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1.
Biosens Bioelectron ; 216: 114655, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-36055130

ABSTRACT

Although enzyme-based signal amplification has been well developed for biosensors, their application in low-abundance biomarker under complicated conditions detection remains challenge. Cortisol is a steroid hormone and a quantitative evaluation of cortisol can objectively assess stress and depression. However, various factors can induce slight cortisol changes in body fluids, and this in turn sets a strict requirement for bedside testing of cortisol for evaluation of stress. Herein, all-in-one calcium nanoflowers (CaHPO4-AM-HRP-SA NFs) integrated with horseradish peroxidase (HRP), α-amylase (α-AM), and streptavidin (SA) have been synthesized to develop a simple but powerful biosensor for cortisol detection. High specific surface area and allosteric modulator provided by the hybrid nanoflowers as inherent advantages significantly boosted the catalytical ability and stability compared with the free enzymes. CaHPO4-AM-HRP-SA NFs also endowed the sensor with two output signals of one sample, leading the as-prepared sensor to realize self-calibration detection. Aside from using a traditional microplate reader to measure the signal, it could also be read out by a handheld blood glucose meter and a mobile phone. The sensor exhibited attractive simplicity and sensitivity with a low LOD of 98.5 pg mL-1. It accomplished the sensitive evaluation of cortisol in rat serum and assessed the antidepressant effects of different medications. The non-invasive and reliable cortisol detection is also achieved in human urine and saliva samples. Overall, we have demonstrated that the sensor can be deployed as a promising platform to evaluate drug efficiency and monitor stress in a simple and non-invasive manner.


Subject(s)
Biosensing Techniques , Animals , Biomarkers , Blood Glucose , Calcium , Depression/diagnosis , Depression/drug therapy , Drug Evaluation , Horseradish Peroxidase , Humans , Hydrocortisone , Rats , Streptavidin , alpha-Amylases
2.
Rev Panam Salud Publica ; 46, sept. 2022
Article in Spanish | PAHO-IRIS | ID: phr-56484

ABSTRACT

[RESUMEN]. Objetivo. Caracterizar y describir las notificaciones de sospechas de reacciones adversas de un grupo de medicamentos que se utilizaron en Colombia, Costa Rica, Cuba, Chile, El Salvador, México y Perú para tratar o prevenir la enfermedad por el coronavirus (COVID-19, por su sigla en inglés) entre el 1 de marzo y el 31 de agosto del 2020. Métodos. Se elaboró una lista de los 13 medicamentos utilizados para tratar o prevenir la COVID-19, según fuentes oficiales y no oficiales. Desde las bases de datos de los programas nacionales de farma- covigilancia de los países participantes, se recopilaron las notificaciones de sospechas de reacciones adversas a estos medicamentos recibidas en el período comprendido entre el 1 de marzo y 31 de agosto de año 2020. Resultados. Se recibieron 3 490 notificaciones de sospechas de reacciones adversas desde los programas de farmacovigilancia de Perú (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72) y El Salvador (n = 3). Los medicamentos con mayor número de notificaciones de reacciones adversas fueron la azitromi- cina, la ivermectina y la hidroxicloroquina. La diarrea fue el evento más frecuente (15,0%). Del total de las sospechas de reacciones adversas, 11,9% fueron notificadas como graves. La más frecuente fue la prolon- gación del intervalo QT posterior al uso de hidroxicloroquina. De estas sospechas de reacciones adversas graves, 54,5% ocurrieron en personas mayores de 65 años. Conclusión. Si bien no es posible establecer una relación causal a partir de la evaluación de informes espon- táneos, el presente estudio confirma la presencia de reacciones adversas, algunas graves, con medicamentos que se utilizaron para tratar o prevenir la COVID-19.


[ABSTRACT]. Objective. Characterize and describe reports of suspected adverse reactions to a group of drugs used in Colombia, Costa Rica, Cuba, Chile, El Salvador, Mexico, and Peru to treat or prevent coronavirus disease (COVID-19) between 1 March and 31 August 2020. Methods. A list of the 13 drugs used to treat or prevent COVID-19 was prepared, based on official and unofficial sources. Drawing on the databases of the national pharmacovigilance programs of the participating countries, reports of suspected adverse reactions to these drugs were collected for the period from 1 March and 31 August 2020. Results. A total of 3 490 reports of suspected adverse reactions were received from the pharmacovigilance programs of Peru (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72), and El Salvador (n = 3). The drugs with the highest number of reported adverse reactions were azithromycin, ivermectin, and hydroxychlo- roquine. Diarrhea was the most frequent event (15.0%). Of the total suspected adverse reactions, 11.9% were reported as serious. The most frequent was QT prolongation following use of hydroxychloroquine. Of these suspected serious adverse reactions, 54.5% occurred in people over 65 years of age. Conclusion. While it is not possible to establish a causal relationship from the evaluation of spontaneous reports, the present study confirms the presence of adverse reactions—some of them serious—involving drugs used to treat or prevent COVID-19.


