Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Metabolic effects of androgen deprivation therapy

The therapeutic effects and side effects of androgen deprivation therapy (ADT), which is a main treatment method for metastatic prostate cancer, are well known, but the metabolic effects have only recently been studied. This review describes the effects of ADT on body habitus, insulin resistance, lipid profiles, diabetes, metabolic syndrome, and cardiovascular morbidity and mortality. The review was done by using KoreaMed and PubMed to search the medical literature related to prostate cancer, ADT, body habitus, lipid profile, diabetes, insulin resistance, metabolic syndrome, and cardiovascular disease. ADT increases fat mass and decreases lean body mass. Fat mostly accumulates in the subcutaneous area. ADT increases total cholesterol, triglycerides, and high-density lipoprotein, as well as the risk for insulin resistance and diabetes. ADT also increases the risk for cardiovascular events, but insufficient evidence is available for a correlation with mortality. ADT changes body habitus and lipid profiles and has different characteristics than those of classic metabolic syndrome, but it is related to insulin resistance and diabetes. ADT increases the risk for cardiovascular events. No consistent guidelines have been proposed for treating the metabolic effects of ADT, but the generally recommended treatment methods for lowering the risk of diabetes and cardiovascular disease should be fully understood. Additional studies are necessary.

Gengivas saudáveis retardam a progressão de aterosclerose nas carótidas / Healthy gums slow the progression of carotid atherosclerosis

Estudos têm associado a doença periodontal com a aterosclerose e as doenças cardiovasculares. Este trabalho apresenta resultados de importante estudo que evidencia essa relação. Esta é a primeira evidência que comprova que a melhora no periodonto, definido pelos aspectos clínicos e microbiológicos, está associada a menor progressão de aterosclerose das carótidas. O trabalho, uma coorte de base populacional,ressalta a importância de uma abordagem multidisciplinar para os pacientes, especialmente dos médicos e cirurgiões-dentistas, para a prevenção e controle das doenças cardiovasculares. Futuros estudos poderão mostrar que a saúde bucal pode ser um importante indicador prognóstico da saúde geral do paciente.

Studies have linked periodontal disease to atherosclerosis and cardiovascular diseases. This paper presents the results of a major study that underscores this relationship. This is the first evidence showing that better periodontal conditions, defined through clinical and microbiological aspects, are associated with less progression incarotid atherosclerosis. This population-based cohort study highlights the importance of a multidisciplinary approach to patients, especially for physicians and dentists, in order to prevent and control cardiovascular diseases. Future studies might well show that oral health could be an important prognostic indicator of general patient health.

Síndrome metabólica em pacientes atendidos em programa de reabilitação cardíaca / Metabolic syndrome among patients enrolled in a cardiac rehabilitation program

Fundamentos: Síndrome metabólica (SM) constitui importante fator de risco para o desenvolvimento de doenças cardiovasculares e, quando associada às cardiopatias, torna-se responsável por alto e crescente número de mortalidade. Objetivo: Estimar a frequência de SM em cardiopatas do Programa de Reabilitação Cardíaca de hospital universitário do Rio de Janeiro. Métodos: Estudo transversal, descritivo, com participantes do programa de Reabilitação Cardíaca,a partir de avaliação antropométrica e laboratorial,utilizando-se para diagnóstico de SM os critérios da International Diabetes Federation, 2005. Resultados: Foram avaliados 40 indivíduos, 26 homens e 14 mulheres, com média de idade 61,1±8,4 anos. De acordo com o índice de massa corporal, 77,5 % apresentavam sobrepeso e obesidade. Os valores médios de circunferência da cintura e relação cintura/altura encontravam-se, em ambos os sexos, superiores ao recomendado. A frequência de SM foi 83,0 %, sendo 77,0 % no sexo masculino e 93,0 % no sexo feminino. Entre os pacientes com diagnóstico de SM, as médias das medidas antropométricas foram significativamente maiores do que entre aqueles sem diagnóstico. Conclusões: Verificou-se elevada frequência de SM nos pacientes submetidos ao programa de RC, alertando para a importância da implementação de ações terapêuticas que visem à reversão da SM em pacientes já cardiopatas.

