Alda Pereira da Silva

Plant extracts with anti-inflammatory properties-A new approach for characterization of their bioactive compounds and establishment of structure-antioxidant activity relationships

Geranium robertianum L. (Geraniacea) and Uncaria tomentosa (Willd.) DC. (Rubiaceae) plant extracts, frequently used in traditional medicine for treatment of inflammatory and cancer diseases, were studied to identify potential bioactive compounds that may justify their therapeutic use and their underlying mechanisms of action. Since some of the pharmacological properties of these plant extracts may be linked to their antioxidant potential, the antioxidant activity, in relation to free radical scavenging, was measured by the ABTS/HRP and DPPH() assays, presenting U. tomentosa the higher activity. The antioxidant activity was also evaluated by scavenging of HOCl, the major strong oxidant produced by neutrophils and a potent pro-inflammatory agent. U. tomentosa was found to be a better protector against HOCl, which may justify its effectiveness against inflammatory diseases. SPE/LC-DAD was used for separation/purification purposes and ESI-MS/MS for identification/characterization of the major non-volatile components, mainly flavonoids and phenolic acids. The ESI-MS/MS methodology proposed can be used as a model procedure for identification/characterization of unknowns without the prerequisite for standard compounds analysis. The ESI-MS/MS data obtained were consistent with the antioxidant activity results and structure-activity relationships for the compounds identified were discussed.

Antioxidants in medicinal plant extracts. A research study of the antioxidant capacity of Crataegus, Hamamelis and Hydrastis.

The antioxidant capacity of extracts of Crataegus oxyacantha, Hamamelis virginiana, Hydrastis canadensis, plants native to Europe and North America which have long been used in herbal medicine for the treatment of cardiac and circulatory functions, has been investigated. The total antioxidant potential conferred by all hydrogen donating antioxidants present in these extracts has been assessed by the ABTS assay and the relative order of antioxidant potential has been established. Gas chromatography coupled to mass spectrometry (GC‐MS) has been used for the chemical identification of the antioxidant volatile compounds present in the extracts. The GC‐MS data were related to the results obtained using the ABTS assay. Copyright

ACP1 genotype, glutathione reductase activity, and riboflavin uptake affect cardiovascular risk in the obese

Erythrocyte acid phosphatase (ACP locus 1), also known as low-molecular-weight protein tyrosine phosphatase, has previously been associated to glycemia, dyslipidemia, and obesity. In this study, ACP1 genotype and activity were tested in 318 women aged 19 to 83 (mean, 51.74 +/- 13.44) years. ACP1 genotype was found to directly correlate to glutathione reductase activity (P < .001) and levels of low-density lipoprotein cholesterol (P = .038). Glutathione reductase activity was in turn found to correlate to a series of cardiovascular risk factors such as systolic arterial pressure (P < .001), total cholesterol levels (P = .018), and low-density lipoprotein cholesterol levels (P = .039). A possible protective effect of ACP1 genotype AA against these cardiovascular risk factors was observed in this study. Furthermore, this work hypothesizes that nutritional riboflavin uptake becomes more crucial as body mass index increases, to counteract oxidative stress and minimize cardiovascular risk. This might be especially true in ACP1 genotypes AC, BC, and CC, which might possibly show the least endogenous protection against oxidative stress.

Sex steroid hormones influence the risk for cervical cancer: modulation by haptoglobin genetic polymorphism.

Sex steroid hormones ingestion (contraceptives and replacement therapy) may influence cervical carcinogenesis. Haptoglobin (Hp), an acute phase protein that has genetic polymorphism, can influence immune response to tumor. Our objective was to study the influence of haptoglobin genetic polymorphism on the risk for development of cervical cancer dependent on sex steroid hormones. A total of 492 Caucasian women, 196 pathologic [high-grade squamous intraepithelial lesions and invasive cervical cancer (HSIL + ICC)], ranging in age from 18 to 81 years, were phenotyped for plasma Hp using a polyacrylamide gel electrophoresis method. The effect of the interaction between the Hp genetic phenotype and steroid hormone therapy was analyzed using a multinomial logistic regression. Hp 1/1 genetic phenotype was associated with the risk for cervical cancer of steroid hormone ingestion: general risk odds ratio (OR)=5.388, P<0.001; for the interaction with carriers of Hp 1/1, OR=6.765, P<0.001; with carriers of Hp 2/1, OR=6.499, P<0.001; and with carriers of Hp 2/2, OR=3.903, P=0.001. The linear trend of risks that result from that interaction is also significant (chi2 =31.8, P<0.001). The higher risk for HSIL + ICC observed in carriers of increasing allele 1 of Haptoglobin probably results from the intense immune suppressor effect of this form of Hp, in addition to that of steroid hormones ingestion.

The Role of Haptoglobin and Its Genetic Polymorphism in Cancer: A Review

Acute phase response is a stereotyped innate nonspecific reaction of the body proceeding specific immune reactions. It ́s a systemic homeostatic reaction of the organism to local and or systemic disturbances caused by infections, tissue injury, trauma, immunologic disorders and neoplasias (Ron D et al 1990, Trautwein C et al 1994, Gruys E et al 2005). Proinflammatory cytokines are released at the place of tissue injury, diffuses locally and systemically to the vascular system and activates receptors on different target cells resulting in the activation of hypothalamic-pituitary-adrenal axis (HPAA), results in the production of growth hormone secretion and induces changes in the concentration of several plasma proteins (Ron D et al 1990, Trautwein C et al 1994, Gruys E et al 2005).

