RESUMEN
Excitable temperament disrupts physiological events required for reproductive development in cattle, but no research has investigated the impacts of temperament on growth and puberty attainment in Bos indicus females. Hence, this experiment evaluated the effects of temperament on growth, plasma cortisol concentrations and puberty attainment in B. indicus heifers. A total of 170 Nelore heifers, weaned 4 months before the beginning of this experiment (days 0 to 91), were managed in two groups of 82 and 88 heifers each (mean ± SE; initial BW=238±2 kg, initial age=369±1 days across groups). Heifer temperament was evaluated via exit velocity on day 0. Individual exit score was calculated within each group by dividing exit velocity into quintiles and assigning heifers with a score from 1 to 5 (1=slowest; 5=fastest heifer). Heifers were classified according to exit score as adequate (ADQ, n=96; exit score⩽3) or excitable temperament (EXC, n=74; exit score>3). Heifer BW, body condition score (BCS) and blood samples were obtained on days 0, 31, 60 and 91. Heifer exit velocity and score were recorded again on days 31, 60 and 91. Ovarian transrectal ultrasonography was performed on days 0 and 10, 31 and 41, 60 and 70, 81 and 91 for puberty evaluation. Heifer was declared pubertal at the first 10-day interval in which a corpus luteum was detected. Exit velocity and exit score obtained on day 0 were correlated (r⩾0.64, P<0.01) with evaluations on days 31, 60 and 91. During the experiment, ADQ had greater (P<0.01) mean BCS and BW gain, and less (P<0.01) mean plasma cortisol concentration compared with EXC heifers. Temperament × time interactions were detected (P<0.01) for exit velocity and exit score, which were always greater (P<0.01) in EXC v. ADQ heifers. A temperament × time interaction was also detected (P=0.03) for puberty attainment, which was delayed in EXC v. ADQ heifers. At the end of the experiment, a greater (P<0.01) proportion of ADQ were pubertal compared with EXC heifers. In summary, B. indicus heifers classified as EXC had reduced growth, increased plasma cortisol concentrations and hindered puberty attainment compared to ADQ heifers. Moreover, exit velocity may serve as temperament selection criteria to optimize development of B. indicus replacement heifers.
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Bovinos/psicología , Hidrocortisona/sangre , Temperamento , Animales , Brasil , Bovinos/sangre , Bovinos/crecimiento & desarrollo , FemeninoRESUMEN
What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment. Methods Patients receiving intravenous polymyxin B treatment were followed throughout the course of treatment. Clinical, dermatoscopic, histologic and immunohistochemical skin properties of patients who presented with SH were studied. Results and discussion Skin hyperpigmentation was noted in 8% of patients (n=20/249); however, clinical, dermatoscopic, histologic and immunohistochemical examinations were performed only in three patients for whom the consent of relatives was obtained. Histologic and immunohistochemical findings showed an abundant melanocyte-pigmented dendritic network. Langerhans cells' hyperplasia and dermal IL-6 overexpression were also found, presumably for an inflammatory process due to polymyxin B use. As polymyxin B causes the release of histamine, which is known for its melanogenic effect, it is possible that skin darkening is associated with this inflammatory mediator. What is new These clinical and dermatoscopic findings contribute to a better understanding of how the pigmentary reaction manifests following intravenous polymyxin B treatment. Conclusion We concluded that hyperpigmentation due to intravenous polymyxin B treatment is associated with an inflammatory process and subsequent melanocyte activation. Although the pigmentary disorder neither influences the outcome of the therapy nor warrants discontinuation of treatment, it nevertheless considerably affects the patient's quality of life.
