D-Penicillamine: The State of the Art in Humans and in Dogs from a Pharmacological and Regulatory Perspective

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration—U.S. FDA, European Medicines Agency—EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.

Análise comparativa do teor de diferentes marcas de vinagres comercializadas no Brasil frente ao especificado no rótulo

Os rótulos de produtos industrializados ao redor do mundo carregam consigo informações importantes sobre a segurança, eficácia e concentrações dos componentes contidos em sua formulação. Na maioria das vezes, essas informações são preconizadas em normas escritas por um grupo colegiado de entidades reguladoras tais como FDA (Food and Drugs Administration), MAPA (Ministério da Agricultura e Pecuária), ANVISA (Agência Nacional de Vigilância Sanitária) e EMA (European Medicines Agency). Existem especificações para medicamentos, cosméticos, produtos para saúde e alimentos que deveriam ser fiéis às características dos conteúdos presentes em seus rótulos. Em alguns casos, os desvios de concentrações podem acarretar em prejuízos à saúde e segurança de seus consumidores. Pensando nessa temática, alunos de graduação em farmácia da universidade Anhanguera Educacional escolheram 9 marcas de vinagres de uso alimentício comercializados no Brasil e analisaram suas concentrações por meio de técnica de titulométrica de ácido-base e compararam os resultados encontrados com os valores demostrados no rótulo de suas respectivas marcas. Os valores encontrados mostraram grande incidência de desvios quanto a concentração de CH3COOH (ácido acético) a 4g por100ml (4%). Pequenos desvios na concentração de alguns alimentos como é o caso do CH3COOH não produzem prejuízos a saúde, no entanto, quando especificados em rótulos os valores devem ser seguidos como medida de boas práticas de fabricação (BPF) e atendimento às normas vigentes.

A simplified SARS-CoV-2 detection protocol for research laboratories

Widespread testing is required to limit the current public health crisis caused by the COVID-19 pandemic. Multiple tests protocols have been authorized by the food and drugs administration (FDA) under an emergency use authorization (EUA). The majority of these protocols are based on the gold-standard RT-qPCR test pioneered by the U.S. Centers for Disease Control and Prevention (CDC). However, there is still a widespread lack of testing in the US and many of the clinical diagnostics protocols require extensive human labor and materials that could face supply shortages and present biosafety concerns. Given the need to develop alternative reagents and approaches to provide nucleic-acid testing in the face of heightened demand and potential shortages, we have developed a simplified SARS-CoV-2 testing protocol adapted for its use in research laboratories with minimal molecular biology equipment and expertise. The protocol utilizes TRIzol to purify the viral RNA from different types of clinical specimens, requires minimal BSL-1 precautions and, given its high sensitivity, can be easily adapted to pooling samples strategies.

Esclerose múltipla: uma abordagem imunológica

Objetivo: Abordar os principais mecanismos imunológicos envolvidos na patogenia da Esclerose Múltipla dando ênfase à neuroinflamação e às intervenções terapêuticas atuais. Métodos: Trata se de uma revisão bibliográfica narrativa, utilizando se as bases de dados: Periódicos da Capes, Biblioteca Virtual em Saúde e Pubmed. Foram incluídos 55 artigos publicados no período de 2004 a 2019. Resultados: A etiopatogenia da Esclerose Múltipla envolve fatores genéticos, imunológicos e ambientais, que em conjunto, induzem processos de quebra da autotolerância imunológica, lesão neuronal, neuroinflamação e neurodegeneração. A neuroinflamação pode ser iniciada por antígenos próprios ou estranhos que são expostos aos leucócitos do sistema nervoso central. Leucócitos periféricos, especialmente, monócitos e linfócitos T e B, podem se infiltrar no sistema nervoso devido a alteração da permeabilidade da barreira hematoencefálica e, juntamente com a micróglia, possuem importante papel na indução de lesões desmielinizantes. A neurodegeneração pode gerar mais estímulos antigênicos. Atualmente existem 17 drogas imunomoduladoras aprovadas pela Food and Drugs Administration para o tratamento da doença, mas diversos estudos estão sendo realizados, visando novas abordagens terapêuticas. Conclusão: A etiologia da Esclerose Múltipla mantem-se uma incógnita, apesar de estudos atuais apontarem teorias sobre possíveis desencadeadores, extrínsecos e intrínsecos da autoimunidade na doença e da própria neuroinflamação, sendo a última um importante fator indutor da lesão tecidual e perpetuador da doença. A identificação de antígenos alvo reconhecidos por linfócitos T e B residentes e pelas micróglias, juntamente com a caracterização de mediadores inflamatórios solúveis é fundamental para elucidar a etiopatogenia da doença e sugerir novas propostas terapêuticas.

