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1.
JAMA ; 326(2): 137-144, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255009

RESUMO

Importance: Platelet-rich plasma injections are used as a treatment for chronic midportion Achilles tendinopathy, but evidence for this treatment is limited. Objective: In adults with midportion Achilles tendinopathy, to assess the effects of a single platelet-rich plasma injection, compared with sham injection, on the outcome of the Victorian Institute of Sport Assessment-Achilles (VISA-A) score (a single composite measure of Achilles tendinopathy severity). Design, Setting, and Participants: A participant-blinded, multicenter randomized clinical trial that included 240 people from 24 sites assigned to either a platelet-rich plasma injection or a sham injection between April 2016 and February 2020. Final follow-up was July 2020. Participants were older than 18 years with midportion Achilles tendon pain for more than 3 months as confirmed by ultrasound, magnetic resonance imaging, or both. Interventions: A single intratendinous platelet-rich plasma injection (n = 121) or a single sham injection (insertion of a subcutaneous dry needle not entering the tendon) (n = 119). Main Outcomes and Measures: The primary outcome was the VISA-A score, measured 6 months after treatment allocation. The VISA-A score contains 8 questions that cover 3 domains of pain, function, and activity, analyzed as a composite score (range, 0 [worst symptoms] to 100 [no symptoms]; minimal clinically important difference in score, 12 points). The primary analysis was adjusted for laterality, age, sex, and baseline VISA-A score. Results: Among 240 patients assigned to a platelet-rich plasma or sham injection (mean age, 52 years; 138 [58%] women), 221 (92%) completed the trial. At 6-month follow-up, mean VISA-A score values in the plasma-rich plasma group vs the sham injection group were 54.4 vs 53.4 (adjusted mean difference, -2.7 [95% CI, -8.8 to 3.3]). The most common adverse events compared between patients in the platelet-rich plasma group vs the sham group were injection site discomfort (97 vs 73 patients), swelling (56 vs 52 patients) and bruising (48 vs 49 patients). Conclusions and Relevance: Among patients with chronic midportion Achilles tendinopathy, treatment with a single injection of intratendinous platelet-rich plasma, compared with insertion of a subcutaneous dry needle, did not reduce Achilles tendon dysfunction at 6 months. These findings do not support the use of this treatment for chronic midportion Achilles tendinopathy. Trial Registration: isrctn.org Identifier: ISRCTN13254422.


Assuntos
Tendão do Calcâneo , Plasma Rico em Plaquetas , Tendinopatia/terapia , Tendão do Calcâneo/diagnóstico por imagem , Doença Crônica , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Método Simples-Cego , Esportes , Falha de Tratamento , Ultrassonografia
2.
AAPS PharmSciTech ; 22(5): 186, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145510

RESUMO

The aim of this study was to investigate the effect of various parameters on the stability of butorphanol tartrate injection and to screen the optimal packaging material. The effect of the headspace oxygen levels, ampoule color, manufacturer, and size on the stability of butorphanol tartrate formulation were evaluated. The headspace oxygen levels controlled by nitrogen purging were found to be particularly effective in improving stability of the butorphanol formulation, especially below 2%. Although it is a photolabile drug, butorphanol tartrate was getting degraded at much higher extent in amber color ampoules in comparison to clear ampoules. The degradation by oxidation was found to be a free radical-mediated process catalyzed by the presence of iron ions leached from the amber ampoules. The ampoule manufacturers also had a significant effect on the stability of butorphanol. Two-milliliter ampoules provided a better stability of the butorphanol tartrate injection than 1mL ampoules as 2-mL ampoules had the lower headspace oxygen level at the same level of oxygen content. The oxidation mechanism of the butorphanol tartrate injection was investigated under various conditions, which include iron powder spiking, removal of excipients, exposure to oxygen/nitrogen, exposure to stainless steel and at different pH. Iron powder spiking, presence of citric acid, exposure to oxygen, exposure to stainless steel, and high pH accelerated the oxidative degradation. The effect of oxygen, iron ion and citric acid is in agreement with a metal-catalyzed oxidation mechanism called Udenfriend reaction. Based on the formulation test results, limiting headspace oxygen level, ampoule color, manufacturer, size, controlling iron ion contamination, and pH are recommended for formulation development. In conclusion, it can be suggested that this study can lead to a better understanding of the degradation mechanism of butorphanol tartrate; hence, it would contribute to the development of butorphanol tartrate injection with improved stability. Virous packaging materials have different effects on the stability of butorphanol tartrate injection, and the leached iron of packaging ampoules and stainless steel can trigger Udenfriend reaction with butorphanol tartrate and citric acid (CA), which lead to the oxydative degradation of butorphanol tartrate injection.


