Evolocumab as treatment in lorlatinib-related hyperlipidemia. / Evolocumab como tratamiento de la dislipemia secundaria a lorlatinib.

Anti-PCSK9 monoclonal antibodies have reduced the risk of cardiovascular events in patients with atheroesclerosis cardiovascular disease. However, its use has not been described in hyperlipidemia associated with lorlatinib, a third-generation ALK tyrosin kinasa inhibitor approved as treatment for ALK-positive non-small cell lung cancer.

Measure of adherence to direct-acting antivirals as a predictor of the effectiveness of hepatitis C treatment.

Background Adherence to direct-acting antivirals could be a predictor response to these treatments in hepatitis C. Objective To assess the ability of three methods of measuring adherence to direct-acting antivirals [pill counts, pharmacy dispensing record and Simplified Medication Adherence Questionnaire (SMAQ)] as predictors of their effectiveness. Setting Study conducted by the pharmacy department of the hospital. Methods: A retrospective study was performed. Patients ≥ 18 years with hepatitis C that started and completed treatment with direct-acting antivirals between the 1st-April-2015 and 28st-February-2016 were enrolled. To evaluate the predictive ability to obtain a response to treatment, Chi squared test, Mann-Whitney-U test and ROC-curves were used. Main outcome measure Adherence to antivirals was assessed by three methods and response to treatment, which was defined as obtaining a viral load of hepatitis C virus ≤ 15UI/ml at week 12 after the end of treatment. Results 128 patients were enrolled. The overall average adherence obtained with SMAQ (99.09%) was similar to the pill counts (96.40%, p = 0.043) and pharmacy dispensing record (91.10%, p = 0.02). There was no correlation between the percentage of patients considered as adherent by SMAQ (99.09%) and the achievement of response to treatment (96.40%, p = 0.999). The ROC-curve obtained for the pill count method shows a global area under the curve of 0.53. For pharmacy dispensing record method, patients with an adherence ≤ 66.66% have a high probability of not achieving response (sensitivity and specificity of 79.00% and 100.00%, respectively). Conclusions Pharmacy dispensing record is shown as the best indicator of adherence to predict therapeutic failure in our study.

Implementation of a pharmaceutical care program for patients with hepatitis C treated with new direct-action antivirals.

Background A pharmaceutical care program is necessary to improve the management of direct-acting antivirals in hepatitis C. Objective Describe health outcomes obtained with the implementation of a pharmaceutical care program in Hepatitis C patients treated with direct-acting antivirals. Setting This study was performed in a pharmacy department of a university hospital. Methods Retrospective study between 1st-April 2015 and 28st-February 2016. Hospital pharmacists implemented interventional measures for validation of antivirals prescriptions, detection of drug-interaction, adverse drug events, education and patient´s adherence to antiviral regimen. Main outcome measure Health and quality outcomes of the implementation of the pharmaceutical care program. Results A total 128 patients were enrolled. The overall sustained virologic response at week 12 post-treatment rate was 96.1% (95% CI 92.7-99.5). Adverse drug events occurred in 90.6% of the patients, and the majority were grade 1-2. Pharmacists made 334 pharmaceutical interventions. 35.5% of these interventions were aimed to resolve negative results of drugs. 80.9% of the negative results of drugs improved or were eliminated with the application of the measures proposed by the pharmacists (p ≤ 0.001). Pharmacists carried out 175 preventive interventions to avoid negative results of drugs. 97.3% of these interventions were accepted and managed to prevent the appearance of negative results of drugs (p = 0.453). Conclusion The implementation of a pharmaceutical care program in patients with hepatitis C treated with direct-acting antivirals has improved the safety in the use of these drugs.

Influencia de las clases de educación física sobre el nivel de actividad física medido a través de una aplicación móvil en adolescentes / Influence of physical education classes on the level of physical activity measured through a mobile application in adolescents