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Antibacterianos/efectos adversos , Hiperpigmentación/inducido químicamente , Melanocitos/metabolismo , Polimixina B/efectos adversos , Administración Intravenosa , Adulto , Antibacterianos/administración & dosificación , Farmacorresistencia Bacteriana Múltiple , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Masculino , Persona de Mediana Edad , Polimixina B/administración & dosificación , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: Bromelain is a mixture of proteolytic enzymes found in various tissues of the pineapple plant (Ananas comosus) and other species of Bromeliaceae. Owing to its proteolytic activity, bromelain has been used in the food, medical, pharmaceutical and cosmetic industries, for its cell renewal, anti-ageing, whitening and anti-cellulite properties. OBJECTIVE: This study evaluated the stability of bromelain (commercial powder) incorporated in topical formulations. METHODS: Bromelain was incorporated at three concentrations, 0.5%, 1.0% and 2.0%, in oil-in-water emulsion and gel, and stored for six months at varying stress conditions. Stability was accessed by measuring the changes in the protein content, enzymatic activity, viscosity, rheology, pH and colour of the selected formulations. RESULTS: The colour of all the samples changed after 180 days of incubation, indicating the concentration-dependence and temperature-sensitive nature of these formulations. No relationship was observed between the changes in the pH, temperature and luminosity exposure in all the samples. Gels proved to be the least preferred base for incorporation of bromelain for use as a topical formulation, owing to its inability to maintain the integrity of bromelain, thereby affecting the formulation characteristics. CONCLUSION: The emulsion-based formulations at all the concentrations of bromelain were more stable than the gel-based formulation over 180 days of evaluation, at a temperature of 5°C, protected from light.
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Bromelaínas/química , Administración Tópica , Bromelaínas/metabolismo , Color , Cosméticos , Reología , Temperatura , ViscosidadRESUMEN
Solar radiation, especially ultraviolet A (UVA) and ultraviolet B (UVB), can cause damage to the human body, and exposure to the radiation may vary according to the geographical location, time of year and other factors. The effects of UVA and UVB radiation on organisms range from erythema formation, through tanning and reduced synthesis of macromolecules such as collagen and elastin, to carcinogenic DNA mutations. Some studies suggest that, in addition to the radiation emitted by the sun, artificial sources of radiation, such as commercial lamps, can also generate small amounts of UVA and UVB radiation. Depending on the source intensity and on the distance from the source, this radiation can be harmful to photosensitive individuals. In healthy subjects, the evidence on the danger of this radiation is still far from conclusive.
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Iluminación , Piel/efectos de la radiación , Luz Solar , Rayos Ultravioleta , HumanosRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. METHODS: Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. RESULTS AND DISCUSSION: There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. WHAT IS NEW AND CONCLUSION: The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.
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Cisplatino/efectos adversos , Cisplatino/química , Composición de Medicamentos/métodos , Hipersensibilidad a las Drogas/etiología , Platino (Metal)/química , Antineoplásicos/efectos adversos , Antineoplásicos/química , Química Farmacéutica/métodos , Cromatografía Líquida de Alta Presión/métodos , Hipersensibilidad a las Drogas/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Xylitol is a natural sugar derived from plants, fruits and vegetables, whose antimicrobial properties are described in the literature. This study aimed to evaluate the antimicrobial effectiveness of C-8 xylitol monoester, for its use as a preservative in cosmetic formulations. The minimum inhibitory concentration (MIC) was determined by the broth macrodilution method, and the antimicrobial effectiveness of C-8 xylitol monoester was determined by using challenge test method. The results obtained in the determination of minimum inhibitory concentration are between 1.0% and 1.25% for Staphylococcus aureus, Escherichia coli and Candida albicans and between 1.0% and 1.5% for Pseudomonas aeruginosa and Aspergillus niger. The amount of 1% of C-8 xylitol monoester was added to the lotion used in the challenge test, observing a rapid decline in the number of CFU g(-1) in stages of evaluation after contamination of the product by all bacteria. The same occurs in relation to C. albicans, which shows a 90% reduction in the number of CFU g(-1). Regarding A. niger, similar reduction is observed when pH value of the lotion is adjusted from 5.5 to 7.0. The results indicate that under the tests conditions, C-8 xylitol monoester has antimicrobial activity and could be considered as an alternative preservative for cosmetic formulations.
