Production of nanocellulose gels and films from invasive tree species.

Wood from invasive tree species Acacia dealbata and Ailanthus altissima was used to produce high value-added nanocellulose. Firstly, bleached pulps were produced from the wood of these tree species after kraft cooking. Afterwards, the resultant pulps were pre-treated by TEMPO-mediated oxidation (Acacia dealbata) or enzymatic hydrolysis (Ailanthus altissima) followed by high-pressure homogenization. Hydrogels were obtained and characterized for their main physical and chemical properties, including rheology measurements. After freeze-drying, the surface properties of the materials were evaluated by inverse gas chromatography. Results showed that nano/micro fibrils could be obtained from the wood of these invasive species. Rheometry studies showed that Acacia-TEMPO cellulose nanofibrils form strong gels with high yield stress point and viscosities (reaching ca. 100,000 Pa·s). Additionally, the surfaces of the obtained nanocelluloses showed a dispersive component of the surface energy near 40 mJ/m2 and a prevalence of the Lewis acidic character over the basic one, as typical for cellulose-based materials. Finally, films with good mechanical and optical properties could be obtained from the cellulose hydrogels. Acacia-TEMPO film (produced by filtration/hot pressing) showed a tensile strength of 79 MPa, Young's modulus of 7.9 GPa, and a transparency of 88%. The water vapor barrier, however, was modest (permeability of 4.9 × 10-6 g/(Pa·day·m)).

Familial hypercholesterolemia: Is there a role for PCSK9 and thrombin generation?

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease. The prevalence of FH has previously been reported as 1 in 500 in the general population. This study aimed to evaluate the proprotein convertase subtilisin/kexin 9 (PCSK9) levels, lipid profile and thrombin generation in FH patients undergoing treatment or not. METHODS: Eighty individuals with FH were selected and distributed in 2 groups: individuals treated with statins alone or conjugate therapy (statin + ezetimibe) (T = 53) and those non treated (NT = 27). PCSK9 levels were determined by ELISA, the lipid profile by colorimetric enzyme method and thrombin generation assay (TGA) by CAT method. RESULTS: Individuals treated with conjugate therapy (statin + ezetimibe) showed a significant reduction in the levels of total cholesterol (TC) low density lipoprotein cholesterol (LDLc) and in the potential for thrombin generation (ETP with low and high concentration of tissue factor), compared to the treated individuals with monotherapy (statins). PCSK9 was positively correlated with increased levels of TC, LDLc and triglycerides, while TGA parameters were positively correlated with PCSK9 and lipid profile. CONCLUSION: PCSK9 levels appear to be associated with components of the lipid and hemostatic profiles, in addition to being influenced by age. In general, our findings suggest that combined therapy for the treatment of FH is associated with a significant improvement in both lipid and hemostatic profiles assessed by TGA, suggesting a reduction in atherogenic and thrombogenic risks and, therefore, more promising compared to the use of statin monotherapy.

Efeito da suplementação com óleo de avocado (Persea americana Mill) na temperatura superficial corpórea de equinos antes e após exercício em esteira / [Effect of supplementation with avocado oil (Persea americana Mill) on body surface temperature of horses before and after exercise on treadmill]

Oito equinos foram distribuídos em delineamento randomizado cruzado, sendo um grupo sem suplementação (GC) e outro grupo suplementado com óleo de avocado (GOAv) por um período de sete semanas. Ao fim da sexta semana, os animais foram submetidos a teste padrão de exercício progressivo (TPEP) e, após sete dias, a teste de baixa intensidade e longa duração (BILD). Após o primeiro ciclo, houve período de descanso "washout" de 30 dias para troca de grupos para o segundo ciclo, que seguiu o protocolo do primeiro. A termorregulação foi avaliada com base na temperatura retal e na temperatura superficial corpórea, obtidas por termografia, de 15 regiões de interesse. A temperatura retal e as imagens termográficas foram obtidas antes, um minuto e 15 minutos após o exercício. Não houve diferença entre os grupos GC e GOAv em nenhum momento. Os resultados obtidos neste estudo revelaram que a suplementação de 5% da matéria seca (MS) com óleo de avocado por seis e sete semanas não influenciou na termorregulação com base na temperatura superficial corpórea dos equinos submetidos ao teste padrão de exercício progressivo (TPEP) e ao exercício de baixa intensidade e longa duração (BILD), respectivamente.(AU)

