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São Paulo, Brazil

Hu Y.,Doheny Eye Institute | Hu Y.,Peking University | Liu L.,Doheny Eye Institute | Lu B.,California Institute of Technology | And 15 more authors.
Ophthalmic Research | Year: 2012

Objective: To evaluate the feasibility of a new technique for the implantation of ultrathin substrates containing stem cell-derived retinal pigment epithelium (RPE) cells into the subretinal space of retina-degenerate Royal College of Surgeon (RCS) rats. Methods: A platform device was used for the implantation of 4-μm-thick parylene substrates containing a monolayer of human embryonic stem cell-derived RPE (hESC-RPE). Normal Copenhagen rats (n = 6) and RCS rats (n = 5) were used for the study. Spectral-domain optical coherence tomography (SD-OCT) scanning and histological examinations were performed to confirm placement location of the implant. hESC-RPE cells attached to the substrate before and after implantation were evaluated using standard cell counting techniques. Results: SD-OCT scanning and histological examination revealed that the substrates were precisely placed in the rat's subretinal space. The hESC-RPE cell monolayer that covered the surface of the substrate was found to be intact after implantation. Cell counting data showed that less than 2% of cells were lost from the substrate due to the implantation procedure (preimplantation count 2,792 ± 74.09 cells versus postimplantation count 2,741 ± 62.08 cells). Detailed microscopic examination suggested that the cell loss occurred mostly along the edges of the implant. Conclusion: With the help of this platform device, it is possible to implant ultrathin substrates containing an RPE monolayer into the rat's subretinal space. This technique can be a useful approach for stem cell-based tissue bioengineering techniques in retinal transplantation research. © 2012 S. Karger AG, Basel.

De Souza Nunes L.S.,Health Science University | De Oliveira R.V.,Health Science University | Holgado L.A.,Health Science University | Nary Filho H.,P I Brnemark Institute | And 2 more authors.
Journal of Oral and Maxillofacial Surgery | Year: 2011

Purpose: Considering the clinical discussion on the necessity of using a barrier membrane in the osteotomy area of sinus lift procedures to prevent fibrous tissue formation in this area and as a physical limit, the aim of this study was to analyze and compare the use of bovine hydroxyapatite (HA) with and without a biologic membrane by histopathologic analysis and immune expression of core binding factor 1 and vascular endothelium growth factor in the sinus lift in rabbits. Materials and Methods: Sixteen male rabbits underwent bilateral sinus lift procedures and were divided into 2 groups according to the sinus filling material: group 1 received bovine HA (Bio-Oss; Geistlich Pharma AG, Wohlhusen, Switzerland) and group 2 received bovine HA and a nonporous polytetrafluorethylene membrane. All groups were sacrificed after 7, 14, 30, and 60 days for microscopic, histomorphometric, and immunohistochemical analyses. Results: Microscopic analysis showed a similar bone repair pattern between the tested groups. New bone formation, soft tissue, and the remaining material were analyzed by histomorphometric analysis. No statistically significant differences (P > .05) were detected between groups for all periods analyzed. In addition, no remarkable differences were noticed in core binding factor 1 or vascular endothelium growth factor immune expression. Conclusion: Taken together, these results show that using a biologic membrane does not improve bone repair induced by bovine HA, as shown by histopathologic and immunohistochemical analyses. © 2011 American Association of Oral and Maxillofacial Surgeons.

Alves Vieira M.D.F.,Federal University of Pelotas | Ferraro A.A.,University of Sao Paulo | Nascimento Souza M.H.D.,Federal University of Rio de Janeiro | Sawaya A.L.,University Federal Of So Paulo
Public Health Nutrition | Year: 2010

Objective To evaluate nutritional recovery patterns in 106 undernourished children assisted by the Center of Nutritional Recovery and Education (CREN, in Portuguese) between January 1995 and December 1999.Design CREN assists undernourished children aged 0 to 72 months living in the southern regions of Sao Paulo, in an outpatient setting. Nutritional status was assessed by Z-scores of weight-for-age, height-for-age and weight-for-height. Nutritional recovery evaluation considered Z-score gains in weight-for-age and height-for-age, grouping into four categories (Z-score increment of 050 between groups). Children with birth weight less than 2500 g were classified as low birth weight (LBW), while those born at term and with LBW were classified as small for gestational age.Setting CREN (Center of Nutritional Recovery and Education in Portuguese), Sao Paulo, Brazil.Subjects One hundred and six children from CREN.Results Among the 106 evaluated children, ninety-eight (925 %) recovered their weight or height and seventy-two (679 %) recovered both. Nearly half of studied children presented a nutritional recovery (increase in Z-score) of more than 050 in height-for-age (462 %) and about 40 % in weight-for-age (387 %). Multivariate analysis showed that treatment duration and initial weight-for-age contributed to weight-for-age Z-score increment, explaining 25 % of the variation; and treatment duration, initial height-for-age and weight-for-age Z-score increment contributed to height-for-age Z-score increment, explaining 62 % of the variation.Conclusions Our findings show that nutritional recovery among children who attended CREN was influenced primarily by the degree of nutritional deficit at admission. It has also been shown that biological variables are more important than socio-economic status in determining the rate of nutritional recovery. © 2010 The Authors.

