Fast determination of free metronidazole in rat plasma and peritoneal fluid using HPLC-UV method.

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 C18 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.

Aromatic and sensorial characterization of "Moscato pyments": an innovative beverage.

Pyment is a type of mead that is produced from the alcoholic fermentation of a honey solution with the addition of grape juice. Due to the demand for new beverages, pyment can be a profitable alternative for both grape and honey producers. Therefore, this work aimed to characterize the aromatic and physicochemical composition of pyments. The pyments were prepared with addition of 10, 20 and 30% of Moscato juice, and compared with Moscato wine and traditional mead. The results showed an increase in the fermentation rates of Moscato-pyments, indicating that the addition of Moscato juice reverses the low fermentative vigor often reported in mead fermentations. Physicochemical parameters showed an increase in total acidity and a decrease in residual sugar and alcohol, depending on Moscato juice concentration. Moscato-pyments showed an intermediate concentration of volatile compounds between the traditional mead and Moscato wine, with a better balance between fruity, floral and buttery, manifesting characteristic aromas of wines made with Moscato grapes and simultaneously, exposing characteristic aromas of honey. The sensory analysis reveals a significant difference between mead, pyments and Moscato wine. In general, pyments were considered, by the panelists, as the most equilibrated with intermediary aroma intensity, floral, fruity and honey aromas, and good persistence in the mouth.

Development and validation of an LC-ESI-QTOF-MS method to measure cefepime in the plasma and peritoneal fluid of rats using microdialysis: Application in a pilot pharmacokinetic study.

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 C18 column (250 × 4.6 mm), a C18 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.

Palladium-Catalyzed Cascade 5-endo-dig Cyclization of Ynamides to Form 4-Alkynyloxazolones.

The selective synthesis of 4-alkynyloxazolones and their further applications as substrates to electrophile-promoted nucleophilic cyclization have been developed. The reaction of ynamides with terminal alkynes proceeded smoothly to give 4-alkynyloxazolones in the presence of a catalytic amount of palladium(II) acetate. The products were obtained with the sequential formation of new C-C and C-O bonds via a cascade procedure. The first step involved a carbon-oxygen bond formation, via a 5-endo-dig closure, which was confirmed by X-ray analyses of the crystalline sample. Subsequently, the reaction of 4-alkynyloxazolones with an electrophilic selenium source gave 3-phenylselanyl benzofuran derivatives via an electrophile-promoted nucleophilic cyclization.

Diorganyl Diselenides and Iron(III) Chloride Drive the Regio- and Stereoselectivity in the Selenation of Ynamides.

We report here our results on the application of ynamides as substrates in the reactions with diorganyl dichalcogenides and iron(III) chloride to give selectively three different types of compounds: E-α-chloro-ß-(organoselenyl)enamides, 4-(organochalcogenyl)oxazolones, and vinyl tosylates. The results reveal that the selectivity in the formation of products was obtained by controlling the functional groups directly bonded to the nitrogen atom of the ynamides. Thus, α-chloro-ß-(organoselenyl) enamide derivatives were exclusively obtained when the TsN- and MsN-ynamides were treated with a mixture of diorganyl diselenides (1.0 equiv) and FeCl3 (3.0 equiv) in dichloroethane (DCE, 3 mL), at room temperature. The 4-(organochalcogenyl)oxazolones were selectively obtained with ynamides having an ester group, directly bonded to the nitrogen atom, upon treatment with a solution of FeCl3 (1.5 equiv) and diorganyl dichalcogenides (1.0 equiv) in dichloromethane (3 mL) at room temperature. Finally, vinyl tosylates were obtained from ynamides having an ester group, directly bonded to the nitrogen atom, by reaction with p-toluenesulfonic acid. We also studied the application of the prepared compounds as substrates for Suzuki and Sonogashira cross-coupling reactions.

Jabuticaba (Plinia trunciflora (O. Berg) Kausel) improved the lipid profile and immune system and reduced oxidative stress in streptozotocin-induced diabetic rats.