Background: Metabolic syndrome is a major risk factor for the development of cardiovascular disease, resulting in a high (and still rising) mortality rate when associated with cardiopathies. Objective: To estimate the frequency of metabolic syndrome in a Cardiac Rehabilitation Program at auniversity hospital in Rio de Janeiro. Methods: Cross-sectional descriptive study conducted with patients participating in a Cardiac Rehabilitation Program, grounded on anthropometric and laboratory assessments, with metabolic syndrome diagnosed through the criteria established by the International Diabetes Federation, 2005. Results: Forty subjects were assessed (26 men and14 women), with a mean age of 61.1±8.4 years. Based on the Body Mass Index, 77.5% were overweight and obese. The mean waist circumference and waist/height values were higher than recommended for both genders, with the overall prevalence of metabolic syndrome reaching 83.0% (77.0% males and 93.0%females). Among patients diagnosed with metabolic syndrome, the mean anthropometric measurements were significantly larger than among those without this diagnosis. Conclusions: A high frequency of metabolic syndrome was found among patients in a Cardiac Rehabilitation Program, underscoring the importance of implementing therapeutic actions aimed at reversing metabolic syndrome among patients with heart disease.

An amperometric cholesterol biosensor based on epoxy resin membrane bound cholesterol oxidase.

Background & objectives: The use of epoxy resin membrane as a support for immobilization of enzyme has resulted into improved sensitivity and stability of biosensors for uric acid, ascorbic acid and polyphenols. The present work was aimed to prepare an improved amperometric biosensor for determination of serum cholesterol required in the diagnostics and management of certain pathological conditions. Methods: Epoxy resin membrane with immobilized cholesterol oxidase was mounted on the cleaned platinum (Pt) electrode with a parafilm to construct a working electrode. This working electrode along with Ag/AgCl as reference and Ag wire as an auxiliary electrode were connected through a three terminal electrometer to construct a cholesterol biosensor. Results: The sensor showed optimum response within 25 sec at pH 7.0 and 45°C. The linear working range of biosensor was 1.0 to 8.0 mM cholesterol. Km and Imax for cholesterol were 5.0 mM and 9.09 μA, respectively. The biosensor measured serum cholesterol. The minimum detection limit of the sensor was 1.0 mM. The mean analytical recoveries of added cholesterol in serum (2.84 and 4.13 mM) were 91.4±2.8 and 92.3±3.1 per cent (n=6), respectively. Within and between assay coefficient of variation (CV) were <2 and <4 per cent, respectively. Biosensor had a storage life of 6 months at 4°C. Interpretation & conclusions: The use of epoxy resin membrane as a support for immobilization of cholesterol oxidase has resulted into an improved amperometric cholesterol biosensor. The present biosensor had an advantage over the existing biosensors as it worked at comparatively lower potential.

Efeito de duas variedades de feijão (Phaseolus vulgaris) no metabolismo lipídico de hamsters / Effect of two beans varieties (Phaseolus vulgaris) in hamster lipid metabolism

Introdução Os feijões comuns, da espécie Phaseolus vulgaris, são amplamente produzidos e consumidos no Brasil. As variedades, carioca e preto ganham destaque na região Sudeste do país. Encontra-se descrita na literatura a ação hipocolesterolemizante de algumas leguminosas, tais como, soja, tremoço e feijão caupi, que podem estar associados à redução do risco de doenças cardiovasculares. Objetivo Avaliar o potencial efeito da adição de farinhas de feijões carioca e preto (Phaseolus vulgaris) no metabolismo lipídico de hamsters alimentados com dieta contendo gordura saturada e colesterol. Métodos A produção das farinhas dos feijões envolveu as etapas de autoclavagem, congelamento, liofilização e moagem. As propriedades hipocolesterolemizantes destas farinhas foram avaliadas por meio de dois ensaios biológicos. Foram utilizados hamsters Golden Syrian, machos com 21 dias, pesando 60 ± 4g, que receberam as dietas experimentais ad libitum. No Ensaio A, os animais foram separados em 3 grupos, diferenciados pela dieta. Todas as dietas eram hipercolesterolemizantes [13.5 por cento de gordura de coco e 0.1 por cento colesterol] e tinham as mesmas quantidades de proteínas, carboidratos, fibras, vitaminas e minerais. O Grupo Controle (C) tinha como fonte protéica a caseína; no Grupo Feijão Carioca (FC) a farinha de feijão carioca representou 15 por cento do peso total da dieta e no Grupo Feijão Preto a farinha de feijão preto representou 15 por cento do peso total da dieta. No Ensaio B, os animais foram separados em três grupos novamente. Desta vez, a única diferença entre os grupos foi quanto a fonte protéica, para o grupo controle (C) somente caseína, para o grupo feijão carioca (FC), 67 por cento de feijão e 7,5 por cento de caseína e para o grupo feijão preto (FP), 62 por cento de feijão e 7,5 por cento de caseína. Nos dois ensaios, após 21 dias de experimento, foi realizada coleta de materiais biológicos (plasma, fígado e fezes). Resultados O processo de produção d...

