Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach’s low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats’ glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.
The global impact of cancer emphasizes the importance of developing innovative, effective and minimally invasive therapies. In the context of superficial cancers, the development of a multifunctional nanoparticle-based system and its in vitro and in vivo safety and efficacy characterization are, herein, proposed as a proof-of-concept. This multifunctional system consists of gold nanoparticles coated with hyaluronic and oleic acids, and functionalized with epidermal growth factor for greater specificity towards cutaneous melanoma cells. This nanoparticle system is activated by a near-infrared laser. The characterization of this nanoparticle system included several phases, with in vitro assays being firstly performed to assess the safety of gold nanoparticles without laser irradiation. Then, hairless immunocompromised mice were selected for a xenograft model upon inoculation of A375 human melanoma cells. Treatment with near-infrared laser irradiation for five minutes combined with in situ administration of the nanoparticles showed a tumor volume reduction of approximately 80% and, in some cases, led to the formation of several necrotic foci, observed histologically. No significant skin erythema at the irradiation zone was verified, nor other harmful effects on the excised organs. In conclusion, these assays suggest that this system is safe and shows promising results for the treatment of superficial melanoma.
Background Symptomatic control is essential in palliative care, particularly in end-of-life, in which the pathophysiological changes that characterize this last phase of life strengthen the need to carry out an early therapeutic review. Hence, we aim to evaluate the prescribing pattern at a palliative care unit at two different time points: on admission and the day of the patient’s death. Methods Quantitative, analytic, longitudinal, retrospective and observational study. Participants were adult patients who were admitted and died in a palliative care unit, in Portugal. Sociodemographic, clinical and pharmacological data were collected, including frequencies and routes of administration of schedule prescribed drugs and rescue drugs, from the day of admission until the day of death. Results 115 patients were included with an average age of 70.0 ± 12.9 years old, 53.9 were male, mostly referred by the Hospital Palliative Care Support Teams. The most common pathology was cancer, mainly in advanced stage. On admission, the median scheduled prescription was seven and “as needed” was three drugs. On the day of death, a decrease of prescriptions was observed. Opioids were always the most prescribed drugs. Near death, there was a higher tendency to prescribe butylscopolamine, midazolam, diazepam and levomepromazine. The most frequent route of drug administration was oral on admission and subcutaneous on the day of death. Conclusions Polypharmacy is a reality in palliative care despite specialist palliative care teams. A reduction of prescribed drugs was verified, essentially due less comorbidity-oriented drugs. Further studies are required to analyse the importance of Hospital Palliative Care Support Teams.
Monoamine oxidase (MAO, type A and B) and semicarbazide-sensitive amine oxidase (SSAO) metabolize biogenic amines, however, the impact of these enzymes in arteries from patients with type 2 diabetes remains poorly understood. We investigated the kinetic parameters of the enzymes to establish putative correlations with noradrenaline (NA) content and patient age in human mesenteric arteries from type 2 diabetic patients. The kinetic parameters were evaluated by radiochemical assay and NA content by high-performance liquid chromatography (HPLC). The activity of MAO-A and SSAO in type 2 diabetic vascular tissues was significantly lower compared to the activity obtained in non-diabetic tissues. In the correlation between MAO-A (Km) and NA content, we found a positive correlation for both the diabetic and non-diabetic group, but no correlation was established for patient age. In both groups, MAO-B (Vmax) showed a negative correlation with age. The results show that MAO-A and SSAO activities and NA content of type 2 diabetic tissues are lower compared to the non-diabetic tissues, while MAO-B activity remained unchanged. These remarks suggest that MAO-A and SSAO may play an important role in vascular tissue as well as in the vascular pathophysiology of type 2 diabetes.
Introduction: Obtaining the best possible medication history is the crucial step in medication reconciliation. Our aim was to evaluate the potential contributions of the main data sources available – patient/caregiver, hospital medical records, and shared electronic health records – to obtain an accurate ‘best possible medication history’.Material and Methods: An observational cross-sectional study was conducted. Adult patients taking at least one medicine were included. Patient interview was performed upon admission and this information was reconciled with hospital medical records and shared electronic health records, assessed retrospectively. Concordance between sources was assessed. In the shared electronic health records, information was collected for four time-periods: the preceding three, six, nine and 12-months. The proportion of omitted data between time-periods was analysed.Results: A total of 148 patients were admitted, with a mean age of 54.6 ± 16.3 years. A total of 1639 medicines were retrieved. Only 29% were collected simultaneously in the three sources of information, 40% were only obtained in shared electronic health records and only 5% were obtained exclusively from patients. The total number of medicines gathered in shared electronic health records considering the different time frames were 778 (three-months), 1397 (six-months), 1748 (nine-months), and 1933 (12-months).Discussion: The use of shared electronic health records provides data that were omitted in the other data sources available and retrieving the information at six months is the most efficient procedure to establish the basis of the best possible medication history.Conclusion: Shared electronic health records should be the preferred source of information to supplement the patient or caregiver interview in order to increase the accuracy of best possible medication history of the patient, particularly if collected within the prior six months.
This article studied the judicialization processes related to the pandemic of the new coronavirus, within the scope of Administrative Law. The cases that reached the Brazilian Federal Supreme Court (FSC), available at the “Painel de Ações COVID-19”, were analyzed, as well as a sample of the cases that reached the state courts, obtained through journalistic reports, consolidated on the “Consultor Jurídico” website. Descriptive analysis and content analysis techniques were used, in the thematic mode, for both sources of information. The following variables were analyzed: procedural classes groups, procedural classes, main subject, notification date, time until the first decision, decisions, decisions groups, and total of cases archived remotely. Near 34% of the actions referred to the flexibilization or tightening of people circulation restrictive measures and the opening of commerce and services, and another 34% referred to budgeting issues, mainly dealing with the suspension of state debts and untying resources to combat the pandemic. The median time until the first decision made by the FSC was less than five days for all categories. The judicialization of COVID-19 pointed out already known flaws in public health and social policies in Brazil, and it can boost several attitudes, both by the Legislative and the Executive, to mitigate these problems. This article demonstrates the importance of observing the responses brought by the judicialization, and of the dialogue between the three powers, to deal with the demands of the pandemic better and with several other demands of society.
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