[RESUMO]. Objetivo. Caracterizar e descrever as notificações de suspeitas de reações adversas a um grupo de medica- mentos utilizados na Colômbia, Costa Rica, Cuba, Chile, El Salvador, México e Peru, para tratar ou prevenir a doença do coronavírus (COVID-19), entre 1o de março e 31 de agosto de 2020. Métodos. Foi elaborada uma lista dos 13 medicamentos usados para tratar ou prevenir a COVID-19, segundo fontes oficiais e não oficiais. A partir das bases de dados dos programas nacionais de farmacovigilância dos países participantes, foram coletadas notificações de suspeitas de reações adversas a esses medicamentos, recebidas no período entre 1o de março e 31 de agosto de 2020. Resultados. Foram recebidas 3.490 notificações de suspeitas de reações adversas dos programas de far- macovigilância do Peru (n = 3.037), Cuba (n = 270), Colômbia (n = 108), Chile (n = 72) e El Salvador (n = 3). Os medicamentos com maior número de notificações de reações adversas foram azitromicina, ivermectina e hidroxicloroquina. A diarreia foi o evento mais frequente (15,0%). Do total de suspeitas de reações adversas, 11,9% foram notificadas como graves. A mais frequente foi o prolongamento do intervalo QT após o uso de hidroxicloroquina. Dessas suspeitas de reações adversas graves, 54,5% ocorreram em pessoas com mais de 65 anos. Conclusão. Embora não seja possível estabelecer uma relação causal com base na avaliação de relatos espontâneos, o presente estudo confirma a presença de reações adversas – algumas graves – a medicamen- tos que foram usados para tratar ou prevenir a COVID-19.


Subject(s)
Pharmacovigilance , Coronavirus Infections , Drug Evaluation , Drug-Related Side Effects and Adverse Reactions , Drug Utilization , Patient Safety , Anti-Infective Agents , Pharmacovigilance , Coronavirus Infections , Drug Evaluation , Drug-Related Side Effects and Adverse Reactions , Drug Utilization , Patient Safety , Anti-Infective Agents , Pharmacovigilance , Coronavirus Infections , Drug Evaluation , Drug-Related Side Effects and Adverse Reactions , Drug Utilization , Patient Safety , Anti-Infective Agents
3.
CNS Neurosci Ther ; 28(8): 1229-1239, 2022 08.
Article in English | MEDLINE | ID: mdl-35642775

ABSTRACT

BACKGROUND: To assess the temporal changes in the characteristics of ischemic stroke drug clinical trials conducted in mainland China in 2005-2021. METHODS: A statistical analysis of registered clinical trials on ischemic stroke was performed using the platform of the Center for Drug Evaluation of China National Medical Products Administration, the Chinese Clinical Trial Registry, and ClinicalTrials.gov websites. RESULTS: From January 1, 2005 to August 1, 2021, a total of 384 registered drug clinical trials on ischemic stroke were identified in mainland China. Over time, the number of trials gradually increased each year, with a significant growth in 2014, from 16 in 2013 to 42 in 2014. Phase IV trials (31.8%) accounted for the majority, followed by phase II (16.4%), phase I (10.9%), and phase III (8.6%). In terms of sponsorship, the proportion of investigator-initiated trials (IITs) (60.7%) was higher than industry-sponsored trials (ISTs) (39.3%). Additionally, trials involving traditional Chinese medicines (TCMs) (36.2%) accounted for the largest proportion, followed by trials involving antithrombotic therapy (19.5%) and cerebral protection agents (16.7%). Furthermore, over the past 17 years, the number of leading drug clinical trial units for ischemic stroke in mainland China has continuously increased. The leading principal units from Beijing, Shanghai, Guangdong, Jiangsu, and Liaoning accounted for the majority of the trials (67.4%). CONCLUSION: In the past 17 years, great progress has been made in the research and development (R&D) of drugs and clinical trials for ischemic stroke in mainland China. The most extensive progress was observed in TCMs, antithrombotic therapy, and cerebral protection agents. More clinical trials are needed to confirm whether the newly developed drugs can improve the clinical efficacy of ischemic stroke. Simultaneously, more pharmaceutical R&D efforts of innovative drugs are warranted.


