Maria Rodrigues - Academia.edu (original) (raw)

Papers by Maria Rodrigues

Arquivos de gastroenterologia

Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivat... more Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be involved in the exacerbation of experimental colitis by nonselective nonsteroidal anti-inflammatory drugs.

Acta crystallographica. Section D, Biological crystallography, 2002

Phytophthora and Pythium species are among the most aggressive plant pathogens, as they invade ma... more Phytophthora and Pythium species are among the most aggressive plant pathogens, as they invade many economically important crops and forest trees. They secrete large amounts of 10 kDa proteins called elicitins that can act as elicitors of plant defence mechanisms. These proteins may also induce a hypersensitive response (HR) including plant cell necrosis, with different levels of toxicity depending on their pI. Recent studies showed that elicitins function as sterol carrier proteins. The crystallographic structure of the highly necrotic recombinant beta-cinnamomin (beta-CIN) from Phytophthora cinnamomi has been determined at 1.8 A resolution using the molecular-replacement method. beta-CIN has the same overall structure as beta-cryptogein (beta-CRY), an elicitin secreted by Phytophthora cryptogea, although it shows a different surface electrostatic potential distribution. The protein was expressed in Pichia pastoris and crystallized in the triclinic space group with two monomers in the asymmetric unit. The interface formed by these two monomers resembles that from beta-CRY dimer, although with fewer interactions.

Oral surgery, oral medicine, oral pathology and oral radiology, 2013

Objective. Oral non-Hodgkin lymphomas (NHLs) are an extensive group of malignant lymphoid cell ne... more Objective. Oral non-Hodgkin lymphomas (NHLs) are an extensive group of malignant lymphoid cell neoplasms that are the second most common group of oral cancers. Subtyping NHL is important to plan for appropriate treatment, and the analysis of clonality is in many instances used for helping in the diagnosis of NHL. Thus, the aim of this study was to analyze immunoglobulin heavy chain (IgH) gene rearrangement in a series of oral B cell lymphomas to investigate the sensitivity of seminested polymerase chain reaction (snPCR). Study Design. Paraffin embedded tissue samples from 16 cases of oral B cell lymphomas were retrieved and subjected to snPCR to investigate the IgH gene rearrangement. Results. The results showed monoclonal IgH rearrangement in 85.7% of the cases studied, as represented by finding one band within the expected range of amplification.

TheScientificWorldJournal, 2012

Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.... more Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

Renal failure, 2004

To now, there are no studies reporting whether thyroid hormones (THs) transport play a role in th... more To now, there are no studies reporting whether thyroid hormones (THs) transport play a role in thyroid hormone dysfunction observed in chronic renal failure (CRF). Therefore, the aim of this study was to investigate the transport of THs in erythrocytes from patients with CRF on hemodialysis (HD). [125I]-L-triiodothyronine ([125I]T3) and [125I]-L-thyroxine ([125I]T4) erythrocytes uptake was measured at 1 min and 5 min. To study L-triiodothyronine (LT3) and L-thyroxine (LT4) efflux from erythrocytes, we preloaded the cells during 180 min with [125I]T3 or [125I]T4 and measured their [125I]T3 or [125I]T4 efflux during 60 min. [125I]T3 uptake in erythrocytes from uremic patients pre-HD was higher than control subjects by 50% at 1 min and by 55% at 5 min. However, [125I]T4 uptake in erythrocytes from uremic patients was significantly lower at 1min (88%) and at 5 min (63%). LT3 efflux rate was lower and LT4 efflux was significantly higher than in control subjects. After 60-min of efflux, LT3 remained in erythrocytes was 80% higher and LT4 was 57% lower than in normal individuals. Neither [125I]T3 and [125I]T4 uptake, nor efflux rates were changed by hemodialysis. Despite the fact that uremic patients on hemodialysis show low serum levels of LT3, changes in LT3 influx and efflux could act as a compensatory mechanism that neutralize thyroid hormone dysfunction in order to maintain the euthyroid state.

