The long-term treatment with tamoxifen can alter the lipid profile of patients with breast cancer. Only a few studies associated the plasma concentrations of tamoxifen, endoxifen, and ...4-hydroxytamoxifen with blood lipids, which is relevant as the distribution of these compounds for the tissues can be changed, negatively affecting the treatment. The variations in lipids also can account for the high interindividual variation in plasma concentrations of these compounds. The aim of this preliminary study was to associate the plasma levels of tamoxifen and the active metabolites with the lipid levels. An observational study of cases was conducted in patients with breast cancer using tamoxifen in a daily dose of 20 mg. The lipids were measured by spectrophotometric methods and the plasma concentrations of tamoxifen, endoxifen, and 4-hydroxytamoxifen by high-performance liquid chromatography. A total of 20 patients were included in the study. The median plasma concentrations of tamoxifen, 4-hydroxytamoxifen and endoxifen were 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL. Triglycerides levels ranged from 59 to 352 mg/dL, total cholesterol from 157 to 321 mg/dL, LDL-c from 72 mg/dL to 176 mg/dL and HDL-C from 25.1 mg/dL to 62.8 mg/dL. There were no significant associations between the plasma concentrations of tamoxifen, 4-hydroxytamoxifen, and endoxifen with the levels of triglycerides and total cholesterol. The multivariate analysis revealed a weak association between plasma concentrations of tamoxifen and the active metabolites with HDL-c, LDL-c and VLDL-c. This finding provides preliminary evidence of the low impact of lipoproteins levels in the exposure to tamoxifen, 4-hydroxytamoxifen and endoxifen.
•Tamoxifen is a is a non-steroidal drug metabolized by cytochrome P-450 into several active metabolites.•There are considerable inter-individual variations in the plasma levels of tamoxifen and the metabolites.•Lipoproteins may influence the plasma concentrations of tamoxifen and the metabolites.•Plasma levels of tamoxifen, endoxifen, and 4-hydroxytamoxifen were not correlated with lipids levels.
O envelhecimento populacional e o impacto na saúde pública, demanda ações articuladas entre as diferentes instituições tanto de gestão em saúde quanto da formação de profissionais voltados para a ...atenção primária à saúde, tendo a pessoa idosa um dos beneficiados dessas ações. Para tanto é necessário um serviço de saúde eficaz, que pode ser exercido através de práticas colaborativas integradas por meio da Educação Interprofissional que vem sendo estimulada através de projetos educacionais voltados para o trabalho em saúde como o Programa de Educação para o Trabalho. Desta forma, propomos relatar experiências vivenciadas por acadêmicas de Farmácia no Programa de Educação para o Trabalho - Interprofissionalidade a partir do desenvolvimento de ações junto às equipes de saúde voltadas para os idosos atendidos em uma Unidade Básica de Saúde do município de Belém (PA), além dos impactos positivos e negativos para a formação profissional. Foram empregadas ações de educação em saúde como rodas de conversa, palestras, jogos interativos e outros dispositivos, tendo como resultado a boa aceitação pelos idosos. A participação no projeto contribuiu estimulando potenciais de melhoria na formação dos profissionais de saúde, despertando o desenvolvimento por meio da inserção precoce nos ambientes de serviço do Sistema Único de Saúde, no entanto foram observadas deficiências relacionadas à efetividade do trabalho interprofissional e colaborativo, especialmente por conta de barreiras institucionais referentes às diferenças curriculares nas graduações em saúde, que ainda impõem distâncias significativas na construção de uma nova aprendizagem.
Petiveria alliacea is a perennial Amazonian shrub used in traditional medicine for many purposes worldwide, including as antirheumatic, antispasmodic, antifungal, and analgesic for pain relief. ...Herein, this review aimed to provide a concise overview of the phytochemistry and antimicrobial, anticancer, and immunomodulatory properties reported in the literature for P. alliacea. The herb is rich in sulfur-containing compounds that possess a broad-spectrum of in vitro antimicrobial activity against pathogenic fungi and bacteria at low concentrations. P. alliacea also showed cytotoxicity and antiproliferative activity against cancer cell lines through sophisticated machinery of cellular damage in vitro. Other compounds such as flavonoids, terpenoids, and benzenoids are commonly identified in P. alliacea extracts, and they may also justify these activities. Despite the great pharmacological potential, clinical trials are required to ensure its effectiveness and safety. This review may raise new trends on the studies as well as contribute to the community by offering data for decision-making with regard to its use in treating diseases.