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Antiinfecciosos/química , Cosméticos , Xilitol/química , Antiinfecciosos/farmacología , Ésteres , Pruebas de Sensibilidad Microbiana , Xilitol/farmacologíaRESUMEN
Interação medicamentosa (IM) é um evento clínico em que os efeitos de um fármaco são alterados pelo uso concomitante ou anterior à ingestão de outro fármaco, alimento ou bebida. O estudo teve como objetivo identificar IM em prescrições da Unidade de Terapia Intensiva (UTI) e do Alojamento Conjunto (AC). Foram avaliadas 36 prescrições da UTI e 274 do AC e as IM foram listadas como "maiores", "moderadas" e "menores", tendo por base o site Drugs.com. Na UTI, foram identificadas 105 interações maiores, 171 moderadas e 18 menores. Na AC, foram identificadas 64 interações maiores, 64 interações moderadas e 4 interações menores. Para as IM classificadas como "maiores", realizou-se estudo comparativo com a base DrugDex/Micromedex® e com o software OPharmacêutico®, constatando-se que a IM de metoclopramida com tramadol, que representava 63,16% das IM da UTI e 100% das IM do AC, não são classificadas como "maiores". A identificação de IM, de relevância clínica, e o seu monitoramento permitem tratamentos mais efetivos com o menor número possível de complicações causadas por IM, diminuindo o tempo de internação e, consequentemente, os custos do hospital.
Drug interaction (DI) is a common clinical occurrence, in which the effects of one drug are altered by the simultaneous or previous use of another drug, food or drink. The aim of this study was to identify DI in medical prescriptions issued in the intensive care unit (ICU) and common shelter (CS) at a public women?s hospital in Brazil. Thirty-six prescriptions from the ICU and 271 prescriptions from the CS were analyzed and the DIs classified as "major", "moderate" and "minor", based on the database at the website Drugs.com. At the ICU, 105 "major", 171 "moderate" and 18 "minor" DIs were identified, while at the CS, the numbers found were 64, 64 and 4, respectively. For major DIs, a comparative analysis was carried out with another database, DrugDex/MicromedexTM, and the program OPharmaceuticoTM, revealing a lack of standardization and conflicting information in the different databases. Pharmacosurveillance in the wards, carried out by a pharmacist to identify the clinically relevant DIs and monitor their clinical manifestations, would enable more effective treatments to be given, with the smallest possible number of complications due to DIs, thus reducing lengths of stay and hospital costs.
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Humanos , Prescripciones de Medicamentos , Sinergismo Farmacológico , Pacientes Internos , Salud de la MujerRESUMEN
Two experiments were conducted to investigate the effects of carbohydrate source and processing on serum progesterone (P4) and insulin concentrations of nonlactating dairy cows. In experiment 1, 12 ovariectomized grazing Gir x Holstein cows were stratified by body weight and body condition score, and randomly assigned to receive a supplement containing either finely ground corn or citrus pulp in a Latin square crossover design. Diets were fed individually, twice daily at a rate of 10.9 kg of dry matter per cow. Cows received a controlled intravaginal P4-releasing insert before the beginning of the study, and inserts were replaced every 7 d. During the first experimental period, cows were adapted to treatments from d 0 to 13 and blood was collected on d 14, whereas during the second experimental period cows were adapted to treatments from d 0 to 6 and blood samples were collected on d 7. In both periods, blood samples were collected immediately before and at 1, 2, 3, 4, 5, and 6 h after the first supplement feeding of the collection day. In experiment 2, the cows utilized in experiment 1 were randomly assigned to receive a supplement based on finely ground corn, coarsely ground corn, or high-moisture corn in a Latin square crossover design. Cows were fed and received the controlled intravaginal P4-releasing insert as in experiment 1. Within each of the 3 experimental periods, cows were adapted to diets from d 0 to 6, and blood samples were collected on d 7 as in experiment 1. Time effects were detected in experiments 1 and 2 because insulin concentrations increased by 1 h (4.6 +/- 0.90 vs. 7.4 +/- 0.91 microIU/mL for 0 and 1 h, respectively) and P4 concentrations decreased by 3 h (1.8 +/- 0.12 vs. 1.2 +/- 0.11 ng/mL for 0 and 3 h, respectively) after supplements were offered. In experiment 2, insulin concentrations were greater in cows fed high-moisture corn compared with those fed coarsely or finely ground corn (8.8 +/- 1.05, 5.7 +/- 1.05, and 6.1 +/- 1.05 microIU/mL, respectively). Data combined from both experiments indicated that cows with median insulin >or=4.5 microIU/mL before supplement feeding had greater P4 concentrations at 1 h, but lesser P4 concentrations at 5 h compared with cows with insulin <4.5 microIU/mL. Carbohydrate processing, but not carbohydrate source, affected serum insulin of nonlactating dairy cows.
