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2.
Drug Deliv ; 28(1): 325-342, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33517789

RESUMO

The aim of the present study was to investigate the pharmacological mechanism of matrine in treatment of COVID-19 combined with liver injury. Potential targets related to matrine, COVID-19 and liver injury were identified from several databases. We constructed PPI network and screened the core targets according to the degree value. Then, GO and KEGG enrichment were carried out. Molecular docking technology was used to verify the affinity between matrine and the crystal structure of core target protein. Finally, real-time RT-PCR was used to detect the effects of matrine on hub gene expression in liver tissue of liver injury mice and lung tissue of lung injury mice to further confirm the results of network pharmacological analysis. The results show that six core targets including AKT1, TP53, TNF, IL6, BCL2L1 and ATM were identified. The potential therapeutic mechanism of matrine on COVID-19 combined with liver injury is closely related to regulate antiviral process, improve immune system and regulate the level of inflammatory factors. Molecular docking showed that matrine could spontaneously bind to the receptor protein and had strong binding force. Real-time RT-PCR demonstrated that matrine could significantly reduce the expression of AKT1, TP53, TNF, IL6 and ATM in mice with liver injury or lung injury (P < 0.05), and increase the expression of BCL2L1 to a certain extent (P > 0.05). Our results indicate that matrine can achieve simultaneous intervention of COVID-19 combined with liver injury by multi-dimensional pharmacological mechanism.


Assuntos
Alcaloides/farmacologia , /epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Simulação de Acoplamento Molecular/métodos , Quinolizinas/farmacologia , Alcaloides/administração & dosagem , Animais , Antivirais/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinolizinas/administração & dosagem , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos
3.
Medicine (Baltimore) ; 100(3): e23805, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545944

RESUMO

BACKGROUND: Tenecteplase is a modified recombinant tissue-plasminogen activator, which is effective and safe in the treatment of acute ischemic stroke. However, the therapeutic dose of tenecteplase has been controversial. The purpose of this study is to systematically investigate the efficacy and safety of different doses of tenecteplase thrombolytic therapy for acute ischemic stroke. METHODS: Computer retrieval of English databases (PubMed, EMBASE, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wanfang, Viper, and Chinese Biomedical Database) is conducted for a randomized controlled clinical study on thrombolytic treatment of acute ischemic stroke with different doses of tenecteplase from the establishment of the database to October 2020. Two researchers independently conduct data extraction and literature quality evaluation on the quality of the included studies, and meta-analysis is conducted on the included literatures using RevMan5.3 software. OUTCOME: In this study, National Institute of Health Stroke Scale (NIHSS) score, Modified Rankin Scale (mRS) score scale, symptomatic intracranial hemorrhage (SICH) incidence, All-cause mortality, and so on are used to evaluate the efficacy and safety of tenecteplase thrombolytic therapy in acute ischemic stroke with different doses. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of different doses of tenecteplase in thrombolytic therapy for acute ischemic stroke. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/2MPCW.


Assuntos
Fibrinolíticos/uso terapêutico , Tenecteplase/uso terapêutico , Fibrinolíticos/administração & dosagem , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Tenecteplase/administração & dosagem
4.
Medicine (Baltimore) ; 100(3): e23847, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545951

RESUMO

BACKGROUND: Sudden hearing loss (SHL) is a disease, at the same time a symptom, which needs to be treated in a timely manner and counts as an emergency health problem in the Department of Otolaryngology. There are many types of sudden hearing loss and among them, the occurrence of all-frequency descending sudden hearing loss and high frequency sudden hearing loss are high. The conventional treatment for these 2 types of sudden hearing loss sometimes is not as effective as expected. Postauricular injection of glucocorticoids could be the most effective treatment method. However, the effectiveness and safety of postauricular injection of glucocorticoid needs to be assessed systematically. METHODS: The protocol for the meta-analysis was conducted under the guidance of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The aim is to undertake a systematic review and meta-analysis on the effectiveness and safety of postauricular injection of glucocorticoid to treat patient diagnosed with all-frequency and high frequency descending sudden hearing loss. We searched through the following databases: English databases (PubMed, EMBASE, Web of Science) and Chinese databases (CNKI, Wanfang databases, CBM, VIP). The final selected articles will be evaluated using Cochrane RCT evaluation criteria. Revman 5.0 will be used for data analysis. Subgroup analysis, sensitivity analysis, and meta regression will detect sources of heterogeneity. Ethics approval was not required for this protocol. The findings will be disseminated through journal articles or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/5Q9NA. RESULTS: Objectively, evaluate the efficacy and safety of postauricular injection of glucocorticoid in treating all-frequency descending sudden hearing loss and high frequency sudden hearing loss. CONCLUSION: To provide evidence-based medicine for glucocorticoid treatment methods in patients with all-frequency descending sudden hearing loss and high frequency descending hearing loss.


