The Cardiorenal Effects of Piper amalago Are Mediated by the Nitric Oxide/Cyclic Guanosine Monophosphate Pathway and the Voltage-Dependent Potassium Channels.

Piper amalago L. is used in Brazilian traditional medicine to treat inflammation, chest pain, and anxiety. This study aimed to investigate the safety and the renal and cardiovascular effects of the volatile oil (VO) and the aqueous (AE) and hydroalcoholic (HE) extracts from P. amalago. The gas chromatography-mass spectrometry analyses identified 47 compounds in the VO, with ß-cyclogermacrene, spathulenol, ß-phellandrene, and α-pinene standing out. Among the 47 compounds also found in AE and HE by liquid chromatography-mass spectrometry, glycosylated flavones, organic acids, amino acids, and amides were highlighted. Some examples of these compounds are methoxy-methylenedioxy cis-cinnamoyl pyrrolidine, methoxy-methylenedioxy trans-cinnamoyl pyrrolidine, and cyclobutene-2,4-bis-(1,3-benzodioxol-5-methoxy-6-yl)-1,3-dicarboxapyrrolidide. The acute toxicity experiments were conducted on female rats (n = 5). The cardiorenal assays (n = 8) and evaluations of vasodilatory effects on the mesenteric vascular bed (n = 5) were conducted on male rats. In either extract or VO, there were no mortality or changes in relative weights or histopathological analysis of the organs. Urinary volume and renal electrolyte excretion were elevated significantly during repeated dose 7-day treatment with different preparations from P. amalago. None of the preparations induced hypotension or changes in cardiac electrical activity. Only HE promoted significant vasodilatory effects in rats' isolated mesenteric vascular beds. These effects were completely abolished in the presence of L-NAME plus 4-aminopyridine. Therefore, P. amalago leaves are safe and present diuretic activity after acute and repeated dose administration over 7 days. Moreover, the HE induced significant vasodilator response in rats' mesenteric vascular beds by NO/cGMP pathway and voltage-dependent K+ channels activation.

Changes in fatty acid composition as a response to glyphosate toxicity in Pseudomonas fluorescens.

Excessive use of herbicides decreases soil biodiversity and fertility. The literature on the xenobiotic response by microorganisms is focused on herbicide biodegradation as a selective event. Non-degradation systems independent of selection could allow the survival of tolerant bacteria in contaminated environments, impacting xenobiotic turnover and, consequently, bioremediation strategies. However, it is uncertain whether the response based on these systems requires selective pressure to be effective. The objective here was to analyze non-degradation phenotypes, enzymatic and structural response systems, of Pseudomonas fluorescens CMA-55 strain, already investigated the production pattern of quorum sensing molecules in response to glyphosate, not present at the isolation site. One mode of response was associated with decrease in membrane permeability and effective antioxidative response for 0-2.30 mM glyphosate, at the mid-log growing phase, with higher activities of Mn-SOD, KatA, and KatB, and presence of fatty acids as nonadecylic acid, margaric and lauric acid. The second response system was characterized by lower antioxidative enzymes activity, presence of KatC isoform, and pelargonic, capric, myristic, stearic, palmitoleic and palmitic acid as principal fatty acids, allowing the strain to face stressful conditions in 9.20-11.50 mM glyphosate at the stationary phase. Therefore, the bacterial strain could modify the fatty acid composition and the permeability of membranes in two response modes according to the herbicide concentration, even glyphosate was not previously selective for P. fluorescens, featuring a generalist system based on physiological plasticity.

Characterization of the Activity of Croton tiglium Oil in Hetter's Very Heavy Phenol-Croton Oil Chemical Peels.

BACKGROUND: Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE: To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS: Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2 > G3. Vascular ectasia: G2 > G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION: Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis.

Fluopsin C for Treating Multidrug-Resistant Infections: In vitro Activity Against Clinically Important Strains and in vivo Efficacy Against Carbapenemase-Producing Klebsiella pneumoniae.

The increasing emergence of multidrug-resistant (MDR) organisms in hospital infections is causing a global public health crisis. The development of drugs with effective antibiotic action against such agents is of the highest priority. In the present study, the action of Fluopsin C against MDR clinical isolates was evaluated under in vitro and in vivo conditions. Fluopsin C was produced in cell suspension culture of Pseudomonas aeruginosa LV strain, purified by liquid adsorption chromatography and identified by mass spectrometric analysis. Bioactivity, bacterial resistance development risk against clinically important pathogenic strains and toxicity in mammalian cell were initially determined by in vitro models. In vivo toxicity was evaluated in Tenebrio molitor larvae and mice. The therapeutic efficacy of intravenous Fluopsin C administration was evaluated in a murine model of Klebsiella pneumoniae (KPC) acute sepsis, using six different treatments. The in vitro results indicated MIC and MBC below 2 µg/mL and low bacterial resistance development frequency. Electron microscopy showed that Fluopsin C may have altered the exopolysaccharide matrix and caused disruption of the cell wall of MDR bacteria. Best therapeutic results were achieved in mice treated with a single dose of 2 mg/kg and in mice treated with two doses of 1 mg/kg, 8 h apart. Furthermore, acute and chronic histopathological studies demonstrated absent nephrotoxicity and moderate hepatotoxicity. The results demonstrated the efficacy of Fluopsin C against MDR organisms in in vitro and in vivo models, and hence it can be a novel therapeutic agent for the control of severe MDR infections.

Inoculation of Schizolobium parahyba with Mycorrhizal Fungi and Plant Growth-Promoting Rhizobacteria Increases Wood Yield under Field Conditions.

Schizolobium parahyba var. amazonicum (Huber ex Ducke) occurs naturally in the Brazilian Amazon. Currently, it is being planted extensively because of its fast growth and excellent use in forestry. Consequently, there is great interest in new strategies to increase wood production. The interaction between soil microorganisms and plants, specifically in the roots, provides essential nutrients for plant growth. These interactions can have growth-promoting effects. In this way, this study assessed the effect of the inoculation with arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) on growth of S. parahyba var. amazonicum under field conditions. We used two native species of arbuscular mycorrhizal fungi, Claroideoglomus etunicatum (Ce), and Acaulospora sp. (Ac); two native strains of Rhizobium sp. (Rh1 and Rh2); and a non-native strain of Burkholderia sp. Different combinations of microorganisms were supplemented with chemical fertilizers (doses D1 and D2) in two planting methods, seed sowing and seedling planting. In seed sowing, the results showed that treatments with Ce/Rh1/Fertilizer D2 and Ac/No PGPR/Fertilizer D2 increased wood yield. In seedling planting, two combinations (Ac/Rh2/Fertilizer D1 and Ac/Rh1/Fertilizer D1) were more effective in increasing seedling growth. In these experiments, inoculation with AMF and PGPR increased wood yield by about 20% compared to the application of fertilizer alone.