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Bovinos/fisiología , Industria Lechera , Carbohidratos de la Dieta/metabolismo , Insulina/sangre , Progesterona/sangre , Animales , Bovinos/metabolismo , Suplementos Dietéticos , Femenino , Lactancia , Distribución Aleatoria , Factores de TiempoRESUMEN
The objective of the present study was to identify disturbances of nitric oxide radical (.NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of.NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 +/- 9.7 years; blood pressure, 148.3 +/- 24.8/90.8 +/- 10.2 mmHg) and in 11 healthy subjects (N: 48.4 +/- 7.0 years; blood pressure, 119.4 +/- 9.4/75.0 +/- 8.0 mmHg). Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 +/- 26.0, N: 54.2 +/- 24.9 micro M), urate (H: 108.5 +/- 18.9, N: 156.4 +/- 26.3 micro M), beta-carotene (H: 1.1 +/- 0.8, N: 2.5 +/- 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 +/- 0.2, N: 0.7 +/- 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3beta,5,6beta-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 +/- 0.2, N: 0.7 +/- 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for.NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although.NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.
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Endotelio Vascular/fisiopatología , Hipertensión/fisiopatología , Peroxidación de Lípido/fisiología , Óxido Nítrico/sangre , Estrés Oxidativo/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Disponibilidad Biológica , Estudios de Casos y Controles , LDL-Colesterol/química , LDL-Colesterol/metabolismo , Cromatografía , Endotelina-1/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipertensión/sangre , Masculino , Persona de Mediana EdadRESUMEN
The objective of the present study was to identify disturbances of nitric oxide radical (ANO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations ofANO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg) and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg).Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1 percent increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 æM), urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 æM), ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for ANO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ANO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Endotelio Vascular , Hipertensión , Peroxidación de Lípido , Óxido Nítrico , Estrés Oxidativo , Disponibilidad Biológica , Estudios de Casos y Controles , LDL-Colesterol , Cromatografía , Endotelina-1 , Ensayo de Inmunoadsorción Enzimática , Hipertensión , VasodilataciónRESUMEN
Nitric oxide (NO) reacts with thiol-containing biomolecules to form S-nitrosothiols (RSNOs). RSNOs are considered as NO reservoirs as they generate NO by homolytic cleavage. Ceruloplasmin has recently been suggested to have a potent catalytic activity towards RSNO production. Considering that NO activity is impaired in hypercholesterolemia and that RSNOs may act as important NO donors, we investigated the relation between concentrations of ceruloplasmin and RSNOs in plasma of hypercholesterolemic (HC) patients compared to normolipidemic (N) controls. Concentrations of ceruloplasmin (0.36 +/- 0.07 x 0.49 +/- 0.11 mg/dl, N x HC), nitrate (19.10 +/- 12.03 x 40.19 +/- 18.70 microM, N x HC), RSNOs (0.25 +/- 0.20 x 0.54 +/- 0.26 microM, N x HC), nitrated LDL (19.51 +/- 6.98 x 35.29 +/- 17.57 nM nitro-BSA equivalents, N x HC), and cholesteryl ester-derived hydroxy/hydroperoxides (CEOOH, 0.19 +/- 0.06 x 1.46 +/- 0.97 microM) were increased in plasma of HC as compared to N. No difference was found for nitrite levels between the two groups (1.01 +/- 0.53 x 1.02 +/- 0.33 microM, N x HC). The concentrations of RSNOs, nitrate, and nitrated LDL were positively correlated to those of total cholesterol, LDL cholesterol, and apoB. Ceruloplasmin levels were directly correlated to apoB and apoE concentrations. Data suggest that: (i) ceruloplasmin may have a role in the enhancement of RSNOs found in hypercholesterolemia; (ii) the lower NO bioactivity associated with hypercholesterolemia is not related to a RSNOs paucity or a defective NO release from RSNOs; and (iii) the increased nitrotyrosine levels found in hypercholesterolemia indicate that superoxide radicals contribute to inactivation of NO, directly generated by NO synthase or originated by RSNO decomposition.
