Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk / Efectos del tratamiento con un suplemento nutricional a base de monacolina K, berberina y coenzima Q10 (lipoK®) sobre el metabolismo lipídico en pacientes con hipercolesterolemia y riesgo cardiovascular moderado

Objective The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. Patients and methods The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. Results In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (−32.4 to 19.7) and increased by 4.5mg/dL (−1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. Conclusion In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk (AU)

Objetivo El uso de suplementos nutricionales para tratar la hipercolesterolemia está aumentando de forma progresiva; sin embargo son necesarios más estudios sobre su eficacia y seguridad. Pacientes y métodos En el presente ensayo clínico fueron incluidos pacientes con hipercolesterolemia y riesgo cardiovascular moderados que fueron tratados con un preparado nutracéutico que contenía 3,75mg de monacolina K, 515mg de berberina y 50mg de coenzima Q10 por comprimido (Lipok®) o con placebo. Se analizaron las variables clínicas y de laboratorio en situación basal y a los 3 y 6 meses. Ningún paciente era diabético y ninguno seguía tratamiento con fármacos hipolipidemiantes u otros suplementos nutricionales con efectos sobre el metabolismo lipídico. Resultados En los pacientes del grupo de intervención y del grupo placebo, el c-LDL basal era de 134,7mg/dL (14,4) y 138,7mg/dL (15,2), respectivamente. A los 3 meses de tratamiento el c-LDL había disminuido 26,1mg/dL (de –32,4 a 19,7) y aumentado 4,5mg/dL (de –1,5 a 10,5) en ambos grupos, respectivamente. En el grupo de intervención se observó un descenso similar del c-no HDL y del colesterol total, mientras que no ocurrieron cambios significativos en ninguno de los 2 grupos en el c-HDL, los triglicéridos y la lipoproteína (a). Se observó un buen perfil de tolerancia y seguridad. Conclusión Este estudio demuestra que la combinación de monacolina K, berberina y coenzima Q10 es eficaz y segura para tratar la hipercolesterolemia en los pacientes con un grado de exceso de c-LDL y de riesgo cardiovascular moderados (AU)

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk.

OBJECTIVE: The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. PATIENTS AND METHODS: The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. RESULTS: In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (-32.4 to 19.7) and increased by 4.5mg/dL (-1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. CONCLUSION: In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.

Nuevas perspectivas en el tratamiento de la hipercolesterolemia desde la disponibilidad de los inhibidores de la proteína PCSK9 / New perspectives in the treatment of hypercholesterolaemia since the availability of PCSK9 inhibitors

Los grandes ensayos clínicos de prevención cardiovascular han demostrado que cuanto más se disminuye el colesterol aterogénico, mayor es el beneficio preventivo, sin que se haya observado un valor umbral por debajo del cual desparezca dicho efecto o se observen efectos negativos para la salud. Por ello, los objetivos de control de la hipercolesterolemia en los pacientes de alto riesgo cardiovascular son cada vez más estrictos. El hecho de que la mayoría de pacientes de alto riesgo no alcancen dichos objetivos hace necesario, entre otras medidas, un uso racional de los fármacos hipolipemiantes disponibles, incluyendo los anticuerpos monoclonales inhibidores de la proteína PCSK9 (iPCSK9). Los iPCSK9 actualmente autorizados para uso clínico, evolocumab y alirocumab, han demostrado una alta potencia para disminuir el colesterolLDL, que puede superar el 60%, y otros efectos favorables sobre el perfil lipídico, incluyendo una disminución también muy acusada del colesterol-noHDL y de la apolipoproteínaB. Así mismo, mediante ensayos clínicos a gran escala ambos fármacos han demostrado un efecto preventivo frente a las enfermedades cardiovasculares y un alto grado de seguridad. Además, en el caso del alirocumab se ha observado una disminución de la mortalidad por todas las causas. Sin embargo, el elevado coste de los iPCSK9 hace necesario ceñir sus indicaciones a los pacientes de mayor riesgo cardiovascular que no puedan controlarse con estatinas de alta potencia y ezetimiba. Es de esperar que las nuevas guías que serán emitidas en un futuro cercano por distintas sociedades científicas definan con mayor detalle en qué pacientes y en qué condiciones pueden utilizarse los iPCSK9, unos agentes que en este momento constituyen el avance más importante de la terapia hipocolesterolemiante de las últimas décadas

