Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN

NASCIMENTO, H. G. ; FERNANDES, L. C. ; SOUSA, M. B. C. . Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN. Publica , v. 2, p. 39-48, 2006.

Avaliação de efeitos biológicos de antiinflamatórios derivados do ácido propiônico através de modelos experimentais em nível molecular e celular

Derivatives of propionic acid NSAIDs are irreversible inhibitors of cyclooxygenase enzyme widely used. The aim of this study was to evaluate, through different experimental models, biological effects of derivatives of propionic acid (fenoprofen, naproxen, ibuprofen and ketoprofen) in cellular and molecular level. The labeling of blood constituents with technetium-99m (99mTc) and morphological analysis of erythrocytes of blood of rats, as well as growth, survival of cultures of Escherichia coli (E. coli) and the assessment of bacterial plasmid electrophoretic profiles were models used for experimental evaluation of possible biological effects of antiinflammatory drugs. The results show that, in general, anti-inflammatory drugs evaluated were not able to alter the labeling of blood constituents with 99mTc, the morphology of red blood cells from blood of rats, as well as the growth of cultures of E. coli and the electrophoretic profile of plasmid DNA. However, naproxen appears to cytotoxic effect on bacterial cultures, plasmids and genotoxic effects in reducing the action of stannous chloride in cultures of E. coli. The use of experimental fast performance and low cost was important for assessment of biological effects, contributing to a better understanding of the properties of propionic acid derivatives studied. anti-inflammatory, blood constituents, technetium-99m, stannous chloride, Escherichia coli; DNA

Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN

NASCIMENTO, H. G. ; FERNANDES, L. C. ; SOUSA, M. B. C. . Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN. Publica , v. 2, p. 39-48, 2006.

Changes in peak expiratory flow and respiratory strength during the menstrual cycle

This study evaluated the spirometry and respiratory static pressures in 17 young women, twice a week for three successive ovulatory menstrual cycles to determine if such variables changed across the menstrual, follicular, periovulatory, early-tomid luteal and late luteal phases. The factors phases of menstrual cycle and individual cycles had no significant effect on the spirometry variables except for peak expiratory flow (PEF) and respiratory static pressures. Significant weak positive correlations were found between the progesterone:estradiol ratio and PEF and between estrogen and tidal volume (r = 0.37), inspiratory time (r = 0.22), expiratory time (r = 0.19), maximal inspiratory pressure (r = 0.25) and maximal expiratory pressure (r = 0.20) and for progesterone and maximal inspiratory pressure (r = 0.32) during the early-to-mid luteal phase. Although most parameters of the spirometry results did not change during the menstrual cycle, the correlations observed between sexual hormones and respiratory control variables suggest a positive influence of sexual female hormones controlling the thoracic pump muscles in the luteal phase

Avaliação das atividades anti-toxoplásmica, antioxidante e antiinflamatória dos monoterpenos timol (lippia sidoides) e estragol (croton zenhtneri)

Toxoplasmosis, a benign disease in normal healthy individuals, can have serious effects in pregnant women and immunocompromised patients. It is a parasitic disease caused by Toxoplasma gondii (Tg), an obligatory intracellular protozoan. The prophylactic and therapeutic arsenal against this parasite is very restricted. Thus, there is an ongoing search for novel drugs and therapeutic strategies. A promising alternative is a rational approach using medicinal plants. This study aimed to standardize methodologies for assessing the toxicological, antiproliferative, antioxidant, antiinflammatory and anti-Toxoplasma effects of Estragole and Thymol compounds isolated from species of plants (Lippia sidoides and Croton zenhtneri) commonly used in the Cariri region of Ceara State, Brazil. First we evaluated in vivo toxicity and conducted a pathological analysis of mice livers. In vivo antiinflammatory activity was assessed using air pouch and paw edema methods. Cytotoxicity assays were performed and antiproliferative, antioxidant and nitric oxide production analyzed. Anti-Toxoplasma activity was evaluated in a congenital experimental model with varying stages of maternal infection using the ME-49 strain and a non- congenital model by using ME-49 and RH strains. The results suggest low to moderate toxicity for both compounds. Thymol was more toxic in vivo and in vitro, having greater pathological repercussion than Estragole. The compounds were inactive for antiproliferative activity. Thymol showed better antioxidant activity, while Estragole stimulated nitric oxide production in macrophages. Both showed significant antiinflammatory activity. In non-congenital Tg infection, both compounds were active only against the ME49 strain. In congenital infection, Estragole (oral route) improved the newborn weight of infected mothers compared with untreated controls. Subcutaneous administration of the two compounds increased the weight of offspring born to infected mothers compared with untreated controls. We concluded that Estragole and Thymol exhibit important biological and anti-Toxoplasma activities. Further studies are needed to elucidate the mechanism of action of these compounds and other possible activities not investigated in the present study