Gallo G.,University Federal Of So Paulo | Ramos T.C.P.,Federal University of Sao Paulo | Ramos T.C.P.,University Federal Of So Paulo | Tavares F.,Brazilian Synchrotron Light Laboratory (LNLS) | And 7 more authors.
Biochemical and Biophysical Research Communications | Year: 2011

Protein tyrosine phosphatases (PTPs) form a large family of enzymes involved in the regulation of numerous cellular functions in eukaryotes. Several protein tyrosine phosphatases have been recently identified in trypanosomatides. Here we report the purification and biochemical characterization of TcPTP1, a protein tyrosine phosphatase from Trypanosoma cruzi, the causing agent of Chagas' disease. The enzyme was cloned and expressed recombinantly in Escherichia coli and purified by Ni-affinity chromatography. Biochemical characterization of recombinant TcPTP1 with the PTP pseudo-substrate pNPP allowed the estimation of a Michaelis-Menten constant Km of 4.5mM and a kcat of 2.8s-1. We were able to demonstrate inhibition of the enzyme by the PTP1b inhibitor BZ3, which on its turn was able to accelerate the differentiation of epimastigotes into metacyclic forms of T. cruzi induced by nutritional stress. Additionally, this compound was able to inhibit by 50% the infectivity of T. cruzi trypomastigotes in a separate cellular assay. In conclusion our results indicate that TcPTP1 is of importance for cellular differentiation and invasivity of this parasite and thus is a valid target for the rational drug design of potential antibiotics directed against T. cruzi. © 2011 Elsevier Inc.

Arevalo J.F.,Clinica Oftalmolgica Centro Caracas | Snchez J.G.,Instituto Nacional Of Investigacin En Oftalmologa | Wu L.,Institute Cirugia Ocular | Berrocal M.H.,University of Puerto Rico at San Juan | And 10 more authors.
Ophthalmology | Year: 2010

Purpose: To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (IVB) (Avastin; Genentech Inc., San Francisco, CA) (1.25 or 2.5 mg) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Design: Retrospective, multicenter, interventional, comparative case series. Participants: We reviewed the clinical records of 180 consecutive patients (207 eyes) with subfoveal CNV secondary to AMD at 9 centers from 8 countries. Methods: Patients were treated with at least 1 injection of IVB 1.25 mg (124 eyes [59.9%]) or 2.5 mg (83 eyes [40.1%]). Patients underwent ETDRS BCVA testing, ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at baseline and 1-, 3-, 6-, 12-, and 24-month visits. Main Outcome Measures: Changes in BCVA and OCT. Results: The mean age of our patients was 74.3±7.5 years. The mean number of IVB injections per eye was 5.1 (range, 124 injections). In the 1.25 mg group, baseline BCVA improved from 20/235 (logarithm of the minimum angle of resolution [logMAR] 1.07) to 20/172 (logMAR 0.92) at 24 months (P<0.0001). Similar BCVA changes were observed in the 2.5 mg group. At baseline, the mean central macular thickness (CMT) by OCT in the 1.25 mg group was 308.4±127.52 μm, which was reduced to 269.35±97.92 μm, 262.1±94.81 μm, 264.03±97.06 μm, 245.91±89.52 μm, and 249.27±89.14 μm at 1, 3, 6, 12, and 24 months, respectively (P<0.0001). Similar changes were observed in the 2.5 mg group. In the 2.5 mg group, systemic complications included 2 new cases (2.6%) of arterial hypertension, 1 case (1.3%) of stroke, and 1 case (1.3%) of death. Conclusions: Primary IVB at a dose of 1.25 or 2.5 mg seems to provide stability or improvement in BCVA, OCT, and FA in subfoveal CNV secondary to AMD at 24 months. Our results show no significant difference regarding BCVA with IVB at doses of 1.25 or 2.5 mg. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2010 American Academy of Ophthalmology.

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