The large clinical trials on cardiovascular prevention have demonstrated that the more atherogenic cholesterol is reduced the greater the preventive benefit, and neither a threshold value below which that effect disappears nor negative effects on health have been observed. Therefore, the objectives of hypercholesterolaemia control in patients at high cardiovascular risk are becoming ever stricter. The fact that most high-risk patients do not achieve these objectives requires, among other measures, rational use of available lipid-lowering drugs, including monoclonal antibodies that inhibit the protein PCSK9 (PCSK9i). The PCSK9i that are currently licensed for clinical use, evolocumab and alirocumab, have shown high potency in lowering LDL-cholesterol, which can exceed 60%, and other favourable effects on lipid profiles, including a very marked reduction of non-HDL cholesterol and apolipoproteinB. Likewise, through large-scale clinical trials, both drugs have demonstrated a preventive effect against cardiovascular diseases, and a high degree of safety. In addition, in the case of alirocumab, a reduction in all-cause mortality has been observed. However, the high cost of the PCSK9i means that prescription is restricted to patients at highest cardiovascular risk who cannot be controlled with high-potency statins and ezetimibe. It is to be hoped that the new guidelines that are to be issued soon by various scientific societies will define in greater detail the patients and the conditions in which we can use PCSK9i, drugs which currently constitute the greatest advance in hypercholesterolaemia of recent decades

[New perspectives in the treatment of hypercholesterolaemia since the availability of PCSK9 inhibitors]. / Nuevas perspectivas en el tratamiento de la hipercolesterolemia desde la disponibilidad de los inhibidores de la proteína PCSK9.

The large clinical trials on cardiovascular prevention have demonstrated that the more atherogenic cholesterol is reduced the greater the preventive benefit, and neither a threshold value below which that effect disappears nor negative effects on health have been observed. Therefore, the objectives of hypercholesterolaemia control in patients at high cardiovascular risk are becoming ever stricter. The fact that most high-risk patients do not achieve these objectives requires, among other measures, rational use of available lipid-lowering drugs, including monoclonal antibodies that inhibit the protein PCSK9 (PCSK9i). The PCSK9i that are currently licensed for clinical use, evolocumab and alirocumab, have shown high potency in lowering LDL-cholesterol, which can exceed 60%, and other favourable effects on lipid profiles, including a very marked reduction of non-HDL cholesterol and apolipoproteinB. Likewise, through large-scale clinical trials, both drugs have demonstrated a preventive effect against cardiovascular diseases, and a high degree of safety. In addition, in the case of alirocumab, a reduction in all-cause mortality has been observed. However, the high cost of the PCSK9i means that prescription is restricted to patients at highest cardiovascular risk who cannot be controlled with high-potency statins and ezetimibe. It is to be hoped that the new guidelines that are to be issued soon by various scientific societies will define in greater detail the patients and the conditions in which we can use PCSK9i, drugs which currently constitute the greatest advance in hypercholesterolaemia of recent decades.

Stomatal and mesophyll conductances to CO2 are the main limitations to photosynthesis in sugar beet (Beta vulgaris) plants grown with excess zinc.

