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

Abstract 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.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Inhibition of Mmp-9 Expression through Nf-Kβ by Natural Compounds as a Possible Therapeutic Adjuvant Strategy in Breast Cancer: A Systematic Review

MMP-9 expression may be induced at the transcriptional level in response to different agents. Due to its fundamental role in cancer progression, the control of MMP expression, especially MMP-9, is the possible target of future adjuvant therapies that seek to reduce metastases and angiogenesis in women with breast cancer. Therefore, the aim of this study was to search in the literature available evidences of extracts/or natural compounds that have potential therapeutic capacity to inhibit MMP-9 expression. Extracts and/or natural compounds identified in this review play a significant role in the inhibition of MMP-9 expression via NF-kβ, and may act on the prevention of metastases from primary breast tumors. The majority of the studies found have shown that natural products are capable of suppressing migration and invasion of breast cancer cells, thus inhibiting the formation of in vitro metastases. Further studies are warranted to understand the potential mechanisms of breast cancer metastasis from signaling cascades intrinsic to the tumor. Moreover, the NF-kβ, followed by Mitogen Activated Protein Kinases / Activator protein 1 (MAPK / AP-1) were the major pathways affected by the extracts and / or compounds studied. These pathways are directly linked to MMP-9 expression.

Toxicity at the cellular level of artificial synthetic flavorings / Toxicidade em nível celular de aromatizantes sintéticos artificiais

The goal of the present study was to evaluate the cytotoxicity and genotoxicity of artificial synthetic flavoring agents cookie and tutti-frutti. To this end, root meristem cells of Allium cepa L. were exposed to these substances in exposure times of 24 and 48 hour using individual doses of 0.3; 0.6 and 0.9 mL and doses combined as follows: 0.3 mL + 0.3 mL; 0.6 mL and 0.9 mL + 0.6 mL + 0.9 mL. After applying the treatments, root meristems were fixed, hydrolyzed, stained and analyzed a total of 5,000 cells using an optical microscope to evaluate each dose and combined treatment. All three doses of cookie flavoring and combined treatments significantly inhibited cell division of the tissue studied. Doses of tutti-frutti caused no change in cell division rate. In addition, doses of both flavorings and treatments combining these solutions induced cell aberrations in a significant number of cells to the A. cepa system. Therefore, under these analytical conditions, cookie flavoring and combined doses were cytotoxic and genotoxic, and tutti-frutti flavoring, although non-cytotoxic, demonstrated genotoxic action.

Objetivou-se neste trabalho avaliar a citotoxicidade e a genotoxicidade de aditivos aromatizantes sintéticos artificiais de biscoito e tutti-frutti. Essa avaliação se deu por meio das células meristemáticas de raízes de Allium cepa L., nos tempos de exposição de 24 e 48 horas, em que estas substâncias foram analisadas individualmente, nas doses de 0,3; 0,6 e 0,9 mL, e associadas entre si, da seguinte forma: 0,3 mL + 0,3 mL; 0,6 mL + 0,6 mL e 0,9 mL + 0,9 mL. Os meristemas de raízes foram fixados, hidrolisados e corados, e em seguida analisados em microscópio óptico, no qual se avaliou para cada dose e tratamento associado um total de 5.000 células. A partir dos resultados obtidos verificou-se que as três doses do aromatizante de biscoito e os tratamentos em associação inibiram significativamente a divisão celular dos tecidos em estudo. Já as doses de tutti-frutti não alteraram o índice de divisão celular das raízes em questão. Verificou-se também que as doses dos dois aromatizantes e os tratamentos em associação, induziram aberrações celulares em número significativo. Portanto, nestas condições de análise, o aditivo de biscoito e as doses associadas foram citotóxicos e genotóxicos, e o de tutti-frutti, apresentou apenas ação genotóxica.

Immunonutrition effects in the treatment of cancer patients and itscomplications - a review / Efeitos da imunonutrição no tratamento de pacientes com câncer esuas complicações – uma revisão

The aim of this study was to review and summarize the data from the literature regarding the effects ofpre- and postoperative immunonutrition in the outcome of cancer patients. The review was conductedthrough literature searches in databases such as Medline/Pubmed, Scielo and Lilacs, from July toSeptember 2014, for articles investigating the effects of immunonutrition related to nutritional recoveryand pre- and post-operative procedures in cancer patients. We found 32 articles, 27 of which met theinclusion criteria, including review articles, case-control studies, epidemiological studies and crosssectionalstudies. From this literature review it was possible to see the benefits of using preoperativeimmunomodulating diet in cancer patients undergoing major abdominal surgery, including reduction ofseptic and inflammatory complications during postoperative period and hence the hospital length of stay.Thus, the use of immunonutrition has been shown to be capable to reverse organic and immunologicalchanges caused by both malnutrition and the tumor itself in cancer patients.

O objetivou deste trabalho foi revisar, de forma sucinta e objetiva, as evidências disponíveis nos bancos de dados digitais, sobre os efeitos da imunonutrição para a resposta ao tratamento de pacientes com câncer em pré e pós-operatório. Foi realizada uma revisão de literatura, por meio de buscas bibliográficas nos bancos de dados informatizados Medline/Pubmed, Scielo e Lilacs, no período de julho a setembro de 2014, de artigos que investigaram os efeitos da imunonutrição na recuperação do estado nutricional e em procedimentos pré e pós-operatório de pacientes com câncer. Foram encontrados 32 artigos, dos quais 27 atenderam aos critérios de inclusão do estudo, compreendendo artigos de revisão, caso-controle,epidemiológicos e transversais. A partir desta revisão de literatura foi possível verificar o benefício do uso da dieta imunomoduladora em pacientes oncológicos submetidos ao tratamento no pré-operatório de cirurgias de grande porte abdominal, diminuindo complicações sépticas e inflamatórias no período pós operatório e consequentemente o tempo de internação hospitalar. Dessa forma, o uso da imunonutrição mostra-se com capacidade de reverter alterações orgânicas e imunológicas causadas tanto pela desnutrição como pelo próprio tumor em pacientes com câncer.