Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug–target interactions, stability, and others, and points out the most relevant aspects for clinical practice.
Highlights
Thirteen different neoplasms were shown to be susceptible to the antidepressant drug sertraline.
The mechanisms of action through which sertraline can kill tumor cells are apoptosis, autophagy, and drug synergism.
Sertraline inhibits TCTP, a tumor protein involved in cell survival pathways, responsible for reducing p53 levels.
The testing of sertraline
in vitro
and
in vivo
resulted in reduced cell counting, shrinking of tumoral masses and increased survival rates.
Dose extrapolation from animals to humans has shown a therapeutic index of sertraline that could support future clinical trials.
Objective: The study aimed to describe the epidemiological profile of the homeless population and report the social impact on healthcare services provided by a voluntary initiative during one-year of follow-up. Method: This is an investigational study, carried out in an important capital-city of southern Brazil, which included 509 individuals in 2019. Findings were divided into three segments: sociodemographic, substance use/abuse and impact on healthcare. Results: The sociodemographic profile found was predominantly male, white, single, heterosexual, educated in elementary or high school, in regular use of legal and/or illegal substances, and living as homeless for less than a year. The impact of assistance provided on the perception of individuals who returned in subsequent actions was evident. Conclusion: The significant increase in the number of homeless people in large urban centers can benefit from the support of non-profit organizations to address the deficiencies faced in accessing basic health services. Based on this, we seek to advance in the development of new policies that improve local healthcare for the vulnerable population, to be more assertive to their needs.
Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. Three hundred eighty-four patients were included; the median age was 39 years and 283 (73.7%) were men. Hosts were 304 (79.2%) HIV-positive, 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplanted (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). Two hundred and seventy-one (70.6%) patients were discharged home and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional AMB mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Patients with CNS cryptococcosis had lower mortality (83/313, 26.5%) when compared with the other categories (P = 0.017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death [odds ratio (OR), 1.03; 95% Confidence Interval (CI), 1.01 to 1.05; P = 0.008 and OR, 1.84; 95% CI, 1.01 to 3.53; P = 0.048, respectively]. Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.
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