RESUMEN

Background: The angiotensin-converting enzyme inhibitor (ACEI) enalapril is often administered to infants and young children with heart failure (HF) in various dosing regimens and formulations not adapted for their age. Methods: This prospective, two-center, open-label 8-week study evaluated an age-appropriate formulation of orodispersible minitablets (ODMTs) of enalapril (0.25 mg and 1 mg) in children aged 0 to 6 years with HF due to congenital heart disease. An age/weight-based dosing schedule was followed. Measures of echocardiographic parameters, blood pressure, heart rate, modified Ross score, and biochemistry were obtained over the 8-week period. The following two groups were assessed: ACEI-naïve and ACEI-pretreated patients. Results: In total, 53 children (age range of 0.05 to 4.8 years) were enrolled and 29 were ACEI-naïve. The average enalapril dose was 0.098 mg/kg (0.06-0.17 mg/kg) in the naïve group and 0.15 mg/kg (0.07-0.3 mg/kg) in pretreated patients. After 8 weeks, the modified Ross score and left ventricular diastolic dimension (LVD) z-score showed a significant decrease in both groups (p < 0.005). During 8 weeks follow-up, there were no difference in the z-scores for the systolic blood pressure (p = 0.071) or heart rate (p = 0.146). Conclusions: Pediatric patients treated with ODMTs of enalapril for 8 weeks had favorable improvements in LVD and HF symptoms.

RESUMEN

Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu-antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu-antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.

Asunto(s)

Antibacterianos , Cobre , Humanos , Cobre/química , Antibacterianos/química , Meropenem , Ampicilina , Iones

RESUMEN

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.

Asunto(s)

Anticolesterolemiantes , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Proproteína Convertasa 9 , LDL-Colesterol , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/complicaciones , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/etiología , Suplementos Dietéticos , Anticolesterolemiantes/farmacología , Anticolesterolemiantes/uso terapéutico

RESUMEN

Hydralazine (HL), a frequently prescribed oral antihypertensive drug, shows redox interactions with transition metals such as copper that are not fully understood. Copper may be present at high concentrations in the digestive tract and can affect oral drugs. An important parameter for such interactions is pH, which changes from acidic in the gastric juice to neutral pH in intestines. In this study, we examined interactions of HL with Cu2+ ions in conditions that mimic pH shift in the digestive tract using UV-Vis, Raman and EPR spectroscopy, cyclic voltammetry and oximetry. In the acidic solution, Cu2+ formed a stable mononuclear complex with two bidentate coordinated HL molecules. On the other hand, at neutral pH, Cu2+ initiated oxidation and degradation of HL. The degradation was more rapid in the HL-Cu2+ system that was initially prepared at acidic pH and then shifted to neutral pH. The formation of the complex at acidic pH increases the availability of Cu2+ for redox reactions after the shift to neutral pH at which Cu2+ is poorly soluble. These results imply that the change of pH along the digestive tract may promote HL degradation by allowing the formation of the complex at gastric pH which makes Cu2+ available for subsequent oxidation of HL at neutral pH.

Asunto(s)

Cobre , Hidralazina , Cobre/química , Oxidación-Reducción , Concentración de Iones de Hidrógeno , Estrés Oxidativo

RESUMEN

The aim of our investigation is to correlate the wholesale data on antibiotic consumption expressed in daily doses per 1000 inhabitants per day (DID) with the resistance rate of invasive pathogen bacteria from 2017 to 2021. The data on antimicrobial resistance were collected from an analysis of the primary isolates of hospitalized patients. According to the CAESAR manual, the selected pathogens isolated from blood culture and cerebrospinal fluids were tested. The consumption of antibiotics for systematic use showed a statistically significant increasing trend (ß = 0.982, p = 0.003) from 21.3 DID in 2017 to 34.5 DID in 2021. The ratio of the utilization of broad-spectrum to narrow-spectrum antibiotics increased by 16% (ß = 0.530, p = 0.358). The most consumed antibiotic in 2021 was azithromycin (15% of total consumption), followed by levofloxacin (13%) and cefixime (12%). A statistically positive significant correlation was discovered between the percentage of resistant isolates of K. pneumoniae and consumption of meropenem (r = 0.950; p = 0.013), ertapenem (r = 0.929; p = 0.022), ceftriaxone (r = 0.924; p = 0.025) and levofloxacin (r = 0.983; p = 0.003). Additionally, the percentage of resistant isolates of E. coli and consumption of ertapenem showed significant correlation (r = 0.955; p = 0.011). Significant correlation with consumption of the antibiotics widely used at the community level, such as levofloxacin, and resistance isolated in hospitals indicates that hospital stewardship is unlikely to be effective without a reduction in antibiotic misuse at the community level.