Eight equines were distributed in a randomized crossover design, one control group (CG) without supplementation and another group supplemented (SG) with avocado oil for a period of six weeks. At the end of the sixth week, the animals were submitted to standard exercise test (SET) and after seven days to the low intensity test (LIT). After the first cycle, there was a 30-day washout rest period to exchange groups for the second cycle, which followed the protocol of the first one. Thermoregulation was evaluated based on rectal temperature and body surface temperature of 15 regions of interest obtained by thermography. Rectal temperature and thermographic images were obtained before, one minute and 15 minutes after exercise. There was no difference between the CG and SG at any time. The results obtained in this study revealed that the supplementation of 5% of dry matter with avocado oil for six and seven weeks did not influence the thermoregulation based on the body surface temperature of the horses submitted to SET and LIT, respectively.(AU)

Efeito do extrato de Bidens pilosa L, Mel e pomadas homeopática e alopática na cicatrização de feridas cutâneas de ratos Wistar / [Effect of Bidens pilosa L, Honey extract and homeopathic and allopathic ointments on the healing of skin wounds of Wistar rats]

Cicatrização de ferida é um processo dinâmico, que tem por objetivo restaurar a continuidade do tecido lesionado. No entanto, em alguns casos, é necessário favorecer condições adequadas para viabilizar o processo fisiológico. Neste estudo foram utilizados ratos Wistar, divididos aleatoriamente entre cinco grupos, com 12 animais cada, sendo eles: grupo P (Bidens pilosa L.), grupo mel, grupo Co1 (pomada comercial alopática), grupo Co2 (pomada comercial homeopática) e grupo CT (controle). As lesões foram geradas por incisão com punch de 8mm, sendo tratadas diariamente de forma tópica. Foram eutanasiados quatro animais por grupo, no terceiro, sétimo e 14º dias do experimento, e o material coletado foi armazenado em formalina 10% e encaminhado para processamento histológico. Posteriormente, realizou-se a contagem de leucócitos mononucleares, fibroblastos e neovasos e avaliou-se a arquitetura de fibras colágenas. Os resultados da contagem foram analisados pela ANOVA, seguida pelo teste de Tukey (P<0,05). O modelo experimental proposto neste estudo demonstrou que todos os tratamentos apresentaram potencial cicatrizante, com exceção do mel. A aplicação tópica do creme do extrato de Bidens pilosa L. a 10% apresentou melhor perfil anti-inflamatório; a pomada alopática apresentou boa aderência à superfície da lesão e a pomada homeopática, grande potencial angiogênico, com menor tempo de cicatrização.(AU)

Wound healing is a dynamic process that aims to restore the continuity of injured tissue. However, in some cases it is necessary to favor adequate conditions to enable the physiological process. Wistar rats were randomly divided into 5 groups with 12 animals each, namely: group P (Bidens pilosa L.), group honey, group Co1 (commercial allopathic ointment), group Co2 (commercial homeopathic ointment) and group CT (control). The lesions were generated by an 8mm punch incision and were treated topically daily. Four animals per group were euthanized on the 3rd, 7th and 14th day of the experiment and the collected material was stored in 10% formalin and sent for histological processing, after which mononuclear, fibroblasts and neovascular leukocytes were counted and collagen fiber architecture was evaluated. Counting results were analyzed by ANOVA, followed by Tukey test (p <0.05). The experimental model proposed in this study showed that all treatments had healing potential, except honey. The topical application of 10% Bidens pilosa L. extract cream showed the best anti-inflammatory profile; Allopathic ointment showed good adhesion to the surface of the lesion and homeopathic ointment showed great angiogenic potential with shorter healing time.(AU)

Effect of Camellia sinensis teas on left ventricular hypertrophy and insulin resistance in dyslipidemic mice.

The control of dyslipidemia using plants is an important subject of studies since it has numerous benefits in cardiovascular protection. The objective of this study was to evaluate the effect of three Camellia sinensis L. teas (green, red, and white) on left ventricular hypertrophy and insulin resistance in low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet. The LDLr-/- mice were divided into four experimental groups: Group C: standard feed; Group CT: standard feed and three teas, Group HL: high-fat feed; HLT Group: high-fat feed and three teas. The three types of tea (green, red, and white) originated from different processing of the Camellia sinensis L. plant, and were administered associated once a day at a dose of 25 mg/kg by gavage for 60 days. The teas partially prevented hyperlipidemia, the decrease of the serum levels of high-density lipoproteins (HDL), insulin resistance, and increased C-reactive protein (CRP) levels, and completely prevented left ventricular hypertrophy in LDLr -/- mice of the HLT group. In conclusion, the three Camellia sinensis L. teas used to control genetic dyslipidemia associated with a high-fat diet can be used as an auxiliary treatment associated with the control of lipid intake, thus promoting cardiac protection against hyperlipidemia.

