ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children`s growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling. The trials were registered at www.clinicaltrials.gov as #NCT00598481 and #NCT00599781. (Blood. 2009; 114: 3216-3226)

Flexural and diametral tensile strength of composite resins

This study evaluated the flexural strength (sf) and the diametral tensile strength (st) of light-cured composite resins, testing the hypothesis that there is a positive relation between these properties. Twenty specimens were fabricated for each material (Filtek Z250- 3M-Espe; AM- Amelogen, Ultradent; VE- Vit-l-escence, Ultradent; EX- Esthet-X, Dentsply/Caulk), following ISO 4049 and ANSI/ADA 27 specifications and the manufacturers’ instructions. For the st test, cylindrical shaped (4 mm x 6 mm) specimens (n = 10) were placed with their long axes perpendicular to the applied compressive load at a crosshead speed of 1.0 mm/min. The sf was measured using the 3-point bending test, in which bar shaped specimens (n = 10) were tested at a crosshead speed of 0.5 mm/min. Both tests were performed in a universal testing machine (EMIC 2000) recording the fracture load (N). Strength values (MPa) were calculated and statistically analyzed by ANOVA and Tukey (a = 0.05). The mean and standard deviation values (MPa) were Z250-45.06 ± 5.7; AM-35.61 ± 5.4; VE-34.45 ± 7.8; and EX-42.87 ± 6.6 for st; and Z250-126.52 ± 3.3; AM-87.75 ± 3.8; VE-104.66 ± 4.4; and EX-119.48 ± 2.1 for sf. EX and Z250 showed higher st and sf values than the other materials evaluated (p < 0.05), which followed a decreasing trend of mean values. The results confirmed the study hypothesis, showing a positive relation between the material properties examined.

Microbiological quality of hamburgers sold in the streets of Cuiabá - MT, Brazil and vendor hygiene-awareness

This study evaluated the microbiological quality of hamburgers and the microbe community on the hands of vendors in Cuiabá, Mato Grosso, Brazil, in relation to vendors´ awareness as to what constitute acceptable food-handling practices as part of a broad-spectrum research programme on street foods in Brazil . Sale of the hamburger known as the 'baguncinha' is common and widespread in urban Cuiabá, Mato Grosso, Brazil. Food inspectors encounter various difficulties in carrying out inspections. One hundred and five hamburgers samples were evaluated using conventional methods including tests for facultative aerobic and/or anaerobic mesophytic bacteria, coliform counts at 45 °C, the coagulase test for Staphylococcus, Gram-staining for the presence of Bacillus cereus, Clostridium sulphite reductase and Salmonella spp. The hamburgers were categorized as unsuitable for human consumption in 31.4% of samples, with those testing positive for coliforms and Staphylococcus at unacceptably high levels by Brazilian standards. High levels of microbiological contamination were detected on the hands of the food handlers and mesophytic bacterial counts reached 1.8 × 10(4) CFU/hand. Interviews were carried out by means of questionnaires to evaluate levels of awareness as to acceptable food handling practices and it was found that 80,1% of vendors had never participated in any kind of training.

Aeromonas detection and their toxins from drinking water form reservoirs and drinking fountains

Aeromonads are inhabitants of aquatic ecosystems and are described as being involved in intestinal disturbances and other infections. A total of 200 drinking water samples from domestic and public reservoirs and drinking fountains located in São Paulo (Brazil), were analyzed for the presence of Aeromonas. Samples were concentrated by membrane filtration and enriched in APW. ADA medium was used for Aeromonas isolation and colonies were confirmed by biochemical characterization. Strains isolated were tested for hemolysin and toxin production. Aeromonas was detected in 12 samples (6.0%). Aeromonas strains (96) were isolated and identified as: A. caviae (41.7%), A. hydrophila (15.7%), A.allosacharophila (10.4%), A. schubertii (1.0%) and Aeromonas spp. (31.2%).The results revealed that 70% of A. caviae, 66.7% of A. hydrophila, 80% of A. allosacharophila and 46.6% of Aeromonas spp. were hemolytic. The assay for checking production of toxins showed that 17.5% of A. caviae, 73.3% of A. hydrophila, 60% of A. allosacharophila, 100% of A. schubertii, and 33.3% of Aeromonas spp. were able to produce toxins. The results demonstrated the pathogenic potential of Aeromonas, indicating that the presence of this emerging pathogen in water systems is a public health concern

Brazil

Brazil has led development of collective rights in Ibero-American states and has developed from consumer origins a general procedure on ""public civil actions"" largely brought by the attorney general. These have a two-stage process, involving a declaration on general liability followed by individuals bringing personal compensation claims.