The aim of this study was evaluating the effects of jabuticaba aqueous extract (JPE - 0.5 g/kg) on serum lipid levels, immune system, and oxidative stress parameters of streptozotocin-induced diabetic rats. Administration of JPE for 30 days, by gavage, was able to reduce serum levels of total cholesterol, non-high density lipoprotein (HDL) cholesterol, and triglycerides in diabetic rats. The HDL cholesterol levels increased in both diabetic and healthy rats after JPE treatment. Total leukocyte and lymphocyte counts reduced in diabetic rats, and JPE treatment prevented these diabetes mellitus (DM)-induced changes in the immune system. In addition, the induction of DM also led to dysregulation in the activity of superoxide dismutase and catalase antioxidant enzymes as well as an increase in oxidative stress markers. Treatments with JPE reduced oxidative stress and modulated antioxidant enzyme activities. These data demonstrate the potential of JPE as an adjuvant treatment option for diabetic patients. PRACTICAL APPLICATIONS: Considering that it is very common to observe dyslipidemia in diabetic patients and that these alterations, combined with the increased oxidative stress levels, also common in these patients, can lead to the development of cardiovascular diseases, JPE would be an alternative treatment adjunct to reduce these risks. In addition, although more studies are needed, JPE has the potential to improve the count of total lymphocytes and leukocytes, which could assist in improving the immune response of these patients, who also commonly have a higher risk of infectious diseases. Thus, JPE could be used by these patients, in combination with conventional treatment, in the form of a nutraceutical rich in phenolic compounds.

Phytochemical Analysis, Antioxidant Activity, Antimicrobial Activity, and Cytotoxicity of Chaptalia nutans Leaves.

OBJECTIVE: This work was to evaluate the chemical constitution of the hydromethanolic (30/70 methanol-water) macerating extract obtained from the leaves of C. nutans, as well as to study the antioxidant, antimicrobial, cytotoxic, and genotoxic activity of the species. Materials and methods. Phytochemical screening, antioxidant activity (total phenolic, total flavonoid, condensed tannins content, DPPH radical, and FRAP), antibacterial activity (P. aeruginosa, B. cereus, E. epidermidis, E. coli, S. aureus, E. faecalis, P. mirabilis, Candida glabrata (clinical isolate), Candida tropicalis (clinical isolate), C. krusei (clinical isolate), and C. albicans (clinical isolate)), and oxidative stress parameters (TBARS, carbonyl protein, and DCFH) were analyzed according to the literature. Toxicity of C. nutans was evaluated using an alternative method, D. melanogaster, as well as a locomotor assay. RESULTS: The phytochemical screening test of methanolic leaves extract revealed the presence of alkaloids, coumarins, quaternary bases, phenolics, flavonoids, tannins, and free steroids. A quantitative phytochemical study indicated the total phenol (30.17 ± 1.44 mg/g), flavonoid (21.64 ± 0.66 mg/g), and condensed tannins (9.58 ± 0.99 mg/g). DPPH (345.41 ± 5.35 µg/mL) and FRAP (379.98 ± 39.25 µM FeSO4/mg sample) show to extract of C. nutans leaves an intermediate value, indicating moderate antioxidant activity of the extract. Antibacterial results revealed only a positive result (antimicrobial activity) for the hexane fraction which significantly inhibited the microorganisms E. epidermidis, C. tropicalis, C. glabrata, and C. krusei at a concentration of 1000 µg/mL. TBARS, carbonyl protein, and DCFH demonstrate that the extract has the ability to protect the cell from protein and lipid damage, as well as the inhibition of oxygen-derived radicals at the three concentrations tested: 0.1, 1, and 10 mg/mL. Regarding the toxicity of C. nutans extract against D. melanogaster, it was found that until the concentration of 15 mg/mL, the extract showed no toxicity and that the LC50 obtained was 24 mg/mL. Results show that the C. nutans extract leaves used to prevent PQ damage were effective in reducing flies' mortality and improving locomotor capacity. CONCLUSION: Our studies demonstrated for the first time that C. nutans crude leaf extract has high antioxidant capacity both in vitro and in vivo through different analysis techniques. These results make it possible to infer future applications in the pharmacological area, evidenced by the low toxicity observed in D. melanogatser, as well as the ability to neutralize different sources of RONS.