Triagem antifúngica de extratos obtidos de espécies vegetais do nordeste brasileiro

The increase in the incidence of fungal infections due to the drug-resistance or to the number of patients with immune alterations such as AIDS, chemotherapy or organ transplantation, has done the research necesseray for new antifungal drugs. The species from Northeastern Brazil may become an important source of innovative natural molecules. To evaluate the antifungal activity of 10 medicinal plants from Northeastern Brazil, traditionally used as antimicrobial agents, 30 crude extracts (CE) were tested in vitro against four standard species of Candida spp. The CE most promising of these plants were evaluated against yeasts of the oral cavity of kidney transplant patients and through a bioassay-guided fractionation. The extracts form leaves of E. uniflora, the stem bark of L. ferrea and leaves of P. guajava showed significant activity against all yeasts evaluated, with MIC values between 15.62 and 62.5 μg/mL. E. uniflora also showed fungicidal properties against all yeasts, especially against Candida dubliniensis. In patients with immune systems compromised, such as transplanted, oral candidiasis manifests mainly due to immunosuppressive therapy, and resistance to conventional antifungals. The CE of E. uniflora presented range of MIC values between 1.95 to 1000 μg/mL, and lower MIC50 and MIC90 values were observed against C. non-albicans. Due the better results, the CE of E. uniflora was elected to performe the bioassay-guided fractionation. Thus it was possible to obtain enriched fractions, which showed good inhibitory ability against ATCC strains of Candida spp. It was also possible to perform experiments to verify the production of biofilm in two strains of C. dubliniensis and action of extracts and fractions on the same. With this, we observed a behavior between the yeast ATCC and clinical isolate. In addition, CE, fractions and subfractions of E. uniflora inhibit planktonic cells to preventing the growth of biofilm. The preliminary chemical characterization of the fractions obtained revealed the presence of polyphenols (especially flavonoids and tannins). Finally, the results suggests that among the plant species studied, E. uniflora showed a pattern very promising as regards the antifungal, requiring further study of purification and structural elucidation of compounds in order to verify that the antifungal effect found can be attributed to a specific compound or some mechanism depends on synergistic the mixture of polyphenols

Purine nucleoside phosphorylase: A potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.

Kinetics and crystal structure of human purine nucleoside phosphorylase in complex with 7-methyl-6-thio-guanosine

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and drugs that inhibit this enzyme may have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Here, we describe kinetics and crystal structure of human PNP in complex with 7-methyl-6-thio-guanosine, a synthetic substrate, which is largely used in activity assays. Analysis of the structure identifies different protein conformational changes upon ligand binding, and comparison of kinetic and structural data permits an understanding of the effects of atomic substitution on key positions of the synthetic substrate and their consequences to enzyme binding and catalysis. Such knowledge may be helpful in designing new PNP inhibitors. © 2005 Elsevier Inc. All rights reserved.

Cytomegalovirus and Toxoplasma gondii seroprevalence in a Brazilian liver transplant waiting list

Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in solid organ transplantation. Disseminated toxoplasmosis after liver transplantation is a rare but fatal event. Serologic screening of the donor and the recipient is essential to prophylactic management, early diagnosis and therapeutic strategies to minimize the consequences of these infections. The aim of the present study was to determine the seroprevalence of CMV and Toxoplasma gondii (TG) in a Brazilian liver transplant waiting list (LTWL). Serological data were collected from 44 candidates on the LTWL between May 2003 and November 2004. Serological investigation of antibodies IgM and IgG against CMV (anti-CMV) and TG (anti-T. gondii) was performed using fluorometry commercial kits. IgG anti-CMV was positive in 37 patients (94.9%) out of 39 available results. There were not IgM anti-CMV positive results. Out of 36 analyzed patients, 22 (61.1%) presented positive IgG anti-T. gondii and none had positive IgM anti-T. gondii. The high CMV seroprevalence among our LTWL reinforces the need for appropriate protocols to avoid related complications, like reactivation and superinfection by CMV. Environmental and drug prophylactic strategies against primary infection and reactivation, as well as early diagnosis and treatment of toxoplasmosis complications, are essential for the good outcome of transplant patients.

The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats - A morphological evaluation

Background: Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies. Objective: The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats. Materials and methods: Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar. Results: After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P > 0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the V f and Vcf (P < 0.05). Conclusions: Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related. © 2007 Blackwell Munksgaard All rights reserved.

Cyclosporine-a and bone density around titanium implants: A histometric study in rabbits

Aim: Cyclosporine A (CsA) is an immunosuppressive agent commonly used to prevent organ transplantation rejection. It has been demonstrated that CsA may negatively affect osseointegration around dental implants. Therefore, the aim of this study was to evaluate the effect of CsA administration on bone density around titanium dental implants. Materials and Methods: Fourteen New Zealand rabbits were randomly divided into 2 groups with seven animals each. The test group (CsA) received daily subcutaneous injection of CsA (10mg/kg body weight) and the control group (CTL) received saline solution by the same route of administration. Three days after the beginning of immunosuppressive therapy, one machined dental implant (7.00 mm in lenght and 3.75 mm in diameter) was inserted bilaterally at the region of the tibial methaphysis. After 4 and 8 weeks the animals were sacrificed and the histometrical procedures were performed to analyse the bone density around the first four threads of the coronal part of the implant. Results: A significant increase in the bone density was observed from the 4- to the 8 week-period in the control group (37.41% + 14.85 versus 58.23% + 16.38 - p <0.01). In contrast, bone density consistently decreased in the test group overtime (46.31% + 17.38 versus 16.28 + 5.08 - p <0.05). In the 8-week period, there was a significant difference in bone density between the control and the test groups (58.23 + 16.38 eand16.28 + 5.08 - p= 0.001). Conclusion: Within the limits of this study, long-term CsA administration may reduce bone density around titanium dental implants during the osseointegration process.

