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2.
Microsurgery ; 44(4): e31166, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38549390

RESUMO

BACKGROUND: Extensive experimental evidence has suggested the potential efficacy of prostaglandin E1 (PGE1) in enhancing flap survival, leading to its widespread empirical use following free flap operation. However, the translation of these experimental findings into clinical benefits remains uncertain. This study aimed to assess the clinical effectiveness of postoperative PGE1 administration on the outcomes of microsurgical reconstruction. METHODS: A retrospective review was conducted for patients who underwent free flap-based reconstruction between September 2020 and November 2022, dividing into two cohorts. For all consecutive cases conducted during the formal half, PGE1 was administered for postoperative 7 days (PGE1 cohort), and for those during the latter, PGE1 was not given (non-PGE1 cohort). The profiles of perfusion-related complications (PRC) were compared between the two cohorts. Further analyses after propensity-score matching were performed. RESULTS: In total, 274 cases were analyzed, consisting of 142 in PGE1 and 132 in non-PGE1 cohort. Baseline characteristics were similar between the two cohorts, except for higher rates of comorbidities and chronic wound-related defects in the PGE1 cohort. Overall PRC developed in 37 cases (13.5%), including 6 (2.1%) total loss and 38 (10.2%) partial necrosis. Compared to the control, the PGE1 cohort exhibited significantly lower rates of overall PRC and partial flap necrosis. This difference remained significant on multivariable analyses. The rate of total flap loss did not differ between the cohorts. Consistent associations were observed in the propensity-score matching analysis. CONCLUSION: Postoperative administration of PGE1 appears to be associated with reduced risks for the development of partial flap necrosis.


Assuntos
Retalhos de Tecido Biológico , Doenças Vasculares , Humanos , Alprostadil/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento , Estudos Retrospectivos , Necrose/etiologia , Necrose/prevenção & controle
3.
Nagoya J Med Sci ; 86(1): 104-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505715

RESUMO

Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.


Assuntos
Técnicas de Imagem por Elasticidade , Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/diagnóstico por imagem , Disfunção Erétil/tratamento farmacológico , Alprostadil/uso terapêutico , Técnicas de Imagem por Elasticidade/métodos , Ereção Peniana/fisiologia , Pênis/diagnóstico por imagem
4.
Cardiol Young ; 34(2): 314-318, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37403735

RESUMO

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.


Assuntos
Permeabilidade do Canal Arterial , Canal Arterial , Cardiopatias Congênitas , Recém-Nascido , Humanos , Alprostadil/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Espasmo
5.
Cell Transplant ; 32: 9636897231214370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38014622

RESUMO

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.


Assuntos
Esclerose Amiotrófica Lateral , Animais , Camundongos , Humanos , Esclerose Amiotrófica Lateral/tratamento farmacológico , Alprostadil/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa , Neurônios Motores
6.
J Cereb Blood Flow Metab ; 43(12): 2029-2039, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37756573

RESUMO

Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14-28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1-61.3) in the CL2020 group and 10.0% (0.3-44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke.Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103).


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Alprostadil/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento , Isquemia Encefálica/tratamento farmacológico
7.
Port J Card Thorac Vasc Surg ; 30(2): 59-61, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37418773

RESUMO

Buerger's disease is a distal segmental nonatherosclerotic vasculopathy that involves the inferior and superior limbs of smoker males younger than 45 years old. This article aims to describe a clinical case and revise the literature about Buerger's disease. A 45-year-old smoker male repeatedly visited the emergency department for refractory pain and inflammatory signs in the right hallux. After developing ulcers in the right foot, Doppler ultrasonography revealed segmental occlusion of distal arteries of that limb. It was also observed in arteriography "corkscrew" collaterals. Autoimmune, thrombophilic and cardiovascular diseases were excluded. Analgesia, antibiotics and alprostadil were implemented. As a result, the patient stopped smoking and was submitted to minor amputation with complete healing, after which he remained asymptomatic. Buerger's disease is a diagnosis of exclusion. Therefore, smoking cessation is the most effective treatment and is crucial to prevent disease progression.