Adenosine deaminase and tuberculous meningitis-A systematic review with meta-analysis

Tuberculous meningitis (TBM) is a severe infection of the central nervous system, particularly in developing countries. Prompt diagnosis and treatment are necessary to decrease the high rates of disability and death associated with TBM. The diagnosis is often time and labour intensive; thus, a simple, accurate and rapid diagnostic test is needed. The adenosine deaminase (ADA) activity test is a rapid test that has been used for the diagnosis of the pleural, peritoneal and pericardial forms of tuberculosis. However, the usefulness of ADA in TBM is uncertain. The aim of this study was to evaluate ADA as a diagnostic test for TBM in a systematic review. A systematic search was performed of the medical literature (MEDLINE, LILACS, Web of Science and EMBASE). The ADA values from TBM cases and controls (diagnosed with other types of meningitis) were necessary to calculate the sensitivity and specificity. Out of a total of 522 studies, 13 were included in the meta-analysis (380 patients with TBM). The sensitivity, specificity and diagnostic odds ratios (DOR) were calculated based on arbitrary ADA cut-off values from 1 to 10 U/l. ADA values from 1 to 4 U/l (sensitivity > 93% and specificity < 80%) helped to exclude TBM; values between 4 and 8 U/l were insufficient to confirm or exclude the diagnosis of TBM (p = 0.07), and values > 8 U/l (sensitivity < 59% and specificity > 96%) improved the diagnosis of TBM (p < 0.001). None of the cut-off values could be used to discriminate between TBM and bacterial meningitis. In conclusion, ADA cannot distinguish between bacterial meningitis and TBM, but using ranges of ADA values could be important to improve TBM diagnosis, particularly after bacterial meningitis has been ruled out. The different methods used to measure ADA and the heterogeneity of data do not allow standardization of this test as a routine.

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer.

The influence of Flutter (R) VRP1 components on mucus transport of patients with bronchiectasis

Background: The Flutter (R) VRP1 combines high frequency oscillation and positive expiratory pressure (PEP). Objective: To separately evaluate the effect of the Flutter (R) VRP1 components (high frequency oscillation and PEP) on mucus transportability in patients with bronchiectasis. Methods: Eighteen patients with bronchiectasis received sessions with the Flutter (R) VRP1 or PEP for 30 min daily in a randomized, crossover study. The treatment duration was four weeks with one of the therapies, one week of a ""wash-out"" period and followed by four more weeks with the other treatment. Weekly secretion samples were collected and evaluated for mucociliary relative transport velocity (RTV), displacement in a simulated cough machine (SCM) and contact angle measurement (CAM). For the proposed comparisons, a linear regression model was used with mixed effects with a significance level of 5%. Results: The Flutter (R) VRP1 treatment resulted in greater displacement in SCM and lower CAM when comparing results from the first (9.6 +/- 3.4 cm and 29.4 +/- 5.7 degrees, respectively) and fourth weeks of treatment (12.44 +/- 10.5 cm and 23.28 +/- 6.2, respectively; p < 0.05). There was no significant difference in the RTV between the treatment weeks for either the Flutter (R) VRP1 or PEP. Conclusion: The use of the Flutter (R) VRP1 for four weeks is capable of altering the respiratory secretion transport properties, and this alteration is related to the high frequency oscillation component. (C) 2011 Elsevier Ltd. All rights reserved.

Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes

Mesenchymal stromal cells (MSCs) suppress T cell responses through mechanisms not completely understood. Adenosine is a strong immunosuppressant that acts mainly through its receptor A(2a) (ADORA2A). Extracellular adenosine levels are a net result of its production (mediated by CD39 and CD73), and of its conversion into inosine by Adenosine Deaminase (ADA). Here we investigated the involvement of ADO in the immunomodulation promoted by MSCs. Human T lymphocytes were activated and cultured with or without MSCs. Compared to lymphocytes cultured without MSCs, co-cultured lymphocytes were suppressed and expressed higher levels of ADORA2A and lower levels of ADA. In co-cultures, the percentage of MSCs expressing CD39, and of T lymphocytes expressing CD73, increased significantly and adenosine levels were higher. Incubation of MSCs with media conditioned by activated T lymphocytes induced the production of adenosine to levels similar to those observed in co-cultures, indicating that adenosine production was mainly derived from MSCs. Finally, blocking ADORA2A signaling raised lymphocyte proliferation significantly. Our results suggest that some of the immunomodulatory properties of MSCs may, in part, be mediated through the modulation of components related to adenosine signaling. These findings may open new avenues for the development of new treatments for GVHD and other inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.

