Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients

Avaliação da qualidade hídrica de um rio do semiárido piauiense

O rio Guaribas foi a principal fonte de renda para a população de Picos, entretanto, a ação antrópica desencadeou mudanças no referido corpo d’água. Assim, o objetivo deste artigo foi averiguar a qualidade de amostras de água do rio Guaribas, coletadas em diferentes pontos no perímetro urbano do município de Picos-PI. Os parâmetros físico-químicos e bacteriológicos analisados foram: alumínio, alcalinidade total, dureza total, potencial de hidrogênio, turbidez, coliforme totais e coliformes fecais. As análises físico-químicas foram realizadas por meio de titulação, potenciômetro e turbidímetro. As analises microbiológicas foram realizadas através do método dos tubos múltiplos. Foram percebidas variações nos parâmetros, principalmente entre a área de menor interferência humana (P0) e o ponto de coleta após a área urbanizada da cidade (P2), onde neste, os maiores valores percebidos foram: 0,5mg.L para o alumínio (número acima do aceitável); 326 mg.L para a dureza; 19,8 UNT para a turbidez; pH levemente ácido (8,1); além do mais, foi percebida a presença de Escherichia coli na maioria do material coletado. Logo, foi possível concluir que q interferência humana através de dejetos de hospitais, esgotos domésticos e resíduos sólidos, afetaram diretamente a qualidade da água do rio estudado

Procjena akutne toksičnosti umjetnih aroma grožđa, šljive i naranče pomoću testova in vivo

The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.U radu je ispitan akutni toksični učinak umjetnih aroma grožđa, šljive i naranče u dozama od 3,5; 7 i 14 mL/kg tijekom 24 i 48 sati na meristemske stanice korijena luka (Allium cepa) te u peroralnim dozama od 0,5; 1; 2; 5 i 10 mL/kg tijekom 7 dana na eritrocite iz koštane srži miševa. Rezultati pokazuju da je izlaganje meristemskih stanica korijena luka umjetnim aromama grožđa, šljive i naranče tijekom 24 i 48 sata inhibiralo diobu stanica te potaklo tvorbu većeg broja mikronukleusa i promjenu strukture diobenog vretena. Promjene su uočene već nakon 24 sata, što potvrđuje znatnu citotoksičnost, genotoksičnost i mutagenost umjetnih aroma. Miševi hranjeni s 2, 5 i 10 mL/kg umjetnih aroma uginuli su prije sedmog dana tretmana. Dodatak umjetnih aroma u dozama od 0,5 i 1 mL/kg smanjio je broj eritrocita u koštanoj srži miševa, a dodatak arome grožđa znatno je potaknuo tvorbu mikronukleusa. Stoga je zaključeno da arome grožđa, šljive i naranče pri navedenim uvjetima imaju izraženi toksični učinak na meristemske stanice korijena luka i eritrocite iz koštane srži miševa

Improvement of in vivo anticancer and antiangiogenic potential of thalidomide derivatives

AbstractThe strategy of antiangiogenic drugs is based on inhibiting formation of new blood vessels as alternative to limit cancer progression. In this work, we investigated the antitumor and antiangiogenic potential of eight thalidomide derivatives. Most of the molecules was not cytotoxic but 2a, 2d and 3d revealed weak antiproliferative activity on HL-60, Sarcoma 180 (S180) and normal peripheral blood mononuclear cells. Thalidomide, 2a and 2b were able to inhibit tumor growth (53.5%, 67.9% and 67.4%, respectively) in S180-bearing mice and presented moderate and reversible toxicity on liver, kidneys and spleens. Both analogs (2a and 2b) inhibited cell migration of endothelial (HUVEC) and melanoma cells (MDA/MB-435) at 50μg/mL. Immunohistochemistry labeling assays with CD-31 (PECAM-1) antibody showed microvascular density (MVD) was significantly reduced in thalidomide, 2a and 2b groups (30±4.9, 64.6±1.8 and 46.5±19.5%, respectively) (p<0.05). Neovascularization evaluated by Chorioallantoic Membrane Assay (CAM) with compounds 2a and 2b showed reduction of vessels’ number (12. 9±2.3 and 14.8±3.3%), neovascularization area (13.1±1.7 and 14.3±1.7%) and total length of vessels (9.2±1.5 and 9.9±1.9%). On the other hand, thalidomide did not alter vascularization parameters. Consequently, addition of thiosemicarbazone pharmacophore group into the phthalimidic ring improved the in vivo antitumor and antiangiogenic potential of the analogs 2a and 2b