Efeito pró-inflamatório de uma lectina purificada da esponja marinha Cliona varians

A galactose and sucrose specific lectin from the marine sponge Cliona varians named CvL was purified by acetone fractionation followed by Sepharose CL 4B affinity chromatography. Models of leukocyte migration in vivo were used to study the inflammatory activity of CvL through of mouse paw oedema and peritonitis. Effect of CvL on peritoneal macrophage activation was analyzed. Effects of corticoids and NSAIDS drugs were also evaluated on peritonitis stimulated by CvL. Results showed that mouse hind-paw oedema induced by sub plantar injections of CvL was dependent dose until 50µg/paw. This CvL dose when administered into mouse peritoneal cavities induced maxima cell migration (9283 cells/µL) at 24 hours after injection. This effect was preferentially inhibited by incubation of CvL with the carbohydrates D-galactose followed by sucrose. Pre-treatment of mice with 3% thioglycolate increases the peritoneal macrophage population 2.3 times, and enhanced the neutrophil migration after 24h CvL injection (75.8%, p<0.001) and no significant effect was observed in presence of fMLP. Finally, Pre-treatment of mice with dexamethason (cytokine antagonist) decreased 65.6%, (p<0.001), with diclofenac (non-selective NSAID) decreased 34.5%, (p<0.001) and Celecoxib (selective NSAID) had no effect on leukocyte migration after submission at peritonitis stimulated by CvL, respectively. Summarizing, data suggest that CvL shows pro-inflammatory activity, inducing neutrophil migration probably by pathway on resident macrophage activation and on chemotaxis mediated by cytokines

Polimorfismos de nucleotídeo único (SNPS) dos genes PPARy2, lipase lipoproteica, receptor de LDL, apolipoproteina C3, e adiponectina podem modular o perfil lipídico de pacientes com a síndrome de Berardinelli-Seip

A Síndrome de Berardinelli-Seip (SBS) é um distúrbio raro do metabolismo dos lipídios, caracterizada pela ausência quase total de tecido adiposo subcutâneo, hipertrigliceridemia, hipoleptinemia e diabetes insulino resistente ou lipoatrófico. Sua etiologia envolve implicações hipotalâmicas, alterações nos receptores de insulina e mutações nos genes AGPAT2, Gng3lg, CAV1 e PTRF. O tecido adiposo secreta diversas substâncias, tais como: leptina, resistina, adiponectina, esteróides, TNF , IL-6, PAI-1, angiotensinogênio, IGF-1. Muitas delas estão associadas ao diabetes mellitus tipo 2, obesidade e hipertensão. Os PPARs são fatores transcricionais pertencentes à superfamília de receptores nucleares ligantes ativados. Sabe-se que o PPAR , é importante para o metabolismo lipídico e glicídico e que o ligante natural do PPAR é derivado do ácido graxo. Nesse sentido, foram avaliados 24 pacientes portadores da SBS, provenientes do Estado do Rio Grande do Norte, com a mediana das idades de 18,5 anos (0,55 a 47 a), sendo 9 (37,5 %) do gênero masculino e 15 (62,5 %) do gênero feminino. Quanto ao grupo étnico, foram classificados em caucasóides (brancos) 21 (87,5 %) e negróides 3 (12,5 %) pacientes. Foram feitas avaliações clínico-endocrinológica, bioquímica, hormonal, molecular e o estudo dos polimorfismos Adiponectina ADIPOQ, PPARγ2 Pro12Ala, LPL-PvuII, APOC3-SstI e LDLR-AvaII em portadores da SBS. Nesta população nós não encontramos nenhuma associação de parâmetros lipídicos e glicídicos com os polimorfismos LPL-PvuII, APOC3-SstI e LDLR-AvaII. Porém, observamos associação entre Adiponectina ADIPOQ e PPARγ2 Pro12Ala e níveis lipídicos mais elevados, sugerindo um papel biológico para estes fatores, indicando estudos mais aprofundados