Effects of Inspiratory Muscle Training on Muscular and Pulmonary Function After Bariatric Surgery in Obese Patients

This study seeks to assess the effect of inspiratory muscle training (IMT) on pulmonary function, respiratory muscle strength, and endurance in morbidly obese patients submitted to bariatric surgery. Thirty patients were randomly assigned to sham muscular training, or to IMT with a threshold device (40% of maximum inspiratory pressure, MIP), for 30 min/day, from the 2nd until 30th postoperative (PO) day. All of them were submitted to a standard respiratory kinesiotherapy and early deambulation protocol. Data on spirometry, maximum static respiratory pressures, and respiratory muscle endurance were collected on the PO days 2, 7, 14, and 30 in a blinded matter. IMT enabled increases in PO MIP and endurance, and an earlier recovery of the spirometry parameters FEV(1), PEF, and FEF(25-75%). Comparing to preoperative values, MIP was increased by 13% at the 30th PO day in the trained group, whereas control group had a reduction of 8%, with higher values for the IMT group (30th PO, IMT-130.6 +/- 22.9 cmH(2)O; controls-112.9 +/- 25.1 cmH(2)O; p < 0.05). Muscular endurance at the 30th PO day was increased in the trained group comparing to preoperative value (61.5 +/- 39.6 s vs 114.9 +/- 55.2 s; p < 0.05), a finding not observed in the control group (81.7 +/- 44.3 vs 95.2 +/- 42.0 s). IMT improves inspiratory muscle strength and endurance and accounts for an earlier recovery of pulmonary airflows in morbidly obese patients submitted to bariatric surgery.

Heart rate and arterial pressure variability in the experimental renovascular hypertension model in rats

This study was conducted in one kidney, one clip (1K1C) Goldblatt hypertensive rats to evaluate vascular and cardiac autonomic control using different approaches: 1) evaluation of the autonomic modulation of heart rate (HR) and systolic arterial pressure (SAP) by means of autoregressive power spectral analysis 2) assessment of the cardiac baroreflex sensitivity; and 3) double blockade with methylatropine and propranolol. The 1K1C group developed hypertension and tachycardia. The 1K1C group also presented reduction in variance as well as in LF (0.23 +/- 0.1 vs. 1.32 +/- 0.2 ms(2)) and HF (6.6 +/- 0.49 vs. 15.1 +/- 0.61 ms(2)) oscillations of pulse interval. Autoregressive spectral analysis of SAP showed that 1K1C rats had an increase in variance and LF band (13.3 +/- 2.7 vs. 7.4 +/- 1.01 mmHg(2)) in comparison with the sham group. The baroreflex gain was attenuated in the hypertensive 1K1C (- 1.83 +/- 0.05 bpm/mmHg) rats in comparison with normotensive sham (-3.23 +/- 0.06 bpm/MmHg) rats. The autonomic blockade caused an increase in the intrinsic HR and sympathetic predominance on the basal HR of 1K1C rats. Overall, these data indicate that the tachycardia observed in the 1K1C group may be attributed to intrinsic cardiac mechanisms (increased intrinsic heart rate) and to a shift in the sympathovagal balance towards cardiac sympathetic over-activity and vagal suppression associated to depressed baroreflex sensitivity. Finally, the increase in the LF components of SAP also suggests an increase in sympathetic activity to peripheral vessels. (c) 2008 Elsevier B.V. All rights reserved.

Influence of Calcium Hydroxide Association on the Physical Properties of AH Plus

Introduction: This study evaluated in vitro the radiopacity, setting time, flow, film thickness, solubility, and dimensional changes of AH Plus sealer pure (Dentsply De Trey Gmbh, Konstanz, Germany) and containing 5% and 10% of calcium hydroxide. Methods: The study was performed according to the requirements of the ISO 6876:2001 standard and the American National Standards Institute/American Dental Association (ANSI/ADA)`s Specification No. 57. The following tests were performed: setting time, flow, film thickness, dimensional stability, radiopacity, and solubility. Data were analyzed statistically by analysis of variance and the Tukey tests with a significance level of 5%. Results: The addition of 5% or 10% calcium hydroxide to AH Plus sealer did not alter significantly the radiopacity or setting time values (p > 0.05). Adding 10% calcium hydroxide reduced the flow compared with pure AH Plus and AH Plus/5% calcium hydroxide. The addition of 5% and 10% calcium hydroxide increased the solubility and expansion of AH Plus. All materials presented expansion valued above those recommended by the ADA. The addition of calcium hydroxide to the sealer resulted in greater film thickness. Conclusions: The addition of 5% calcium hydroxide did not affect most physical properties of AH Plus sealer. (J Endod 2010;36:1048-1051)