Assuntos
Analgésicos Opioides/química , Butorfanol/química , Contaminação de Medicamentos/prevenção & controle , Embalagem de Medicamentos/normas , Ferro/análise , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/metabolismo , Butorfanol/administração & dosagem , Butorfanol/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Embalagem de Medicamentos/métodos , Estabilidade de Medicamentos , Injeções Subcutâneas , Ferro/metabolismo , Oxirredução
3.
Medicine (Baltimore) ; 100(22): e26190, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087885

RESUMO

BACKGROUND: Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS. METHODS: We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated. RESULTS: Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo. CONCLUSIONS: Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hidradenite Supurativa/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Casos e Controles , Hidradenite Supurativa/psicologia , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Placebos/administração & dosagem , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico
4.
Medicine (Baltimore) ; 100(25): e26469, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160454

RESUMO

RATIONALE: With the absence of ophthalmopathy, thyroid dermopathy especially lesions at atypical locations is a very rare presentation. We herein report an original case of bilateral breast myxedema caused by Grave's disease. PATIENT CONCERNS: A 21-year-old unmarried woman presented with a 4-month history of Grave's disease and a 1-month history of progressive bilateral breast enlargement. She had symmetrical bilateral breast enlargement with redness and nonpitting thickening of the skin, diffusely enlarged thyroid glands, and no exophthalmos. DIAGNOSIS: Ultrasonography, magnetic resonance imaging scan, and skin biopsy confirmed the diagnosis of bilateral breast myxedema. INTERVENTIONS: The patient was treated with multipoint subcutaneous injections of triamcinolone acetonide in each breast every month. OUTCOMES: The bilateral breast returned approximately to its normal size after therapy for 6 months. CONCLUSIONS: Our case illustrates that multipoint subcutaneous injection of glucocorticoids is beneficial for bilateral breast myxedema.


Assuntos
Doenças Mamárias/tratamento farmacológico , Glucocorticoides/administração & dosagem , Doença de Graves/complicações , Mixedema/tratamento farmacológico , Biópsia , Mama/diagnóstico por imagem , Mama/patologia , Doenças Mamárias/diagnóstico , Doenças Mamárias/etiologia , Doenças Mamárias/patologia , Feminino , Humanos , Injeções Subcutâneas , Imageamento por Ressonância Magnética , Mixedema/diagnóstico , Mixedema/etiologia , Mixedema/patologia , Pele/diagnóstico por imagem , Pele/patologia , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagem , Ultrassonografia Mamária , Adulto Jovem
5.
J Zoo Wildl Med ; 52(2): 538-547, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130396

RESUMO

A recently characterized fungal pathogen, Emydomyces testavorans, has been associated with ulcerative shell disease and significant morbidity in Western pond turtles. Voriconazole is a second-generation triazole antifungal medication that prevents fungal growth through disruption of ergosterol synthesis, causing abnormalities in the fungal cell membrane. Preliminary reports of minimum inhibitory concentrations (MIC) indicate that voriconazole is effective in vitro against E. testavorans. Ultraperformance liquid chromatography was used to measure voriconazole plasma concentrations in blood samples from healthy Western pond turtles after administration of a single SC injection of 10 mg/kg and after multiple doses (10 mg/kg SC q48h for seven doses). The data were analyzed using a naïve pooled approach. Mean (SE) observed time to maximum concentration was 2 (0.18) h for a single dose and 50 (2.2) h for multiple doses; the multiple-dose trial observed mean (SE) maximum concentration was 12.4 (2.2) µg/ml, and observed mean (SE) trough concentration was 1.7 (0.7) µg/ml. Multifocal skin sloughing following the single-dose trial was observed in one turtle and there was a significant increase in polychromatophilic cells amongst the study turtles after the multiple-dose voriconazole trial. No other adverse effects were observed. When voriconazole was administered at 10 mg/kg SC q48h, observed trough plasma concentrations were consistently higher than reported E. testavorans MIC concentrations. Further study is needed to determine the clinical safety and in vivo efficacy of this dose in Western pond turtles.