Repurposing cilostazol for Raynaud's phenomenon

: Raynaud's Phenomenon (RP) results from exaggerated cold-induced vasoconstriction. RP patients suffer from vasospastic attacks and compromised digital blood perfusion leading to triple color change at the level the fingers. Severe RP may cause ulcers and threaten tissue viability. Many drugs have been used to alleviate the symptoms of RP. These include calcium-channel blockers, cGMP-specific phosphodiesterase type 5 inhibitors, prostacyclin analogs, and angiotensin receptor blockers. Despite their variety, these drugs do not treat RP but rather alleviate its symptoms. To date, no drug for RP has been yet approved by U.S Food and Drugs Administration. Cilostazol is a selective inhibitor of phosphodiesteraseIII, originally prescribed to treat intermittent claudication. Owing to its antiplatelet and vasodilating properties, cilostazol is being repurposed as a potential drug for RP. This review focuses on the different lines of action of action of cilostazol serving to enhance blood perfusion in RP patients.

Oxidative Stress Markers and the Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.

A simplified SARS-CoV-2 detection protocol for research laboratories

Widespread testing is required to limit the current public health crisis caused by the COVID-19 pandemic. Multiple tests protocols have been authorized by the food and drugs administration under an emergency use authorization (EUA). The majority of these protocols are based on the gold-standard RT-qPCR test pioneered by the U.S. Centers for Disease Control and Prevention. However, there is still a widespread lack of testing in the US and many of the clinical diagnostics protocols require extensive human labor and materials, such as RNA extraction kits, that could face supply shortages and present biosafety concerns. Given the need to develop alternative reagents and approaches to allow nucleic-acid testing in the face of heightened demand and potential shortages, we have developed a simplified SARS-CoV-2 testing protocol adapted for its use in laboratory research with minimal molecular biology equipment and expertise. The protocol requires minimal BSL1 biosafety level precautions and facilities.

Relationship between transformational leadership and personality with the commitmment to the organisation (Case study at food and drugs administration republic of Indonesia)

The purpose of this study is to study whether there is a relationship between Transformational Leadership and Personality with the coommitment to Organization both partially and simultaneously. The population of this study are head office employees which is 1,413 employees. The formula determines the number of samples based on Slovin, after the calculation, it is obtained a sample of 312 samples. The research instrument is a questionnaire. The collected data are tested by using correlation analysis techniques. The results has showed that: 1. Transformational leadership partially relates to the commitment to the organization, 2. Partial personality has related to the commitment,to the organization 3. Transformational leadership and personality simultaneously correlate positively to the commitment organization having the ratio of 0.770, then the functional relationship is obtained by equation = 27,589 + 0,725X1 + 0,17 X2 and the coefficient of determination or contribution of transformational leadership and personality simultaneously to the commitment to the organization is 59,3%. Keywords: Transformational Leadership, Personality and Commitment to Organizations.

A literature review of drugs for the treatment of COVID-19

Objectives: To review the published evidence of repurposed drugs, antivirals and biologics for the treatment of COVID-19. Materials and Methods: A literature review was conducted in several databases and research portals. Search terms included COVID-19, SARS-Cov-2, MERS, MERS-CoV, SARS, SARS-CoV, coronavirus, beta-coronavirus, influenza, pneumonia and several drugs considered for use in COVID-19. Results: There is a paucity of clinical evidence regarding the safety and efficacy of most agents being considered for the treatment of COVID-19. However, based on promising preliminary research the US Food and Drugs Administration has authorized the emergency use of hydroxychloroquine and remdesivir for hospitalized COVID-19 patients. To date, the most robust evidence for lopinavir-ritonavir (LPV/r) found that it was no better than standard care. Overwhelming evidence suggests that corticosteroids increase mortality, nosocomial infections and lengthen hospitalization in SARS and MERS patients, and should be used cautiously in patients with severe respiratory symptoms. Additionally, low level evidence suggests that tocilizumab may be useful to reduce the cytokine storm precipitated by SARS-CoV-2 infection. Conclusions: Hydroxychloroquine and remdesivir have surged to the front of the race to repurpose drugs in the fight against COVID-19. With hundreds of ongoing trials it is envisaged that indisputable evidence would be provided for prophylactic and therapeutic use of drugs and biologics within the next few months. However, in our setting it would be worthwhile to consider the availability and accessibility of some of these agents.