*The effects of zinc (Zn) toxicity on photosynthesis and respiration were investigated in sugar beet (Beta vulgaris) plants grown hydroponically with 1.2, 100 and 300 microM Zn. *A photosynthesis limitation analysis was used to assess the stomatal, mesophyll, photochemical and biochemical contributions to the reduced photosynthesis observed under Zn toxicity. *The main limitation to photosynthesis was attributable to stomata, with stomatal conductances decreasing by 76% under Zn excess and stomata being unable to respond to physiological and chemical stimuli. The effects of excess Zn on photochemistry were minor. Scanning electron microscopy showed morphological changes in stomata and mesophyll tissue. Stomatal size and density were smaller, and stomatal slits were sealed in plants grown under high Zn. Moreover, the mesophyll conductance to CO(2) decreased by 48% under Zn excess, despite a marked increase in carbonic anhydrase activity. Respiration, including that through both cytochrome and alternative pathways, was doubled by high Zn. *It can be concluded that, in sugar beet plants grown in the presence of excess Zn, photosynthesis is impaired due to a depletion of CO(2) at the Rubisco carboxylation site, as a consequence of major decreases in stomatal and mesophyll conductances to CO(2).

Mesophyll conductance to CO2 in Arabidopsis thaliana.

The close rosette growth form, short petioles and small leaves of Arabidopsis thaliana make measurements with commercial gas exchange cuvettes difficult. This difficulty can be overcome by growing A. thaliana plants in 'ice-cream cone-like' soil pots. This design permitted simultaneous gas exchange and chlorophyll fluorescence measurements from which the first estimates of mesophyll conductance to CO(2) (g(m)) in Arabidopsis were obtained and used to determine photosynthetic limitations during plant ageing from c. 30-45 d. Estimations of g(m) showed maximum values of 0.2 mol CO(2) m(-2) s(-1) bar(-1), lower than expected for a thin-leaved annual species. The parameterization of the response of net photosynthesis (A(N)) to chloroplast CO(2) concentrations (C(c)) yielded estimations of the maximum velocity of carboxylation (V(c,max_Cc)) which were also lower than those reported for other annual species. As A. thaliana plants aged from 30 to 45 d, there was a 40% decline of A(N) that was entirely the result of increased diffusional limitations to CO(2) transfer, with g(m) being the largest. The results suggest that in A. thaliana A(N) is limited by low g(m) and low capacity for carboxylation. Decreased g(m) is the main factor involved in early age-induced photosynthetic decline.

[Giving up the tobacco habit through the application of the Smoker's Aid Program in the Chantrea Health Centre]. / Abandono del hábito tabáquico mediante la aplicación del programa de ayuda al fumador en el centro de salud de Chantrea.

INTRODUCTION: This is a prospective descriptive study of intervention without aleatory assignation, carried out in the Chantrea Health Centre. Its aim is to determine the characteristics of the smokers who are taking part in two interventions by the Smokers' Aid Program (Programa de Ayuda al Fumador-PAF), and to evaluate the factors that influence the latter's success. MATERIAL AND METHODS: The characteristics of 100 smokers were analyzed. They were offered one of the two PAF interventions: Minimal Intervention 1 (MN1): they are given a support brochure in the first consultations, contacted by telephone after one month and called to consultation after 6 months to measure CO. Minimal Intervention 2 (MN2): the smoker makes 5 consultations of support in giving up smoking (+ or - nicotine patches) with the doctor, nurse or social worker indiscriminately. The factors that were influential in abandoning the habit with 65 subjects were evaluated. RESULTS: 60% of the subjects were male with an average age of 41 (DE 29). 29% showed a pathology related to tobacco, with no relation found between this and the success of the interventions. Those who chose MN2 (38%) had started tobacco consumption at an earlier age and were more dependent on nicotine. Of the 65 smokers who completed the program, 37% continued not to smoke after 6 months. Those who managed to give up smoking were of a greater average age, had spent more years smoking and belonged above all to the MN1 intervention. DISCUSSION: Notable successes are achieved if the actions are carried out by the First Aid Team. We find no significant differences between the characteristics of those who give up smoking and those who do not. Not even a serious pathology, related to tobacco, is predictive of success. The smoker's dependence on nicotine must be taken into account in the intervention.