Assuntos
Tromboangiite Obliterante , Humanos , Masculino , Pessoa de Meia-Idade , Tromboangiite Obliterante/diagnóstico , Artérias , Alprostadil/uso terapêutico , Dor/tratamento farmacológico , Fumar/efeitos adversos
8.
Esophagus ; 20(3): 581-586, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36877412

RESUMO

BACKGROUND: To evaluate the long-term efficacy of transoral incisionless fundoplication (TIF) with Medigus Ultrasonic Surgical Endostapler (MUSE) for gastroesophageal reflux disease (GERD). METHODS: A total of 16 patients with proton pump inhibitor-dependent gastroesophageal reflux disease had undergone TIF by MUSE in Shanghai General Hospital (Shanghai, China)from March 2017 to December 2018. Patients were followed up at 6 months, and the GERD-health-related quality of life (GERD-HRQL) questionnaire score, the GERD questionnaire (GERD-Q) score, high-resolution esophageal manometry (HREM) and 24 h esophageal pH parameters, the Hill grade of the gastroesophageal flap valve (GEFV) and daily Proton pump inhibitor (PPI) consumption before and after procedure were compared. Patients also were followed up at 3 years and 5 years using a structured questionnaire via phone which evaluated symptoms of reflux, dose of PPI medication and side effects. RESULTS: Follow-up data were collected from 13 patients, ranging from 38 to 63 months, 53 months on average. 10/13 patients reported symptomatic improvement and daily PPI consumption was stopped or halved in 11/13. After procedure, the mean scores of GERD-HRQL and GERD-Q were significantly increased. The mean DeMeester score, the mean acid exposure time percentage and the mean number of acid reflux episodes were significantly lower. The mean rest pressure at lower esophageal sphincter (LES) had no significant difference. CONCLUSION: TIF by MUSE has significant efficacy in the treatment of PPI-dependent GERD, which can improve symptoms and life quality of patients, and reduce the acid exposure time for long-term. Chictr.org.cn. TRIAL REGISTRATION: ChiCTR2000034350.


Assuntos
Fundoplicatura , Refluxo Gastroesofágico , Humanos , Fundoplicatura/efeitos adversos , Fundoplicatura/métodos , Alprostadil/uso terapêutico , Qualidade de Vida , Inibidores da Bomba de Prótons/uso terapêutico , Ultrassom , Resultado do Tratamento , China , Refluxo Gastroesofágico/diagnóstico
9.
Pediatr Cardiol ; 44(6): 1327-1332, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36538050

RESUMO

Prostaglandin E1 (PGE) is used in patients with ductal-dependent congenital heart disease (CHD). Side effects of apnea and fever are often dose dependent and occur within 48 h after initiation. We initiated a standardized approach to PGE initiation after our institution recognized a high incidence of side effects and a wide variety of starting doses of PGE. Neonates with prenatally diagnosed ductal-dependent CHD were identified, started on a standardized protocol that started PGE at 0.01 mcg/kg/min, and evaluated for PGE related side effects. Compliance, outcomes and dose adjustments during the first 48 h post-PGE initiation were evaluated. Fifty patients were identified (25 pre-intervention; 25 post-intervention). After intervention, compliance with the protocol was 96%, and apnea or fever occurred in 28% (compared to 63% pre-intervention, p = 0.015). Dose adjustments (either increase or decrease) prior to cardiac surgery were similar in both cohorts (60%, 52%, p = 0.569). There were no mortalities or emergent procedures performed due to ductus arteriosus closure. Standardizing a protocol for initiating PGE in prenatally diagnosed ductal-dependent CHD was successful and reduced the incidence of apnea, fever, and sepsis evaluations. A starting dose of 0.01 mcg/kg/min did not cause increased adverse effects.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Permeabilidade do Canal Arterial , Cardiopatias Congênitas , Recém-Nascido , Humanos , Alprostadil/uso terapêutico , Prostaglandinas , Apneia/induzido quimicamente , Apneia/tratamento farmacológico , Cardiopatias Congênitas/cirurgia , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/tratamento farmacológico
10.
Sex Med Rev ; 10(4): 764-781, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36210096

RESUMO

INTRODUCTION: Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem. OBJECTIVES: Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications. METHODS: This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using the extensive literature search to identify the latest scientific reports on the topic. RESULTS: In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment. CONCLUSION: Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases. Hamzehnejadi M, Tavakoli MR, Homayoun F et al. Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review. Sex Med Rev 2022;10:764-781.


