Aline Siqueira Ferreira

Evaluation of inadequate anti-retroviral treatment in patients with HIV/AIDS

INTRODUCTION Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. METHODS A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. RESULTS The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 ± 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/ lamivudine was used, the patients were less compliant (χ² = 4.468, 1 degree of freedom, p = 0.035). CONCLUSIONS The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.

Leishmania amazonensis : Xylitol as inhibitor of macrophage infection and stimulator of macrophage nitric oxide production

Xylitol is a sugar alcohol being explored for clinical uses. The aim was to evaluate the effects of xylitol on Leishmania amazonensis-infected J774A.1 macrophages. Macrophages were infected with L. amazonensis for 3h, washed and incubated with 2.5 or 5.0% xylitol for 24, 48, and 72 h at 37 degrees C. Infection indexes for macrophages incubated only in medium were compared to those treated with xylitol. Cell viability and nitric oxide production were determined each time. Xylitol did not affect L. amazonensis or J774A.1 cell viabilities. Xylitol at 5.0% stimulated nitric oxide production by macrophages at 72 h (p<0.01). At 2.5 and 5.0%, xylitol inhibited nitric oxide production by L. amazonensis at 48 h (p<0.05) when compared to control. Infection indexes were significantly lower at 72 h (p<0.05), (16.9% and 9.6%) in cells cultivated with 2.5 and 5.0% xylitol, respectively, compared to control (38.4%). Results suggest a potential leishmanicidal action of the xylitol on infected macrophages.

A Fast and Cost-Effective Method for Identifying a Polymorphism of Interleukin 28B Related to Hepatitis C

Approximately 170 million people are chronic carriers of hepatitis C virus (HCV). Patients with chronic hepatitis C are currently treated with pegylated interferon and ribavirin (PEG-IFN/RBV). A genome-wide association with PEG-IFN/RBV treatment response and a single nucleotide polymorphism (rs12979860) has been identified near the interleukin 28B gene that encodes interferon-λ-3. In this paper, we describe an innovative, fast, and low-cost multiplex polymerase chain reaction with confronting two-pair primers that detects the rs12979860 polymorphism. The assay is internally controlled and does not require the use of restriction endonucleases or special equipment. Moreover, the assay decreases costs, being about 40% cheaper than direct sequencing methods.

Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers

BACKGROUND Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. OBJECTIVES The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. METHODS This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. RESULTS A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m [range, 1.56-1.80 m]; and body mass index, 25 [4] kg/m(2) [range, 18-29 kg/m(2)]). For RSP, mean (SD) C(max) values were 12.6 (2.7) and 16.0 (2.3) ng/mL for the test and reference formulations, respectively. For 9-OH-RSP, mean Cmax values were 17.8 (1.3) and 21.0 (1.7) ng/mL for the test and reference formulations. The 90% CIs for the mean test/ reference ratios for RSP C(max), AUC(0-120), and AUC(0-∞) were 74% to 82%, 75% to 85%, and 76% to 85%, respectively, and 83% to 87%, 75% to 79%, and 75% to 78% for 9-OH-RSP. The related adverse events (headache, low back pain, drowsiness, standing hypotension, local postvenipuncture ecchymoses, insomnia, nausea, and vomiting) were transient and mild. CONCLUSIONS This single-dose study found that the test and reference formulations of oral RSP 2 mg did not meet the Brazilian and US regulatory criteria for bioequivalence in these fasting, healthy volunteers. The study formulations appeared to be well tolerated.

Biological Properties of Sucupira Branca (Pterodon emarginatus) Seeds and Their Potential Usage in Health Treatments

Publisher Summary This chapter outlines the potential usage of sucupira branca seeds for health promotion and disease prevention. Pterodon emarginatus produces large quantities of viable seeds, which can be harvested directly from the fruit of the tree, or collected on the ground after the fall of the fruit. There is a growing interest in plants as new drug sources, and the genus Pterodon is attracting investigation because of its successful use in folk medicine. The Pterodon emarginatus seed preparation commonly used in folk medicine is a good source of a variety of active compounds, which suggests a proven therapeutic action. Pterodon emarginatus essential oil (EO) and the hexanic fraction (HF) from Pterodon emarginatus seeds showed a significant diminution of the number of writhings at 500 mg/kg, and their action was similar to that of indomethacin (5 mg/kg, p.o.), used as anti-inflammatory reference drug. In the formalin test, both EO and the seed methanolic fraction (MF) presented a biphasic licking response; this means that they act on the earlier phase, which seems to be caused predominantly by c-fiber activation due to peripheral stimulation. They also act on the later phase, which seems to be caused by tissue and functional changes in the dorsal horn of the spinal cord and is accompanied by inflammatory mediator release. Owing to its antimicrobial and antioxidative properties, Pterodon emarginatus could be used as an additive in the food industry. More studies should be performed to ensure the safety of Pterodon emarginatus in scientific applications.

UGT1A1*28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients: Outcomes from a case–control study

Abstract Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions’ to the liver disease scenario. Our aim was to assess UGT1A1 genotypes’ frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case–control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)–polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine–adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1*28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.

