RESUMO
Instruct clinicians on counterfeit drugs and their implications for patient health. Counterfeit drugs imperil patients around the globe, and their penetration into the United States, Canada, and Western Europe is only increasing over time. In addition to inserting counterfeit drugs in the legitimate drug supply, rogue Internet pharmacies and consumer purchases while traveling abroad allow counterfeit drugs to endanger patients. Pharmacists need to understand the nature and severity of the issue and directly counter it through personal actions to secure a legitimate drug supply, such as by using verified distributors and examining the shipment packaging, product packaging, the bottle, and the label for evidence to determine if it is counterfeit or has been tampered with. They can also indirectly counter it through patient education and by working with other key stakeholders in the health care system. Given the risk to patients, pharmacists have an important role to play in limiting patient use of counterfeit drugs.
Assuntos
Medicamentos Falsificados , Farmácias , Canadá , Europa (Continente) , Humanos , Farmacêuticos , Estados UnidosRESUMO
BACKGROUND: In December 2019, a novel coronavirus (SARS-CoV-2) causing symptomatic illness (COVID-19) occurred in Wuhan, China. Travel-associated cases were reported in many other countries leading to epidemic transmission. The number of cases has increased rapidly but laboratory diagnosis is limited. METHODS: We collected samples from two groups of patients diagnosed with COVID-19 for experiments. In one group, 63 serum samples were analyzed IgG and IgM antibodies by enzyme-linked immunosorbent assay (ELISA) and 35 healthy serum samples were served as controls. In the other group, 91 plasma samples were analyzed by colloidal gold-immunochromatographic assay (GICA) for IgG and IgM antibodies and 35 healthy plasma samples were served as controls. Throat swab samples for nucleic acids retest were collected from 81/91 of these participant. RESULTS: The sensitivity of the combined ELISA IgM and IgG detection was 55/63 (87.3%). Sensitivity of the com-bined GICA IgM and IgG detection was 75/91 (82.4%). Both methods were negative for healthy controls and had a specificity of 100%. In 81 cases, the follow up throat swab samples were retested by RT-PCR, showing that 42 cases were positive. The sensitivity was 51.9% (42/81). The area under the receiver operating characteristic (ROC) curve for IgG (AUC(IgG)) was 0.934. The area under the ROC curve for IgM (AUC(IgM)) was 0.812. The area under the ROC curve for IgG + IgM (AUC(IgG+IgM)) was 0.983. CONCLUSIONS: The serological test of SARS-CoV-2 can be used as an important supplement to the existing RT-PCR test for the specific and rapid diagnosis of COVID-19. AUC(IgG) > AUC(IgM) indicates that IgG has better classification performance than IgM. AUC(IgG + IgM) > AUC(IgG) indicates that the combination of IgG and IgM has better classification performance than IgG alone.
Assuntos
Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Imunoglobulina G/análise , Imunoglobulina M/análise , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II- restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64-76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR-ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR-ligand complexes.
Assuntos
Ligantes , Peptídeos/genética , Receptores de Antígenos de Linfócitos T/genética , Sequência de Aminoácidos , Animais , Células Cultivadas , Hemoglobinas/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Hibridomas/imunologia , Cinética , Camundongos , Camundongos Transgênicos , Muramidase/imunologia , Fragmentos de Peptídeos/imunologia , Peptídeos/química , Peptídeos/imunologia , Ligação Proteica , Receptores de Antígenos de Linfócitos T/imunologia , Baço/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Timo/imunologiaRESUMO
The purpose of this study was to examine relationships between objective and self-report measures of physical activity and muscle strength among healthy adults ranging in age from 20 to 91 years. Participants (n = 412) were mostly Caucasian men (48 %) and women (52 %) 43.9 ± 16.1 year of age with a body mass index (BMI) of 26.4 ± 4.8 kg/m(2). Physical activity was measured objectively with an accelerometer and by self-report with the Paffenbarger Physical Activity Questionnaire. Upper and lower body muscle strength were measured with an isokinetic dynamometer and handgrip strength with a static dynamometer. Multivariate regression assessed relationships between physical activity and muscle strength. The strongest correlates of upper body strength including handgrip strength were gender (r = -0.861 to -0.716), age (r = -0.445 to -0.241), BMI (r = 0.134-0.397), and physical activity (r = 0.093-0.186). The strongest correlates of lower body strength were gender (r = -0.772 to -0.634), age (r = -0.663 to -0.445), BMI (r = 0.160-0.266), and physical activity (r = -0.139 to 0.151). The strongest correlates of muscle strength were gender (explaining 40-74 % of the variance), age (6-44 %), and BMI (2-16 %), while physical activity correlations were weaker (1-3 %). Conflict surrounding the influence of a physically active lifestyle on muscle strength with age may be due to the stronger influences of other factors that supersede those of physical activity whether measured objectively or by self-report methods.