Assuntos
Glucocorticoides/uso terapêutico , Perda Auditiva Súbita/tratamento farmacológico , Pavilhão Auricular , Glucocorticoides/administração & dosagem , Humanos , Injeções , Metanálise como Assunto , Ondas de Rádio , Revisões Sistemáticas como Assunto , Resultado do Tratamento
5.
Medicine (Baltimore) ; 100(3): e23887, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545956

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional bowel disorder. The global incidence of IBS is as high as 9% to 23%, accounting for about 50% of outpatients in gastroenterology, and the new case detection rate is 0.2% every year. IBS has become a global gastrointestinal functional disease. Although IBS is not a life-threatening disease, it seriously affects the quality of life of patients, causing huge economic and mental burden to individuals, society and families. Lipi Guben decoction (LPGBD) is an important auxiliary treatment for IBS, but lack of robust Evidence-based medicine evidence proving its efficacy. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of LPGBD in the treatment of IBS. METHODS: In this randomized controlled trial, a total of 100 eligible patients will be allocated to the blank control group or LPGBD group in a ratio of 1:1. The treatment period was 12 weeks. The primary outcome measure will be the total clinical effective rate. The Secondary outcomes will include IBS clinical symptom scores, IBS-Severity Scoring System, IBS-Quality of life, Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Bristol Stool Form Scale. The safety outcome will include Echocardiogram, blood examination (including blood routine test, liver function test, and renal function test), urine routine test and stool routine test. The evaluation indicators and all safety results will be performed at baseline, week 4, week 8 and week 12. RESULTS: This study will be helpful to evaluate the efficacy and safety of LPGBD in the treatment of IBS. CONCLUSION: LPGBD may improve the clinical efficacy of patients with IBS, which has important value in practical application. TRIAL REGISTRATION: Chictr20000039617, registration time: November 3, 2020.


Assuntos
Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Adolescente , Adulto , Idoso , Diarreia/patologia , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Fármacos Gastrointestinais/administração & dosagem , Humanos , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
6.
Medicine (Baltimore) ; 100(3): e23895, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545958

RESUMO

BACKGROUND: Several previous trials have attempted to compare the efficacy of femoral nerve block (FNB) and local infiltrative analgesia (LIA) for patients received anterior cruciate ligament (ACL) reconstruction, but reached inconsistent conclusions. The primary purpose of this present research was to compare the FNB and LIA in the reconstruction of ACL. METHODS: This investigation was conducted and then reported on the basis of Strengthening the Reporting of Observational studies in the Epidemiology checklist. From our registry database, we retrospectively determined 688 patients who received the primary reconstruction of ACL from 2016 to 2019 at our academic institutions. This current retrospective cohort study was approved through the institutional review committee at our hospital. Inclusion criteria contained the primary or autograft bone-patellar tendine-bone reconstruction of ACL in the patients over 16 years of age. Patients in the LIA group underwent intraoperative infiltration at the harvested site after tendon harvest, with use of 2 mg/mL of ropivacaine 20 mL and 5 mg/mL of epinephrine, respectively. After the reconstruction of ACL, 5 Lg/mL of epinephrine, and 20 mL of ropivacaine (2 mg/mL) were injected at the site of surgical trauma. The patient in FNB group was given 40 mL of ropivacaine (2 mg/mL), and the ropivacaine was injected into femoral nerve sheath at femoral triangle level. The primary outcome was the consumption of morphine 24 h after the operation. And the secondary results involved the complications, functional results, and the scores of pain. RESULTS: It is assumed that the efficacy of LIA in the early postoperative pain is no less than that of FNB. For our study, the major limitation is the lack of randomization. Nevertheless, these data were prospectively harvested, with high response rate of patient. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6277).