Avaliação citológica em base líquida de fármacos moduladores estrogênicos

Hormone therapy is an important tool in the treatment of breast cancer and tamoxifen represents one of the most important drugs used in this type of treatment. Recently other drugs based on the inhibition of aromatase had been developed, this enzyme is responsible for the synthesis of estrogenic esteroids from the androgenic ones. The objective of this study would be the development of a quantitative cytological model of murine estral analysis that allowed the characterization of different hormone drugs effect over vaginal epithelium. The technique of monochromatic staining with Evans blue (C.I. 23860) showed to be efficient in the qualitative and quantitative classification of the cycle. It had been observed differences in the cytological standard of animals submitted to the studied drugs; tamoxifen presented a widening of phases of lesser maturation (diestrais), while anastrozole and exemestane increased the duration of the phases of larger maturation (estrais). The data were analysed through a cubical non linear regression (spline) which allowed a better characterization of the drugs, suggesting a proper cytological profile to the antagonism of the estrogen receptor (tamoxifen), aromatase competition (anastrozole) and inhibition of the enzyme (exemestane)

Efeito do ácido alfa-lipóico sobre biomarcadores de estresse oxidativo, inflamação e fatores de risco cardiovascular em hipertensos

Alpha-lipoic acid (ALA) is a potent antioxidant with favourable anti-inflammatory, metabolic and endothelial effects, and has been widely investigated due to its potential against cardiovascular risk factors. This study aimed to evaluate the effect of oral ALA supplementation on oxidative stress biomarkers, inflammation and cardiovascular risk factors in patients with hypertension. This is a double-blind placebo-controlled randomized clinical trial, where the intervention was evaluated prospectively comparing results in both groups. The sample consisted of 64 hypertensive patients who were randomly distributed into ALA group (n = 32), receiving 600 mg / day ALA for twelve weeks and control group (n = 32), receiving placebo for the same period. The following parameters were evaluated before and after intervention: lipid peroxidation, content of reduced glutathione (GSH), enzymatic activities of glutathione peroxidase (GPx) and superoxide dismustase, ultrasensitive C-reactive protein (hs-CRP), triglycerides, total cholesterol and fractions, fasting glucose and anthropometric indicators. There was a statistically significant reduction (p <0.05) in serum concentrations of total cholesterol, very low density lipoprotein (VLDL), high density lipoprotein (HDL), triglycerides and blood glucose. There was a reduction in body weight and waist, abdominal and hip circumferences in the group that received ALA. In addition, there was a statistically significant increase (p <0.05) in the contents of reduced glutathione (GSH) and glutathione peroxidase (GPx) in the group receiving ALA. Oral administration of ALA appears to be a valuable adjuvant therapy, which may contribute to decrease the damage caused by oxidative stress and other risk factors associated with the atherosclerotic process

Estudo da preferência manual durante o desenvolvimento ontogenético em sagüi comum ( Callithix jacchus)

The study of manual preference is a widely used approach to investigate cerebral laterality in nonhuman primates. However, in New World primates, little is known about the ontogenesis of hand use asymmetry, in both forced and spontaneous activities, as well as how they correlate with sexual hormones. Accordingly, a longitudinal study was conducted on the manual preference of 6 female and 4 male common marmosets (Callithrix jacchus). The study included the record of forced tests to reach for the food using only one hand (forced activity) and activities such as grooming (auto and social), scratching, grasping the food and hanging, in weekly sessions from the infantile (4 months) to the early adult phase (15 months). Feces samples were also collected, at least once a week, to evaluate the level of gonadal steroids and their influence on these behaviors. In the forced activity, the results confirm the influence of the development period on manual preference during feeding, shown by the increase in lateral stability when grasping the food between the juvenile and adult phases. During this period, a sexual hormone effect on development was also observed, mainly of progesterone in females and androgen in males, but no difference between sexes was found. In the females, progesterone also influenced the manual preference index, with a proportional increase in the degree of manual asymmetry during puberty. With respect to spontaneous activities, the animals showed proportional use of both hands when scratching, hanging, holding the food and grooming. A positive correlation was also found between the preference for holding the food in forced activities and in spontaneous activities