Assuntos
Antifúngicos/sangue , Tartarugas/sangue , Voriconazol/sangue , Animais , Antifúngicos/farmacocinética , Área Sob a Curva , Esquema de Medicação , Feminino , Meia-Vida , Injeções Subcutâneas , Masculino , Voriconazol/farmacocinética
6.
Adv Ther ; 38(6): 3129-3142, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33948925

RESUMO

INTRODUCTION: Octreotide acetate subcutaneous injection is indicated to treat acromegaly and the symptoms of carcinoid tumors and vasoactive intestinal peptide tumors (VIPomas). This formative human factors study assessed the octreotide acetate pen injector and accompanying instructions for use (IFU) with self-trained participants. METHODS: The study enrolled patients with diagnoses of acromegaly, carcinoid tumors, or VIPomas and healthcare practitioners (HCPs) who treat patients with these diagnoses. The IFU provided a stepwise process with illustrations to train participants on using the pen injector. Participants familiarized themselves with the pen injector and the IFU before administering 2 unaided injections into skin-like pads; administering the full dose into the pad was considered a successful injection. The investigators evaluated each injection by performance measures-specific tasks necessary to safely and correctly administer the medication-and subjective measures, which included participant comments, feedback from questions, and suggestions for improvements. RESULTS: The study enrolled 11 participants-8 patients and 3 HCPs. Participants had a success rate of 100% for both injections. Errors included 1 participant priming the pen with the incorrect dose and 2 participants not holding the injector button for 10 s after the injection. Neither error led to a failed injection. To improve the IFU, participants suggested changing the order of wording on the priming step, clarifying illustrations of the plunger, and stronger indications to hold the injector button. CONCLUSION: The octreotide pen injector and IFU were usable by self-trained participants. Participant errors and suggestions provided a foundation for recommendations to improve the IFU.


Assuntos
Octreotida , Humanos , Injeções Subcutâneas , Autoadministração
7.
Biomed Pharmacother ; 139: 111649, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33957565

RESUMO

Visceral hypersensitivity and impaired gut barrier are crucial contributors to the pathophysiology of irritable bowel syndrome (IBS), and those are mediated via corticotropin-releasing factor (CRF)-Toll like receptor 4-pro-inflammatory cytokine signaling. Phlorizin is an inhibitor of sodium-linked glucose transporters (SGLTs), and known to have anti-cytokine properties. Thus, we hypothesized that phlorizin may improve these gastrointestinal changes in IBS, and tested this hypothesis in rat IBS models, i.e., lipopolysaccharide (LPS) or CRF-induced visceral hypersensitivity and colonic hyperpermeability. The visceral pain threshold in response to colonic balloon distention was estimated by abdominal muscle contractions by electromyogram, and colonic permeability was measured by quantifying the absorbed Evans blue in colonic tissue. Subcutaneous (s.c.) injection of phlorizin inhibited visceral hypersensitivity and colonic hyperpermeability induced by LPS in a dose-dependent manner. Phlorizin also blocked CRF-induced these gastrointestinal changes. Phlorizin is known to inhibit both SGLT1 and SGLT2, but intragastric administration of phlorizin may only inhibit SGLT1 because gut mainly expresses SGLT1. We found that intragastric phlorizin did not display any effects, but ipragliflozin, an orally active and selective SGLT2 inhibitor improved the gastrointestinal changes in the LPS model. Compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, NG-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor and naloxone, an opioid receptor antagonist reversed the effects of phlorizin. In conclusions, phlorizin improved visceral hypersensitivity and colonic hyperpermeability in IBS models. These effects may result from inhibition of SGLT2, and were mediated via AMPK, NO and opioid pathways. Phlorizin may be effective for the treatment of IBS.


Assuntos
Colo/metabolismo , Hiperalgesia/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Florizina/uso terapêutico , Músculos Abdominais/efeitos dos fármacos , Animais , Colo/efeitos dos fármacos , Hormônio Liberador da Corticotropina/farmacologia , Relação Dose-Resposta a Droga , Eletromiografia , Injeções Subcutâneas , Lipopolissacarídeos/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Naloxona/farmacologia , Permeabilidade , Florizina/antagonistas & inibidores , Florizina/farmacologia , Ratos , Ratos Sprague-Dawley
8.
J Drugs Dermatol ; 20(5): 498-502, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33938685