Effect of Camellia sinensis teas on left ventricular hypertrophy and insulin resistance in dyslipidemic mice

The control of dyslipidemia using plants is an important subject of studies since it has numerous benefits in cardiovascular protection. The objective of this study was to evaluate the effect of three Camellia sinensis L. teas (green, red, and white) on left ventricular hypertrophy and insulin resistance in low-density lipoprotein receptor knockout (LDLr-/-) mice fed a high-fat diet. The LDLr-/- mice were divided into four experimental groups: Group C: standard feed; Group CT: standard feed and three teas, Group HL: high-fat feed; HLT Group: high-fat feed and three teas. The three types of tea (green, red, and white) originated from different processing of the Camellia sinensis L. plant, and were administered associated once a day at a dose of 25 mg/kg by gavage for 60 days. The teas partially prevented hyperlipidemia, the decrease of the serum levels of high-density lipoproteins (HDL), insulin resistance, and increased C-reactive protein (CRP) levels, and completely prevented left ventricular hypertrophy in LDLr -/- mice of the HLT group. In conclusion, the three Camellia sinensis L. teas used to control genetic dyslipidemia associated with a high-fat diet can be used as an auxiliary treatment associated with the control of lipid intake, thus promoting cardiac protection against hyperlipidemia.

Evaluation of potential biomarkers for the diagnosis and monitoring of Systemic Lupus Erythematosus using the Cytometric Beads Array (CBA).

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune, multisystemic disease. Currently diagnosis depends on complex criteria developed by the American College of Rheumatology. Moreover, the lack of specific biomarkers also challenges the diagnosis. METHODS: Inflammatory biomarkers such as IL-8, IP-10, MIG, MIP-1α and RANTES were measured in serum samples from SLE patients and subjects in control groups (patients with other autoimmune diseases and healthy individuals). Forty-six SLE patients (22 patients with low activity, SLEDAI-2 K ≤ 4, 24 patients with moderate/high activity, SLEDAI-2 K > 4), 42 patients with other autoimmune diseases (OAD group), and 8 healthy volunteers participated in this study. RESULTS: MIG (p < .001) and RANTES (p < .001) concentrations in SLE patients and healthy controls, and IP-10 concentrations in SLE patients with different disease activities (low activity, p < .01, moderate/high activity, p < .05) differed significantly. IL-8 (p < .001) and MIP-1α (p < .001) concentrations in SLE patients differed from those in patients from the OAD group. IL-8 (p < .05), IP-10 (p < .01), MIG (p < .05), MIP-1α (p < .001), and RANTES (p < .05) were correlated with SLE activity; their concentrations in SLE patients with low and moderate/high activity differed significantly. CONCLUSIONS: Given the findings of this study, one can envision the possibility of future use of some of these cytokines to assist in the screening of SLE patients, or even in monitoring disease activity.

Comparação dos parâmetros bioquímicos entre gestação única e gemelar de ovelhas da raça Dorper durante gestação, parto e pós-parto / Comparison of biochemical parameters between single and twin pregnancies of Dorper breed ewes during gestation, lambing and postpartum

Nas ovelhas, a demanda de nutrientes aumenta durante a gestação, especialmente nas últimas seis semanas, quando ocorre maior desenvolvimento do feto. Os objetivos deste trabalho foram estudar o perfil bioquímico de ovelhas durante a gestação e no periparto imediato, comparando-se gestação única com gemelar. Foram utilizadas 60 ovelhas, Dorper, divididas em dois grupos experimentais com base no diagnóstico de gestação ultrassonográfico: grupo 1: 30 ovelhas com feto único; grupo 2: 30 ovelhas com gestação gemelar. Em nove momentos de coleta, foram mensurados no soro sanguíneo: ureia, creatinina, proteína total (PT), albumina, globulina, aspartato aminotransferase (AST), gamaglutamiltransferase, fosfatase alcalina, colesterol e triglicérides. O peso vivo das ovelhas do G2 foi maior que do G1 em todos os momentos, inclusive quando estavam vazias. Houve diferença entre as ovelhas do G1 e do G2 nos valores de PT, albumina, AST e triglicérides. A partir de 120 dias de gestação, o perfil proteico se modificou, com menores níveis de ureia, PT, albumina e globulina, mostrando que a demanda metabólica se intensificou no último mês da gestação. Os níveis de colesterol e triglicérides diminuíram de 140 dias de gestação para o parto. Este trabalho mostrou que a gestação proporcionou mudanças significativas no metabolismo da ovelha, principalmente no terço final da gestação, quando há maior necessidade de acompanhamento para evitar a incidência de doenças metabólicas.(AU)

