Hemodynamic changes with two lipid emulsions for treatment of bupivacaine toxicity in swines

PURPOSE: To compare the hemodynamic changes following two different lipid emulsion therapies after bupivacaine intoxication in swines. METHODS: Large White pigs were anesthetized with thiopental, tracheal intubation performed and mechanical ventilation instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization (Swan-Ganz catheter). After a 30-minute resting period, 5 mg.kg-1 of bupivacaine by intravenous injection was administered and new hemodynamic measures were performed 1 minute later; the animals were than randomly divided into three groups and received 4 ml.kg-1 of one of the two different lipid emulsion with standard long-chaim triglyceride, or mixture of long and medium-chain triglyceride, or saline solution. Hemodynamic changes were then re-evaluated at 5, 10, 15, 20 and 30 minutes. RESULTS: Bupivacaine intoxication caused fall in arterial blood pressure, cardiac index, ventricular systolic work index mainly and no important changes in vascular resistances. Both emulsion improved arterial blood pressure mainly increasing vascular resistance since the cardiac index had no significant improvement. On the systemic circulation the hemodynamic results were similar with both lipid emulsions. CONCLUSION: Both lipid emulsions were efficient and similar options to reverse hypotension in cases of bupivacaine toxicity.To compare the hemodynamic changes following two different lipid emulsion therapies after bupivacaine intoxication in swines. Large White pigs were anesthetized with thiopental, tracheal intubation performed and mechanical ventilation instituted. Hemodyna3028793sem informaçãosem informaçã

Ruiniform relief in sandstones: the examples of Vila Velha, Carboniferous of the Paraná Basin, Southern Brazil

Vila Velha is a remarkable group of natural sculptures in Palaeozoicsandstones of the Paraná. Basin in Southern Brazil. The sculptures,which resemble the ruins of an old stone city, have resulted from thecombination of Cenozoic weathering and erosive processes with the existing attributes of the sedimentary rocks (texture, cementing oxides,sedimentary and brittle structures). A particular geomorphologic settingwith eroded inselbergs, and a differential iron and manganese cementationduring lateritization phases are other factors controlling thatexceptional landscape, the ruiniform relief. Despite being a naturalheritage of inestimable value, Vila Velha is threatened by large-scaletourism, with severe risks for its conservation

Alternative herbicides to control glyphosate-resistant biotypes of Conyza bonariensis and C. canadensis

Após sucessivos anos, aplicações do herbicida glyphosate em pomares de citros no Estado de São Paulo selecionaram biótipos resistentes de Conyza bonariensis e C. canadensis. Na ocorrência de plantas daninhas resistentes em uma área agrícola, tornam-se necessárias mudanças nas práticas de manejo para obtenção de adequado controle das populações resistentes, bem como para a redução da pressão de seleção sobre outras espécies. Assim, este trabalho foi realizado com o objetivo de identificar herbicidas alternativos para controle de biótipos de Conyza spp. resistentes ao herbicida glyphosate, com aplicações em diferentes estádios fenológicos da planta daninha. Três experimentos foram conduzidos em campo, em pomares de citros em formação, sobre plantas de buva em estádio fenológico de dez folhas e no pré-florescimento. Para plantas no estádio de dez folhas, controle satisfatório foi obtido com aplicações de glyphosate + bromacil + diuron (1.440 + 1.200 + 1.200 g ha-1), glyphosate + atrazina (1.440 + 1.500 g ha-1) e glyphosate + diuron (1.440 + 1.500 g ha-1). Quando em estádio de pré-florescimento de Conyza spp., a aplicação do herbicida amônio-glufosinato, na dose de 400 g ha-1, isolado ou associado a MSMA, bromacil+diuron, metsulfuron, carfentrazone e paraquat, foi a alternativa viável para controle dos biótipos resistentes ao glyphosate.After successive years, glyphosate applications on São Paulo-Brazil citrus orchards selected resistant biotypes of Conyza bonariensis and C. canadensis. The occurrence of herbicide-resistant weed biotypes at some agricultural area makes it necessary to change the management practices to reach effective control of the selected resistant populations, as well as to reduce selection pressure on the other species. Thus, this work aimed to identify the alternative herbicides to control glyphosate-resistant biotypes of Conyza spp., with applications at different weed phenological stages. Three trials were developed under field conditions: in citrus orchards under formation, in plants with phenological stages of ten leaves and at pre-flowering. For plants at the ten leaf stage, satisfactory control was reached with applications of glyphosate + bromacil + diuron (1,440 + 1,200 + 1,200 g ha-1), glyphosate + atrazine (1,440 + 1,500 g ha-1) and glyphosate + diuron (1,440 + 1,500 g ha-1). For Conyza spp. plants at the pre-flowering stage, ammonium-glufosinate application, at the rate of 400 g ha-1, isolated or associated to MSMA, bromacil+diuron, metsulfuron, carfentrazone and paraquat, was a viable alternative to control glyphosate-resistant biotypes.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Mitochondrial Fatty Acid β-Oxidation Disorders: From Disease to Lipidomic Studies—A Critical Review