RESUMO

BACKGROUND: To date no precise data are available for extrusion forces related to the G-prime and G-double-prime of fillers in combination with different 27G and 30G needles. Therefore, the objective of this study was to analyze extrusion forces of various product-needle-combinations containing two different 27G and two different 30G needles in combination with fillers of a wide range of elastic moduli starting from 2.0 – 166.0 Pa. MATERIAL AND METHODS: Four different fillers with the following elastic moduli 1.87, 11.65, 61.80, 165.50 Pa were combined with four different needles: 27G ½”, internal diameter: 0.300 μm; 27G ½”, internal diameter: 0.241 μm; 30G ½”, internal diameter: 0.241 μm and 30G ½“, internal diameter: 0.240 μm. Product-needle-combination were subjected to uni-axial mechanical testing and the respective extrusion force was measured. RESULTS: The results of this study revealed that the G-prime and the G-double-prime of a product are statistically significantly related to their extrusion force, with higher G-prime/G-double-prime products requiring higher extrusion forces. The results additionally revealed that whether the size of the needle was described as 27G or 30G by the respective manufacturer statistically significant differences between the measured extrusion forces were detected. CONCLUSION: Injectors need to be aware that not every 27G/30G needle has the same extrusion force even though the external diameter is similar (27G or 30G); this might additionally influence the ability to withdraw blood during a pre-injection aspiration manoeuvre. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5237.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Injeções Subcutâneas/instrumentação , Agulhas , Preenchedores Dérmicos/química , Módulo de Elasticidade , Ácido Hialurônico/química , Injeções Subcutâneas/métodos , Reologia
9.
J Drugs Dermatol ; 20(5): 529-533, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33938690

RESUMO

BACKGROUND: Poly-l-lactic acid (PLLA) is an injectable volumizer with biostimulatory properties used for volumetric structural rejuvenation in patients with facial fat volume loss but has increasingly been utilized for off-face applications. OBJECTIVE: The objectives of this randomized, double-blind, placebo-controlled single center study was to assess the safety and effectiveness of PLLA for the treatment of lower extremity cellulite in adult women. METHODS: 31 healthy women were enrolled in the study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections combined with subcision, into each of the glutes or thighs. Follow-up visits were at 1, 3, and 6 months after treatment. Assessments included live ratings, rating of standardized pictures by a blinded evaluator, patient questionnaires, safety, and tolerability ratings. RESULTS: At the 3 and 6-month follow-up, there was a statistically significant change in the global aesthetic improvement scale (GAIS) compared to baseline as assessed by blinded investigators. Significant improvements were shown in the cellulite severity scale (CSS) as well as in the subject satisfaction questionnaires. Treatments were found to be tolerable, and no severe treatment-related adverse events occurred. CONCLUSION: Repeated PLLA treatments combined with subcision are effective and safe in improving the appearance of cellulite. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5380.


Assuntos
Celulite/tratamento farmacológico , Celulose/administração & dosagem , Técnicas Cosméticas/efeitos adversos , Ácido Láctico/administração & dosagem , Manitol/administração & dosagem , Satisfação do Paciente , Adulto , Celulite/diagnóstico , Celulite/psicologia , Celulose/efeitos adversos , Método Duplo-Cego , Estética , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Ácido Láctico/efeitos adversos , Extremidade Inferior , Manitol/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Índice de Gravidade de Doença , Inquéritos e Questionários/estatística & dados numéricos , Resultado do Tratamento
11.
MMWR Morb Mortal Wkly Rep ; 70(20): 739-743, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34014910

RESUMO

U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), adapted by CDC from global guidance developed by the World Health Organization (WHO), provides evidence-based guidance on contraceptive use for U.S. health care providers (1). During January-February, 2021, CDC evaluated the 2019 WHO recommendation on self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (2). CDC adopted the WHO recommendation on the basis of moderate-certainty evidence that self-administered DMPA-SC is safe and effective, and has higher continuation rates compared with provider-administered DMPA. The new U.S. SPR recommendation states that self-administered DMPA-SC should be made available as an additional approach to deliver injectable contraception. Provider-administered DMPA should remain available. Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be offered in a noncoercive manner through a shared decision-making process between patients and their health care providers, with a focus on patient preferences and equitable access to the full range of contraceptive methods.