La literatura científica ha demostrado a través de diversos métodos (cuestionarios y acelerómetros, principalmente) que las clases de educación física (EF) influyen positivamente en el logro de las recomendaciones de actividad física (AF) en la población escolar. Sin embargo, el uso de nuevas tecnologías como los teléfonos móviles o smartphone, parecen ser una interesante herramienta de bajo costo que también podrían ayudar a determinar el nivel de AF. Por tanto, el objetivo del presente estudio fue describir como influye la clase de EF en el número de pasos diarios en escolares que utilizaron una aplicación móvil “RuntasticPedometer” para monitorear dicha variable. La muestra estuvo compuesta por 50 estudiantes (edad media de 14.1 +/-1.6 años) pertenecientes al Instituto de Educación Secundaria “Melchor de Macanaz” de la localidad de Hellín (Albacete, España). Tras analizar los datos, se observaron diferencias significativas (p<0.05) durante los días en que los escolares realizaron la clase de EF y los que no (9.950 vs. 8.023 pasos/día,respectivamente). Además, la variación entre los días con y sin EF también fueron estadísticamente diferentes entre niños y niñas (2.644 vs. 1.579 pasos/día, respetivamente).Finalmente, se podría concluir que las clases de EF parecen influir positivamente en el aumento del número de pasos en escolares, lo que elevaría las posibilidades de que estos niños y niñas logren los parámetros mínimos de AF recomendada por las diversas organizaciones de salud. Por otro lado, cabe señalar que el uso de nuevas tecnologías de uso masivo como los smartphone, podrían ser una interesante herramienta a validar orientadas al monitoreo de la AF.

The scientific literature has demonstrated through various methods (questionnaires and accelerometers, mainly), the classes of physical education (PE) positively influence the achievement of the recommendations of physical activity (PA) in the school population. However, the use of new technologies such as mobile phones or smartphone, appear to be an interesting inexpensive tool that could also help determine the level of AF. Therefore, the objective of this study was to describe as PE class influences in the daily number of steps in school who used a mobile application "Runtastic Pedometer" to monitor the variable. The sample consisted of 50 students (mean age 14.1 +/- 1.6 years) belonging to the Institute of Secondary Education "MelchorMacanaz" from the Hellín (Albacete, Spain). After analyzing the data, significant differences (p <0.05) were observed during the days when the school made PE class and those without (8,023 vs. 9,950 steps / day, respectively). Moreover, the variations between days with and without EF were also statistically different between boys and girls (2,644 vs. 1,579 steps/day,respectively). Finally, one could conclude that PE classes seem positively influence the increase in the number of steps in school raising the chances that these children achieve the minimum standards recommended HF various health organizations. On the other hand, it notes that the use of new technologies in widespread use as the smartphone could be an interesting tool to validate oriented monitoring AF.

Acute effect of whey peptides upon blood pressure of hypertensive rats, and relationship with their angiotensin-converting enzyme inhibitory activity.

SCOPE: The aim of this study was to investigate the antihypertensive effect of a peptide fraction (PepC) obtained from a whey protein concentrate following hydrolysis by Cynara cardunculus, as well as of its fraction with MW below 3 kDa (PepCF). Both these concentrates encompassed peptides that exhibited potent in vitro inhibition of angiotensin-converting enzyme (ACE): two were released from α-lactalbumin--KGYGGVSLPEW and DKVGINYW, and one from ß-lactoglobulin--DAQSAPLRVY. METHODS AND RESULTS: Upon oral administration, by gastric intubation, of 400 mg/kg body weight (bw) of those peptide concentrates, or 5 mg/kg bw of the corresponding synthetic peptides, to 12 wk-old spontaneously hypertensive rats (SHR), the systolic and diastolic blood pressures were monitored by the tail-cuff method--before, and 2, 4, 6, 8 and 24 h afterwards. Water and zofenopril (5 mg/kg bw)--a known ACE-inhibitor, were used as negative and positive controls, respectively. Acute administration of PepC, PepCF, KGYGGVSLPEW, DKVGINYW and DAQSAPLRVY caused antihypertensive effects in SHR; the maximum effect occurred by 4 h and 6 h after administration of the peptide concentrates and the synthetic peptides, respectively. PepC and KGYGGVSLPEW also showed ACE-inhibitory activity in vivo: the pressor effect of angiotensin I was significantly lower, and the response to bradykinin increased when the rats were pre-treated with either product. CONCLUSION: Our results strongly suggest that PepC will be effective as nutraceutical ingredient for the formulation of functional foods aimed at hypertension control.

Long-term intake of a milk casein hydrolysate attenuates the development of hypertension and involves cardiovascular benefits.

