Since its enactment in 2000, the European Orphan Medicinal Products Regulation has allowed the review and approval of approaching 70 treatments for some 55 different conditions in Europe. Success does not come without a price, however. Many of these so-called “orphan drugs” have higher price points than treatments for more common diseases. This has been raising debate as to whether the treatments are worth it, which, in turn risks blocking patient access to treatment. To date, orphan drugs have only accounted for a small percentage of the overall drug budget. It would appear that, with increasing numbers of orphan drugs, governments are concerned about the future budget impact and their cost-effectiveness in comparison with other healthcare interventions. Orphan drugs are under the spotlight, something that is likely to continue as the economic crisis in Europe takes hold and governments respond with austerity measures that include cuts to healthcare expenditures. Formally and informally, governments are looking at how they are going to handle orphan drugs in the future. Collaborative proposals between EU governments to better understand the value of orphan drugs are under consideration. In recent years there has been increasing criticism of behaviours in the orphan drug field, mainly centring on two key perceptions of the system: the high prices of orphan drugs and their inability to meet standard cost-effectiveness thresholds; and the construct of the system itself, which allows companies to gain the benefits that accrue from being badged as an orphan drug. The authors hypothesise that, by examining these criticisms individually, one might be able to turn these different “behaviours” into criteria for the creation of a system to evaluate new orphan drugs coming onto the market. It has been acknowledged that standard methodologies for Health Technology Assessments (HTA) will need to be tailored to take into account the specificities of orphan drugs given that the higher price-points claimed by orphan drugs are unlikely to meet current cost-effectiveness thresholds. The authors propose the development of a new assessment system based on several evaluation criteria, which would serve as a tool for Member State governments to evaluate each new orphan drug at the time of pricing and reimbursement. These should include rarity, disease severity, the availability of other alternatives (level of unmet medical need), the level of impact on the condition that the new treatment offers, whether the product can be used in one or more indications, the level of research undertaken by the developer, together with other factors, such as manufacturing complexity and follow-up measures required by regulatory or other authorities. This will allow governments to value an orphan drug that fulfilled all the criteria very differently from one that only met some of them. An individual country could determine the (monetary) value that it places on each of the different criteria, according to societal preferences, the national healthcare ...
Due to the increase of bacterial resistance, medicinal alternatives are being explored. Punica granatum L. is an effective herbal extract with broad spectrum of action and bactericidal, antifungal, anthelmintic potential and being able to modulate the immune response. The aim was to evaluate the antimicrobial activity of pomegranate glycolic extract (PGE) against the periodontal pathogen Porphyromonas gingivalis by using Galleria mellonella as in vivo model. Fifteen larvae were used per group. Injection of high concentration (200, 100, and 25 mg/mL) of PGE showed a toxic effect, leading them to death. A suspension of P. gingivalis (106 cells/mL) was inoculated in the left last proleg and PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) were injected into the right proleg. The larvae were then kept at 37°C under the dark. Injection of PGE at any dose statistically improved larvae survival rates. The data were analysed (log-rank test, Mantel-Cox, P < 0.05) and showed that all concentrations of PGE (12.5, 6.25, 3.1, and 2.5 mg/mL) presented higher larval survival rates, with significant statistical difference in relation to control group (P. gingivalis). In conclusion, the PGE had antimicrobial action against P. gingivalis in vivo model using G. mellonella.
The aim was to evaluate in vitro possible interactions, gene expression, and biofilm formation in species of Candida albicans, Streptococcus mitis, and Streptococcus sanguinis and their in vivo pathogenicity. The in vitro analysis evaluated the effects of S. mitis and S. sanguinis on C. albicans's biofilm formation by CFU count, filamentation capacity, and adhesion (ALS1, ALS3, HWP1) and transcriptional regulatory gene (BCR1, CPH1, EFG1) expression. In vivo studies evaluated the pathogenicity of the interaction of the microorganisms on Galleria mellonella, with analyses of the CFU per milliliter count and filamentation. In vitro results indicated that there was an observed decrease in CFU (79.4-71.5%) in multi-species biofilms. The interaction with S. mitis inhibited filamentation, which seems to increase its virulence factor with over-expression of genes ALS1, ALS3, and HWP1 as well the interaction with S. sanguinis as ALS3 and HWP1. S. mitis upregulated BRC1, CPH1, and EFG1. The histological images of in vivo study indicate an increase in the filamentation of C. albicans when in interaction with the other species. It was concluded that S. mitis interaction suggests increased virulence factors of C. albicans, with periods of lower virulence and proto-cooperation in the interaction with S. sanguinis.
