Two morphotypes versus two chemotypes of Psidium cattleyanum: Chemical and pharmacological comparison and a rational approach for marker selection.

Psidium cattleyanum has two morphotypes: one with yellow fruits and other with red fruits. The leaves are popularly used as anti-inflammatory. However, no distinction is made between the types. Therefore, this study compared chemical and pharmacological data of both morphotypes to select proper biomarkers to ensure P. cattleyanum leaves quality. After extraction optimization by experimental design, 28 samples were analyzed by HPLC. Using Principal Component Analysis, it was possible to detect two chemotypes, unrelated to the color of the fruits. However, the extracts obtained from both chemotypes seemed to play similar anti-inflammatory effect, demonstrated by anti-chemotactic activity. The compounds common to both chemotypes were isolated and identified as hyperoside, miquelianin and quercitrin; these compounds also demonstrated anti-inflammatory potential. Since both chemotypes played similar activity, along with the isolated flavonoids, these flavonoids were selected as biomarkers for quality control of P. cattleyanum leaves. Following ICH guidelines, a HPLC method was validated. In summary, this study demonstrated that hyperoside, miquelianin and quercitrin can be used as biomarkers for quality control of P. cattleyanum leaves and a method was developed and validated to be used interchangeably for both morpho- and chemotypes.

PK/PD modeling of daptomycin against MRSA and MRSE and Monte Carlo simulation for bacteremia treatment.

OBJECTIVES: The aim of this study was to investigate the effect of daptomycin against methicillin-resistant staphylococci (MRSA and MRSE) bacteremia using computer modeling. METHODS: A pharmacokinetic/pharmacodynamic (PK/PD) modeling strategy to explain the data from an in vitro dynamic model employing time-kill curves for MRSA and MRSE was proposed. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed. Monte Carlo simulations were performed using pharmacokinetic parameters and pharmacodynamic data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. Simulations were conducted to assess the reduction in the number of colony-forming units (CFU)/mL for 18 days of treatment with daptomycin at doses of 6, 8, and 10 mg/kg/24 h or 48 h with variations in creatinine clearance (CLCR): 15-29 mL/min/1.73 m2, 30-49 mL/min/1.73 m2, 50-100 mL/min/1.73 m2, as well as for defining the probability of reaching the target fAUC/MIC = 80 in the same dose and clearance range. A PK/PD model with saturation in the number of bacteria in vitro, growth delay, and bacterial death, as well as Hill's factor, was used to describe the data for both MRSA and MRSE. RESULTS: Monte Carlo simulations showed that for MRSA there was a reduction > 2 log CFU/mL with doses ≥ 6 mg/kg/day in 75th percentile of the simulated population after 18 days of treatment with daptomycin, whereas for MRSE this reduction was observed in 95th percentile of the population. CONCLUSIONS: The presented in vitro PK/PD model and associated modeling approach were able to characterize the time-kill kinetics of MRSA and MRSE. Our study based on PTAs suggests that doses ≥ 6 mg/kg/day of daptomycin should be used to treat bacteremia caused by MRSA and MRSE in patients with CLCR of 15-29 mL/min/1.73 m2. For patients with CLCR ≥ 50 mL/min/1.73 m2, it would be necessary to employ a dose of 10 mg/kg/day to treat complicated bacteremias.

Polyphenolic Composition and in Vitro Antihypertensive and Anti-Inflammatory Effects of Cuphea lindmaniana and Cuphea urbaniana.

The present study investigates the chemical composition, anti-inflammatory, and antihypertensive activities, in vitro, from extracts of Cuphea lindmaniana and Cuphea urbaniana leaves. The extraction was performed ultrasound-assisted, and UHPLC/MS analysis was in positive mode ionization. The anti-inflammatory activity of the extracts and miquelianin were assayed at concentrations 0.001-10 µg/mL by chemotaxis on rat polymorphonuclear neutrophils. The antihypertensive activity was performed by angiotensin-converting enzyme (ACE) inhibition. From the nineteen proposed compounds, six of them are described for the first time in this genus. The extracts displayed antichemotactic effect with a reduction of 100 % of the neutrophil migration, in vitro, in most concentrations. The ACE-inhibition presented results ranging from 19.58 to 22.82 %. In conclusion, C. lindmaniana and C. urbaniana extracts contain a rich diversity of flavonoids and display in vitro anti-inflammatory and antihypertensive potential. Thus, this study could serve as a scientific baseline for further investigation, on developmental novel products with therapeutic actions.

Intravenous contrast use and acute kidney injury: a retrospective study of 1,238 inpatients undergoing computed tomography.