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Ceruloplasmina/metabolismo , Hipercolesterolemia/sangre , Mercaptoetanol , Compuestos Nitrosos/sangre , S-Nitrosotioles , Tirosina/análogos & derivados , Apolipoproteínas B/sangre , Ácido Ascórbico/sangre , Catálisis , Colesterol/sangre , Ésteres del Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Peróxido de Hidrógeno/sangre , Lipoproteínas LDL/sangre , Nitratos/sangre , Nitritos/sangre , Tirosina/sangre , Ácido Úrico/sangre , Vitamina E/sangreRESUMEN
BACKGROUND: The oxidative stress associated with HIV infection may be important for the progression of the disease because reactive oxygen species activate the nuclear transcription factor NF-kappaB, which is obligatory for HIV replication. PATIENTS AND METHODS: The activities of the antioxidant enzymes superoxide dismutase (SOD, EC 1.15.1.1) and glutathione peroxidase (GPx, EC 1.11.1.9) of blood plasma and peripheral blood mononuclear cells, as well as the plasma levels of ascorbate, alpha-tocopherol and beta-carotene, were measured in 75 subjects with HIV infection and in 26 controls. The HIV-infected patients were classified according to the Walter Reed Army Institute criteria. RESULTS: The extracellular SOD (EC-SOD) of blood plasma activity was decreased in HIV-infected patients compared to controls, while the SOD activity of mononuclear cells decreased with the HIV-associated disease progression. GPx activities and alpha-tocopherol concentration of HIV-infected patients neither differed as compared to controls nor in relation to disease progression. Lower concentrations of ascorbate and beta-carotene were found in HIV-infected patients than in controls. A positive correlation between CD4 lymphocyte counts and the SOD activities of plasma and mononuclear cells was found. CONCLUSION: These results suggest that abnormalities of antioxidant defence, mainly of SOD activity, are related to the progression of the HIV infection.
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Antioxidantes/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Adulto , Ácido Ascórbico/sangre , Relación CD4-CD8 , Progresión de la Enfermedad , Femenino , Glutatión Peroxidasa/metabolismo , Humanos , Leucocitos Mononucleares/enzimología , Leucocitos Mononucleares/virología , Masculino , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Vitamina E/sangre , beta Caroteno/sangreRESUMEN
Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.
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Antioxidantes/análisis , LDL-Colesterol/metabolismo , Hiperlipidemias/sangre , Hipertensión/sangre , Peroxidación de Lípido/fisiología , Peróxidos Lipídicos/sangre , Estudios de Casos y Controles , Humanos , Estrés Oxidativo/fisiologíaRESUMEN
Lipid peroxidation and lipid-derived oxidized products have been implicated in the pathogenesis of a variety of human diseases. To clarify the role of oxidative stress in essential hypertension and hypercholesterolemia the in vitro oxidative susceptibility of LDL, the antioxidant status and the lipid peroxide content of blood plasma were examined in hypercholesterolemic (HC), hypertensive (H), hypercholesterolemic/hypertensive (HH) and normolipidemic/normotensive subjects (N). Plasma ascorbate and lipid-soluble antioxidants were lower, while LDL oxidizability, CE-OOH and TL-OOH were higher in H, HC, and HH groups than in the N group. No difference was observed among groups for PL-OOH and isoprostanes. In summary, the results show that: 1) lipid- and water-soluble antioxidants are lower in hypercholesterolemic and hypertensive patients as compared to normal subjects, whereas the lipid peroxide content and the LDL susceptibility to oxidation were higher; 2) total cholesterol, LDL-cholesterol, apoB and CE-OOH were negatively correlated with the content of a-tocopherol; 3) there was a positive correlation between the content of lipid-soluble antioxidants and the resistance of LDL to oxidation; and 4) CE-OOH and TL-OOH were positively correlated with total cholesterol and LDL-cholesterol.