Efeito fotodinâmico da curcumina em micelas de cetrimida sobre cepas de candida susceptíveis e resistentes a fluconazol

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Características morfológicas do osso alveolar de ratos tratados com ciclosporina-A ou tracolimus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O perfil de ensino das disciplinas de bioética, ética profissional (ou deontologia) e odontologia legal das faculdades de odontologia brasileiras

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação morfométrica e estereométrica dos tecidos periodontais de ratos imunossuprimidos por Tracolimus (FK506)

Pós-graduação em Odontologia - FOAR

Aspectos da toxoplasmose na clínica de pequenos animais

Toxoplasmosis, a zoonosis of worldwide distribution, has importance in human and veterinary medicine. Animals can be direct or indirect source of infection to man, and this intermediate host, the disease may be responsible for encephalitis and deaths due to congenital form as coinfection in neonates and patients with acquired immunodeficiency syndrome. The man and animals can acquire the disease by eating undercooked meat or cures, infected with tissue cysts, as well as food and water contaminated with oocysts. Iatrogenic, such as, blood transfusion and organ transplantation are other less frequent routes of transmission. The causative agent of this disease is Toxoplasma gondii, a protozoan obligate intracellular coccidian. In small animals, the infection has been reported in several countries, promoting varied clinical manifestations and uncommon but severe and fatal, which is a challenge in the clinical diagnosis of small animals, especially when the nervous system involvement. Thus, constitute the purpose of this review address the participation of small animals in the spread of the disease, clinical aspects related to it, as well as discuss methods of diagnosis, therapeutic measures, prophylaxis and control of this disease.

Percepções de profissionais de uma organização de procura de órgãos sobre a entrevista com familiares de potenciais doadores

In the last twenty years, and more expressively in the past decade, the search for improvement in the organ transplantation system has contributed to the achievement of positive results in the Brazilian statistics related to the survival of transplanted individuals. However, for a transplantation to be performed, a number of phases must be followed by professionals working in organ search services. The phase that generates the greatest tension is undoubtedly that of family interviews, as it involves both the feelings of relatives who are facing a recent loss and those of interviewers who need to know how to deal with families at this time. The goal of this study was to apprehend perceptions of professionals working for an Organ Search Organization concerning interviews with relatives of potential donors. The qualitative methodology was used by adopting the Collective Subject Discourse for data organization. Interviews were conducted with six staff members of an organ search service whose experience as interviewers comprised from eight to fourteen years of work. It was possible to apprehend the professionals’ perceptions of family interviews and identify facilitating and hindering factors in this phase of the donation process. Such factors mainly involve: contact with the teams assisting patients, the difficult moment that families are experiencing and the teams’ as well as the institution’s preparation for rendering this type of service. The balance between the offer of and demand for organs in Brazil will only be achieved by means of an efficient and effective structure in transplantation organ search services and increased donation consent rates to be obtained by adequate communication between interviewers and relatives

Cyclosporin A-induced new cementum formation: a morphometric evaluation in the periapical region of rats

Cyclosporin A (CsA) is a potent immunosuppressor used in organ transplantation and in the management of various autoimmune diseases. Recent studies have shown that CsA stimulates deposition of cementum on root surfaces. The aim of this study was to evaluate the periapical cementum thickness and the apical foramen width in CsA-treated rats. Rats weighing 50 g were treated with a daily injection of 10 mg/kg body weight of CsA in the chow for 60 days. The cementum of the mandibular 1st molars was histologically and morphometricaly examined by analysis of 5-microm-thick serial buccolingual paraffin sections stained with hematoxylin and eosin. Histometric and stereologic analyses revealed the presence of large amounts of cementum in all root surfaces, particularly abundant in the periapical region and obliterating the foramen. The volume density of cementoblasts did not increase. Five to 90 days after the termination of CsA therapy, there was no reduction of cementum thickness. These results suggest that cementum deposition is not reversible after cessation of CsA treatment.

Síntese e avaliação farmacológica de pró-fármacos derivados do ácido micofenólico úteis na prevenção e no tratamento da rejeição de transplantes

Pós-graduação em Ciências Farmacêuticas - FCFAR

Motivos da recusa à doação de órgãos apontados familiares de pessoas com morte encefálica

Purpose: Study aiming to understand the reasons for the refusal to donate organs by relatives of potential donors living in the Mid-Western region of the São Paulo state. Method: Qualitative study performed after data collection by the Organ Procurement Organization (OPO) Division of a reference hospital in the region. Relatives were contacted to participate in a semi-structured interview, and after the subjects in the study were characterized, four guiding questions were presented; their respective answers were recorded to be transcribed later. The Analysis of Content method proposed by Bardin was used to organize the speeches. Results: From 2006 to 2008, 30 (35.3%) families contacted by OPO have refused to agree with the organ donation. From that universe, 16 family members were interviewed. Data was systematized in three major themes: The experience of being informed on a family member’s brain death, decision concerning to the organ donation and aspects that would facilitate the decision to agree with the organ donation. Conclusion: the identification of reasons for the refusal and the suggestions presented has provided subsidies to improve the organ donation for transplantation process.