The best-known etiologies of hyperinsulinemic hypoglycemia are insulinoma, non-insulinoma pancreatogenous hypoglycemic syndrome, autoimmune processes, and factitious hypoglycemia. In 2009, a disease ...not associated with classic genetic syndromes and characterized by the presence of multiple pancreatic lesions was described and named insulinomatosis. We present the clinical and pathologic features of four patients with the diagnosis of insulinomatosis, aggregated new clinical data, reviewed extensively the literature, and illustrated the nature and evolution of this recently recognized disease. One of our patients had isolated (without fasting hypoglycemia) postprandial hypoglycemia, an occurrence not previously reported in the literature. Furthermore, we reported the second case presenting malignant disease. All of them had persistent/recurrent hypoglycemia after the first surgery even with pathology confirming the presence of a positive insulin neuroendocrine tumor. In the literature review, 27 sporadic insulinomatosis cases were compiled. All of them had episodes of fasting hypoglycemia except one of our patients. Only two patients had malignant disease, and one of them was from our series. The suspicion of insulinomatosis can be raised before surgery in patients without genetic syndromes, with multiple tumors in the topographic investigation and in those who had persistent or recurrent hypoglycemia after surgical removal of one or more tumors. The definitive diagnosis is established by histology and immunohistochemistry and requires examination of the "macroscopically normal pancreas." Our case series reinforces the marked predominance in women, the high frequency of recurrent hypoglycemia, and consequently, a definitive poor response to the usual surgical treatment.
Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and ...safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.
The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.
NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of -20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay.
We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.
Estimates of nitrogen deposition play a key role in better understanding the human impacts on the nitrogen biogeochemical cycle. This paper examines the concentration of reactive nitrogen (Nr) in the ...atmosphere and the average dry deposition in the state of São Paulo, Brazil. The Nr species that were measured were in the gaseous (NO2, NH3 and HNO3) and particulate phases (NH4+, NO3−). Denuder-based samplers were spatially distributed in six sites to account for different types of land cover and urbanization. Samples were collected over 2 years (2015–2017). The dominant form of inorganic Nr in the atmosphere was the gaseous NO2 at all sampling sites, which represented 79% of the total. The average concentrations of NH3, HNO3, NH4+ and NO3− were 10%, 3%, 6% and 2% of the total Nr, respectively. The average Nr dry deposition in São Paulo State was 10.6 kg N ha−1 yr−1. The highest average deposition of Nr was found in the SP sampling site and is related to intense vehicular traffic, waste management and industrial activities. This work suggests that dry deposition of Nr into the Atlantic Forest next to São Paulo municipality can exceed the critical nitrogen load suggested for most forests. This implies that human activities in the surrounding areas may be affecting the integrity of one of the most important biodiversity hotspots in South America. These results will contribute to improve Nr budget estimates and to advance Nr deposition modelling approaches.
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•The dominant forms of Nr in the atmosphere are the gaseous NO2 and NH3 species.•The highest deposition fluxes are related to the human activities in urban areas.•Spatial analysis of Nr dry deposition in the State of São Paulo, Brazil.
ABSTRACT
A severe re‐emergingzoonosis, leptospirosis, is caused by pathogenic spirochetes of the genus Leptospira. Several studies have identified leptospiral surface proteins with the ability to ...bind ECM and plasma components, which could mediate adhesion and invasion through the hosts. It has been shown that Mce of pathogenic Leptospira spp. is an RGD (Arg‐Gly‐Asp)‐motif‐dependent virulence factor, responsible for infection of cells and animals. In the present article, we decided to further study the repertoire of the Mce activities in leptospiral biological properties. We report that the recombinant Mce is a broad‐spectrum ECM‐binding protein, capable of interacting with laminin, cellular and plasma fibronectin and collagen IV. Dose–response interaction was observed for all the components, fulfilling ligand–receptor requirements. Mce is a PLG binding protein capable to recruit this component from NHS, generating PLA in the presence of PLG activator. Binding of Mce was also observed with the leukocyte cell receptors αLβ2 (CD11a/CD18)‐LFA‐1 and αMβ2 (CD11b/CD18)‐Mac‐1, suggesting the involvement of this protein in the host immune response. Indeed, virulent Leptospira L1‐130 was capable of binding both integrins, whereas culture‐attenuated M‐20 strain only bind to αMβ2 (CD11b/CD18)‐Mac‐1. To the best of our knowledge, this is the first work to describe that Mce surface protein could mediate the attachment of Leptospira interrogans to human cell receptors αLβ2(CD11a/CD18) and αMβ2(CD11b/CD18).