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR) and normotensive control rat strains (WKY and NWR). Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Composição tecidual e centesimal e teor de colesterol da carne de cordeiros terminados em confinamento com dietas contendo níveis crescentes de resíduo úmido de cervejaria / Tissue and centesimal composition and cholesterol of the meat of lambs feedlot with diets with different levels of brewery's residue

Este estudo teve como objetivo avaliar a influência de diferentes níveis de substituição do alimento concentrado por resíduo úmido de cervejaria sobre a composição tecidual, a composição centesimal e o teor de colesterol da carne de cordeiros terminados em confinamento. Foram utilizados 25 cordeiros, machos, não-castrados, da raça Texel, distribuídos aleatoriamente em cinco tratamentos compostos por níveis de substituição do alimento concentrado por resíduo úmido de cervejaria, sendo: 0 por cento, 25 por cento, 50 por cento, 75 por cento e 100 por cento de substituição. Foram utilizadas uma dieta composta de feno de Tifton-85 e uma mistura concentrada em uma relação volumoso: concentrado de 40:60, com base na matéria seca (MS). O alimento concentrado foi constituído por milho desintegrado, farelo de soja, mistura mineral e resíduo úmido de cervejaria, sendo que suas proporções variaram de acordo com os tratamentos. As dietas foram formuladas para serem isoprotéicas, baseados no teor de proteína bruta (PB) do tratamento com maior nível de resíduo. Os cordeiros foram abatidos após um período experimental de 77 dias. Observou-se, na secção entre a 9ª e a 11ª costelas, que os pesos de osso, músculo e gordura diminuíram linearmente e a proporção de músculo aumentou linearmente com o incremento do nível de resíduo. Verificou-se aumento linear na proporção de umidade no músculo Longissimus dorsi com o aumento do resíduo úmido de cervejaria nas dietas dos cordeiros.

The purpose of this experiment was to evaluate the influence of different levels of substitution of the concentrate by brewery's residue on the tissue composition, centesimal composition and cholesterol content in the meat of lambs finished in feedlot. Twenty-five male, non castrated Texel lambs were used, distributed in five treatments, which consisted in the levels of brewery's residue replacing concentrate, being 0 percent, 25 percent, 50 percent, 75 percent and 100 percent of substitution. Diet's composition was Tifton-85 hay and concentrate mixture, in a relation roughage:concentrate of 40:60, on dry matter (DM). The concentrate was composed of corn ground grain, soybean meal, mineral mix and brewery's residue, and its proportion varied in accordance with the treatments. The diets were formulated to be isoproteics, based on the crude protein (CP) level of the treatment with the higher level of residue. The lambs were slaughtered after 77 days of experiment. It was observed, in the section between 9th and 11th ribs, that the weights of bone, muscle and fat had linearly decreased, and the proportion of muscle had linearly increased with the increase of the level of the residue. There was a linear increase in the proportion of humidity in the Longissimus dorsi muscle with the increase of the brewery's residue on the lamb's diets.

Effect of cholesterol and 7-beta hydroxycholesterol on glutathione status and nitric oxide production in murine peritoneal macrophages.