In sheep, nutrient demand increases during gestation, particularly in the last six weeks, when the fetuses develop. The objectives of this study were to evaluate the biochemical profile of ewes during pregnancy and in the immediate peripartum comparing single with twin pregnancies. Sixty ewes of Dorper breed were divided into two groups by pregnancy ultrasonographic diagnosis: 1 - 30 ewes with single fetus gestation; 2 - 30 ewes with twin pregnancy. In nine collection moments the following parameters were measured: urea, creatinine, total protein (TP), albumin, globulin, aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, cholesterol and triglycerides. The weight of G2 sheep was higher than G1 since they were empty. There were differences in G1 and G2 sheep metabolism in TP, Albumin, AST and Triglycerides. From 120 days of pregnancy, the protein profile changed, with lower levels of urea, TP, albumin and globulin, showing that the metabolic demand intensified in the last month of pregnancy. The levels of cholesterol and triglycerides decreased from 140 days of pregnancy to lambing day. This study showed that gestation provided significant changes in the ewe's metabolism, especially in the final third of gestation, when there is a greater need to follow the animals to avoid the incidence of metabolic diseases.(AU)

Toxicological Evaluation of Essential Oil From the Leaves of Croton argyrophyllus (Euphorbiaceae) on Aedes aegypti (Diptera: Culicidae) and Mus musculus (Rodentia: Muridae).

Plant-derived essential oils can be used as insecticides for vector control. However, to establish their safety, it is necessary to perform toxicological studies. Herein, we evaluated the chemical composition and insecticidal activity of the essential oil from the leaves of Croton argyrophyllus on the third- and fourth-instar larvae and adult Aedes aegypti (L., 1762). We also evaluated the acute toxicity of the essential oil in adult female Mus musculus. The lethal concentration 50 (LC50) and 90 (LC90) of C. argyrophyllus essential oil on larvae of Ae. aegypti were 0.31 and 0.70 mg ml-1, respectively, and 5.92 and 8.94 mg ml-1, respectively, on Ae. aegypti adults. The major components of the essential oil were spathulenol (22.80%), (E)-caryophyllene (15.41%), α-pinene (14.07%), and bicyclogermacrene (10.43%). It also displayed acute toxicity in adults of Mus musculus; the intraperitoneal and oral lethal dose 50 (LD50) were 2,000 mg kg-1 and 2,500 mg kg-1, respectively. The results showed that the essential oil from C. argyrophyllus leaves has insecticidal activity on Ae. aegypti larvae and adults at an average lethal concentration below the median lethal dose needed to cause acute toxicity in the common mouse.

Synergism of thymol, carvacrol and eugenol in larvae of the cattle tick, Rhipicephalus microplus, and brown dog tick, Rhipicephalus sanguineus.

The effects of combinations of the monoterpenes thymol and carvacrol and the phenylpropanoid eugenol in larvae of Rhipicephalus microplus (Canestrini, 1888) (Acari: Ixodidae) and Rhipicephalus sanguineus sensu lato (s.l.) (Acari: Ixodidae) were assessed by the larval packet test. The CompuSyn program was used to make qualitative assessments of the effects (synergistic, additive and antagonistic) of the associations. The effects of all combinations tested against R. microplus larvae were synergistic, with combination indices (CIs) <0.70. When tested against R. sanguineus, eight of the mixtures showed a synergistic effect (CI < 0.70); only the carvacrol + thymol mixture at LC50 presented a moderate synergistic effect, with CIs between 0.70-0.90. This study is the first to determine the effects of the interactions of these substances in the control of these two tick species. The combinations of carvacrol + thymol, carvacrol + eugenol and thymol + eugenol have synergistic effects in R. microplus and R. sanguineus s.l. larvae.

Developing a methodology to predict PM10 concentrations in urban areas using generalized linear models.