Subject(s)
Clinical Trials as Topic , Ischemic Stroke , China , Drug Evaluation , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke/drug therapy
4.
Lab Chip ; 22(12): 2364-2375, 2022 Jun 14.
Article in English | MEDLINE | ID: mdl-35551303

ABSTRACT

There is a growing interest in developing personalized treatment strategies for each cancer patient, especially those with non-small cell lung carcinoma (NSCLC) which annually accounts for the majority of cancer related deaths in the US. Yet identifying the optimal NSCLC treatment strategy for each cancer patient is critical due to a multitude of mutations, some of which develop following initial therapy and can result in drug resistance. A key difficulty in developing personalized therapies in NSCLC is the lack of clinically relevant assay systems that are suitable to evaluate drug sensitivity using a minuscule amount of patient-derived material available following biopsies. Herein we leverage 3D printing to demonstrate a platform based on miniature microwells in agarose to culture cancer cell spheroids. The agarose wells were shaped by 3D printing molds with 1000 microwells with a U-shaped bottom. Three NSCLC cell lines (HCC4006, H1975 and A549) were used to demonstrate size uniformity, spheroid viability, biomarker expressions and drug response in 3D agarose microwells. Results show that our approach yielded spheroids of uniform size (coefficient of variation <22%) and high viability (>83% after 1 week-culture). Studies using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) drugs gefitinib and osimertinib showed clinically relevant responses. Based on the physical features, cell phenotypes, and responses to therapy of our spheroid models, we conclude that our platform is suitable for in vitro culture and drug evaluation, especially in cases when tumor sample is limited.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Drug Evaluation , Drug Resistance, Neoplasm , ErbB Receptors/metabolism , Humans , Lung Neoplasms/pathology , Mutation , Protein Kinase Inhibitors/therapeutic use , Sepharose
5.
JAMA Intern Med ; 182(6): 690, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35435943

Subject(s)
Drug Evaluation , Humans
6.
Neuromuscul Disord ; 32(4): 271-283, 2022 04.
Article in English | MEDLINE | ID: mdl-35396092

ABSTRACT

Using external controls based on real-world or natural history data (RWD/NHD) for drug evaluations in Duchenne muscular dystrophy (DMD) is appealing given the challenges of enrolling placebo-controlled trials, especially for multi-year trials. Comparisons to external controls, however, face risks of bias due to differences in outcomes between trial and RWD/NHD settings. To assess this bias empirically, we conducted a multi-institution study comparing mean 48-week changes in North Star Ambulatory Assessment (NSAA) total score between trial placebo arms and RWD/NHD sources, with and without adjustment for baseline prognostic factors. Analyses used data from three placebo arms (235 48-week intervals, N = 235 patients) and three RWD/NHD sources (348 intervals, N = 202 patients). Differences in mean ΔNSAA between placebo arms and RWD/NHD sources were small before adjustment (-1.2 units, 95% CI: [-2.0 -0.5]) and were attenuated and no longer statistically significant after adjustment (0.1 units (95% CI: [-0.6, 0.8]). Results were similar whether adjusting using multivariable regression or propensity score matching. This consistency in ΔNSAA between trial placebo arms and RWD/NHD sources accords with prior findings for the six-minute walk distance, provides a well-validated framework for baseline adjustment of prognostic factors, and supports the suitability of RWD/NHD external controls for drug evaluations in ambulatory DMD.