International journal for parasitology, 2005

In the present study, we evaluate the naturally acquired antibody response to the Plasmodium viva... more In the present study, we evaluate the naturally acquired antibody response to the Plasmodium vivax apical membrane antigen 1 (PvAMA-1), a leading vaccine candidate against malaria. The gene encoding the PvAMA-1 ectodomain region (amino acids 43-487) was cloned by PCR using genomic DNA from a Brazilian individual with patent P. vivax infection. The predicted amino acid sequence displayed a high degree of identity (97.3%) with a previously published sequence from the P. vivax Salvador strain. A recombinant protein representing the PvAMA-1 ectodomain was expressed in Escherichia coli and refolded. By ELISA, this recombinant protein reacted with 85 and 48.5% of the IgG or IgM antibodies, respectively, from Brazilian individuals with patent P. vivax malaria. IgG1 was the predominant subclass of IgG. The frequency of response increased according to the number of malaria episodes, reaching 100% in individuals in their fourth malaria episode. The high degree of recognition of PvAMA-1 by human antibodies was confirmed using a second recombinant protein expressed in Pichia pastoris (PV66/AMA-1). The observation that recognition of the bacterial recombinant PvAMA-1 was only slightly lower than that of the highly immunogenic 19 kDa C-terminal domain of the P. vivax Merozoite Surface Protein-1 was also important. DNA sequencing of the PvAMA-1 variable domain from 20 Brazilian isolates confirmed the limited polymorphism of PvAMA-1 suggested by serological analysis. In conclusion, we provide evidence that PvAMA-1 is highly immunogenic during natural infection in humans and displays limited polymorphism in Brazil. Based on these observations, we conclude that PvAMA-1 merits further immunological studies as a vaccine candidate against P. vivax malaria. q

Revista Da Sociedade Brasileira De Medicina Tropical, 1999

HIV-1 da região de Ribeirão Preto, SP, Brasil. O retinol plasmático foi dosado por HPLC e as rese... more HIV-1 da região de Ribeirão Preto, SP, Brasil. O retinol plasmático foi dosado por HPLC e as reservas hepáticas de vitamina A avaliadas pelo teste do RDR (relative dosis response). Os pacientes com AIDS a p resentaram subnutrição significativa, com alterações mais marcantes nas medidas antropométricas relacionadas à gordura corporal, com relativa preservação dos parâmetros relacionados com a massa muscular (subnutrição marasmática). Valores de retinol plasmático abaixo de 1,05µmol/L foram verificados em 25% dos pacientes com AIDS e em 17,3% dos pacientes infectados pelo HIV. Valores do RDR indicativos de baixa reserva corporal de vitamina A ocorreram em 28% dos indivíduos estudados. Não houve correlação dos níveis de retinol sérico com o número de linfócitos CD4 + , com o tempo de diagnóstico clínico de AIDS, com a PCT e o IGB. 1 4 0 4 8 -900, Ribeirão Preto, SP, Brasil. Recebido para publicação em 21/5/98. Revista da Sociedade Brasileira de Medicina Tropical 32(2):119-124, mar-abr, 1999.

Acta cirúrgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia, 2014

To determine the behavior of intraocular pressure and its relationship with infusion pressure in ... more To determine the behavior of intraocular pressure and its relationship with infusion pressure in vitrectomy, phacofragmentation and phacoemulsification surgeries in rabbits. Intraocular pressure fluctuation was measured in 24 eyes of 12 rabbits submitted to vitrectomy, phacofragmentation and phacoemulsification procedures (eight eyes per group). The procedures were divided according to the force of aspiration of the instrument. Intraocular pressure was monitored with a computerized polygraph by means of a cannula introduced into the vitreous chamber. Intraocular pressure showed a mean variation from 33 mmHg (maximum) to 6 mmHg (minimum). Vitrectomy showed the greatest difference between weak and strong aspiration. The greatest fluctuations occurred during procedures with strong aspiration, with phacoemulsification showing the widest variation, with maximum peaks almost reaching 50 mmHg. The infusion pressure varied less than the intraocular pressure, especially at the lowest pressures. The fluctuation of intraocular pressure during ocular surgeries was not great. The higher the aspiration pressure, the higher the intraocular pressure. The infusion pressure did not show a good correlation with intraocular pressure.