Assuntos
Anticoncepcionais Femininos/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Injeções Subcutâneas , Autoadministração , Estados Unidos
12.
N Engl J Med ; 384(19): 1800-1809, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33979488

RESUMO

BACKGROUND: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment. METHODS: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire-6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]). RESULTS: Overall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). In patients with a blood eosinophil count of less than 300 cells per microliter, the annualized rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (rate ratio, 0.59; 95% CI, 0.46 to 0.75; P<0.001). At week 52, improvements were greater with tezepelumab than with placebo with respect to the prebronchodilator FEV1 (0.23 vs. 0.09 liters; difference, 0.13 liters; 95% CI, 0.08 to 0.18; P<0.001) and scores on the ACQ-6 (-1.55 vs. -1.22; difference, -0.33; 95% CI, -0.46 to -0.20; P<0.001), AQLQ (1.49 vs. 1.15; difference, 0.34; 95% CI, 0.20 to 0.47; P<0.001), and ASD (-0.71 vs. -0.59; difference, -0.12; 95% CI, -0.19 to -0.04; P = 0.002). The frequencies and types of adverse events did not differ meaningfully between the two groups. CONCLUSIONS: Patients with severe, uncontrolled asthma who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life than those who received placebo. (Funded by AstraZeneca and Amgen; NAVIGATOR ClinicalTrials.gov number, NCT03347279.).


Assuntos
Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Método Duplo-Cego , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem
13.
Einstein (Sao Paulo) ; 19: eRC6064, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33978100

RESUMO

We report the cases of two adolescent siblings with severe atopic dermatitis, who, despite weighing approximately 40kg, presented a good response to dupilumab with the off-label dose for individuals aged 12 years and weighing 60kg. Both had already used cyclosporine, azathioprine, methotrexate and oral corticosteroids for long periods, plus topical treatments with no adequate disease control. Skin lesions were constant and widespread, with frequent skin infections and very poor quality of life, with numerous physical and psychosocial consequences, such as dropping out of school activities due to severe itching, appearance and bullying. They also showed delayed growth and development. In 2018, dupilumab, an immunobiological agent, was approved for treatment of moderate to severe atopic dermatitis in adults and, in 2019, extended to the 12-17-year age group. Although it had already been approved by the Brazilian Health Surveillance Agency, the 200mg presentation (indicated for the weight of patients) was not available, with no expected arrival date. Therefore, weighing the risks and benefits of the situation of both, we chose to treat them with an adult dose (loading dose of 600mg subcutaneously, and 300mg subcutaneously every 2 weeks) despite the low weight. So far, they have received eight injections, showing significant improvement of disease and quality of life. There were no major adverse effects, only worsening of allergic conjunctivitis in one of them. The patients and their family are very satisfied, and we believe that the therapy has been successful.


Assuntos
Dermatite Atópica , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Brasil , Criança , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Injeções Subcutâneas , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Aging (Albany NY) ; 13(8): 10955-10972, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33861726

RESUMO

Currently, the prevalence of obesity in aging populations is fast growing worldwide. Aging induced by D-galactose (D-gal) is proven to cause the worsening of cardiac dysfunction in pre-diabetic rats via deteriorating cardiac mitochondrial function. Hyperbaric oxygen therapy (HBOT) has been shown to attenuate D-gal-induced cognitive deterioration through decreased inflammation and apoptosis. We tested the hypothesis that HBOT alleviates D-gal induced cardiac dysfunction via improving mitochondrial function in pre-diabetic rats. Wistar rats (n=56) were fed normal diet or high-fat diet for 12 weeks. For subsequent 8 weeks, they were subcutaneously injected either vehicle (0.9% normal saline) or D-gal (150mg/kg/day). Rats were randomly subdivided into 7 groups at week 21: sham-treated (normal diet fed rats with vehicle (NDV), high-fat diet fed rats with vehicle (HFV), normal diet fed rats with D-gal (NDDg), high-fat diet fed rats with D-gal (HFDg)) and HBOT-treated (HFV, NDDg, HFDg). Sham rats received ambient pressure of oxygen while HBOT-treated ones received 100% oxygen given once daily for 60 minutes at 2 atmosphere absolute. HBOT reduced metabolic impairments, mitochondrial dysfunction and increased autophagy, resulting in an improvement of cardiac function in aged pre-diabetic rats.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/terapia , Oxigenação Hiperbárica , Obesidade/complicações , Estado Pré-Diabético/terapia , Envelhecimento/efeitos dos fármacos , Animais , Apoptose , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Galactose/administração & dosagem , Galactose/toxicidade , Humanos , Injeções Subcutâneas , Masculino , Mitocôndrias Cardíacas/patologia , Obesidade/metabolismo , Obesidade/terapia , Estresse Oxidativo , Oxigênio/administração & dosagem , Estado Pré-Diabético/complicações , Ratos , Ratos Wistar
16.
Biochem Biophys Res Commun ; 554: 166-172, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33798943