Assuntos
Analgésicos/uso terapêutico , Reconstrução do Ligamento Cruzado Anterior , Bloqueio Nervoso , Dor Pós-Operatória/prevenção & controle , Analgésicos/administração & dosagem , Nervo Femoral , Humanos , Medição da Dor , Estudos Retrospectivos , Resultado do Tratamento
7.
J Healthc Eng ; 2021: 8864522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552457

RESUMO

Objectives: The outbreak of coronavirus disease 2019 (COVID-19) was first reported in December 2019. Until now, many drugs and methods have been used in the treatment of the disease. However, no effective treatment option has been found and only case-based successes have been achieved so far. This study aims to evaluate COVID-19 treatment options using multicriteria decision-making (MCDM) techniques. Methods: In this study, we evaluated the available COVID-19 treatment options by MCDM techniques, namely, fuzzy PROMETHEE and VIKOR. These techniques are based on the evaluation and comparison of complex and multiple criteria to evaluate the most appropriate alternative. We evaluated current treatment options including favipiravir (FPV), lopinavir/ritonavir, hydroxychloroquine, interleukin-1 blocker, intravenous immunoglobulin (IVIG), and plasma exchange. The criteria used for the analysis include side effects, method of administration of the drug, cost, turnover of plasma, level of fever, age, pregnancy, and kidney function. Results: The results showed that plasma exchange was the most preferred alternative, followed by FPV and IVIG, while hydroxychloroquine was the least favorable one. New alternatives could be considered once they are available, and weights could be assigned based on the opinions of the decision-makers (physicians/clinicians). The treatment methods that we evaluated with MCDM methods will be beneficial for both healthcare users and to rapidly end the global pandemic. The proposed method is applicable for analyzing the alternatives to the selection problem with quantitative and qualitative data. In addition, it allows the decision-maker to define the problem simply under uncertainty. Conclusions: Fuzzy PROMETHEE and VIKOR techniques are applied in aiding decision-makers in choosing the right treatment technique for the management of COVID-19.


Assuntos
/tratamento farmacológico , Tomada de Decisão Clínica/métodos , Técnicas de Apoio para a Decisão , Lógica Fuzzy , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Humanos , Pandemias
8.
FASEB J ; 35(3): e21419, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33566370

RESUMO

In the early phase of the Coronavirus disease 2019 (COVID-19) pandemic, it was postulated that the renin-angiotensin-system inhibitors (RASi) increase the infection risk. This was primarily based on numerous reports, which stated that the RASi could increase the organ Angiotensin-converting enzyme 2 (ACE2), the receptor of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in rodents. RASi can theoretically antagonize the potential influence of angiotensin II (Ang II) on ACE2. However, while Ang II decreases the ACE2 levels in cultured cells, there is little evidence that supports this phenomenon in living animals. In this study, we tested whether Ang II or Ang II combined with its antagonist would alter the ACE2 and other molecules associated with the infection of SARS-CoV-2. Male C57BL6/J mice were administered vehicle, Ang II (400 ng/kg/min), or Ang II with losartan (10 mg/kg/min) for 2 weeks. ACE2 knockout mice were used as a negative control for the ACE2 assay. We found that both Ang II, which elevated blood pressure by 30 mm Hg, and Ang II with losartan, had no effect on the expression or protein activity of ACE2 in the lung, left ventricle, kidney, and ileum. Likewise, these interventions had no effect on the expression of Transmembrane Protease Serine 2 (TMPRSS2) and Furin, proteases that facilitate the virus-cell fusion, and the expression or activity of Tumor Necrosis Factor α-Convertase (TACE) that cleaves cell-surface ACE2. Collectively, physiological concentrations of Ang II do not modulate the molecules associated with SARS-CoV-2 infection. These results support the recent observational studies suggesting that the use of RASi is not a risk factor for COVID-19.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Angiotensina II/farmacologia , /metabolismo , Losartan/farmacologia , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Animais , Furina/genética , Furina/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Losartan/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Vasoconstritores/farmacologia
9.
Trials ; 22(1): 111, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522946