This study assessed the capacity of adhesion, the detachment kinetic and the biofilm formation by Staphylococcus aureus isolated from food services on stainless steel and polypropylene surfaces (2 × ...2 cm) when cultivated in a meat-based broth at 28 and 7 °C. It was also to study the efficacy of the sanitizers sodium hypochlorite (250 mg/L) and peracetic acid (30 mg/L) in inactivating the bacterial cells in the preformed biofilm. S. aureus strains adhered in high numbers regardless the assayed surface kind and incubation temperature over 72 h. Cells detachment of surfaces revealed high persistence over the incubation period. Number of cells needed for biofilm formation was noted at all experimental systems already after 3 days. Peracetic acid and sodium hypochlorite were not efficient in completely removing the cells of S. aureus adhered on polypropylene and stainless steel surfaces. From these results, the assayed strains revealed high capacity to adhere and form biofilm on polypropylene and stainless steel surfaces under different growth conditions. Moreover, the cells in biofilm matrix were resistant for total removal when submitted to the exposure to sanitizers.
Background:
Little information is available regarding the incidence and clinical outcome of the SARS-CoV2 infection in patients with multiple sclerosis (pwMS).
Objective:
To determine the incidence, ...clinical outcome, and impact of COVID-19 on pwMS.
Methods:
This observational study was prospectively performed on a cohort of pwMS (N = 11,560) followed up by 47 out of 51 Brazilian MS referral centers that registered pwMS with COVID-19 at the REDONE platform from 13 March to 4 June 2020.
Results:
The incidence of COVID-19 for pwMS patients was 27.7/10,000 patients and for the general population was 29.2/10,000 inhabitants. A total of 94 (77 women) pwMS patients, aged 40 ± 10.25 years, presenting 9.9 ± 8.6 years of MS disease duration, developed the COVID-19, most of them (87%) exhibited the mild form of the disease. Eighty (96%) patients maintained the use of MS disease-modifying treatment (DMT) during COVID-19 pandemic and 14 patients were not in use of DMTs.
Conclusion:
Incidence of COVID-19 in Brazilian pwMS was not different from those observed for the general Brazilian population. Most pwMS exhibited mild COVID-19, despite the maintenance of the underlying MS treatment.
The application of algal biomass in the soil represents an alternative of efficient use of fertilizers. In the present study, the environmental impacts generated by the application of 1 kg of ...nitrogen from the algal biomass (biofertilizer) were analyzed through life cycle analysis. Nitrogen was recovered from a meat processing industry effluent in a high-rate algal pond. Impacts related to the entire biofertilizer chain were mainly impacting on climate changes (115 kgCO2eq). Other categories (particle formation, terrestrial acidification, freshwater eutrophication and freshwater ecotoxicity) were not very representative. Biomass cultivation was the most critical step regarding energy and time consumption. On the other hand, the use of effluent as the culture medium for microalgae growth reduced impact categories, such as freshwater eutrophication. Results showed that microalgae cultivation and harvesting steps need to be technologically developed, especially when compared to a conventional fertilizer already established in the market. In order to make microalgae biofertilizer environmental advantageous, alternatives should be beforehand: i) the use of photovoltaic energy instead of hydropower energy; ii) the use of a nitrogen richer effluent; iii) and the consideration of an environmental compensation for the treatment of effluent can be accounted for, disregarding the biomass production stage.
•This study evaluated microalgae biofertilizer in a life cycle assessment.•Nitrogen was recovered from a meat processing industry effluent.•Biomass cultivation was the most critical step.•Impacts related to the biofertilizer chain were mainly impacting on climate changes.•Life cycle as a tool to guide the development of new and more competitive products.
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