Present study was conducted to observe the effect of cholesterol and oxidized cholesterol (7beta-hydroxycholesterol,7beta-OH) on the nitric oxide (NO) production and the redox ratio by lipopolysaccharide-stimulated macrophages. Dose-dependent decrease in NO levels was seen with both cholesterol and 7beta-OH at different incubation intervals (6,12,18,24 hr) and concentrations (2.5,5,7.5microg/ml). On comparison, a significant decrease in the NO was observed at 24 hr interval in 7beta-OH exposed cells with all respective concentrations of cholesterol. Incubation with 7beta-OH also resulted in significant increase in levels of oxidized glutathione (GSSG) and decrease in reduced glutathione (GSH), while cholesterol showed no effect on GSSG levels. Moreover, GSH levels were lowered only at highest concentration (7.5microg/ml), and at longer incubation intervals (18,24 hr) with cholesterol exposure. This altered the redox status in both cholesterol/7beta-OH treated macrophages. Increased redox ratio and decreased NO levels indicated increased oxidative stress and decreased vasodilation by 7beta-OH compared to cholesterol.

Expression of 3b-Hydroxysteroid dehydrogenase and P450 side chain cleavage enzyme in the human uterine endometrium

The enzyme complex 3b-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. The expression of 3beta-HSD in human uterine endometrium during the menstrual cycle and decidua was examined in an effort to understand its role during ova implantation. 3beta-HSD was weakly expressed in the glandular epithelium of the proliferative phase and moderately expressed in the glandular epithelium of secretory phase of the endometrium. In the decidua of the ectopic pregnancy, 3beta-HSD was strongly expressed. The human uterine endometrial 3beta-HSD was identified as being the same type as the placental 3beta-HSD by RT-PCR and sequence analysis. In addition to the expression of 3beta-HSD, P450scc was expressed in the decidua of the ectopic pregnancy. These results suggest that pregnenolone might be synthesized from cholesterol by P450scc de novo and then, it is converted to progesterone by 3beta-HSD in the uterine endometrium. The data implies that the endometrial 3beta-HSD can use not only the out-coming pregnenolone from the adrenal gland but also the self- made pregnenolone to produce progesterone. The de novo synthesis of progesterone in the endometrium might be a crucial factor for implantation and maintenance of pregnancy.

Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically

Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.

Avaliaçäo hormonal, bioquímica e citológica em mulheres com idade entre 40 e 55 anos, sem reposiçäo hormonal, no interior de Pernambuco - Brasil / Hormonal, biochemical and cytological evaluation of women between 40 aand 55 years old, withouuut hormonal replacement therapy, in the rural area of the state of Pernambuco - Brazil

O climatério é marcado por mudanças somáticas e psíquicas. Costuma iniciar numa faixa etária que vai de 40 a 55 anos de idade. Este estudo analisou cinqüenta mulheres (n=50) que näo faziam uso de reposiçäo hormonal e medicaçäo para cardiopatias, residentes no interior de Pernambuco - Brasil. Foram realizadas dosagens bioquímicas no sangue com os seguintes resultados: glicose - 86,7 porcento das mulheres eram normoglicêmicas e 13,3 porcento hiperglicêmicas, com média de 102,43 mg/dl. Transaminase (TGP) com média de 16,38 unidade F.R./ml, 97,8 porcento com níveis normais. O colesterol total apresentou média igual a 222,3 mg/dl. 77,8 porcento das mulheres se apresentaram hipercolesterolêmicas. Na avaliaçäo hormonal a dosagem de estradiol e progesterona foi realizada dividindo a amostra estudada em três grupos: A, B e C. O grupo A, formado por mulheres com ciclos menstruais normais (n=31), utilizado como controle, apresentou 90,32 porcento com níveis normais de estradiol. O grupo B, composto por mulheres com ciclos irregulares (n=6) onde 100 porcento das pacientes estavam dentro da normalidade para esta fase. O grupo C, representado por mulheres menopausadas (n=13), acima de doze meses de amenorréia, 69,23 porcento apresentaram níveis dentro do esperado e 30,77 porcento acima. A média do nível de estradiol foi 58,12 pg/ml (p<0,00174). Na determinaçäo da progesterona, o grupo A obteve 100 porcento das pacientes apresentando níveis dentro da normalidade. O grupo B também 100 porcento dentro da normalidade. No grupo C, 84,62 porcento estavam dentro da normalidade para a faixa etária e 15,38 porcento com níveis acima do esperado. A média geral foi 4,11 ng/ml. Na citologia foram encontrado 68,9 porcento dos esfregaços normotróficos, 24,4 porcento hipotróficos e 6,7 porcento säo atróficos. As mulheres menopausadas apresentaram um grande percentual de normotrofismo apesar de mostrarem baixos os níveis de estradiol. Os níveis de progesterona sofreram um decréscimo significativo porém sem alterar o trofismo cérvico-vaginal, mostrando que näo existe uma correlaçäo direta. Os resultados sugerem que a reposiçäo hormonal deve ser bastante criteriosa e estudada caso a caso, levando em grande consideraçäo os níveis de estradiol e progesterona e o padräo de trofismo cérvico-vaginal