OBJECTIVE: To determine the incidence of nephropathy induced by intravenous contrast in hospitalized patients undergoing computed tomography (CT). MATERIALS AND METHODS: This was a retrospective cohort study involving 1,238 patients who underwent CT with or without intravenous administration of a contrast agent (iopromide). The primary outcome measure was acute kidney injury (AKI), as defined by the traditional criteria-an absolute or relative increase in serum creatinine (SCr) ≥ 0.5 mg/dL or ≥ 25% over baseline, respectively, at 2-3 days after contrast administration-and the newer, Kidney Disease: Improving Global Outcomes (KDIGO) criteria-an absolute or relative increase in SCr ≥ 0.3 mg/dL or ≥ 50% over baseline, respectively, at 2-7 days after contrast administration. RESULTS: The overall incidence of AKI was 11.52% when the KDIGO criteria were applied. Univariate logistic regression demonstrated a significant association between an absolute post-CT increase in SCr ≥ 0.5 mg/dL and AKI, although that association did not retain significance in the multivariate analysis. Multivariate logistic regression initially found an association between an absolute post-CT increase in SCr ≥ 0.3 mg/dL and advanced age, although that association was not maintained after correction. We found no association between AKI and the risk factors evaluated. CONCLUSION: We identified no criteria for contrast-induced nephropathy after CT; nor did we find AKI to be associated with the classical risk factors.

OBJETIVO: Determinar a incidência de nefropatia induzida por contraste intravenoso em pacientes hospitalizados submetidos a tomografia computadorizada (TC). MATERIAIS E MÉTODOS: Estudo de coorte retrospectivo que alocou 1.238 pacientes submetidos a TC sem ou com contraste (iopromida). O desfecho primário foi nefropatia induzida por contraste, definida pelo critério antigo - aumento absoluto ou relativo na creatinina sérica (SCr) ≥ 0,5 mg/dL ou ≥ 25%, respectivamente, durante 2-3 dias após a administração -, e o novo, Kidney Disease Improving Global Outcomes (KDIGO) - aumento absoluto ou relativo na SCr ≥ 0,3 mg/dL ou ≥ 50%, respectivamente, durante 2-7 dias após a administração. RESULTADOS: A incidência de lesão renal aguda foi de 11,52% aplicando os critérios KDIGO. A regressão logística univariada demonstrou significância relacionada à associação entre aumento absoluto da SCr ≥ 0,5 mg/dL após TC e lesão renal aguda. A regressão logística multivariada encontrou, inicialmente, associação entre aumento absoluto da SCr ≥ 0,3 mg/dL após TC e idade avançada, mas a associação não foi mantida após correção. Não foi encontrada associação entre lesão renal aguda e os fatores de risco avaliados. CONCLUSÃO: Não foram encontrados critérios para nefropatia induzida por contraste após TC ou associação de lesão renal aguda com fatores de risco clássicos.

Psidium L. genus: A review on its chemical characterization, preclinical and clinical studies.

The Myrtaceae family is considered one of the largest known botanical families and the genus Psidium is among the most economically interesting. Psidium genus comprises approximately 112 species, and it has been extensively studied, mainly because of Psidium guavaja species. Phytochemical investigations confirmed the presence of phenolics as the main compounds, as well as the essential oils, which were also widely investigated. Pharmacological studies report analgesic, anthelminthic, acaricidal, antihiperglicemic, among other biological activities for different species. The present review covers the relevant literature until 2019 and outlines the current data on chemical composition, preclinical and clinical studies on Psidium species, as well as the main possible mechanisms of action responsible for the described activities. Therefore, it can provide a reference for pharmaceutical research and clinical application of this genus.

Intravenous contrast use and acute kidney injury: a retrospective study of 1,238 inpatients undergoing computed tomography / Uso de contraste intravenoso e lesão renal aguda: estudo retrospectivo de 1.238 pacientes internados submetidos a tomografia computadorizada

Abstract Objective: To determine the incidence of nephropathy induced by intravenous contrast in hospitalized patients undergoing computed tomography (CT). Materials and Methods: This was a retrospective cohort study involving 1,238 patients who underwent CT with or without intravenous administration of a contrast agent (iopromide). The primary outcome measure was acute kidney injury (AKI), as defined by the traditional criteria-an absolute or relative increase in serum creatinine (SCr) ≥ 0.5 mg/dL or ≥ 25% over baseline, respectively, at 2-3 days after contrast administration-and the newer, Kidney Disease: Improving Global Outcomes (KDIGO) criteria-an absolute or relative increase in SCr ≥ 0.3 mg/dL or ≥ 50% over baseline, respectively, at 2-7 days after contrast administration. Results: The overall incidence of AKI was 11.52% when the KDIGO criteria were applied. Univariate logistic regression demonstrated a significant association between an absolute post-CT increase in SCr ≥ 0.5 mg/dL and AKI, although that association did not retain significance in the multivariate analysis. Multivariate logistic regression initially found an association between an absolute post-CT increase in SCr ≥ 0.3 mg/dL and advanced age, although that association was not maintained after correction. We found no association between AKI and the risk factors evaluated. Conclusion: We identified no criteria for contrast-induced nephropathy after CT; nor did we find AKI to be associated with the classical risk factors.