RESUMO
3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment.
Assuntos
Alucinógenos/farmacologia , Drogas Ilícitas/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Serotoninérgicos/farmacologia , Interações Medicamentosas , Europa (Continente)/epidemiologia , Alucinógenos/efeitos adversos , Alucinógenos/farmacocinética , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Prevalência , Serotoninérgicos/efeitos adversos , Serotoninérgicos/farmacocinética , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The effect of differing levels of mobility and walking disability on level of physical activity (PA) performed in persons with multiple sclerosis (PwMS) is unknown. We aimed to quantify the association between mobility and walking impairment and PA levels in PwMS. METHODS: We assessed mobility and walking impairment in >3000 North American Research Committee on Multiple Sclerosis registrants using the Patient Determined Disease Steps scale (score of 0-2 = no, 3-6 = moderate, ≥7 = severe impairment) and 12-Item Multiple Sclerosis Walking Scale (MSWS-12) score (divided into quartiles, score of 0-25 = least walking impairment, 76-100 = most). Level of PA performance (metabolic equivalent [MET] minutes/week) was estimated using the Godin Leisure-Time Exercise Questionnaire. Multivariable regression and general linear models were used to assess the impact of walking and mobility impairment on PA levels. RESULTS: Moderate and severe mobility impairment was associated with performance of 183 and 319 fewer MET minutes/week and a 65% and 90% reduced odds of performing ≥500 MET minutes/week of PA compared to no impairment (mean ± SD: 447 ± 413 MET minutes/week) (p < 0.05 for all). Compared to the first quartile of MSWS-12 score (mean ± SD: 475 ± 401), the second, third and fourth quartiles were associated with performance of 127, 216 and 268 fewer MET minutes/week and 51%, 71% and 77% reduced odds of achieving ≥ 500 MET minutes/week of PA (p < 0.05 for each). Limitations of our study include possible recall bias, use of a patient-reported rather than objective outcome and assumptions made when calculating MET minutes. CONCLUSION: Mobility and walking impairment are associated with less physical activity in PwMS.
Assuntos
Exercício Físico , Limitação da Mobilidade , Esclerose Múltipla/fisiopatologia , Caminhada , Adulto , Idoso , Estudos Transversais , Avaliação da Deficiência , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/psicologia , Análise Multivariada , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: We sought to examine the effect of atorvastatin therapy on exercise leg blood flow in healthy middle-aged and older-men and women. BACKGROUND: The vasodilatory response to exercise decreases in humans with aging and disease and this reduction may contribute to reduced exercise capacity. METHODS: We used a double-blind, randomly assigned, placebo-controlled protocol to assess the effect of atorvastatin treatment on exercising leg hemodynamics. We measured femoral artery blood flow (FBF) using Doppler ultrasound and calculated femoral vascular conductance (FVC) from brachial mean arterial pressure (MAP) before and during single knee-extensor exercise in healthy adults (ages 40-71) before (PRE) and after (POST) 6 months of 80 mg atorvastatin (A: 14 men, 16 women) or placebo (P: 14 men, 22 women) treatment. FBF and FVC were normalized to exercise power output and estimated quadriceps muscle mass. RESULTS: Atorvastatin reduced LDL cholesterol by approximately 50%, but not in the placebo group (p < 0.01). Atorvastatin also increased exercise FBF from 44.2 ± 19.0 to 51.4 ± 22.0 mL/min/W/kg muscle whereas FBF in the placebo group was unchanged (40.1 ± 16.0 vs. 39.5 ± 16.1) (p < 0.01). FVC also increased with atorvastatin from 0.5 ± 0.2 to 0.6 ± 0.2 mL/min/mmHg/W/kg muscle, but not in the placebo subjects (P: 0.4 ± 0.2 vs. 0.4 ± 0.2) (p < 0.01). CONCLUSIONS: High-dose atorvastatin augments exercising leg hyperemia. Statins may mitigate reductions in the exercise vasodilatory response in humans that are associated with aging and disease.