Biliary proteins from hepatic bile of rats fed curcumin or capsaicin inhibit cholesterol crystal nucleation in supersaturated model bile.

Following our earlier observations that curcumin and capsaicin are antilithogenic in mice and hamsters, attempts were now made to understand the manner in which these spice principles were acting. For this purpose, the hepatic biles of rats fed a control, lithogenic, and lithogenic diet supplemented with curcumin or capsaicin were subjected to gel filtration chromatography (sepharose-4B-Cl) and the LMW protein fractions were tested for their ability to influence cholesterol crystal growth in model bile. The LMW protein fraction from the lithogenic group bile shortened the nucleation time and increased the crystal growth rate and final crystal concentration. But with the LMW protein fractions from the biles of rats on the lithogenic group supplemented with curcumin or capsaicin, the nucleation times were prolonged and the crystal growth rates and final crystal concentrations were decreased. The LMW fractions were further purified into three different sugar specific proteins by affinity chromatography. A higher proportion of LMW proteins from the lithogenic group bile was bound to Con-A whereas higher proportions of LMW proteins from the groups fed with curcumin and capsaicin were respectively bound to wheat germ agglutinin and Helix pomatia lectin. The Con-A bound fraction obtained from the lithogenic group showed a pro-nucleating effect. In contrast, the WGA-bound fraction obtained from curcumin group or the Helix pomatia lectin bound fraction obtained from capsaicin group showed a potent antinucleating activity.

Niveles de colesterol sanguineo en poblaciones infantiles entre 6 y 10 años de dos estratos socioeconómicos diferentes / Serum cholesterol levels in children

Teniendo en cuenta que los niveles de colesterol sérico constituyen un factor predisponente para la aparición de enfermedades cardiovasculares y siendo un factor prevenible y detectable desde la infancia, se realizó un estudio clínico epidemiológico donde se determinaron las concentraciones de colesterol total sérico empleando el método enzimático (REFLOTRON), en 288 niños bogotanos con edades comprendidas entre los 6 y los 10 años de edad, de ambos sexos y pertenecientes a dos estratos socioeconómicos diferentes, con el fin de determinar los valores promedio y las posibles diferencias entre los dos sexos, grupos de edad y estrato socioeconómico. Dentro de los resultados, se obtuvieron valores promedio de colesterol total de 167,271 +/- 28,173 mg/dl, con diferencias significativas entre los promedios de la población de nivel socioeconómico medio alto y los de medio bajo (t<0,05). No se encontraron diferencias significativas en cuanto a la edad ni al sexo

Liquid membrane phenomenon in the actions of digitalis.

The liquid membrane phenomenon in the actions of digitalis glycosides (digitoxin, digoxin and ouabain) has been studied. Formation of liquid membranes, in series with a supporting membrane, by digitalis alone and by digitalis in association with lecithin and cholesterol has been demonstrated. The results obtained on the transport of relevant permeants, viz. sodium, potassium and calcium ions and dopamine, adrenaline, noradrenaline and serotonin, in the presence of the liquid membrane generated by digitalis in association with lecithin and cholesterol indicate that the liquid membrane barrier to transport may have a relevance with the biological actions of digitalis.