P01-565 - Functional impairment prevalence in Brazilian frailty elderly

Introduction Health life expectation could be defined in many ways. The notion of health life can considered, for example, physical, mental or social well-being; disease consequences; functional impairment; successful aging. Functional independence in daily activities is a key aspect on frailty elderly quality of life. This independence is related with elderly social and leisure activities, which improves their physical and mental health and brings sense to their life. Objectives Data obtained in other countries could not represent the national population; the objective was to describe a Brazilian frailty elderly sample. Aims Determine functional impairment prevalence in Brazilian frailty elderly. Methods 8769 frailty elderly were examined. Social data, tobacco and alcohol consumption were verified and the functional activities questionnaire was applied from May, 2009 to August, 2010. Results Female elderly was predominant (68.1%). They were almost married (47.3%), followed by widow (37.9%), single (9%), divorced (5.9%). White people were predominant (69.9%); black (14.9%) and brown (15.2%) were presented at the same proportion. Only 13.1% were smokers and 4.3% drank alcohol. The majority (78.7%) were younger than 80 years-old. Functional impairment prevalence was 9.5% in the 60–69 years old group; 18.9% in 70–79 years old group; 36.8% in 80–89 years old group and 61.3% in 90–99 years old group. Conclusions The prevalence of functional impairment increased with aging and we presented data obtained in a Brazilian sample. These data can be used to compare functional impairment in different countries and to stimulate elderly independence during their aging.

P01-563 - Prevalence of cognitive impairment in Brazilian frailty elderly

Introduction Accelerate aging is a worldwide problem. In underdeveloped countries, it is occurring without adequate planning and is attributed due to falling mortality and fertility, which contributed to increase life expectancy. However, aging was not accompanied by improvement in living conditions and health assistance. Poor sanitation and diet, low incomes and education levels contributed to increasing the prevalence of chronic diseases in elderly. Objectives Data obtained in other countries could not represent the national population; objective was to describe a Brazilian frailty elderly sample. Aims Determine cognitive impairment prevalence in Brazilian frailty elderly. Methods 1952 frailty elderly were analyzed. Social data, tobacco and alcohol consumption were verified and mini-mental state examination was applied from February to August in 2010. Results Female elderly was predominant (68.8%). They were almost married (47.5%), followed by widow (37%), single (8.1%), divorced (7.4%). White people were predominant (69.2%); black (14.6%) and brown (16.2%) were presented at the same proportion. 823 frailty elderly (64.9%) studied until 4 years; 7.7% studied between 4–8 years; 1.9% went to college and 25.6% were illiterate. Only 10.6% were smokers and 2.8% drank alcohol. The majority (79.4%) were younger than 80 years-old. Cognitive impairment prevalence were 17.2% in illiterate; 15.2% in elderly who studied until 4 years and lower, 5.3%, in the group who studied between 4–8 years. Conclusions The prevalence of cognitive impairment was dependent on years of study and we presented data obtained in a Brazilian sample. These data can be used to compare cognitive impairment in different countries.

Growth of Kluyveromyces marxianus yeasts strains in deproteined whey obtained from dairy industry

Natalia Oliveira Calil, Humberto Moreira Hungaro, Flavio Oliveira Ferraz, Aline Siqueira Ferreira, Silvio Silverio da Silva 1 Department of Food and Toxicology, Faculty of Pharmacy, Federal University of Juiz de Fora Juiz de Fora, MG – Brazil 2 Departament of Biotechnology (DEBIQ), University of Sao Paulo – EEL-USP Lorena-SP3 Brazil Faculdades Integradas Teresa D’Avila – FATEA – Lorena – SP – Brazil

An effective and biocompatible antibiofilm coating for central venous catheter

The aim of this study was to investigate the in vitro and in vivo efficacy and the tissue reaction of an antibiofilm coating composed of xylitol, triclosan, and polyhexamethylene biguanide. The antimicrobial activity was analyzed by a turbidimetric method. Scanning electron microscopy was used to evaluate the antiadherent property of central venous catheter (CVC) fragments impregnated with an antibiofilm coating (I-CVC) in comparison with noncoated CVC (NC-CVC) fragments. Two in vivo assays using subcutaneous implantation of NC-CVC and I-CVC fragments in the dorsal area of rats were performed. The first assay comprised hematological and microbiological analysis. The second assay evaluated tissue response by examining the inflammatory reactions after 7 and 21 days. The formulation displayed antimicrobial activity against all tested strains. A biofilm disaggregation with significant reduction of microorganisms adherence in I-CVC fragments was observed. In vivo antiadherence results demonstrated a reduction of early biofilm formation of Staphylococcus aureus ATCC 25923, mainly in an external surface of the I-CVC, in comparison with the NC-CVC. All animals displayed negative hemoculture. No significant tissue reaction was observed, indicating that the antibiofilm formulation could be considered biocompatible. The use of I-CVC could decrease the probability of development of localized or systemic infections.