Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase

Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43) and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL) to low density lipoproteins (LDL) and very low density lipoproteins (VLDL) by cholesteryl ester transfer protein (CETP) was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing reverse cholesterol transport.Os óxidos de colesterol são aterogênicos e podem afetar a atividade de diversas enzimas importantes para o metabolismo lipídico. Este estudo investigou o efeito dos óxidos 7β-hidroxicolesterol, 7-cetocolesterol, 25-hidroxicolesterol, colestan-3β,5α,6β-triol, 5,6β-epoxicolesterol, 5,6α-epoxicolesterol e 7α-hidroxicolesterol na esterificação do colesterol por ação da lecitina colesterol aciltransferase (LCAT, EC 2.3.1.43) e a posterior transferência dos óxidos esterificados da lipoproteína de alta densidade (HDL) para as lipoproteínas de baixa densidade (LDL) e muito baixa densidade (VLDL) mediada pela proteína de transporte de éster de colesterol (CETP). Para atingir os objetivos, HDL enriquecida com concentrações crescentes de óxidos de colesterol foi incubada com plasma fresco pobre em lipoproteínas, como fonte de LCAT; posteriormente a esterificação do colesterol e dos óxidos de colesterol foi medida pelo consumo do colesterol livre e dos óxidos livres presentes na HDL. As determinações de colesterol e dos óxidos de colesterol foram realizadas por cromatografia gasosa. 14C-óxidos de colesterol foram incorporados nas subfrações HDL2 e HDL3 e posteriormente incubados com plasma fresco, contendo LCAT e CETP. A transferência dos ésteres de óxidos de colesterol foi medida e quantificada pela presença desses ésteres na LDL e VLDL. Todos os óxidos de colesterol estudados foram esterificados pela LCAT após incorporação nas partículas de HDL e competiram com a esterificação do colesterol nativo. A esterificação do colesterol pela LCAT foi inversamente relacionada à concentração de óxidos de colesterol. A esterificação dos óxidos de colesterol foi maior na HDL3 e a transferência desses ésteres foi maior a partir da HDL2 para a LDL e VLDL. Estes resultados indicam que a esterificação do colesterol pela LCAT é inibida nas partículas de HDL enriquecidas com óxidos de colesterol e que os ésteres de óxidos de colesterol são eficientemente transferidos para a LDL e VLDL. Portanto, sugere-se que os óxidos de colesterol exercem parte de seu efeito aterogênico pela inibição da esterificação do colesterol na superfície da HDL, causando um distúrbio no transporte reverso do colesterol, além de aumentar o potencial aterogênico da LDL e VLDL.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Caryocar brasiliense supercritical CO2 extract possesses antimicrobial and antioxidant properties useful for personal care products

The cosmetic and pharmaceutical industries have an increasing interest in replacing synthetic antimicrobials in dermatological products due to increased microbial resistance to conventional antimicrobial agents. Pequi (Caryocar brasiliense) is a native fruit tree of the Brazilian Cerrado, specifically used in cosmetics, in the food industry, and for medicinal purposes. Leishmanicidal and antifungal activities have been reported previously. This study was designed to evaluate the antimicrobial and antioxidant activities of a C. brasiliense extract obtained by supercritical CO2 extraction. The minimum inhibitory concentrations (MICs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by the classical microdilution method. Antiseptic activity against these organisms was evaluated by the plate diffusion method. The antioxidant potential of the extract was evaluated using a method based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The extract's chemical profile was analyzed for the presence of alkaloids, saponins, anthraquinones, steroids, tannins, flavonoids, and phenolic compounds according to standard colorimetric methods. The C. brasiliense supercritical CO2 extract exhibits antimicrobial activity against all bacteria tested. It also possesses antioxidant activity, when compared to a vitamin E standard. The C. brasiliense supercritical CO2 extract may be useful for the development of personal care products, primarily for antiseptic skin products that inactivate, reduce, prevent, or arrest the growth of microorganisms with the inherent intent to mitigate or prevent disease as well as products that minimize damage caused by free radicals.147

Evaluation of the cytotoxicity and phototoxicity of Caryocar brasiliense supercritical carbon dioxide extract

Caryocar brasiliense Camb (Pequi) is a typical Brazilian Cerrado fruit tree. Its fruit is used as a vitamin source for culinary purposes and as a source of oil for the manufacture of cosmetics. C. brasiliense supercritical CO2 extracts exhibit antimicrobial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and also possess antioxidant activity. This study was designed to evaluate the in vitro cytotoxicity and phototoxicity of the supercritical CO2 extract obtained from the leaves of this species. In vitro cytotoxicity and phototoxicity of C. brasiliense supercritical CO2 extracts were assessed using a tetrazolium-based colorimetric assay (XTT) and Neutral Red methods. We found that the C. brasiliense (Pequi) extract obtained by supercritical CO2 extraction did not present cytotoxic and phototoxic hazards. This finding suggests that the extract may be useful for the development of cosmetic and/or pharmaceutical products