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Humanos , Antioxidantes/análisis , LDL-Colesterol , Hiperlipidemias , Hipertensión/sangre , Peroxidación de Lípido/fisiología , Peróxidos Lipídicos/sangre , Estudios de Casos y Controles , Estrés Oxidativo/fisiologíaRESUMEN
Oxidized lipoproteins and antioxidants were detected during the course of hypercholesterolemia development in cholesterol-fed rabbits. Lipid peroxides in blood plasma and very-low-, low-, and high-density lipoproteins (beta-VLDL, LDL, and HDL) were increased during the course of hypercholesterolemia. The content of phospholipid peroxides increased in beta-VLDL and LDL in parallel to that of cholesterol, whereas the amount of alpha-tocopherol was decreased either in lipoproteins or blood plasma. Ascorbate and urate concentrations were also decreased. Lipid peroxides were positively correlated with volume and area of atherosclerotic lesions, suggesting a relation between the concentrations of lipid peroxides in blood plasma and the progression of atheromatous lesions.
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Arteriosclerosis/sangre , Arteriosclerosis/patología , Lipoproteínas/sangre , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Colesterol/sangre , Colesterol en la Dieta/administración & dosificación , Colesterol en la Dieta/efectos adversos , Progresión de la Enfermedad , Hipercolesterolemia/sangre , Hipercolesterolemia/patología , Peróxidos Lipídicos/sangre , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Oxidación-Reducción , Conejos , Triglicéridos/sangreRESUMEN
Lipoprotein oxidation plays a key role in the initiation and progression of atherosclerosis. Peroxynitrite is a powerful oxidant and nitrating species formed by the reaction of nitric oxide with superoxide radical. Peroxynitrite can oxidize lipoproteins and generate nitrotyrosine either from free or protein-bound tyrosine. Nitrotyrosine has been used as a fingerprint for peroxynitrite reaction in vivo. In this study, the content of nitrotyrosine bound to beta-VLDL apoproteins was determined in New Zealand rabbits before and at 15, 30, 45 and 60 days of cholesterol feeding. A significant increase of nitrotyrosine bound to beta-VLDL apoproteins was observed in parallel with the hypercholesterolemia induced by 1% cholesterol enriched diet. These data indicate that apolipoprotein-bound nitrotyrosine may be used as a biomarker of peroxynitrite production during the development of atherosclerosis in this experimental model.
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Arteriosclerosis/metabolismo , Lipoproteínas VLDL/metabolismo , Nitratos/metabolismo , Tirosina/análogos & derivados , Animales , Arteriosclerosis/sangre , Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Colesterol/sangre , Hipercolesterolemia/sangre , Lipoproteínas VLDL/sangre , Masculino , Nitratos/sangre , Conejos , Triglicéridos/sangre , Tirosina/sangre , Tirosina/metabolismoRESUMEN
The activities of superoxide dismutase (SOD, EC 1.15.1.1), glutathione peroxidase (GPx, EC 1.11.1.9) and the levels of alpha-tocopherol and oxidized lipoproteins were investigated in the plasma of New Zealand rabbits either before or after cholesterol-diet induced hypercholesterolemia. Plasma SOD activity increased while GPx activity decreased after 60 days of cholesterol feeding. However, in the cholesterol-fed rabbits the release of superoxide dismutase fraction C from vasculature by heparin was lower than that in control rabbits. The levels of triglyceride hydroperoxides increased in low density and high density lipoproteins after feeding rabbits with the cholesterol-rich diet during 60 days. Also, a trend for increasing cholesteryl ester hydroperoxides was observed in beta-very low density and high density lipoproteins. An increase in alpha-tocopherol concentration (microM) was observed in very low density and low density lipoprotein fractions, but after normalization of these results to the cholesterol content of lipoprotein particles only the alpha-tocopherol content of low density lipoprotein remained higher after 60 days of cholesterol feeding. The data suggest that low glutathione peroxidase and superoxide dismutase fraction C activities may facilitate intravascular lipoprotein oxidation by oxidant species generated by the endothelium or blood cells.