Avaliação da importância de modelos no ensino de biologia através da aplicação de um modelo demonstrativo da junção intercelular desmossomo

The present work involved the development of a representative model of the desmosome junction and its application to 172 students divided into beginners (1o semester of Nutrition and Biological Sciences) and veterans (2o of Nutrition and 4o of Biological Sciences) to test its effectiveness on the teaching-learning process. It was found that 78% of beginners and 82% of veterans were female; 98% had between 17 and 30 years-old; the majority (61% and 50%, beginners and veterans, respectively) assumed it was the first occasion they had contact with a model although at least 90% of them recognized the main represented structure (the desmosome); the majority of both groups said that the model allowed the recognition of junctional structures; 97% of beginners and 99% of the veterans declared that their knowledge about intercellular junctions and desmosome enhanced and 72% of beginners affirmed that their teachers possess models for practical classes compared to 33% in veterans. The attribution of scores exceeding 7 to the model revealed that its use in practical lessons is productive.O presente trabalho consistiu na elaboração de um modelo demonstrativo da junção desmossomo e na sua aplicação a 172 estudantes divididos em iniciantes (1o semestres de Nutrição e Ciências Biológicas) e veteranos (2o de Nutrição e 4o de Ciências Biológicas) para testar sua eficácia para o processo de ensino-aprendizagem. Verificou-se que 78% dos iniciantes e 82% dos veteranos eram do sexo feminino; 98% tinham entre 17 e 30 anos de idade; a maioria (61% e 50%, iniciantes e veteranos, respectivamente) afirmaram que era a primeira vez que tiveram contato com um modelo embora pelo menos 90% deles reconheceram a principal estrutura representada (o desmossomo); a maioria de ambos os grupos afirmaram que o modelo permitiu o reconhecimento das estruturas juncionais; 97% dos iniciantes e 99% dos veteranos afirmaram que seu conhecimento sobre junções intercelulares e desmossomo melhorou e 72% dos iniciantes disseram que seus professores dispõem de modelos para as aulas práticas contra apenas 33% dos veteranos. A atribuição de notas acima de 7 ao modelo revelou que sua utilização em aulas práticas é profícua.Palavras-chave: instrumentos, junções, aulas práticas

Potencial citotóxico, genotóxico e citoprotetor de extratos aquosos de Caesalpinia pyramidalis Tul., Caesalpinia ferrea Mart. e Caesalpinia pulcherrima Sw.

The legumenous Caesalpinia pyramidalys, Caesalpinia ferrea and Caesalpinia pulcherrima are widely used in folk medicine in many countries. Thus, this study aimed to cytogenetically evaluate, through the use of meristematic roots cells of Allium cepa, after the exposure times 24 and 48 hours, the cytotoxic potential of aqueous extracts, at concentrations 1 g/500 mL and 1 g/1000 mL, obtained from the inner bark of Caesalpinia pyramidalis, the pod of Caesalpinia ferrea and the leaves of Caesalpinia pulcherrima, and also verify the modulatory potential of these extracts on cellular alterations induced by Paracetamol. The treatment groups used were: negative control – distilled water; positive control – 0.008 mg/mL Paracetamol solution; plant aqueous extract control – water fraction from the plants at concentrations 1 g/500 mL and 1 g/1000 mL; and simultaneous treatment – water fraction from the plants at concentrations 1 g/500 mL and 1g/1000 mL associated with 0.008 mg/mL Paracetamol solution. The Chi-square statistical test was used at 5% probability for data analysis. The results showed that C. pyramidalis and C. ferrea had a significant antiproliferative effect on the cells of the test organism, at both concentrations (1 g/500 mL and 1 g/1000 mL) and at both times of exposure, thus being cytotoxic. All three plants promoted significant cytoprotective effect on the Paracetamol-treated meristematic root cells of A. cepa, thus showing, under the studied conditions, antimutagenic potential. Further studies using these plants should be carried out in order to properly define the cytotoxic and cytoprotective potential of pau-ferro’s pod, catingueira’s inner bark and flamboyazinho’s leaves.Os objetivos do presente trabalho foram avaliar, por meio das células meristemáticas de raízes de Allium cepa, nos tempos de exposição 24 e 48 horas, o potencial citotóxico de extratos aquosos, nas concentrações de 1g/500ml e 1g/1000ml, provenientes da entrecasca de Caesalpinia pyramidalis, da vagem de Caesalpinia ferrea e das folhas de Caesalpinia pulcherrima, e verificar o potencial modulador destes extratos frente as aberrações celulares induzidas por Paracetamol a partir dos seguintes grupos tratamentos:  controle negativo – água destilada; controle positivo – solução de Paracetamol a 0,008mg/ml, controle extrato aquoso da planta – fração aquosa de uma das plantas na concentração de 1g/500ml ou 1g/1000ml,  tratamento simultâneo - fração aquosa de uma das plantas na concentração de 1g/500ml ou 1g/1000ml associada a solução de Paracetamol a 0,008mg/ml. As raízes de A. cepa após os tratamentos foram fixadas em solução de Carnoy, hidrolisadas em ácido e coradas com orceína acética a 2%. Em seguida fez-se o esmagamento dos meristemas e montagem das lâminas. Analisou-se 5.000 células para cada grupo tratamento em microscopia de campo claro (40x), e utilizou-se o teste estatístico Qui-quadrado a 5% para análise dos dados. A partir dos resultados obtidos verificou-se que C. pyramidalis e C. ferrea nas duas concentrações e nos dois tempos de exposição avaliados tiveram efeito antiproliferativo significativo as células do organismo de prova utilizado, mostrando-se citotóxicas. Também foi observado que os respectivos tratamentos simultâneos de cada planta, nas duas concentrações e nos dois tempos de exposição avaliados, não diferiram do índice de divisão celular do seu respectivo controle extrato aquoso da planta. As três plantas promoveram efeito citoprotetor significativo as células meristemáticas de raízes de A. cepa tratadas com Paracetamol, demonstrando, nas condições analisadas, potencial antimutagênico. Os resultados obtidos aqui com A. cepa sugerem a realização de mais estudos, com outros sistemas testes e diferentes esquemas de tratamento, para assim se definir, com propriedade, o real potencial citotóxico e antimutagênico destas plantas

