuous ergospirometric incremental test on a cycloergometer with 20 to 25 W min(-1) increments. Data were analyzed by two-way ANOVA with Tukey post hoc test. Level of significance was set at 5%. Results: The OC use effect for the variables relative and absolute oxygen uptake VO(2) mL kg(-1) min(-1); VO(2), L min(-1), respectively), carbon dioxide output (VCO(2), L min(-1)), ventilation (VE, L min(-1)), heart rate (HR, bpm), respiratory exchange ratio (RER) and power output (W) data, as well as the interaction between OC use and exercise effect on the peak of test and at the AT level did not differ significantly between the active groups (G1 and G2) and the sedentary groups (G3 and G4). As to the exercise effect, for all variables studied, it was noted that the active groups presented higher values for the variables VO(2), VCO(2), VE and power output (p<.05) than the sedentary groups. The RER and HR were similar (p>.05) at the peak and at the AT level between G1 vs. G3 and G2 vs. G4. Conclusions: Long-term use of OC containing EE 0.20 mg plus GEST 0.15 mg does not affect aerobic capacity at the peak and at the AT level of exercise tests. (C) 2010 Elsevier Inc. All rights reserved.

Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (p < 0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (p < 0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development.