Subject(s)
Muscular Dystrophy, Duchenne , Drug Evaluation , Humans , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/drug therapy , Physical Therapy Modalities
7.
Molecules ; 27(3)2022 Jan 27.
Article in English | MEDLINE | ID: mdl-35164096

ABSTRACT

A determination method for trace 24-epibrassinolide (EBL) in plant tissues was developed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The plant tissue samples were extracted using a methanol-formic acid solution, and the corresponding supernatant was purified with ODS C18 solid-phase extraction column. The extracts were separated using a Zorbax Eclipse Plus C18 (2.1 mm × 50 mm, 1.8 µm) column with methanol and 0.1% formic acid as the mobile phase. The ion source for the mass spectrometry was an electrospray ionization source with positive ion mode detection. The linear range of the target compound was 0.7~104 µg/kg, the limit of detection (LOD) was 0.11~0.37 µg/kg, the limit of quantification (LOQ) was 0.36~1.22 µg/kg, the recovery rate was 84.0~116.3%, and the relative standard deviation (RSD%) was 0.8~10.5. The samples of maize plumule, brassica rapeseed flower, and marigold leaf were detected using the external standard method. The optimization of the extraction method and detection method of EBL improved the detection sensitivity, laid a foundation for the artificial synthesis of EBL, improved the extraction rate of EBL, and provided a theoretical basis for the study of EBL in many plants.


Subject(s)
Brassica napus/chemistry , Brassinosteroids , Flowers/chemistry , Plant Leaves/chemistry , Zea mays/chemistry , Brassinosteroids/chemistry , Brassinosteroids/isolation & purification , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drug Evaluation , Tandem Mass Spectrometry
8.
Clin Pharmacol Ther ; 112(2): 210-223, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34656074

ABSTRACT

Changes that accompany older age can alter the pharmacokinetics (PK), pharmacodynamics (PD), and likelihood of adverse effects (AEs) of a drug. However, older adults, especially the oldest or those with multiple chronic health conditions, polypharmacy, or frailty, are often under-represented in clinical trials of new drugs. Deficits in the current conduct of clinical evaluation of drugs for older adults and potential steps to fill those knowledge gaps are presented in this communication. The most important step is to increase clinical trial enrollment of older adults who are representative of the target treatment population. Unnecessary eligibility criteria should be eliminated. Physical and financial barriers to participation should be removed. Incentives could be created for inclusion of older adults. Enrollment goals should be established based on intended treatment indications, prevalence of the condition, and feasibility. Relevant clinical pharmacology data need to be obtained early enough to guide dosing and reduce risk for participation of older adults. Relevant PK and PD data as well as patient-centered outcomes should be measured during trials. Trial data should be analyzed for differences in PK, PD, effectiveness, and safety arising from differences in age or from the presence of conditions common in older adults. Postmarket evaluations with real-world evidence and drug labeling updates throughout the product lifecycle reflecting new knowledge are also needed. A comprehensive plan is needed to ensure adequate evaluation of the safety and effectiveness of drugs in older adults.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Polypharmacy , Aged , Drug Evaluation , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Humans , Prevalence
9.
Life Sci ; 289: 120211, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34875251

ABSTRACT

AIMS: The current study aims to investigate the effect of Yupingfeng (YPF) powder on immunosuppression, and explore the possible mechanisms. MAIN METHODS: Firstly, the monomer components of YPF powder were analyzed by UPLC-QTOF-MS combined with UNIFI automatic analysis platform, then the mechanism of YPF on immunosuppressive treatment was investigated using network pharmacological method, and finally the prediction was verified in a Candida albicans (Can)-induced immunosuppressive BALB/c mouse model. KEY FINDINGS: 98 monomer compounds in YPF were obtained. Through virtual analysis and screening on the oral utilization and drug likeness properties of the components, 47 effective components were got. 9 core targets obtained were enriched in IL-17 signaling pathway. In the mouse model, YPF could reduce the number of Can and alleviate Can-induced inflammation in the kidney effectively, upregulate Can-induced low proportion of CD4+/CD8+ of splenic lymphocytes, and increase Can-induced low activity of IL-17 pathway. SIGNIFICANCE: These results demonstrate that YPF could improve the immunity of Can-induced immunosuppression in BALB/c mice through upregulating the activity of IL-17 pathway.


Subject(s)
Candida albicans/immunology , Candidiasis , Drugs, Chinese Herbal , Immune Tolerance/drug effects , Animals , Candidiasis/drug therapy , Candidiasis/immunology , Chromatography, High Pressure Liquid , Disease Models, Animal , Drug Evaluation , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/pharmacology , Male , Mass Spectrometry , Mice , Mice, Inbred BALB C , Powders
10.
Tissue Eng Part B Rev ; 28(2): 421-436, 2022 04.
Article in English | MEDLINE | ID: mdl-34010074