RESUMO

Although influenza vaccines are effective for reducing viral transmission and the severity of clinical symptoms, influenza viruses still induce considerable morbidity and mortality worldwide. Seasonal influenza viruses infect the upper respiratory tract initially but then often induce severe pulmonary complications in the lower respiratory tract. Therefore, influenza vaccines that prevent viral infection at both the upper and lower respiratory tracts are highly anticipated. Here, we examined whether using different vaccination routes for priming and boosting achieved protection in both regions of the respiratory tract. To this end, we used inactivated whole-virion influenza vaccines to immunize mice either subcutaneously or intranasally for both priming and boosting. Regardless of the route used for boosting, the levels of virus-specific IgG in plasma were higher in mice primed subcutaneously than those in control mice, which received PBS only. In addition, intranasal priming followed by subcutaneous boosting induced higher levels of virus-specific IgG in plasma than those in control mice. The levels of virus-specific nasal IgA were higher in mice that were primed intranasally than in control mice or in mice primed subcutaneously. Furthermore, intranasal priming but not subcutaneous priming provided protection against viral challenge in the upper respiratory tract. In addition, when coupled with subcutaneous boosting, both subcutaneous and intranasal priming protected against viral challenge in the lower respiratory tract. These results indicate that intranasal priming followed by subcutaneous boosting induces both virus-specific IgG in plasma and IgA in nasal washes and protects against virus challenge in both the upper and lower respiratory tracts. Our results will help to develop novel vaccines against influenza viruses and other respiratory viruses.


Assuntos
Anticorpos Neutralizantes/imunologia , Vacinas contra Influenza/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Orthomyxoviridae/imunologia , Infecções Respiratórias/prevenção & controle , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Modelos Animais de Doenças , Vacinas contra Influenza/imunologia , Injeções Subcutâneas/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Orthomyxoviridae/isolamento & purificação , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia
17.
Int Arch Allergy Immunol ; 182(7): 631-636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33887728

RESUMO

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma, and venom allergy. Compliance is essential for SCIT to obtain maximal benefit as it is a long-term treatment. OBJECTIVES: This study aimed to determine the level of real-life SCIT compliance in pediatric patients and the associated factors. Additional aims were to determine how SCIT compliance was affected by the COVID-19 pandemic and why some patients dropped out SCIT. METHOD: Pediatric patients diagnosed with allergic rhinitis, allergic asthma, or venom allergy that received SCIT between September 2012 and July 2020 were analyzed. RESULTS: The study included 201 children (66.7% male) with a median (interquartile range) age of 12.8 years (9.4-15.2) at the time of the first SCIT injection. The overall compliance rate before COVID-19 pandemic was 86.1%. Short SCIT follow-up time and venom anaphylaxis were found to be risk factors for drop out. The leading causes of drop outs were moving to another city/country (32.1%), symptom improvement (17.8%), treatment ineffectiveness (14.2%), and adverse reactions (14.2%). Among the 108 patients that were still receiving SCIT during the COVID-19 pandemic, 31 (28.7%) dropped out the therapy. The most frequent reasons for drop-out were fear of being infected with COVID-19 (35.4%) and thinking that the AIT practise stopped due to COVID-19 pandemic (29%). Male gender and older age were found to be the independent risk factors for drop-out of SCIT. CONCLUSIONS: Real life compliance in children was found 13.9% and it was higher than adults. Nearly one-third of children dropped out during the CO-VID-19 pandemic. Male gender and older age are associated with SCIT drop-out during the COVID-19 pandemic.


Assuntos
COVID-19 , Dessensibilização Imunológica , Hipersensibilidade Imediata/terapia , Cooperação do Paciente/estatística & dados numéricos , Adolescente , COVID-19/prevenção & controle , COVID-19/psicologia , Criança , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/psicologia , Dessensibilização Imunológica/estatística & dados numéricos , Feminino , Humanos , Injeções Subcutâneas , Modelos Logísticos , Masculino , Cooperação do Paciente/psicologia , Pacientes Desistentes do Tratamento/psicologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Turquia
18.
Cancer Sci ; 112(6): 2481-2492, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33792132