Evaluation of the flow rate of 3 endodontic sealers: Sealer 26, AH Plus, and MTA Obtura

Objective. The aim of this study was to evaluate the flow rate of 3 endodontic sealers: Sealer 26, AH Plus, and MTA Obtura. Study design. According to the method proposed by the American Dental Association (ADA specification no. 57), the sealers were placed between 2 glass slabs under a weight of 120 g. The diameters of the formed discs were measured with a digital paquimeter. The test was repeated 5 times for each sealer. Results. The results were expressed as arithmetic means, and the statistical analysis was performed through Tukey test. AH Plus showed significantly superior flow rate compared with Sealer 26 and MTA Obtura. There was no statistically significant difference between flow rates presented by Sealer 26 and MTA Obtura. Conclusion. Within the limitations of this in vitro study, it was concluded that all of the the endodontic sealers tested presented greater flow than the minimum recommended in the ADA 57 specification. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:e47-e49)

Evaluation of the radiopacity of some commercial and experimental root-end filling materials

Objective. The aim of the present study was to evaluate the radiopacity of 5 root end filling materials (white MTA Angelus, MTA Bio, light-cured MTA, Sealepox RP, and Portland cement clinker with bismuth oxide and calcium sulfate). Method. Five specimens, 10 mm in diameter and 1 mm in thickness according to specification ISO 6876: 2001 were fabricated from each material and radiographed using Insigth occlusal films close to a graduated aluminum step-wedge (2 to 16 mm in thickness). Radiographs were digitized and compared to the aluminum step-wedge. The radiographic density data were converted into millimeters of aluminum (mm Al), using the Digora 1.51 software. Results were evaluated statistically using the analysis of variance (ANOVA) followed by Tukey test. The level of significance was set at 5% (P<.05%). Results. Radiopacity values ranged from 1.21 mm Al (light-cured MTA) to 6.45 mm Al (MTA Angelus). Comparison between materials showed significant difference (P<.05) between MTA Angelus and all other materials, between Sealepox RP and MTA Bio, and between light-cured MTA and Portland cement clinker. Light-cured MTA was significantly less radiopaque than all other materials. No significant difference (P>.05) was found between MTA Bio and Portland cement clinker. Conclusions. All retrograde filling materials evaluated showed greater radiopacity than dentin. All the materials, except light-cured MTA met the minimum radiopacity standards of 3 mm Al recognized by the ISO 6876: 2001 and ADA n.57. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e35-e38)

The Influence of Calcium Chloride on the Setting Time, Solubility, Disintegration, and pH of Mineral Trioxide Aggregate and White Portland Cement with a Radiopacifier

This study evaluated the influence of addition of 10% calcium chloride (CaCl(2)) on the setting time, solubility, disintegration, and pH of white MTA (WMTA) and white Portland cement (WPC). A test of the setting time was performed following the #57 ADA specifications and a test of the final setting time according to the ASTM. For the solubility tests disintegration and pH, Teflon rings were filled with the cements and weighed after setting. After 24 h in a desiccator, they were once again weighed. Thereafter, they were immersed in MiliQ water for 24 and 72 h and 7, 14, and 28 days, with maintenance in the desiccator and weighing between periods. The pH of water in which the rings were immersed was measured immediately after contact with them and in the other periods. The addition of CaCl(2) provided a significant reduction (50%) in the initial setting time of cements. The final setting time of WMTA was reduced in 35.5% and the final setting time of WPC in 68.5%. The WMTA with CaCl(2) absorbed water and gained weight with time, except for in the 24-h period. The addition of CaCl(2) to the WPC reduced its solubility. The addition of CaCl(2) increased the pH of WMTA in the immediate period and at 24 and 72 h and for WPC in the immediate period and at 24 h. The addition of CaCl(2) to WMTA and WPC reduced the setting times and solubility of both and increased the pH of cements in the initial periods. (J Endod 2009;35:550-554)