Assuntos
Disfunção Erétil , Alprostadil/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Disfunção Erétil/etiologia , Humanos , Masculino , Prostaglandinas/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Tadalafila/uso terapêutico , Dicloridrato de Vardenafila/uso terapêutico
11.
BMJ Open Ophthalmol ; 7(1)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-36161847

RESUMO

OBJECTIVE: This study aimed to investigate the anatomical and functional changes in patients with central retinal artery occlusion (CRAO) (n=21) treated with 10 µg/day intravenous liposomal prostaglandin E1 (lipo-PGE1). METHODS AND ANALYSIS: We used best-corrected visual acuity (BCVA), central retinal thickness with spectral domain optical coherence photography, optical intensity ratio (OIR) with imageJ software and retinal vessel diameter with fundus photography as indicators. Data were analysed using Tukey's multiple comparisons, Wilcoxon test or Spearman's correlation analysis as appropriate. RESULTS: BCVA was significantly improved at 1 month and 3 months after the initial visit (from 2.18±0.60 to 1.54±0.84 and 1.53±0.88, p=0.030 and p=0.027, respectively). The ratio of retinal vein diameter to optic disc diameter increased in the first month (from 0.40%±0.13% to 0.52%±0.16%, p=0.005). In addition, the OIR at the initial visit was significantly correlated with BCVA at 3 months (p=0.006, r=0.58). No severe adverse effects were observed. CONCLUSION: The results showed that visual acuity and retinal vein constriction improved after lipo-PGE1 therapy. In addition, the OIR in the initial phase can be an indicator of visual prognosis after treatment with PGE1 in patients with CRAO.


Assuntos
Alprostadil , Oclusão da Artéria Retiniana , Alprostadil/uso terapêutico , Humanos , Retina/diagnóstico por imagem , Oclusão da Artéria Retiniana/tratamento farmacológico , Vasos Retinianos/diagnóstico por imagem , Acuidade Visual
12.
Toxicol In Vitro ; 85: 105479, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36152787

RESUMO

Considering the rapidly increasing prevalence of obesity worldwide, the number of weight control drugs is very few. Incretin-based therapies are currently being developed to achieve weight control, and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) are used in incretin-based therapies. This study aimed to investigate the cytotoxicity of exenatide, a GLP-1A, on 3T3-L1 adipocytes and the effect of exenatide on the expression of adipogenesis-related genes, insulin and glucose levels, and apoptosis. Cytotoxic activity of exenatide on 3T3-L1 adipocytes was determined by MTT method. Gene expression levels were determined by qPCR. Apoptosis studies were performed on the Muse Cell Analyzer. C1q/TNF-related protein-3 (CTRP3) expression levels were found to be higher in exenatide treated adipocyte cells than in control cells (p < 0.001). Adipocyte cells treated with exenatide were found to have lower PPAR-γ gene expression levels when compared to control adipocyte cells (p < 0.001). Intracellular insulin (p < 0.001) and glucose levels were higher in 3T3-L1 adipocytes treated with exenatide compared to control adipocyte cells. Total apoptosis increased approximately 1.5 times as a result of exenatide administration. The increase in CTRP3 gene expression, which is thought to be a new biomarker for obesity, and the decrease in PPAR-γ gene expression indicate that exenatide is a promising new pharmacotherapeutic agent in the treatment of obesity by regulating the expression of genes related to adipogenesis and lipogenesis and inducing apoptosis.


Assuntos
Adipogenia , Incretinas , Camundongos , Animais , Exenatida/farmacologia , Exenatida/genética , Exenatida/uso terapêutico , Incretinas/metabolismo , Incretinas/farmacologia , Incretinas/uso terapêutico , Alprostadil/metabolismo , Alprostadil/farmacologia , Alprostadil/uso terapêutico , Complemento C1q/genética , Complemento C1q/metabolismo , Complemento C1q/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Adipócitos , Células 3T3-L1 , PPAR gama/metabolismo , Obesidade/genética , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Insulina/farmacologia , Insulina/metabolismo , Glucose/metabolismo , Apoptose , Expressão Gênica , Diferenciação Celular
13.
Expert Rev Clin Immunol ; 18(11): 1095-1106, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36083692

RESUMO

INTRODUCTION: Type 1 interferons play a key role in the pathogenesis of systemic lupus erythematosus (SLE). An important clinical question is whether inhibiting the type 1 interferon pathway reduce the disease activity in SLE patients. This review evaluates the safety and efficacy of the monoclonal antibody against the type 1 interferon alpha receptor, anifrolumab, in patients with SLE. AREAS COVERED: Key terms (SLE, type 1 interferon, anifrolumab) were used to query the PubMed database for phase 1, 2 and 3 clinical trials of anifrolumab for SLE patients. Phase 1 studies showed anifrolumab has non-linear pharmacokinetics and the optimal safe dose is 300 mg given intravenously every four weeks. The MUSE (phase 2) and the TULIP-2 (phase 3) trials showed that anifrolumab when added to standard therapy significantly reduced disease activity in SLE patients. Common adverse events associated with anifrolumab were upper respiratory and urinary infections as well as shingles. EXPERT OPINION: Anifrolumab is an exciting new therapeutic for SLE patients. Additional analyses of the combined TULIP-1 and TULIP-2 datasets as well as future studies with anifrolumab will generate yet more data in SLE. No doubt anifrolumab will be studied in other diseases where type I interferons play an important role.