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal cancers in humans. The inhibition of peptidyl-prolyl cis/trans isomerase (Pin1) gene expression may have great potential in the treatment of HCC. N-Acetylgalactosamine (GalNAc) was used to target the liver. Cholesterol-modified antimicrobial peptide DP7 (DP7-C) acts as a carrier, the GalNAc-siRNA/DP7-C complex increases the uptake of GalNAc-siRNA and the escape of endosomes in hepatocytes. In addition, DP7-C nanoparticles and hydrogel-assisted GalNAc-Pin1 siRNA delivery can effectively enhance the stability and prolong the silencing effects of Pin1 siRNA. In an orthotopic liver cancer model, the GalNAc-Pin1 siRNA/DP7-C/hydrogel complex can potentially regulate Pin1 expression in hepatocellular carcinoma cells and effectively inhibit tumor progression. Our study proves that Pin1 siRNA is an efficient method for the treatment of HCC and provides a sustainable and effective drug delivery system for the suppression of liver cancer.


Assuntos
Acetilgalactosamina/química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Peptidilprolil Isomerase de Interação com NIMA/antagonistas & inibidores , RNA Interferente Pequeno/administração & dosagem , Animais , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Composição de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrogéis/química , Injeções Subcutâneas , Neoplasias Hepáticas/genética , Camundongos , Peptidilprolil Isomerase de Interação com NIMA/genética , Proteínas Citotóxicas Formadoras de Poros/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacologia , Termodinâmica , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Int J Pharm ; 602: 120530, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33811964

RESUMO

The pain felt during injection, typically delivered via a hypodermic needle as a single bolus, is associated with the pressure build-up around the site of injection. It is hypothesized that this counterpressure is a function of the target tissue as well as fluid properties. Given that novel vaccines target different tissues (muscle, adipose, and skin) and can exhibit a wide range of fluid properties, we conducted a study of the effect of volumetric flow rate, needle size, viscosity and rheology of fluid, and hyaluronidase as an adjuvant on counterpressure build-up in porcine skin and muscle tissues. In particular, we found a significant increase in counterpressure for intradermal (ID) injections compared to intramuscular (IM) injections, by an order of magnitude in some cases. We also showed that the addition of adjuvant affected the tissue back pressure only in case of subcutaneous (SC) injections. We observed that the volumetric flow rate plays an important role along with the needle size. This study aims to improve the current understanding and limitations of liquid injectability via hypodermic needles, however, the results also have implications for other technologies, such as intradermal jet injection where a liquid bleb is formed under the skin.


Assuntos
Agulhas , Seringas , Animais , Injeções Intradérmicas , Injeções Intramusculares , Injeções a Jato , Injeções Subcutâneas , Suínos
20.
Mar Drugs ; 19(4)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920475

RESUMO

dHG-5 (Mw 5.3 kD) is a depolymerized glycosaminoglycan from sea cucumber Holothuria fuscopunctata. As a selective inhibitor of intrinsic Xase (iXase), preclinical study showed it was a promising anticoagulant candidate without obvious bleeding risk. In this work, two bioanalytical methods based on the anti-iXase and activated partial thromboplastin time (APTT) prolongation activities were established and validated to determine dHG-5 concentrations in plasma and urine samples. After single subcutaneous administration of dHG-5 at 5, 9, and 16.2 mg/kg to rats, the time to peak concentration (Tmax) was at about 1 h, and the peak concentration (Cmax) was 2.70, 6.50, and 10.11 µg/mL, respectively. The plasma elimination half-life(T1/2ß) was also about 1 h and dHG-5 could be almost completely absorbed after s.c. administration. Additionally, the pharmacodynamics of dHG-5 was positively correlated with its pharmacokinetics, as determined by rat plasma APTT and anti-iXase method, respectively. dHG-5 was mainly excreted by urine as the unchanged parent drug and about 60% was excreted within 48 h. The results suggested that dHG-5 could be almost completely absorbed after subcutaneous injection and the pharmacokinetics of dHG-5 are predictable. Studying pharmacokinetics of dHG-5 could provide valuable information for future clinical studies.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/farmacocinética , Glicosaminoglicanos/farmacocinética , Holothuria/metabolismo , Animais , Biotransformação , Monitoramento de Medicamentos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/isolamento & purificação , Glicosaminoglicanos/administração & dosagem , Glicosaminoglicanos/isolamento & purificação , Meia-Vida , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Tempo de Tromboplastina Parcial , Ratos Sprague-Dawley , Eliminação Renal
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