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The aim of this study was to investigate the penetration of cefepime into rat peritoneal fluid by microdialysis and to determine the relationship between unbound drug plasma and tissue concentration in healthy animals and in a sepsis model established through cecal ligation and puncture-induced peritonitis. Probe recovery was performed by dialysis and retrodialysis. Cefepime was administered at a dose of 110 mg/kg intravenously. Samples were collected for about 4 h, and concentrations were determined by liquid chromatography-electrospray ionization-QTOF MS. Tissue penetration was also determined. Probe recovery in vivo was 38.78% ± 3.31% and 38.83% ± 2.74% in the control and peritonitis groups, respectively. Cefepime was rapidly distributed in the peritoneal fluid in both groups. The peritoneal fluid/plasma cefepime ratio was 0.38 and 0.32 for the control and peritonitis groups, respectively. Cefepime concentrations were above the MIC of 4 mg/L for the main enterobacteria. The infection model that was used had no apparent effect on the pharmacokinetics of cefepime in rats. This was the first study to determine free cefepime concentrations in the peritoneal fluid of healthy rats and rats with experimental peritonitis., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Peritonitis refers to the inflammatory reaction of the peritoneum to aggression. In addition, it contributes significantly to sepsis. The presence of free concentrations of antimicrobials above the minimum inhibitory concentration at the site of infection is critical to therapeutic response. Metronidazole (MTZ) is an antimicrobial used to treat peritonitis because of its effectiveness against anaerobic microorganisms. This study investigates free MTZ concentrations in peritoneal microdialysate in Wistar rats. A C 18 column (150 × 4.0 mm, 5 μm) was used for the analysis conducted at 40°C under isocratic conditions. The mobile phase consisted of acetonitrile and an aqueous solution of 50-mM monobasic phosphate buffer and 0.1% triethylamine, with pH 3.0 (10:90, v/v). MTZ calibration was linear in the range of 0.5-30.0 μg/ml. The intra- and inter-day precision was satisfactory with relative standard deviation ≤5.67%. The accuracy ranged from 90.64 to 103.77%, and the lower limit of quantification was 0.5 μg/ml. The developed method was successfully applied in a pilot pharmacokinetic study after MTZ administration (30 mg/kg, intravenously) in rats. The main advantage of the employed method is that it does not require sample processing and protein removal steps. This is the first study to be conducted using MTZ in rats., (© 2022 John Wiley & Sons, Ltd.)

Cefepime (CEF) is a cephalosporin and can be administered in secondary peritonitis together with metronidazole to treat sepsis. This study aimed to develop and validate an LC-ESI-QTOF-MS method for the quantification of cefepime in the plasma and peritoneal microdialysate of healthy Wistar rats. Chromatographic separation was performed using a CLC-ODS C 18 column (250 × 4.6 mm), a C 18 pre-column (4 mm, 5 μm) and isocratic elution. Gallic acid was used as the internal standard. The mobile phase consisted of (A) ultrapure water (pH adjusted to 3.5) and (B) acetonitrile (80:20, v/v) at 0.8 ml/min. Quantification was performed using a mass spectrometer with electrospray ionization in positive mode to monitor ions with m/z 481.1322 (CEF) and m/z 171.0288 (IS). The method was validated for selectivity, precision, accuracy, linearity, stability, lower limit of quantification, carryover, recovery and matrix effect. Calibration was done in the ranges 1-40 and 1-100 μg/ml for the peritoneal microdialysate and plasma, respectively. Plasma extraction recovery ranged from 93.9 to 99.9%. The technique was validated and successfully applied in a pilot pharmacokinetic study for estimating the free concentration of CEF in the peritoneal microdialysate of rats for the first time., (© 2022 John Wiley & Sons Ltd.)

Skin aging is a gradual process that leads to wrinkle formation, laxity, and overall changes in skin appearance. In recent years, the demands to noninvasive treatments for facial rejuvenation increased, along with a variety of technologies and devices, such as radiofrequency. The present study aimed to evaluate the clinical effects of a multipolar radiofrequency and pulsed electromagnetic field treatment for face and neck rejuvenation. Eleven patients with mild to moderate grades of photoaging underwent eight radiofrequency and pulsed electromagnetic field treatment sessions, once a week. Clinical photographs were taken before and a week after the end of the treatment, and improvement of facial skin parameters was evaluated by two different investigators. Significant improvement in skin laxity was observed in all eleven patients (100%). Improvement in facial contour was noted in 73% and 100% of patients when analyzed by investigators A and B, respectively. The score for overall improvement in skin condition was 3 ± 0.78 for investigator A and 3.6 ± 0.67 for investigator B. All patients were satisfied with the procedure and noted significant improvement in the skin. The combined multipolar radiofrequency and pulsed electromagnetic field device is effective and safe for treatment of aged skin in Brazilian patients.

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.