- Factors influencing long-term heart failure mortality in patients with obstructive hypertrophic cardiomyopathy in Western Sweden: probable dose-related protection from beta-blocker therapy. [Journal Article]
- OHOpen Heart 2019; 6(1):e000963
- CONCLUSIONS: In population-based HOCM cohorts heart failure is a dominant cause of death and on multivariate analysis beta-blocker therapy was associated with a dose-dependent cardioprotective effect on total, disease-related as well as heart failure-related mortality.
- Gene Variants at Loci Related to Blood Pressure Account for Variation in Response to Antihypertensive Drugs Between Black and White Individuals. [Journal Article]
- HHypertension 2019 Jul 22; :HYPERTENSIONAHA11812177
- Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compa…
Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the β-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.
- Analysis of beta-blocker bioconcentration in brown planaria (Girardia dorotocephala) and its effects on regeneration. [Journal Article]
- ESEnviron Sci Pollut Res Int 2019 Jul 20
- Production, distribution, and disposal of pharmaceutical products, including beta-blockers, have become a global issue. Beta-blockers are known to persist in the environment months after their releas…
Production, distribution, and disposal of pharmaceutical products, including beta-blockers, have become a global issue. Beta-blockers are known to persist in the environment months after their release and may result in the disruption of the homeostatic system in non-target organisms. Here, we study the bioconcentration of three of the most commonly used beta-blockers and their effect on the regeneration of Girardia dorotocephala, a freshwater brown planarian. Acute toxicity tests determined LC50s for acebutolol, metoprolol, and propranolol to be 778 mg/L, 711 mg/L, and 111 mg/L, respectively. The quantification and analysis of beta-blocker bioconcentration during acute exposure were performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After 4 days of exposure to beta-blockers, the bioconcentration drastically decreased for all three beta-blockers at all exposure levels, suggesting that an effective mechanism to reduce uptake or excrete beta-blockers could be present. Additionally, Girardia dorotocephala were cut proximal to the head and the quality of regeneration was documented from each fragment daily. No significant difference was visually observed after 2 weeks of regeneration between the brown planarians placed in beta-blocker solution and those placed in control solution.
- Metoprolol and metoprolol acid degradation in UV/H2O2 treated wastewaters: An integrated screening approach for the identification of hazardous transformation products. [Journal Article]
- JHJ Hazard Mater 2019 Jul 06; 380:120851
- Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study descri…
Advancements on analytical strategies to determine the chemicals present in treated wastewater are necessary to clearly link their occurrence with the ecotoxicity of such effluents. This study describes the development of an integrated screening approach to determine the highest number of pharmaceutical transformation products (TPs) in a single run. The identification of TPs was based on the comparison of detected features with literature sources, compound prediction tools, in-house libraries and reference standards using high-resolution mass spectrometry (HRMS). This integrated approach allowed a better estimation (in silico) of the ecotoxicological contribution of the individual TPs identified. As a proof of concept, this methodology was applied for identification of the TPs generated from metoprolol and its main human metabolite (metoprolol acid) in pure water, hospital wastewater and industrial wastewater treated by UV/H2O2. Twenty-four TPs with potential ecotoxicological implications were identified and their presence was pinpointed as a function of the treated wastewater. An integrated screening approach has been developed using four different screening methodologies in the same run. Additionally, the metabolite MTPA has been considered as a target pollutant in UV/H2O2 experiments.
- The effects of intraperitoneal metoprolol administration on healing of bone defects in rat tibia: a pilot study. [Journal Article]
- COClin Oral Investig 2019 Jul 16
- CONCLUSIONS: Metoprolol did not reduce bone-active cytokine: IL-1β, IL-6, and RANKL. It also did not elevate IL-10 expression levels. Thus, it does not appear to decrease osteoclastogenesis.Results from this animal model help us understand any effect of metoprolol on bone healing by potential contribution to different real-world clinical research.
- Isolated Bilateral Pinna Swelling: A Rare Initial Presentation of Leprosy. [Case Reports]
- OAOpen Access Maced J Med Sci 2019 Jun 15; 7(11):1815-1817
- CONCLUSIONS: Isolated involvement of pinna in a patient without lesions in other body parts is an unusual initial presentation of leprosy. However, leprosy should be kept as a rare differential diagnosis of isolated lesions on the ear in patients not responding to conventional treatment.