A methodology to predict PM10 concentrations in urban outdoor environments is developed based on the generalized linear models (GLMs). The methodology is based on the relationship developed between atmospheric concentrations of air pollutants (i.e. CO, NO2, NOx, VOCs, SO2) and meteorological variables (i.e. ambient temperature, relative humidity (RH) and wind speed) for a city (Barreiro) of Portugal. The model uses air pollution and meteorological data from the Portuguese monitoring air quality station networks. The developed GLM considers PM10 concentrations as a dependent variable, and both the gaseous pollutants and meteorological variables as explanatory independent variables. A logarithmic link function was considered with a Poisson probability distribution. Particular attention was given to cases with air temperatures both below and above 25°C. The best performance for modelled results against the measured data was achieved for the model with values of air temperature above 25°C compared with the model considering all ranges of air temperatures and with the model considering only temperature below 25°C. The model was also tested with similar data from another Portuguese city, Oporto, and results found to behave similarly. It is concluded that this model and the methodology could be adopted for other cities to predict PM10 concentrations when these data are not available by measurements from air quality monitoring stations or other acquisition means.

The association of HPV genotype with the regression, persistence or progression of low-grade squamous intraepithelial lesions.

BACKGROUND: Human papillomavirus (HPV) is a highly prevalent sexually transmitted virus causing cytological alterations that precede cervical cancer. Approximately 130 genotypes have been sequenced. Low-grade squamous intraepithelial lesions (LSIL) are the most frequent cytological alteration and have an uncertain behavior. OBJECTIVES: To analyze the frequency of HPV types in LSIL and their association with the regression, persistence or progression of these lesions. METHODS: A cohort study of forty patients with LSIL cytology was conducted from December 2007 to March 2011. The follow-up lasted two years and included cytology and colposcopy. HPV detection was performed using PCR, and genotyping was performed using PCR-specific and RFLP techniques. RESULTS: DNA-HPV was detected in 87% (35/40) of the cases, with oncogenic HPV accounting for 76%; type 16 in 32% (11/35) and type 18 in 20%. LSIL regression, persistence and progression rates at the end of the study were 60%, 23% and 17%, respectively. There was 50% regression in lesions in the high oncogenic risk group (types 16 and 18). CONCLUSION: HPV 16 was the most frequent genotype found in LSIL. The persistence and progression of the LSIL were related to the persistence of oncogenic HPV. The longer the follow-up time, the lower the LSIL persistence rate and the higher its regression rate; the progression rate remained stable. In addition to the presence of oncogenic HPV, other factors are necessary for the progression of LSIL.

Lack of association between potential prothrombotic genetic risk factors and arterial and venous thrombosis.

Recent studies have shown an association between thrombosis and factor VII (FVII), tissue factor (TF), and angiotensin-converting enzyme (ACE). This suggests that individuals with FVII-402 G/A, FVII-401 G/T, TF+5466 A/G, and ACE-287 insertion/deletion (I/D) polymorphisms present an increased risk of venous thrombosis, heart disease, and ischemic stroke compared with controls. In this study, we investigated the frequencies of these polymorphisms and their association with arterial and venous thrombosis. For the FVII-402 G/A polymorphism, there were 57.3% heterozygote (HT) genotypes and 8.3% homozygote (HM) genotypes in the patients, and 45.2% HT genotypes and 15.4% HM genotypes in the controls. For the FVII-401 G/T polymorphism, there were 37.5% HT genotypes and 3.1% HM genotypes in the patients, and 32.7% HT genotypes and 4.8% HM genotypes in the controls. The polymorphism TF+5466 A/G was not found in any of the samples analyzed. For the ACE-287 I/D polymorphism, there were 43 (40.6%) HT genotypes and 63 (59.4%) HM genotypes in the controls and 28 (45.2%) HT genotypes and 34 (54.8%) HM genotypes in the patients. No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.

Leptin in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-ß protein (Aß) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function.

Heritability and lifestyle factors in chronic low back pain: results of the Australian twin low back pain study (The AUTBACK study).