Roles and Responsibilities: Asking Nurses and Physicians What They Know, Do Not Know and Want to Know about the Other's Profession

oai:jripe.journals.sfu.ca:article/253Background: In 2015, an Institute of Medicine (IOM) report acknowledged that interprofessional education (IPE) had focused on academic learning yet had not been well assimilated into clinical practice. The aim of this study was to gather data from practicing clinicians to inform a curriculum that could be integrated into practice environment educational regimens.Methods and Findings: A qualitative description approach was utilized to analyze data gathered via focus groups conducted with practicing nurses and physicians. Participants were asked to describe what they knew, did not know, and wanted to know about each others profession, and what they felt would be the best method of delivery for this information. Findings indicate a lack of understanding of the roles and responsibilities of the other profession and genuine interest in learning more.Conclusions: Integrating IPE into practice environment education is of interest and would be beneficial to healthcare professionals for improving patient care, safety, and professional rapport

HIV pharmaceutical care in primary healthcare: Improvement in CD4 count and reduction in drug-related problems

AbstractBackground: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient’s response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group. Methods: We conducted a prospective controlled intervention study with patients paired by gender and initial T CD4+ lymphocyte (CD4) count. HIV-infected patients of a public outpatient service were enrolled for the study by consecutive and convenience sampling. Patients selected for the study were divided into a control group and an intervention group. Both groups were followed for one year; however, only the intervention group received pharmaceutical care. The primary outcome was the drug related problem (DRP) analysis for the intervention group. Secondary outcomes were CD4 count and viral load evaluation for both groups. Results: There was a total of 143 patients enrolled in this study, with 53 (37.06%) patients in the control group and 90 (62.94%) patients in the intervention group. A total of 202 pharmacist interventions with 193 pharmacist-patient and 9 pharmacist-physician interventions were proposed. After one year of pharmaceutical care, a reduction of 38.43% between the initial and final DRP was found (p=0.0001). The most common DRPs found were related to medication safety. The intervention group showed a mean increase of 84% for the CD4 count in comparison with that observed in the control group. The viral load was not significantly different between the final and initial mean values for both groups. Conclusion: Pharmacist appointments enabled identification, prevention, and solving of drug related problems, especially those related to drug safety. Also, pharmacist interventions improved adherence and increased HAART effectiveness as suggested by the higher elevation in the CD4 count seen in the intervention group in comparison with the control group

Influence of Soy Lecithin Administration on Hypercholesterolemia

Recent studies suggest that lecithin-rich diet can modify cholesterol homeostasis and hepatic lipoprotein metabolism. Considering the phytotherapeutic impact of lecithin, this work hypothesizes that lecithin administration in hypercholesterolemic patients may reduce cholesterol concentrations by increasing biliary secretion. Total cholesterol and LDL were evaluated after soy lecithin administration in hypercholesterolemic patients. One soy lecithin capsule (500 mg/RP-Sherer) was administrated daily. One-two months before the treatment beginning, blood samples were collected for total lipids and cholesterol fractions analysis. The results showed a reduction of 40.66% and 42.00% in total cholesterol and of 42.05% and 56.15% in LDL cholesterol after treatment for one and two months, respectively. A significant reduction in total cholesterol and LDL-cholesterol concentrations was observed during the first month of treatment, suggesting that the administration of soy lecithin daily may be used as a supplemental treatment in hypercholesterolemia

Clinical relevancy and risks of potential drug–drug interactions in intensive therapy

AbstractPurposeEvaluate the potential Drug–Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®.MethodsProspective study (January–December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient.ResultsDuring the study 1844 pDDIs were identified and distributed in 405 pairs (medication A×medication B combination). There was an average of 5.00±5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to “avoid concomitant use” or “suspension of medication”, while 306 had as recommendation “continuous and adequate monitoring”.ConclusionThe high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management

Impact Of Pharmacist Interventions On Drug-related Problems And Laboratory Markers In Outpatients With Human Immunodeficiency Virus Infection.

Substantial complexity has been introduced into treatment regimens for patients with human immunodeficiency virus (HIV) infection. Many drug-related problems (DRPs) are detected in these patients, such as low adherence, therapeutic inefficacy, and safety issues. We evaluated the impact of pharmacist interventions on CD4+ T-lymphocyte count, HIV viral load, and DRPs in patients with HIV infection. In this 18-month prospective controlled study, 90 outpatients were selected by convenience sampling from the Hospital Dia-University of Campinas Teaching Hospital (Brazil). Forty-five patients comprised the pharmacist intervention group and 45 the control group; all patients had HIV infection with or without acquired immunodeficiency syndrome. Pharmaceutical appointments were conducted based on the Pharmacotherapy Workup method, although DRPs and pharmacist intervention classifications were modified for applicability to institutional service limitations and research requirements. Pharmacist interventions were performed immediately after detection of DRPs. The main outcome measures were DRPs, CD4+ T-lymphocyte count, and HIV viral load. After pharmacist intervention, DRPs decreased from 5.2 (95% confidence interval [CI] =4.1-6.2) to 4.2 (95% CI =3.3-5.1) per patient (P=0.043). A total of 122 pharmacist interventions were proposed, with an average of 2.7 interventions per patient. All the pharmacist interventions were accepted by physicians, and among patients, the interventions were well accepted during the appointments, but compliance with the interventions was not measured. A statistically significant increase in CD4+ T-lymphocyte count in the intervention group was found (260.7 cells/mm(3) [95% CI =175.8-345.6] to 312.0 cells/mm(3) [95% CI =23.5-40.6], P=0.015), which was not observed in the control group. There was no statistical difference between the groups regarding HIV viral load. This study suggests that pharmacist interventions in patients with HIV infection can cause an increase in CD4+ T-lymphocyte counts and a decrease in DRPs, demonstrating the importance of an optimal pharmaceutical care plan.10631-