Brazilian Journal of Infectious Diseases, 2007

This study determined the total frequency of patients with AIDS and ophthalmologic problems befor... more This study determined the total frequency of patients with AIDS and ophthalmologic problems before and after the introduction of combined highly active antiretroviral therapy (HAART), regardless of the use of this treatment; it also determined the frequency of external ocular diseases, intraocular infections and inflammations, and problems of the anterior portion of the optic nerve in these two groups of patients; and it determined the differences in the frequency of ophthalmologic problems in patients receiving HAART or not. This was a retrospective study of 207 patients examined using the same protocol, from June 1995 to February 1998 (n=58, pre-HAART era) and from March 1998 to May 2005 (n=149, HAART era). The frequency of ophthalmologic problems was significantly higher in the pre-HAART group, with a predominance of intraocular infections and inflammations. Comparison of patients receiving HAART or not revealed that ocular involvement tended to be reduced in the treated group and that treatment was effective in preventing infectious diseases; however, the prevalence of external ocular diseases was similar in the patients receiving HAART or not. As a consequence of HAART, we observed a reduction in the frequency of ocular problems, especially intraocular infections and inflammations. However, this benefic influence was less important in the ocular surface or in external ocular disease.

Journal of microbiology and biotechnology, Jan 28, 2013

The emergence of microcarrier technology has brought a renewed interest in anchorage-dependent ce... more The emergence of microcarrier technology has brought a renewed interest in anchorage-dependent cell culture for high-yield processes. Well-known in vaccine production, microcarrier culture also has potential for application in other fields. In this work, two types of microcarriers were evaluated for small-scale monoclonal antibody (mAb) production by CHOK1 cells. Cultures (5 ml) of microporous Cytodex 3 and macroporous CultiSpher-S carriers were performed in vented conical tubes and subsequently scaled-up (20 ml) to shake-flasks, testing combinations of different culture conditions (cell concentration, microcarrier concentration, rocking methodology, rocking speed, and initial culture volume). Culture performance was evaluated by considering the mAb production and cell growth at the phases of initial adhesion and proliferation. The best culture performances were obtained with Cytodex 3, regarding cell proliferation (average 1.85 ± 0.11 × 10(6) cells/ml against 0.60 ± 0.08 × 10(6) cells/ ml for CultiSpher-S), mAb production (2.04 ± 0.41 μg/ml against 0.99 ± 0.35 μg/ml for CultiSpher-S), and culture longevity (30 days against 10-15 days for CultiSpher-S), probably due to the collagen-coated dextran matrix that potentiates adhesion and prevents detachment. The culture conditions of greater influence were rocking mechanism (Cytodex 3, pulse followed by continuous) and initial cell concentration (CultiSpher-S, 4 × 10(5) cells/ml). Microcarriers proved to be a viable and favorable alternative to standard adherent and suspended cultures for mAb production by CHO-K1 cells, with simple operation, easy scale-up, and significantly higher levels of mAb production. However, variations of microcarrier culture performance in different vessels reiterate the need for optimization at each step of the scale-up process.

Methods in molecular biology (Clifton, N.J.), 2014

Microcarrier technology opened new perspectives for anchorage-dependent cell culture, by providin... more Microcarrier technology opened new perspectives for anchorage-dependent cell culture, by providing increased surface areas for cell adhesion and proliferation, and therefore improving both cell and product yields obtained in these cultures. The establishment of a successful microcarrier culture depends on many factors, such as the type of microcarrier, the cells, and the culture conditions. In this chapter, the basic steps required for the evaluation and optimization of a microcarrier culture for the purpose of production of recombinant proteins are described, for both solid and porous microcarriers.