Essential hypertension is considered a serious health problem and diet can play an important role in its prevention and treatment. The aim of this study was to evaluate the effect of the long-term intake of a product based on milk casein hydrolysate on the development of hypertension in spontaneously hypertensive rats (SHR). A daily dose of 800 mg/kg body weight of the casein hydrolysate product was administered dissolved in drinking water during 6 weeks. Systolic and diastolic blood pressures were measured weekly by the tail-cuff method. Endothelial function in aorta and mesenteric segments, left ventricular hypertrophy, endothelial nitric oxide synthase (eNOS) expression in aorta and plasmatic angiotensin conversion enzyme (ACE) activity were also evaluated at the end of treatment. The development of hypertension was attenuated in the group treated with the casein hydrolysate product; in this sense the systolic blood pressure increased 33±3 mmHg in control group and only 18±5 mmHg in the treated group during the experimental period. In addition, the treatment improved aorta and mesenteric acetylcholine relaxations and increased the eNOS expression in aorta. Left ventricular hypertrophy decreased in treated SHR accompanied by a significant decrease in interstitial fibrosis. These results warrant evaluation in humans to determine if the product based on a casein hydrolysate could be used as a functional food ingredient to prevent blood pressure increased with additional cardiovascular benefits.

Astaxanthin-enriched-diet reduces blood pressure and improves cardiovascular parameters in spontaneously hypertensive rats.

The aim of this study was to investigate the effects of astaxanthin-enriched diet on blood pressure, cardiac hypertrophy, both vascular structure and function and superoxide ((*)O(2-)) production in spontaneously hypertensive rats (SHR). Twelve-week-old SHR were treated for 8 weeks with an astaxanthin-enriched diet (75 or 200mg/kg body weight per day). Systolic blood pressure was monitorized periodically during the study by the tail cuff method. At the end of the study animals were sacrificed and heart, kidneys and aorta were removed. Left ventricular weight/body weight ratio was used as left ventricular hypertrophy index (LVH). Vascular function and structure were studied in conductance (aortic rings) and resistance (renal vascular bed) arteries. Also (*)O(2-) production was evaluated by lucigenin-enhanced chemiluminescence. Systolic blood pressure was lower in astaxanthin-treated groups than the control group from the first week of treatment, and LVH was significantly reduced. Astaxanthin improved endothelial function on resistance arteries, but had no effect on aorta. These effects were accompanied by a decrease in oxidative stress and improvements in NO bioavailability. Taken together, these results show that diet supplemented with astaxanthin has beneficial effects on hypertension, by decreasing blood pressure values, improving cardiovascular remodeling and oxidative stress.

In vitro antioxidant activity of pravastatin provides vascular protection.

The production of reactive oxygen species plays roles during the development of endothelial dysfunction and it represents a significant prognostic factor for evaluating the risk of cardiovascular disease. Although statins target cholesterol biosynthesis, the beneficial effects on cardiovascular disease remain to be fully elucidated. In this work, we explored the in vitro effects of pravastatin on vascular functionality. We studied the effect of the incubation with this statin on acetylcholine relaxation using aorta from spontaneously hypertensive rats (SHR). Consistent with a cholesterol-independent mechanism of action, we show that pravastatin induces a significant improvement of endothelium-dependent relaxation that is not completely reversed by mevalonic acid. Assays with 250microM of lucigenin were carried out to verify whether such action could be mediated by the scavenger properties of pravastatin. Treatment of aortic rings derived from Wistar rats with lucigenin promotes superoxide generation (O(2)(-)) and the subsequent loss of both endothelium-dependent and independent relaxations. The addition of pravastatin reduced the lucigenin-triggered O(2)(-) levels as well as its inhibitory effects on acetylcholine- and sodium nitroprusside-dependent responses. These effects were not counteracted by mevalonic acid, further supporting the idea that the effects of pravastatin do not entail alterations in cholesterol biosynthesis. In conclusion, this study can contribute to elucidate the mechanism responsible for the antioxidant activity of pravastatin, and describes relationship between a scavenger effect of pravastatin and the improvement of vascular reactivity.

Vasorelaxant activity of phthalazinones and related compounds.

Several series of dihydrostilbenamide, imidazo[2,1-a]isoindole, pyrimido[2,1-a]isoindole and phthalazinone derivatives were obtained and their vasorelaxant activity was measured on isolated rat aorta rings pre-contracted with phenylephrine (10(-5)M). Some phthalazinones attained, practically, the total relaxation of the organ at micromolar concentrations. For the most potent compound 9h (EC(50)=0.43microM) the affinities for alpha(1A), alpha(1B) and alpha(1D) adrenergic sub-receptors were determined.

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.