Resumo Objetivo: Determinar a incidência de nefropatia induzida por contraste intravenoso em pacientes hospitalizados submetidos a tomografia computadorizada (TC). Materiais e Métodos: Estudo de coorte retrospectivo que alocou 1.238 pacientes submetidos a TC sem ou com contraste (iopromida). O desfecho primário foi nefropatia induzida por contraste, definida pelo critério antigo - aumento absoluto ou relativo na creatinina sérica (SCr) ≥ 0,5 mg/dL ou ≥ 25%, respectivamente, durante 2-3 dias após a administração -, e o novo, Kidney Disease Improving Global Outcomes (KDIGO) - aumento absoluto ou relativo na SCr ≥ 0,3 mg/dL ou ≥ 50%, respectivamente, durante 2-7 dias após a administração. Resultados: A incidência de lesão renal aguda foi de 11,52% aplicando os critérios KDIGO. A regressão logística univariada demonstrou significância relacionada à associação entre aumento absoluto da SCr ≥ 0,5 mg/dL após TC e lesão renal aguda. A regressão logística multivariada encontrou, inicialmente, associação entre aumento absoluto da SCr ≥ 0,3 mg/dL após TC e idade avançada, mas a associação não foi mantida após correção. Não foi encontrada associação entre lesão renal aguda e os fatores de risco avaliados. Conclusão: Não foram encontrados critérios para nefropatia induzida por contraste após TC ou associação de lesão renal aguda com fatores de risco clássicos.

Cuphea spp.: antichemotactic study for a potential anti-inflammatory drug.

Cuphea genus (Lythraceae) popularly known in Brazil as "sete-sangrias", it's described as antimicrobial, anti-inflammatory, diuretic and antihypertensive mainly. Investigating the chemotactic ability plays an important role in the identification of new anti-inflammatory agents. Thus, this research aims to assay the antichemotactic activity of hydroethanolic extracts of C. calophylla, C. carthagenensis, C. glutinosa, and C. racemosa as well as the compounds miquelianin and myricitrin. The antichemotactic activity of the hydroethanolic extracts, miquelianin, and myricitrin were assayed at concentrations 0.001 to 10 µg/mL in the lipopolysaccharide-induced chemotaxis on rat polymorphonuclear neutrophils. All the assayed samples displayed antichemotactic activity with reduction of the neutrophil migration in the range of 4.46-100%, and an IC50 value in the range of 0.30-1.24 µg/mL. Thus, this study demonstrates that the extracts hydroethanolic of Cuphea species, miquelianin, and myricitrin display a significant antichemotactic activity. Therefore, in future studies, extracts from Cuphea spp. could be used as anti-inflammatory drugs.

Time-kill curves of daptomycin and Monte Carlo simulation for the treatment of bacteraemia caused by Enterococcus faecium.

OBJECTIVES: The aim of this study was to investigate the effect of daptomycin against vancomycin-resistant Enterococcus faecium bacteraemia using computer modelling. METHODS: Data obtained in vitro from time-kill curves were evaluated by PK/PD modelling and Monte Carlo simulations to determine the logarithmic reduction in the number of colony-forming units (CFU)/mL over 18 days of daptomycin treatment at 6, 8, and 10 mg/kg doses every 24 or 48 h and with variations in creatinine clearance (CLCR) of 15-29, 30-49, and 50-100 mL/min/1.73 m2. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for an area under the unbound drug concentration-time curve/minimum inhibitory concentration (fAUC/MIC) > 36 at the same doses and CLCR. RESULTS: Static time-kill model was employed to investigate the antibacterial efficacy of constant daptomycin concentrations. The time-kill curve analysis was performed using mathematical modelling based on a Hill coefficient factor. There was an expressive reduction (> 2 Log CFU/mL) over 18 days of daptomycin treatment in 75th percentile of individuals with CLCR of 15-100 mL/min/1.73 m2) with daptomycin 6-10 mg/kg/day, except for daptomycin every 48 h. Using fAUC/MIC > 36, PTA was > 90% at MICs ≤ 2 µg/mL. CONCLUSIONS: Higher daptomycin doses were associated with higher mortality in time-kill curves. The simulations indicated that independent of the CLCR the therapeutic responses of VRE occur with doses of daptomycin ≥ 6 mg/kg/day and daptomycin every 48 h is insufficient to treat enterococcal bacteraemia.