ReviewThis article belongs to the Special Issue Lipid Metabolism in Pathology and Health.Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.This research was funded by FCT/MEC (PIDDAC) for their financial support to LAQVREQUIMTE (UIDB/50006/2020), CESAM (UIDP/50017/2020 + UIDB/50017/2020 + LA/P/0094/2020), and the RNEM-Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125), financed by FCT/MCTES through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. Ana Moreira thanks the research contract under the research unit LAQV-REQUIMTE. Inês M. S. Guerra (2021.04754.BD) and Helena B. Ferreira (2020.04611.BD) are grateful to FCT for the PhD grants. Tânia Melo thanks the Junior Researcher contract in the scope of the Individual Call to Scientific Employment Stimulus 2020 (CEECIND/01578/2020). The authors are thankful to the COST Action EpiLipidNET, CA19105-Pan-European Network in Lipidomics, and EpiLipidomics.info:eu-repo/semantics/publishedVersio

Effects of total parenteral nutrition associated with glutamine, enteral fluid therapy, with or without glutamine, and fluid therapy on the lipidogram of horses subjected to starvation after laparotomy

ABSTRACT In order to evaluate the effect of total parenteral nutrition associated with glutamine and enteral fluid therapy, associated or not with glutamine, on the lipidogram of horses subjected to starvation (phase 1) and refeeding (phase 2), 16 adult healthy horses were used, mixed breed, aged between four and fourteen years and average weight of 248.40 ± 2.28kg, divided into four experimental groups, with four animals per group: Group ENTGL: enteral fluid therapy with electrolytes associated with glutamine; Group PARGL: total parenteral nutrition associated with glutamine; Group ENTFL: enteral fluid therapy with electrolytes; and Group PARFL: parenteral fluid therapy. This study was divided into two phases: phase 1 and phase 2. Phase 1 consisted of performing exploratory laparotomy and beginning of starvation, in addition to the administration of treatments, according to the group, while phase 2 consisted of re-feeding the animals. Total cholesterol values remained within the normal range for the species throughout the experimental period, but there was a slight increase during phase 1, followed by a decrease in values in phase 2. Hypertriglyceridemia in the ENFL, ENTGL and PARFL groups during phase 1 occurred because of the negative energy balance. The provision of enteral fluid therapy with electrolytes and an energy source, with or without glutamine, or parenteral fluid therapy were not effective in reversing the effects of negative energy balance. Thus, therapeutic protocols that combine enteral or parenteral fluid therapy for prolonged periods and food deprivation need additional nutritional support to avoid the deleterious effects of negative energy balance

Initial Results of the International Efforts in Screening New Agents against Candida auris

This article belongs to the Special Issue Biology, Immunology, Epidemiology, and Therapy of Fungal Infections: A Themed Issue Dedicated to Professor David A. Stevens.Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.his work was accomplished with support from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, within the scope of the Capes-PrInt Program—Financing Code 001info:eu-repo/semantics/publishedVersio

Structural assessment, toxicity, and increased antimicrobial activity

Scorpion venom is a rich source of biologically active components and various peptides with high-potential therapeutic use that have been characterized for their antimicrobial and antiproliferative activities. Stigmurin is a peptide identified from the Tityus stigmurus venom gland with high antibacterial and antiproliferative activities and low toxicity. Amino acid substitutions in peptides without a disulfide bridge sequence have been made with the aim of reducing their toxicity and increasing their biological activities. The purpose of this study was to evaluate the structural conformation and structural stability, as well as antimicrobial, antiproliferative, and hemolytic activities of two peptide analogs to Stigmurin, denominated StigA6 and StigA16. In silico analysis revealed the α-helix structure for both analog peptides, which was confirmed by circular dichroism. Data showed that the net charge and hydrophobic moment of the analog peptides were higher than those for Stigmurin, which can explain the increase in antimicrobial activity presented by them. Both analog peptides exhibited activity on cancerous cells similar to the native peptide; however, they were less toxic when tested on the normal cell line. These results reveal a potential biotechnological application of the analog peptides StigA6 and StigA16 as prototypes to new therapeutic agents.publishersversionpublishe