Određivanje hranjivih, fizikalno-kemijskih i strukturnih svojstava ploda biljke Mauritia flexuosa i njezinih nusproizvoda u svrhu biotehnološkog razvoja održivih proizvoda

Research background. Commercialization of Mauritia flexuosa (buriti) fruits in Brazil is at an early stage. Herein, we evaluate the nutritional value of pulp, peel and endocarp samples from buriti fruits, perform macroscopic and microscopic evaluations and analyze their physicochemical properties. Experimental approach. Size and mass, pH, sugar and protein contents, soluble/insoluble fiber, total titratable acidity and energy value of the samples were analyzed. Mineral profiling was performed by energy dispersive X-ray fluorescence spectrometry, and fatty acids and phytosterols were determined by gas chromatography-mass spectrometry. Samples were also submitted to differential scanning calorimetry coupled to a thermal analyzer, and microstructure, morphology, surface and viscosity were evaluated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) with copper radiation. Rheological behavior was also studied. Results and conclusions. Lyophilized pulp had higher nutritional content of minerals, proteins, carbohydrates and energy than in natura pulp. Lyophilized pulp and its by-products showed suitable yields (>17.31%) and low aw, and potassium, manganese and monounsaturated fatty acid contents. Peels showed elevated amounts of saturated and polyunsaturated fatty acids and phytosterols (β-sitosterol and stigmasterol), and endothermic behavior. The reductions of calcium, magnesium and manganese ranging from 18.5 to 22.7% were observed following the lyophilization. Drying processes generated semi-crystalline powders. Both peels and endocarp contained higher amounts of insoluble fiber and lower contents of sugars. Similar results were obtained by microscopic morphological analysis, differential scanning calorimetry and XRD analysis. Pulp and endocarp exhibited pseudoplastic non-Newtonian behavior, and flow behavior index values were lower than 1, while peels presented dilatant behaviour. Thus, physicochemical and nutritional characterization of pulp and by-products, such as peels and endocarp, are essential to support scientific research and exploration of new sustainable products. Novelty and scientific contribution. Processing and conservation techniques, like lyophilization, maintain the good quality of nutritional contents and bioactive compounds of buriti whole fruits, and can be used to extend their shelf life, preserve alimentary characteristics and provide wider purposes and availability. Such parameters may generate income and food security for local and regional communities.Pozadina istraživanja. Komercijalizacija ploda biljke Mauritia flexuosa (lokalnog naziva buriti) je u Brazilu još u ranoj fazi razvoja. U ovom smo radu ispitali hranjivu vrijednost uzoraka pulpe, kore i endokarpa plodova biljke buriti, proveli makro- i mikroskopske analize te odredili fizikalno-kemijska svojstva plodova. Eksperimentalni pristup. Ispitani su veličina i masa, pH-vrijednost, udjeli šećera i proteina, omjer topljivih i netopljivih vlakana, ukupna titracijska kiselost i energetska vrijednost uzoraka. Sastav mineralnih tvari određen je rendgenskom fluorescentnom spektrometrijom, a masne kiseline i fitosteroli plinskom kromatografijom u kombinaciji s masenom spektrometrijom. Uzorci su također ispitani diferencijalnom pretražnom kalorimetrijom u kombinaciji s toplinskom analizom. Mikrostruktura, morfološka svojstva, površina i viskoznost uzoraka određeni su pretražnom elektronskom mikroskopijom i