ABSTRACT

Osteoarthritis (OA) is a severely painful and debilitating disease of the joint, which brings about degradation of the articular cartilage and currently has few therapeutic solutions. Two-dimensional (2D) high-throughput screening (HTS) assays have been widely used to identify candidate drugs with therapeutic potential for the treatment of OA. A number of small molecules which improve the chondrogenic differentiation of progenitor cells for tissue engineering applications have also been discovered in this way. However, due to the failure of these models to accurately represent the native joint environment, the efficacy of these drugs has been limited in vivo. Screening systems utilizing three-dimensional (3D) models, which more closely reflect the tissue and its complex cell and molecular interactions, have also been described. However, the vast majority of these systems fail to recapitulate the complex, zonal structure of articular cartilage and its unique cell population. This review summarizes current 2D HTS techniques and addresses the question of how to use existing 3D models of tissue-engineered cartilage to create 3D drug screening platforms with improved outcomes. Impact statement Currently, the use of two-dimensional (2D) screening platforms in drug discovery is common practice. However, these systems often fail to predict efficacy in vivo, as they do not accurately represent the complexity of the native three-dimensional (3D) environment. This article describes existing 2D and 3D high-throughput systems used to identify small molecules for osteoarthritis treatment or in vitro chondrogenic differentiation, and suggests ways to improve the efficacy of these systems based on the most recent research.


Subject(s)
Cartilage, Articular , Osteoarthritis , Chondrogenesis , Drug Evaluation , High-Throughput Screening Assays , Humans , Osteoarthritis/drug therapy
11.
Drug Discov Today ; 27(1): 49-64, 2022 01.
Article in English | MEDLINE | ID: mdl-34400352

ABSTRACT

Drug-repurposing technologies are growing in number and maturing. However, comparisons to each other and to reality are hindered because of a lack of consensus with respect to performance evaluation. Such comparability is necessary to determine scientific merit and to ensure that only meaningful predictions from repurposing technologies carry through to further validation and eventual patient use. Here, we review and compare performance evaluation measures for these technologies using version 2 of our shotgun repurposing Computational Analysis of Novel Drug Opportunities (CANDO) platform to illustrate their benefits, drawbacks, and limitations. Understanding and using different performance evaluation metrics ensures robust cross-platform comparability, enabling us to continue to strive toward optimal repurposing by decreasing the time and cost of drug discovery and development.


Subject(s)
Drug Evaluation , Drug Repositioning , Biomedical Technology/methods , Biomedical Technology/trends , Computational Biology , Drug Evaluation/methods , Drug Evaluation/standards , Drug Repositioning/methods , Drug Repositioning/trends , Humans , Medical Informatics
12.
Drug Discov Today ; 27(1): 215-222, 2022 01.
Article in English | MEDLINE | ID: mdl-34555509

ABSTRACT

Artificial Intelligence (AI) relies upon a convergence of technologies with further synergies with life science technologies to capture the value of massive multi-modal data in the form of predictive models supporting decision-making. AI and machine learning (ML) enhance drug design and development by improving our understanding of disease heterogeneity, identifying dysregulated molecular pathways and therapeutic targets, designing and optimizing drug candidates, as well as evaluating in silico clinical efficacy. By providing an unprecedented level of knowledge on both patient specificities and drug candidate properties, AI is fostering the emergence of a computational precision medicine allowing the design of therapies or preventive measures tailored to the singularities of individual patients in terms of their physiology, disease features, and exposure to environmental risks.


Subject(s)
Artificial Intelligence , Drug Design/trends , Drug Development/trends , Drug Evaluation , Precision Medicine , Biomedical Technology/methods , Biomedical Technology/trends , Decision Support Techniques , Drug Evaluation/methods , Drug Evaluation/trends , Humans , Medical Informatics , Precision Medicine/methods , Precision Medicine/trends
13.
Appl Biochem Biotechnol ; 194(1): 302-322, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34762271