Disfunção sexual feminina e níveis dos hormônios esteroidais em mulheres obesas atendidas no ambulatório de cirurgia bariátrica do hospital universitário Onofre Lopes em Natal/RN

A disfunção sexual corresponde a alterações em uma ou mais fases da resposta sexual humana e apresenta maior prevalência na população feminina. Ademais, a participação de alguns fatores como obesidade e níveis dos hormônios esteroidais na disfunção sexual feminina (DSF) permanece incerta. O presente estudo deteve-se na análise da ocorrência de DSF numa população de mulheres portadoras de obesidade, cadastradas no Ambulatório de Cirurgia Bariátrica do Hospital Universitário Onofre Lopes, da Universidade Federal do Rio Grande do Norte, no município de Natal, RN. O estudo foi realizado em uma amostra composta por trinta e uma mulheres, com idade entre 20 e 50 anos, com índice de massa corpórea (IMC) > 30 Kg/m2. A todas as pacientes foi aplicado um questionário composto por uma seção com dados socio-econômicos, e outra abordando a saúde sexual feminina, sendo esta última correspondente ao Female Sexual Function Index (FSFI), para diagnóstico de DSF. A partir dessa caracterização, as pacientes foram reunidas nos grupos CD (pacientes com disfunção, n= 9) e SD (sem disfunção, n= 22). Para a análise do efeito da obesidade na DSF, as pacientes foram reunidas nos grupos 1 (6 pacientes com IMC grau I e II: entre 30 e 40 Kg/m2) e 2 (25 com IMC grau III: acima de 40). Para o estudo da participação dos hormônios esteroidais foram determinadas as concentrações séricas de cortisol, estradiol e dehidroepiandrosterona (DHEA) pelo método de quimiluminescência. A análise estatística dos dados foi realizada usando os testes ANOVA, MANOVA (Pillai), além de análise de Cluster. Para identificar as diferenças entre os domínios do FSFI, foi usado o teste T de Student. A significância considerada para todos os testes foi para p< 0,01. Das pacientes estudadas, 25,8% apresentaram DSF de acordo com o escore total do FSFI. A análise estatística posterior evidenciou que as diferenças ocorreram para os domínios desejo, excitação e orgasmo. Não foi encontrada relação da presença de DSF com os diferentes graus de obesidade ou com os níveis hormonais dos esteróides cortisol, estradiol ou DHEA. Contudo, foi encontrado aumento significativo nos níveis séricos de estradiol para o grupo 1, que corresponde ao de menor índice de IMC. Estes resultados mostram que a prevalência de DSF não diferiu entre os graus I,II e III de obesidade das pacientes deste estudo mas, quando presente, a disfunção ocorre nos domínios desejo, excitação e orgasmo. A maior concentração de estradiol encontrada nas pacientes de menor índice de IMC sugere uma possível relação entre as duas variáveis que precisa ser investigada em estudos futuros.

Estudo etnofarmacológico e fitoquímico das espécies medicinais Cleome spinosa Jacq, Pavonia varians Moric e Croton cajucara Benth