Transactions of The Royal Society of Tropical Medicine and Hygiene, 2004

In order to evaluate the association between serum vitamin A levels and ocular lesions attributab... more In order to evaluate the association between serum vitamin A levels and ocular lesions attributable to non-complicated malaria, 200 patients seen consecutively at the Malaria Outpatient Clinic of FUNASA, Manaus, Amazonas, Brazil were included in this study. Ophthalmologic examination consisted of indirect binocular ophthalmoscopy under medicamentous mydriasis, biomicroscopy with a portable slit lamp and measurement of central visual acuity. Vitamin A serum concentration was determined by HPLC, and deficiency was defined as serum values equal to or lower than 0.35 μmol/l. Serum vitamin A values between 0.36 and 0.70 μmol/l were considered as marginal levels. Hypovitaminosis A (≤0.70 μmol/l serum levels) was observed in 33% (66/200) of the patients. Ocular lesions were associated with serum levels ≤0.35 μmol/l (P<0.001). Vitamin A deficiency was more frequent in patients with high parasitaemia (P=0.029) and their first episode of malaria (P=0.016). None of the patients showed clinical or ophthalmologic signs attributable to hypovitaminosis A.

New Biotechnology, 2000

The high dose requirements of biopharmaceutical products led to the development of mammalian cell... more The high dose requirements of biopharmaceutical products led to the development of mammalian cell culture technologies that increase biomanufacturing capacity. The disposable Wave bioreactor is one of the most promising technologies, providing ease of operation and no cross-contamination, and using an innovative undulation movement that ensures good mixing and oxygen transfer without cell damage. However, its recentness demands further characterization. This study evaluated the residence time distribution (RTD) in Wave, allowing the characterization of mixing and flow and the comparison with ideal models and a Stirred tank reactor (STR) used for mammalian cell culture. RTD was determined using methylene blue with pulse input methodology, at three flow rates common in mammalian cell culture (3.3 × 10−5 m3/h, 7.9 × 10−5 m3/h, and 1.25 × 10−4 m3/h) and one typical of microbial culture (5 × 10−3 m3/h). Samples were taken periodically and the absorbance read at 660 nm. It was observed that Wave behavior diverted from ideal models, but was similar to STR. Therefore, the deviations are not related to the particular Wave rocking mechanism, but could be associated with the inadequacy of these reactors to operate in continuous mode or to a possible inability of the theoretical models to properly describe the behavior of reactors designed for mammalian cell culture. Thus, the development of new theoretical models could better characterize the performance of these reactors.► Residence time distribution in Wave and Stirred tank bioreactors was evaluated. ► Wave behavior diverts from ideal models. ► Wave and Stirred tank reactors behave similarly. ► New models need to be developed to describe mammalian cell culture reactors behavior.

Brazilian Journal of Infectious Diseases, 2008

Studies carried out in various populations have reported an association between some HLA specific... more Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I), 103 patients with AIDS without tuberculosis (Group II) and 423 healthy individuals not infected with HIV (Group III) were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR). Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 p=0.026; HLA-B41 p= 0.037; HLA-DRB1*10 p=0.037; HLA-DQB1*5 p=0.009. Group I x Group III (control): HLA-A31 p = 0.000008; odds ratio (OR)=31.75; HLA-B41 p=0.003; HLA-DQB1*5 p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I), suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS.

Acta Ophthalmologica Scandinavica, 2003

Purpose: To evaluate the human leucocyte antigen (HLA) class 1 (HLA-A and HLA-B) and HLA class 2 ... more Purpose: To evaluate the human leucocyte antigen (HLA) class 1 (HLA-A and HLA-B) and HLA class 2 (HLA-DRB1 and HLA-DQB1) allele profiles in the susceptibility to cytomegalovirus retinitis (CMV-R) in patients with AIDS.Methods: Cytomegalovirus retinitis was clinically diagnosed by indirect binocular ophthalmoscopy. Human leucocyte antigens class 1 were typed using a complement-dependent microlymphocytotoxicity assay, and HLA class 2 alleles were identified using amplified DNA hybridized to sequence-specific oligonucleotide primers.Results: The frequencies of HLA class 1 antigens and HLA class 2 alleles observed in patients and controls were similar; however, HLA-A31 antigen was over-represented in patients with AIDS, independent of the presence of CMV-R.Conclusion: There was no association between HLA molecules/alleles and CMV-R in Brazilian patients with AIDS. However, the results support the role of the HLA system in the susceptibility to developing AIDS.