ABSTRACT

The most important role of tissue engineering is to develop a biomaterial with a property that mimics the extracellular matrix (ECM) by enhancing the lineage-specific proliferation and differentiation with favorable regeneration property to aid in new tissue formation. Thus, to develop an ideal scaffold for bone repair, we have fabricated a composite nanofiber by the coaxial electrospinning technique. The coaxial electrospun nanofiber contains the core layer, consisting of polyvinyl alcohol (PVA) blended with oregano extract and mesoporous silica nanoparticles (PVA-OE-MSNPs), and the shell layer, consisting of poly-ε-caprolactone blended with collagen and hydroxyapatite (PCL-collagen-HAP). We evaluated the physicochemical properties of the nanofibers using X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). In vitro biocompatibility, cell adhesion, cell viability, and osteogenic potential were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenlytetrazolium bromide (MTT), calcein AM, and alkaline phosphatase (ALP) activity and Alizarin Red staining in NIH 3T3/MG-63 cells. The results showed that the nanoparticle-incorporated coaxial nanofiber was observed with bead-free, continuous, and uniform fiber morphology with a mean diameter in the range of 310 ± 125 nm. From the biochemical studies, it is observed that the incorporation of nanofiber with HAP and MSNPs shows good swelling property with ideal porosity, biodegradation, and enhanced biomineralization property. In vitro results showed that the scaffolds with nanoparticles have higher cell adhesion, cell viability, ALP activity, and mineralization potential. Thus, the fabricated nanofiber could be an appropriate implantable biomaterial for bone tissue engineering.


Subject(s)
Coated Materials, Biocompatible , Materials Testing , Nanofibers , Osteogenesis/drug effects , Silicon Dioxide , Animals , Cell Line , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Drug Evaluation , Mice , Nanofibers/chemistry , Nanofibers/therapeutic use , Porosity , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology
14.
HU rev ; 48: 1-8, 2022.
Article in Portuguese | LILACS | ID: biblio-1371594

ABSTRACT

Introdução: O Brasil, assim como outros países, vem alterando seu perfil demográfico elevando o número de pessoas idosas, o que repercute em mudanças não só para sociedade, mas também para saúde pública. Este grupo de pacientes é mais vulnerável devido à fisiologia inerente ao envelhecimento, logo se tornam mais propensos ao uso de medicamentos que podem causar outros problemas de saúde. Essa probabilidade de risco é uma preocupação atual e levou a criação de métodos que norteiam os prescritores para adequarem suas terapêuticas neste grupo de pacientes. Um destes métodos é o critério de Beers, que é atualizado periodicamente trazendo uma lista de medicamentos potencialmente inapropriados (MPIs) para idosos. Objetivo: Avaliar a prescrição de pacientes idosos internados no Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF/Ebserh) quanto à prevalência do uso de MPI e polifarmácia, no período de julho a agosto de 2019. Material e Métodos: Estudo observacional descritivo e retrospectivo, cujos dados foram coletados de prontuários pacientes idosos com idade igual ou superior a 65 anos para obtenção dos resultados que foram avaliados estatisticamente. Resultados: Foram avaliados 187 prontuários, e observada prevalência de 80,2% da prescrição de MPIs, sendo os mais prevalentes omeprazol e benzodiazepínicos. A maioria dos pacientes tiveram polifarmácia (95,7%). Conclusão: Os resultados convergem com base no critério de Beers, para necessidade de adequar a terapia de pacientes idosos. É necessário também avaliar os benefícios e alternativas quanto aos MPIs mais prevalentes, além de realizar estudos observacionais sobre possíveis efeitos adversos que possam ser consequência do uso desses medicamentos, com objetivo de aperfeiçoar a terapia farmacológica e aprimorar a farmacoeconomia, melhorando assim a qualidade de vida dos pacientes idosos.


Introduction: Brazil, like other countries, has been changing its demographic profile, increasing the number of elderly people, which reflects in changes not only for society, but also for public health. This group of patients is more vulnerable due to the inherent physiology of aging, so they become more likely to use medications that can cause other health problems. This risk probability is a current concern and has led to the creation of methods that guide prescribers to adapt their therapies in this group of patients. One of these methods is the Beers criterion, which is periodically updated with a list of potentially inappropriate medications (PIM) for the elderly. Objective: To evaluate the prescription of elderly patients hospitalized at the University Hospital of Juiz de Fora (HU-UFJF/Ebserh) regarding the prevalence of the use of PIM and polypharmacy, from July to August 2019. Material and Methods: Descriptive and retrospective observational study, whose data were collected from medical records of elderly patients aged 65 years or older to obtain the results that were statistically evaluated. Results: A total of 187 medical records were evaluated, and a prevalence of 80.2% of the prescription of PIMs was observed, the most prevalent being omeprazol and benzodiazepines. Most patients had polypharmacy (95.7%). Conclusion: The results converge, based on the Beers criterion, for the need to suit the therapy of elderly patients. It is also necessary to evaluate the benefits and alternatives regarding the most prevalent PIMs, in addition to conducting observational studies on possible adverse effects that may be a consequence of the use of these medications, aiming to refine pharmacological therapy and improve pharmacoeconomics, thus improving quality of life of elderly patients.


