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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., (Copyright © 2023 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

The use of multitarget drugs has evolved as an alternative to "magic bullets" for the treatment of complex diseases such as cancer, in order to affect simultaneously several targets relevant to the disease. We have designed and synthesized a series of dual agents as both Eg5 inhibitors and calcium channel blockers, bearing a 4-aryldihydropyrimidine core. Compound 2 (aryl: 3-nitrophenyl) was selected as potential dual agent due to displaying both activities: it is a vasorelaxant agent (>90% relaxation at 10 -5 M in KCl-precontracted aorta rings), it decreases the response to calcium and it is cytotoxic to MCF-7 (breast), HCT-116 (colon) and A-549 (lung) cancer cell lines. The dual mechanism of action was confirmed by blocking (-)-BAY K8644-induced vascular contraction and production of monopolar spindles, typical of Eg5 inhibition. Docking suggests that both ( R ) and ( S )-enantiomers could bind Eg5., (This journal is © The Royal Society of Chemistry 2019.)

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.

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 β-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., (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)