Journal of Molecular Histology, 2009

Activity of metalloproteinases 2 and 9 (MMP-2 and 9) during promotion and progression of rat live... more Activity of metalloproteinases 2 and 9 (MMP-2 and 9) during promotion and progression of rat liver carcinogenesis was investigated in a modified resistant hepatocyte model. Development of preneoplastic liver lesions positive for glutathione S-transferase 7-7-(GST-P 7-7-positive PNL) and tumors besides hepatocytes positive for proliferating cell nuclear antigen (PCNA) were quantified and compared to MMP-2 and-9 activity using gelatin zymography. Marked increases in GST-P 7-7-positive PNL development, PCNA labeling indices, MMP-2 (pro, intermediate and active forms) and pro-MMP-9 activity were observed after proliferative stimulus induced by 2-acetylaminofluorene (2-AAF) exposure cycles. After 2-AAF withdrawal, increase in MMP-2 activity was detected only in neoplastic mixed lesions, whereas active MMP-9 was increased in both PLN and neoplastic tissues. Our findings suggest that MMP-2 may be associated with proliferative events induced by 2-AAF rather than with selective growth of PNL and that MMP-9 could be associated with progression of PNL and neoplastic mixed lesions.

The humanized anti-pl85HER2 antibody, humAb4D5-8, has completed Phase II clinical trials for pl85... more The humanized anti-pl85HER2 antibody, humAb4D5-8, has completed Phase II clinical trials for pl85HER2-overexpressing breast cancer. Here, this antibody is used as a building block to engineer a disulfide-linked Fv (dsFv) ÃŸ-lactamase fusion protein for use in antibody-dependent enzymemediated prodrug therapy using cephalosporin-based prodrugs. Three Fv variants were designed with an interchain disulfide bond buried at the VL/VH interface and secreted from Escherichia coli. One variant, dsFv3 (VL L46C VH D101C), has similar affinity for antigen (Kd = 0.7 nM) as the wild-type Fv and was used to construct a fusion protein in which ÃŸ-lac tamase, RTEM-1, is joined to the carboxy terminus of V,,. The dsFv3-ÃŸlactamase fusion protein secreted from E. coli efficiently activates a cephalothin doxorubicin prodrug (PRODOX, kca/km = 1.5 x 10s s'1 NT1).

Clinics (São Paulo, Brazil), 2013

OBJECTIVE: The objective of this study was to assess the effects of resistance training on oxidat... more OBJECTIVE: The objective of this study was to assess the effects of resistance training on oxidative stress markers in the livers of ovariectomized rats. METHOD: Adult Sprague-Dawley rats were divided into the following four groups (n = 8 per group): shamoperated sedentary, ovariectomized sedentary, sham-operated resistance training, and ovariectomized resistance training. During the resistance training period, the animals climbed a 1.1-m vertical ladder with weights attached to their tails; the sessions were conducted 3 times per week, with 4-9 climbs and 8-12 dynamic movements per climb. The oxidative stress was assessed by measuring the levels of reduced glutathione and oxidized glutathione, the enzymatic activity of catalase and superoxide dismutase, lipid peroxidation, vitamin E concentrations, and the gene expression of glutathione peroxidase.

Acta Cirurgica Brasileira, 2014

To analyze the epidemiological features of patients with esophageal cancer according to the histo... more To analyze the epidemiological features of patients with esophageal cancer according to the histopathological types: squamous cell carcinoma or adenocarcinoma.