Subject(s)
Drug Prescriptions , Aging , Health of the Elderly , Polypharmacy , Drug Evaluation , Drug Therapy , Drug-Related Side Effects and Adverse Reactions , Drug Utilization , Potentially Inappropriate Medication List , Hospitalization
16.
MAbs ; 14(1): 1979447, 2022.
Article in English | MEDLINE | ID: mdl-34923919

ABSTRACT

Targeting immune checkpoint receptors expressed in the T cell synapse induces active and long-lasting antitumor immunity in preclinical tumor models and oncology patients. However, traditional nonhuman primate (NHP) studies in healthy animals have thus far demonstrated little to no pharmacological activity or toxicity for checkpoint inhibitors (CPIs), likely due to a quiescent immune system. We developed a NHP vaccine challenge model in Mauritius cynomolgus monkey (MCMs) that elicits a strong CD8+ T cell response to assess both pharmacology and safety within the same animal. MHC I-genotyped MCMs were immunized with three replication incompetent adenovirus serotype 5 (Adv5) encoding Gag, Nef and Pol simian immunodeficiency virus (SIV) proteins administered 4 weeks apart. Immunized animals received the anti-PD-L1 atezolizumab or an immune checkpoint-targeting bispecific antibody (mAbX) in early development. After a single immunization, Adv5-SIVs induced T-cell activation as assessed by the expression of several co-stimulatory and co-inhibitory molecules, proliferation, and antigen-specific T-cell response as measured by a Nef-dependent interferon-γ ELIspot and tetramer analysis. Administration of atezolizumab increased the number of Ki67+ CD8+ T cells, CD8+ T cells co-expressing TIM3 and LAG3 and the number of CD4+ T cells co-expressing 4-1BB, BTLA, and TIM3 two weeks after vaccination. Both atezolizumab and mAbX extended the cytolytic activity of the SIV antigen-specific CD8+ T cell up to 8 weeks. Taken together, this vaccine challenge model allowed the combined study of pharmacology and safety parameters for a new immunomodulatory protein-based therapeutic targeting CD8+ T cells in an NHP model.


Subject(s)
Adenoviridae , CD8-Positive T-Lymphocytes/immunology , SAIDS Vaccines , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus/immunology , Animals , Drug Evaluation , Macaca fascicularis , Male , SAIDS Vaccines/genetics , SAIDS Vaccines/immunology , SAIDS Vaccines/pharmacology , Simian Acquired Immunodeficiency Syndrome/genetics , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/prevention & control , Simian Immunodeficiency Virus/genetics
17.
FASEB J ; 36(1): e22090, 2022 01.
Article in English | MEDLINE | ID: mdl-34907595

ABSTRACT

Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid the innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites. We hypothesized that immunomodulators that can jumpstart and activate innate immune responses at surgical sites, would likely reduce infection at surgical sites. We used three immunomodulators; fMLP (formyl-Methionine-Lysine-Proline), CCL3 (MIP-1α), and LPS (Lipopolysaccharide), based on their documented ability to elicit strong inflammatory responses; in a surgical wound infection model with Pseudomonas aeruginosa to evaluate our hypothesis. Our data indicate that one-time topical treatment with these immunomodulators at low doses significantly increased proinflammatory responses in infected and uninfected surgical wounds and were as effective, (or even better), than a potent prophylactic antibiotic (Tobramycin) in reducing P. aeruginosa infection in wounds. Our data further show that immunomodulators did not have adverse effects on tissue repair and wound healing processes. Rather, they enhanced healing in both infected and uninfected wounds. Collectively, our data demonstrate that harnessing the power of the innate immune system by immunomodulators can significantly boost infection control and potentially stimulate healing. We propose that topical treatment with these immunomodulators at the time of surgery may have therapeutic potential in combating SSI, alone or in combination with prophylactic antibiotics.


Subject(s)
Immunologic Factors/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/immunology , Surgical Wound Infection/drug therapy , Animals , Drug Evaluation , Mice , Mice, Knockout , Pseudomonas Infections/immunology , Surgical Wound Infection/immunology , Surgical Wound Infection/microbiology
20.
Genève; Organisation mondiale de la Santé; 2022. (WHO/2019-nCoV/therapeutics/2022.2).
in French | WHO IRIS | ID: who-355155
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