In Women with Previous Pregnancy Hypertension, Levels of Cardiovascular Risk Biomarkers May Be Modulated by Haptoglobin Polymorphism

Preeclampsia (PE) may affect the risk for future cardiovascular disease. Haptoglobin (Hp), an acute phase protein with functional genetic polymorphism, synthesized in the hepatocyte and in many peripheral tissues secondary of oxidative stress of PE, may modulate that risk through the antioxidant, angiogenic, and anti-inflammatory differential effects of their genotypes. We performed a prospective study in 352 women aged 35 ± 5.48 years, which 165 had previous PE, 2 to 16 years ago. We studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein (CRP), myeloperoxidase (MPO), and nitric oxide metabolites (total and nitrites), and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL, and apolipoproteins A and B). Finally, we study the influence of Hp genetic polymorphism on all these biomarkers and as a predisposing factor for PE and its remote cardiovascular disease prognosis. Previously preeclamptic women either hypertensive or normotensive presented significant differences in those risk biomarkers (MPO, nitrites, and ALT), whose variation may be modulated by Hp 1/2 functional genetic polymorphism. The history of PE may be relevant, in association with these biomarkers to the cardiovascular risk in premenopausal women.

Epistatic Interaction of CYP1A1 and COMT Polymorphisms in Cervical Cancer

There is a clear association between the excessive and cumulative exposure to estrogens and the development of cancer in hormone-sensitive tissues, such as the cervix. We studied the association of CYP1A1 M1 (rs4646903) and COMT (rs4680) polymorphisms in 130 cervical cancer cases (c-cancer) and 179 controls. The CYP1A1 TT genotype was associated with a lower risk for c-cancer (OR = 0.39, p = 0.002). The allele C of CYP1A1 was a risk for c-cancer (OR = 2.29, p = 0.002). Women with COMT LL genotype had a higher risk of developing c-cancer (OR = 4.83, p < 0.001). For the interaction of the CYP1A1&COMT, we observed that TC&HL genotypes had a greater risk for c-cancer (OR = 6.07, p = 0.006) and TT&HL genotypes had a protection effect (OR = 0.24, p < 0.001). The CYP1A1 TT and COMT LL genotypes had higher estradiol levels in c-cancer (p < 0.001 and p = 0.037, resp.). C-cancer is associated with less production of 2-methoxy-estradiol resultant of functional polymorphisms of CYP1A1 and COMT, separately. CYP1A1 and COMT work in a metabolic sequence and their interaction could lead to an alternative pathway of estrogen metabolism with production of 16-OH-estrone that is more proliferative.

Optimal Linearization of Nonlinear Control Models

Most of the existing linearization methods for nonlinear flight dynamics are based on the first order approximation of the model in the neighborhood of a given reference or equilibrium point. The resulting linear model approximates the nonlinear flight within relatively small variations of the state and the control around the reference point. However, the range of the domain within which the linearized model is valid is not known precisely. Besides, such an approach only applies for differentiable functions. The present paper deals with approximating a nonlinear model by a linear one in the state and control domains. Such a linearization problem is termed as optimal linearization. Existing approaches about optimal linearization deal with cases for which the functions underlying the nonlinear models are continuous, and require multidimensional integral computation. Therefore, these approaches may not be efficient for high dimension nonlinear dynamical systems. The proposed method leads to a linear regression problem based on a suitable sampling of the state and control domains, and its solution is found through a straightforward matrix inversion procedure. The method is applied to a nonlinear UAV model with much better results than using classical linearization.

PP004. The polymorphism C677T of methylenetetrahydrofolate reductase (MTHFR), may increase risk for future higher blood pressure in women with previous hypertension in pregnancy

INTRODUCTION The MTHFR is a key enzyme in the folate cycle involved in homocysteine remethylation. The T allele of MTHFR C677T polymorphism is associated with lower activity inhibiting the DNA methylation and protecting from oxidative stress. OBJECTIVES To evaluate the MTHFR genotype-phenotype relationship during and after pregnancy comparing hypertensive with normotensive women. METHOD A sample of 380 women with 32.54±6.478 years old, 181 normotensive (NT) and 199 hypertensive (HBP) being 70.3% above 34 weeks of gestation. A subgroup 63 women with history of preeclampsia were studied 3-6 years postpartum and compared with 59 controls. The MTHFR was evaluated by PCR-RFLP using DNA extracted from peripheral blood. Statistical analysis evaluated with appropriated tests. RESULTS The distribution of genotypes of the MTHFR was different according to blood pressure (BP), it was observed that the TT genotype had lower frequency in HBP (p<0.001). In the subgroup CC+CT the MPO levels were higher in HBP as well as nitrites, leucocytes, neutrophils, Apo B, BMI, waist and ratio waist/hip compared with NT (p<0.001, p=0.04, p=0.042, p=0.035, p=0.03, p=0.022, p=0.026, respectively). There were differences between levels of BP systolic and diastolic between women previously HBP and NT of CC+CT compared with TT carriers (p<0.001). CONCLUSION The MTHFR may modulate blood pressure (BP) and cardiovascular risk. TT genotype with increased expression of antioxidant enzymes, may be a protective factor for future hypertension and cardiovascular risk compared with women CC and CT genotypes with higher levels of circulating biomarkers of inflammation.