BACKGROUND: Heritability and population-specific lifestyle factors are considered to significantly contribute to chronic low back pain (LBP), but traditional population studies fail to (1) adjust for genetics; and (2) use standard and validated definitions for LBP and for lifestyle factors. METHODS: Using a classical and a co-twin control study design and validated definitions for chronic LBP and lifestyle variables, we explored the relative contribution of genetics and environment on the prevalence of chronic LBP in a sample of adult Australian twins. RESULTS: Data from 105 twin pairs showed that the prevalence of chronic LBP is significantly determined by genetic factors (heritability = 32%). Additionally, monozygotic twins were five times more likely to have chronic LBP than dizygotic twins when one of the siblings of the pair was affected. In a case-control analysis (n = 38 twin pairs), an exploratory analysis showed higher prevalence of chronic LBP associated with light walking exercises and vigorous gardening or heavy work around the house. Daily time spent in sitting was also positively associated with chronic LBP, but not moderate physical activities such as jogging, cycling and gentle swimming. In the final multivariate model, only time spent in vigorous gardening or heavy work around the house remained associated with chronic LBP (odds ratio 6.5; 95% confidence interval 1.47-28.8). CONCLUSIONS: The type, frequency and duration of physical activity may be important to understand risk factors for chronic LBP. The causation path between chronic LBP and people's engagement in activities involving frequent bending and twisting such as gardening and housework should be further investigated.

Validation of otolith daily increments in early juveniles of shanny Lipophrys pholis.

To assess the periodicity of micro-increment formation in otoliths of Lipophrys pholis, 90 early juveniles were immersed in alizarin red S or tetracycline hydrochloride for 24 h and sacrificed after 10, 20 and 30 days. The number of micro-increments viewed under light microscopy was significantly related to the duration of the experimental period, and the slopes of the linear regressions were not significantly different from 1. This study indicates that micro-increments in sagittae were deposited daily and can be used as reliable sources of age information for L. pholis.

HLA-A, HLA-B and HLA-DRB1 haplotype frequencies in Piauí's volunteer bone marrow donors enrolled at the Brazilian registry.

This study aimed to report the antigen and haplotype frequencies (HFs) of volunteer bone marrow donors (VBMDs) from the state of Piauí who were enrolled in the National Volunteer Bone Marrow Donor Registry (REDOME). The research subjects were 21,943 volunteer bone marrow donors, predominantly young adult women (53.3%). The most frequent allelic group was HLA-A2, followed by -DRB1*13, -DRB1*04, -DRB1*07, -B*15, -B∗35, -B*44, -A*24 and -A*03. Of the 2,704 haplotypes observed, the three most frequent haplotypes were A*29 B*44 DRB1*07 (1.45%), A*01 B*08 DRB1*03 (1.4%) and A*03 B*07 DRB1*15 (0.92%). These three haplotypes were in linkage disequilibrium. PCA showed that 98% of the VBMDs have HLA allele frequencies that are very similar to those from Teresina, the capital city of Piauí. According to the PCA results, these municipalities are distributed with a close proximity to Teresina, which in turn has a close genetic proximity to the Hispanic ethnicity, intermediate proximity to Caucasians and Africans and a distant kinship to Amerindians. The hierarchical proximity of the population of Piauí to the Portuguese and Hispanic populations to shows the strong influence of the latter on the former.

Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy.

GSTM1 (glutathione S-transferase mu 1) and GSTT1 (glutathione S-transferase theta 1) are critical enzymes for detoxification of endogenous and environmental carcinogens. Constitutive GST gene polymorphisms may be associated with increased risk for cancer development. We made an explorative study of a Brazilian population with malignant glioma to determine whether GSTM1 and GSTT1 genetic polymorphisms influence the response to intranasal administration of perillyl alcohol and the survival rate. Patients were stratified into groups according to clinical presentation, tumor classification, and tumor location. Circulating DNA was extracted from blood plasma or serum, and genotypes were detected by multiplex PCR. The cohort included 95 patients with recurrent malignant glioma included in a Phase I/II clinical trial with perillyl alcohol and 100 matched healthy control subjects. GSTM1 frequency was similar in patients with glioma (44%) and healthy controls (54%), but GSTT1 deletion was found in 11.5% patients, contrasting with 36% in controls. A longer survival rate was associated with a lack of GSTM1 deletion (31 weeks) and a deletion for GSTT1 (28 weeks). A poor survival rate was associated with GSTM1 deletion (23 weeks) and with a lack of a GSTT1 deletion (19 weeks). A significantly lower frequency of GSTT1 deletion in glioma patients compared to healthy controls indicates that GSTT1 deletion may exert a protective role against gliomagenesis, influence therapeutic response to intranasal perillyl alcohol treatment, and increase overall survival, especially considering tumor topography.