rendgenskom difrakcijom s bakrom kao izvorom zračenja. Također su istražena i reološka svojstva plodova. Rezultati i zaključci. Liofilizirana pulpa imala je veće udjele mineralnih tvari, proteina, ugljikohidrata i veću energetsku vrijednost od netretirane pulpe. Prinos liofilizirane pulpe i njezinih nusproizvoda bio je zadovoljavajući (>17,31 %), a aktivitet vode te udjeli kalija, mangana i mononezasićenih masnih kiselina bili su niski. Kora ploda imala je veće udjele zasićenih i polinezasićenih masnih kiselina i fitosterola (β-sitosterola i stigmasterola) od pulpe, te je imala endotermna svojstva. Nakon liofilizacije opaženo je smanjenje udjela kalcija, magnezija i mangana, i to od 18,5 do 22,7 %. Sušenjem je dobiven polukristalični prah. Kora i endokarp ploda sadržavali su veće količine netopljivih vlakana i manje udjele šećera. Slični su rezultati dobiveni morfološkom analizom, diferencijalnom pretražnom kalorimetrijom i rendgenskom difrakcijom. Pulpa i endokarp imali su pseudoplastične nenjutonovske značajke, vrijednosti indeksa protjecanja bile su manje od 1, dok je kora imala dilatantna svojstva. Zaklljučeno je da je određivanje fizikalno-kemijskih i hranjivih svojstava pulpe i njezinih nusproizvoda kao što su kora i endokarp nužno za podržavanje ovog znanstvenog istraživanja i razvoja novih održivih proizvoda. Novina i znanstveni doprinos. Postupci obrade i čuvanja hrane, kao što je liofilizacija, omogućuju održavanje kakvoće hranjivih sastojaka i bioaktivnih spojeva plodova biljke buriti, produžuju njihovo vrijeme skladištenja, zadržavaju prehrambene značajke i proširuju njihovu uporabu i dostupnost. Takve značajke proizvoda mogu donijeti prihod i povećati sigurnost hrane u lokalnim i regionalnim zajednicama

Correlations between Risk Factors for Breast Cancer and Genetic Instability in Cancer Patients- A Clinical Perspective Study

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Molecular epidemiological studies have identified several risk factors linking to the genes and external factors in the pathogenesis of breast cancer. In this sense, genetic instability caused by DNA damage and DNA repair inefficiencies are important molecular events for the diagnosis and prognosis of therapies. Therefore, the objective of this study was to analyze correlation between sociocultural, occupational, and lifestyle risk factors with levels of genetic instability in non-neoplastic cells of breast cancer patients. Total 150 individuals were included in the study that included 50 breast cancer patients submitted to chemotherapy (QT), 50 breast cancer patients submitted to radiotherapy (RT), and 50 healthy women without any cancer. Cytogenetic biomarkers for apoptosis and DNA damage were evaluated in samples of buccal epithelial and peripheral blood cells through micronuclei and comet assay tests. Elder age patients (61–80 years) had higher levels of apoptosis (catriolysis by karyolysis) and DNA damage at the diagnosis (baseline damage) with increased cell damage during QT and especially during RT. We also reported the increased frequencies of cytogenetic biomarkers in patients who were exposed to ionizing radiation as well as for alcoholism and smoking. QT and RT induced high levels of fragmentation (karyorrhexis) and nuclear dissolution (karyolysis) and DNA damage. Correlations were observed between age and karyorrhexis at diagnosis; smoking and karyolysis during RT; and radiation and karyolysis during QT. These correlations indicate that risk factors may also influence the genetic instability in non-neoplastic cells caused to the patients during cancer therapies