Os medicamentos inibidores da bomba de prótons (IBP) surgiram na década de 1980, com o intuito de tratar distúrbios gástricos, reduzindo a produção de ácido clorídrico. Os medicamentos desta classe disponíveis no Brasil incluem o Omeprazol, Lansoprazol, Pantoprazol, Rabeprazol, Dexlansoprazol e Esomeprazol. Estudos apontam ligação entre o uso prolongado de omeprazol e algumas doenças podendo desencadear nefrite intersticial aguda, evento adverso potencialmente grave e que pode cursar com lesão renal aguda. Além disso, pesquisadores têm observado que o uso prolongado de IBP pode também aumentar o risco de progressão da doença renal crônica (DRC). Com o crescimento da prescrição e o uso inadequado dessa classe de medicamentos, torna-se importante o estudo dos efeitos do uso prolongado dos IBP sobre a função renal em usuários de medicamentos de uso contínuo no tratamento da Hipertensão Sistêmica Arterial.
Objective: Treponema denticola “T. denticola” is a pathogen associated with periodontal diseases that exhibits capacity for adherence, invasion, and colonization of host tissues, which allows alternating its location and damage in different sites of human body. This review aimed to discuss different studies that detected T. denticola in atherosclerotic plaques, demonstrating the importance of periodontal disease on the systemic health and the necessity of exploring the outcome of this colonization apart from the oral cavity. Methodology: Fifty-five studies were identified and gathered in this review according to the following topics: Periodontal disease, atherosclerosis and T. denticola. In vitro and in vivo studies published between 2002 and 2020 were searched on PubMed, raising relevant insights about the role of T. denticola and its association with the systemic disease, atherosclerosis, focusing on the bacterial tissue invasion and development of atherosclerosis. Results: After bibliographic review, it was possible to identify studies demonstrating the presence of T. denticola and other oral pathogens in cardiac or vascular tissues and in blood serum, as well, there is research in which other evidence of a relationship with atherosclerosis is shown. Conclusion: The invasion of periodontal pathogens and its toxins associated to the host’s immune and inflammatory response may contribute to the development of atherosclerosis.
Objetivos: A resistência dos microrganismos perante o uso indevido dos fármacos é atualmente um dos problemas de saúde pública, tornando-se necessárias pesquisas sobre compostos naturais com atividade antimicrobiana, como a Casearia sylvestris. Este estudo objetivou avaliar a atividade antimicrobiana do extrato glicólico de Casearia sylvestris sobre cepas-padrão de Candida albicans (ATCC 18804) e Candida glabrata (ATCC 9030) em cultura planctônica, verificando a concentração inibitória mínima e concentração microbicida mínima (CIM e CMM) e também sua ação sobre biofilmes. Metodologia: O extrato glicólico de C. sylvestris, de origem comercial, foi obtido na concentração de 200 mg/ml (20%) eluídos em 80% de propilenoglicol. Os valores da CIM e CMM foram determinados pelo método de microdiluição em caldo, segundo Clinical and Laboratory Standards Institute (CLSI), normas M27-A2, com modificações. Logo, foram iniciados os testes em biofilmes monotípicos de 48h, com troca de caldo a cada 24h, destes micro-organismos. Após submetido aos tratamentos o biofilme foi preparado para o teste metabólico de MTT. Resultados: Candida albicans apresentou CMM em 50 mg/mL, em Candida glabrata não observou-se CIM e CMM. No teste de MTT os resultados mostraram efetividade da concentração de 25 mg/mL sobre Candida glabrata, com redução de ≥ 29%, em Candida albicans não observou-se resultados significativos nas concentrações analisadas. Conclusão: O extrato apresentou efeito antimicrobiano contra os gêneros testados. Salienta-se também a importância de testes in vitro e in vivo que corroborem os resultados apresentados, com finalidade de aumentar o embasamento da aplicação do extrato.
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