Assuntos
Interferon Tipo I , Lúpus Eritematoso Sistêmico , Adulto , Humanos , Receptor de Interferon alfa e beta , Alprostadil/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico
14.
Sci Rep ; 12(1): 15363, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100635

RESUMO

As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE1) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE1 is very common. This study aimed to investigate the use of Lipo-PGE1 and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE1 in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE1, judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE1. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE1 use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE1 were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE1. However, there still remains a number of inappropriate uses of Lipo-PGE1. To further improve the rational use of Lipo-PGE1, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.


Assuntos
Alprostadil , Uso Off-Label , Alprostadil/uso terapêutico , China , Humanos , Microesferas , Farmacêuticos
15.
Biol Trace Elem Res ; 200(11): 4807-4816, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35508889

RESUMO

Obesity is a chronic disease associated with increased morbidity and mortality. The rapidly increasing prevalence of obesity makes it a global health problem, while treatment options remain limited. Given the potential of boron in the treatment of obesity, the aim of this study is to investigate the anti-adipogenic activity of the newly synthesised boron glycine monoester compound (BGM) using 3T3-L1 adipocytes by analysing lipid accumulation, CTRP3 and PPARy gene expression, oxidative stress and apoptotic effects. 3T3-L1 fibroblast cells (ATCC® CL-173) were transformed into adipocyte cells in vitro. Fat accumulation in the 3T3-L1 adipocyte cells was detected by Oil Red O staining. Gene expression levels were determined with qPCR. Biochemical analyzes were performed using spectrophotometric method (CAT, ALP and ACP) and ELISA kit (TAS, TOS, NADP-IDH). Apoptosis studies were performed on the muse cell nalyser using the Muse Annexin V & Dead Cell Assay Kit. When BGM-treated cells were compared to control adipocyte cells, lipid accumulation decreased in a dose-dependent manner. BGM-treated adipocyte cells had higher CTRP3 expression levels and lower PPAR-γ gene expression levels compared to control adipocyte cells (p < 0.001). While BGM application increased the TAS level, it showed an antioxidant effect by regulating the activity of oxidative metabolism enzymes (p < 0.001). BGM application increased total apoptosis by 1.5-fold. These results show that BGM is a potential therapeutic agent for obesity by regulating the expression of genes related to adipogenesis and lipogenesis in adipocyte cells and by affecting the activity of enzymes of oxidative metabolism and apoptosis.


Assuntos
Boro , PPAR gama , Células 3T3-L1 , Adipócitos , Adipogenia , Alprostadil/metabolismo , Alprostadil/farmacologia , Alprostadil/uso terapêutico , Animais , Anexina A5/metabolismo , Anexina A5/farmacologia , Anexina A5/uso terapêutico , Antioxidantes/metabolismo , Apoptose , Boro/farmacologia , Diferenciação Celular , Glicina/farmacologia , Lipogênese , Camundongos , NADP/metabolismo , NADP/farmacologia , NADP/uso terapêutico , Obesidade/metabolismo , Estresse Oxidativo , PPAR gama/genética , PPAR gama/metabolismo
16.
Ann Rheum Dis ; 81(7): 962-969, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35580976

RESUMO

OBJECTIVES: In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results. METHODS: TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient. RESULTS: Most patients (78%-85%) had concordant BICLA and SRI(4) outcomes (Cohen's Kappa 0.6-0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p≤0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients. CONCLUSIONS: Across trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials. TRIAL REGISTRATION NUMBERS: NCT02446912 and NCT02446899.