In this present work an ethnographic research was performed with 84 native medicinal specimens from the Litoral Norte Riograndense, from which two plants Cleome spinosa Jacq e Pavonia varians Moric were submitted to ethnobotanic, phytochemistry and pharmacologic investigations. Additionally, a phytopharmacological research of the medicinal specimen Croton cajucara Benth ( native plant of the Amazon region of Brazil) was improved. The obtained phytochemical results of the C. spinosa and P. varians showed the presence of flavonoids constituents, among other components. The two flavonoids (2S)-5-hydroxy-7,4 -dimethoxy-flavanone and 5,4 -dihydroxy-3,7,3 -trimethoxy-flavone were isolated from C. spinosa. The antioxidant activity of the hydroalcoholic extracts of C. spinosa and P. varians solubilized in the microemulsion systems SME-1 and SME-4, was evaluated in the DPPHmethod. The used SME systems [obtained with Tween 80: Span 20 (3:1) and isopropyl myristate (IPM)] improved the dissolution of those tested polar extracts, with higher efficacy to the SME-1 system (in which ethanol was included as cosurfactant). The CE50 values evidenced for P. varians were 114 [g/mL (SME-1) and 246 [g/mL (SME-4); for C. spinosa it was 224 [g/mL (SME-1) and 248 [g/mL (SME-4), being the system SME-1 more effective for both tested extracts. The hydroalcoholic extracts of P. varians (HAE-PV) was also submitted to pharmacological screening for antinociceptive activity in animal models. The oral administration of this extract (100, 300 and 1000 mg/kg) inhibited the acetic acid-induced writhing in mice. The higher inhibition (74%) was evidenced to the 1000 mg/kg administered dose. Its effect on the central nervous system (CNS) was investigated by tail flick and formalin-method and reveled that it has negligible antinociceptive action on the CNS. After taking consideration of HAE-PV interaction, Pavonia varians Moric could be used as a potent analgesic agent in case of peripheral algesia, without affecting the CNS. The phytochemical study of the stem bark of Croton cajucara Benth lead to the isolation of 19-nor-clerodanetype diterpenes, as well as to the separation of its fixed oil FO-CC. This non polar oil material reveled to be rich in sesquiterpenes and 19-nor-clerodanes components. The biologic effect of OF-CC was evaluated in the development in vitro of the fungis phytopatogens such as Fusarium oxysporum, Rhizoctonia solani and Sclerotium rolfsii. Significant inhibitory effect of the tested fungis (at 0,2 mg.mL-1 dosage) were comproved. A Mass Spectrometry study of clerodane-type diterpenes was developed in order to identify characteristic fragments on mass spectrometra of both clerodane and 19-nor-clerodane presenting an α,β-insaturated carbonyl moiety at ring A of the decalin-system. For that study, mass spectroscopy data were analysed for 19-nor-clerodanes [trans-dehydrocrotonin (DCTN), trans-crotonin (CTN), cis-cajucarin B (c-CJC-B), and cajucarinolide (CJCR)] and for clerodanes [isosacacarin (ISCR) and transcajucarin A (t-CJC-A)] obtained from the stem bark of C. cajucara, and also clerodane-type from other species. The trans-junction of the enone-system clerodanes was clear correlated with the presence of the characteristic ions at m/z 95, 121 e 205. Meanwhile, the characteristics ions at m/z 122 e 124 were correlated to cis-junction. The trans-junction of the enone-system 19-nor-clerodanes showed characteristics ions at m/z 161, 134 e 121. This study could be successful employed for identification of clerodane constituents from other specimens without any additional spectroscopic analyses, as well as a previously phytochemical analyzes in clerodane project search

Changes in peak expiratory flow and respiratory strength during the menstrual cycle

This study evaluated the spirometry and respiratory static pressures in 17 young women, twice a week for three successive ovulatory menstrual cycles to determine if such variables changed across the menstrual, follicular, periovulatory, early-tomid luteal and late luteal phases. The factors phases of menstrual cycle and individual cycles had no significant effect on the spirometry variables except for peak expiratory flow (PEF) and respiratory static pressures. Significant weak positive correlations were found between the progesterone:estradiol ratio and PEF and between estrogen and tidal volume (r = 0.37), inspiratory time (r = 0.22), expiratory time (r = 0.19), maximal inspiratory pressure (r = 0.25) and maximal expiratory pressure (r = 0.20) and for progesterone and maximal inspiratory pressure (r = 0.32) during the early-to-mid luteal phase. Although most parameters of the spirometry results did not change during the menstrual cycle, the correlations observed between sexual hormones and respiratory control variables suggest a positive influence of sexual female hormones controlling the thoracic pump muscles in the luteal phase