- The Protective Effect of Nitroglycerin, N-Acetyl Cysteine and Metoprolol in CCL4 Induced Animal Model of Acute Liver Injury. [Journal Article]
- OAOpen Access Maced J Med Sci 2019 Jun 15; 7(11):1739-1743
- CONCLUSIONS: All the tested drugs proved in having a hepatoprotective effect when they are given orally to animals. The histopathological sections of the liver tissue supported the real effect of these drugs in the management of ALI.
- Secondary Analysis of Electronic Health Records: Comparative Effectiveness: Propensity Score Analysis [BOOK]
- BOOKSpringer: Cham (CH)
- In this chapter, we use a case study conducted using the MIMIC-II database, “Efficacy of Rate Control Medications in Atrial Fibrillation with Rapid Ventricular Response (Afib with RVR) amongst Critic…
In this chapter, we use a case study conducted using the MIMIC-II database, “Efficacy of Rate Control Medications in Atrial Fibrillation with Rapid Ventricular Response (Afib with RVR) amongst Critically Ill Patients”, as an example to demonstrate the concepts of propensity score analysis in EHR data research. In this study we investigated which of the three most commonly used rate control agents performed best as a sole agent to reach rate control for patients with Afib with RVR.
- Enhanced removal of pharmaceuticals in a biofilter: Effects of manipulating co-degradation by carbon feeding. [Journal Article]
- CChemosphere 2019 Jul 05; 236:124303
- Biofilm reactors are a promising biotechnology to eliminate pharmaceuticals from wastewater during tertiary treatment or in water works for drinking water production. This study aimed at investigatin…
Biofilm reactors are a promising biotechnology to eliminate pharmaceuticals from wastewater during tertiary treatment or in water works for drinking water production. This study aimed at investigating the effects of pulsed carbon feeding for promoting the co-degradation of indigenous pharmaceuticals from pre-treated wastewater in a fixed-bed porous biofilm reactor (slow sand filter). The addition of acetate (carbon source) resulted in three different enhancement/limitation effects, which were compound dependent: 1) atenolol and iohexol experienced enhanced co-degradation followed by constant (acetate independent) degradation; 2) metoprolol, iomeprol, diclofenac, propranolol and sulfamethizole co-degradation dependent on aerobic turnover, but inhibited at higher acetate concentrations (60-300 mg C/L); 3) sulfadiazine, sulfamethoxazole and trimethoprim were removed independently of oxygen and acetate concentration. Carbamazepine, ditriazoic acid, iopromide; tramadol and venlavaxine were not removed at any acetate dosage. Biofilm reactors can be employed for polishing treated wastewater, and the addition of a primary carbon source can enhance the performance of the bioreactor.
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- Effects of absorption-modifying excipients on jejunal drug absorption in simulated fasted and fed luminal conditions. [Journal Article]
- EJEur J Pharm Biopharm 2019 Jul 12
- Oral administration of drug products is the preferred administration route. In recent decades there has been an increase in drug candidates with low solubility and/or low permeability. To increase th…
Oral administration of drug products is the preferred administration route. In recent decades there has been an increase in drug candidates with low solubility and/or low permeability. To increase the possibility of oral administration for the poorly permeating drugs, the use of absorption modifying excipients (AMEs) has been proposed. These types of AMEs may also affect the regulatory assessment of a novel drug delivery system if they affect the absorption of a drug from any of the four BCS classes. The effects of AMEs have previously been investigated in various animal models, including the single-pass intestinal perfusion (SPIP) in rats. To further improve the biorelevance and the in vivo predictiveness of the SPIP model, four compounds (atenolol, enalaprilat, ketoprofen, metoprolol) were perfused in fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) together with the AMEs N-acetyl-cysteine, caprate, or sodium dodecyl sulfate. For the highly soluble and poorly permeating compounds enalaprilat and atenolol (BCS class III), the flux was increased the most by the addition of SDS in both FaSSIF and FeSSIF. For ketoprofen (BCS class II), the flux decreased in the presence of all AMEs in at least one of the perfusion media. The flux of metoprolol (BCS class I) was not affected by any of the excipients in none of simulated prandial states. The changes in magnitude in the absorption of the compounds were in general smaller in FeSSIF than in FaSSIF. This may be explained by a reduced free concentration AMEs in FeSSIF. Further, the results in FeSSIF were similar to those from intrajejunal bolus administration in rat in a previous study. This suggests that the biorelevance of the SPIP method may be increased when investigating the effects of AMEs, by the addition of intraluminal constituents representative to fasted and/or fed state to the inlet perfusate.