Assuntos
Glucocorticoides , Lúpus Eritematoso Sistêmico , Alprostadil/uso terapêutico , Anticorpos Monoclonais Humanizados , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Am J Respir Crit Care Med ; 206(2): 170-177, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426776

RESUMO

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Adulto , Alprostadil/uso terapêutico , Método Duplo-Cego , Hemorragia , Heparina/uso terapêutico , Humanos , Projetos Piloto
18.
Artigo em Inglês | MEDLINE | ID: mdl-35270724

RESUMO

Self-efficacy (SE) has been shown to be positively correlated with quality of life (QOL) among patients with type 2 diabetes mellitus (T2DM). Medication understanding (MU) on the other hand, leads to good adherence that indirectly improves QOL. Measuring self-efficacy in medication understanding is useful to ascertain patient's confidence in medication adherence. However, there is a lack of studies on the relationship between self-efficacy in medication understanding with QOL. This study aimed to determine the relationship between self-efficacy in medication understanding and QOL, and the factors associated with QOL in elderly with T2DM on polypharmacy. A cross-sectional study was conducted on these populations at primary care specialist clinic. Malay version of MU in SE questionnaire (MUSE) was used. Higher scores showed a better understanding. A revised Version Diabetic Quality of Life-13 (RVDQOL-13) questionnaire was used with lower scores indicating higher QOL. A total of 321 patients participated, with the majority being male (58.3%), Malay (84.7%), a predominant age group of 60−69 (75.7%) with mean age (±SD) of 66.7 (±0.286) years old. The median (IQR) of MUSE was high­30 (4)­while the RVDQOL-13 was low­19 (8)­which demonstrated high QOL. Inverse correlation was found between MUSE and QOL (r −0.14, p < 0.01). Multiple linear regression analysis demonstrated that MUSE score (ß −0.282; 95% CI: (−5.438, −2.581); p < 0.001), low-income group (ß −0.144; 95% CI: (−3.118, −0.534); p = 0.006) and duration of medications ≥240 days (ß −0.282; 95% CI: (−5.438, −2.581); p < 0.001) were associated with better QOL, while medications ≥10 (ß 0.109; 95% CI: 0.214, 4.462; p = 0.031) and those with pills and insulin (ß 0.193; 95% CI: 1.206, 3.747; p < 0.001) were associated with poor QOL. In conclusion, higher MUSE is associated with better QOL. Findings suggest emphasizing self-efficacy in medication understanding in the management of elderly with T2DM on polypharmacy to improve QOL.


Assuntos
Diabetes Mellitus Tipo 2 , Qualidade de Vida , Idoso , Alprostadil/uso terapêutico , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Polimedicação , Autoeficácia
19.
Cell Mol Biol (Noisy-le-grand) ; 68(8): 123-128, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36800822

RESUMO

The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic hemorrhagic shock (HS). 80 patients with traumatic HS treated in Feicheng Hospital Affiliated to Shandong First Medical University and Tai'an City Central Hospital from January 2018 to January 2022 were enrolled and divided into observation group (n=40) and control group (n=40) according to the randomized control method.  Patients in the control group were given alprostadil alone (5 g alprostadil + 10 mL normal saline) in addition to conventional treatment, while those in the observation group received edaravone (30 mg edaravone + 250 mL normal saline) on the basis of treatment in the control group. The patients in both groups were treated via intravenous infusion once a day for 5 days. 24 hours (h) after resuscitation, venous blood were collected to detect serum biochemical indicators such as blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine serum inflammatory factors. Lung lavage fluid was collected to examine pulmonaryfunction indicators such as myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) activity and to observe the oxygenation index (OI). Blood pressure was measured at admission and 24 h after surgery. The observation group had significantly lowered serum BUN, AST and ALT (p<0.05), the content of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as well as oxidative stress indexes like superoxide dismutase (SOD) and malondialdehyde (MDA) (p<0.05) and pulmonary function indicators (p<0.05) but overtly increased content of SOD and OI. Furthermore, the blood pressure in the observation group dropped to 30 mmHg at admission and rose to the normal range. Alprostadil combined with edaravone effectively reduces inflammatory factors and improves oxidative stress and pulmonary function in patients with traumatic HS, whose efficacy is significantly better than that of alprostadil alone.


Assuntos
Choque Hemorrágico , Humanos , Choque Hemorrágico/tratamento farmacológico , Edaravone/uso terapêutico , Edaravone/farmacologia , Alprostadil/uso terapêutico , Alprostadil/farmacologia , Solução Salina/farmacologia , Hemorragia , Inflamação/tratamento farmacológico , Superóxido Dismutase , Estresse Oxidativo
20.
Sex Med Rev ; 10(4): 764-781, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37051966

RESUMO

INTRODUCTION: Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem. OBJECTIVES: Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications. METHODS: This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using the extensive literature search to identify the latest scientific reports on the topic. RESULTS: In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment. CONCLUSION: Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases.


Assuntos
Disfunção Erétil , Masculino , Humanos , Disfunção Erétil/etiologia , Alprostadil/uso terapêutico , Prostaglandinas/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Inibidores da Fosfodiesterase 5/efeitos adversos
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