RESUMO

OBJECTIVES: To evaluate whether a single high dose of oral cholecalciferol improves the respiratory outcomes as compared with placebo among adults COVID-19 patients at moderate risk of clinical complications. TRIAL DESIGN: The CARED trial is an investigator-initiated, multicentre, randomized, parallel, two-arm, sequential, double-blind and placebo-controlled clinical trial. It was planned as a pragmatic trial since the inclusion criteria are broad and the study procedures are as simple as possible, in order to be implemented in the routine clinical practice in general wards in the pandemic setting and a middle-income country context. The sequential design involves two stages. The first stage will assess the effects of vitamin D supplementation on blood oxygenation (physiological effects). The second stage will assess the effects on clinical outcomes. PARTICIPANTS: Participants of either gender admitted to general adult wards in 21 hospital sites located in four provinces of Argentina are invited to participate in the study if they meet the following inclusion criteria and none of the exclusion criteria: Inclusion criteria SARS-CoV-2 confirmed infection by RT-PCR; Hospital admission at least 24 hours before; Expected hospitalization in the same site ≥24 hours; Oxygen saturation ≥90% (measured by pulse oximetry) breathing ambient air; Age ≥45 years or at least one of the following conditions: ○ Hypertension; ○ Diabetes; ○ At least moderate COPD or asthma; ○ Cardiovascular disease (history of myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or valve replacement surgery); ○ Body mass index ≥30; Willingness to sign informed consent (online supplementary material 1 and 2). EXCLUSION CRITERIA: Age <18 years; Women in childbearing age; >= 72 hs since current admission; Requirement for a high dose of oxygen (>5 litres/minute) or mechanical ventilation (non-invasive or invasive); History of chronic kidney disease requiring haemodialysis or chronic liver failure; Inability for oral intake. Chronic supplementation with pharmacological vitamin D; Current treatment with anticonvulsants; History of: ○ Sarcoidosis; ○ Malabsorption syndrome; ○ Known hypercalcemia or serum calcium >10.5 mg/dL; Life expectancy <6 months; Known allergy to study medication; Any condition at discretion of investigator impeding to understand the study and give informed consent. INTERVENTION AND COMPARATOR: The intervention consists in a single oral dose of 500.000 IU of commercially available cholecalciferol soft gel capsules (5 capsules of 100.000 IU) or matching placebo MAIN OUTCOMES: The primary outcome for the first stage is the change in the respiratory Sepsis-related Organ Failure Assessment (SOFAr) score between pre-treatment value and the worst value recorded during the first 7 seven days of hospitalization, the death or discharge, whichever occurs first. The SOFAr score measured as the ratio between the pulse oximetry saturation (SpO2) and FiO2 (27, 28) is used instead of the arterial partial pressure of oxygen (PaO2). SOFAr score is a 4-points scale, with higher values indicating deeper respiratory derangement as follows: 1 PaO2 <400; 2 PaO2 <300; 3 PaO2 <200; 4 PaO2 <100. The primary outcome for the second stage is the combined occurrence of requirement ≥40% of FiO2, invasive or non-invasive ventilation, up to 30 days or hospital discharge. RANDOMISATION: A computer-generated random sequence and the treatment assignment is performed through the web-based randomization module available in the electronic data capture system (Castor®). A randomization ratio 1:1, stratified and with permuted blocks was used. Stratification variables were diabetes (yes/no), age (≤60/>60 years) and the site. BLINDING (MASKING): Double-blind was achieved by using placebo soft gel capsules with the same organoleptic properties as the active medication. Central management of the medication is carried out by a pharmacist in charge of packaging the study drug in unblinded fashion, who have no contact with on-site investigators. Medication is packaged in opaque white bottles, each containing five soft gel capsules of the active drug or matching placebo, corresponding to complete individual treatment. Treatment codes are kept under the pharmacist responsibility, and all researchers are unaware of them. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The first stage is planned to include 200 patients (100 per group), the second stage is planned to include 1064 additional patients. The total sample size is 1264 patients. TRIAL STATUS: Currently the protocol version is the number 1.4 (from October 13th, 2020). The recruitment is ongoing since August 11th, 2020, and the first subject was enrolled on August 14th. Since then, 21 sites located in four provinces of Argentina were initiated, and 167 patients were recruited by January 11th, 2021. We anticipate to finish the recruitment for the first stage in mid-February, 2021, and in August, 2021 for the second stage. TRIAL REGISTRATION: The study protocol is registered in ClinicalTrials.gov (identifier number NCT04411446 ) on June 2, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
/dietoterapia , Colecalciferol/administração & dosagem , Pandemias , Vitaminas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , /virologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Admissão do Paciente , Ensaios Clínicos Pragmáticos como Assunto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento
10.
Trials ; 22(1): 109, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522951

RESUMO

OBJECTIVES: To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. TRIAL DESIGN: A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. PARTICIPANTS: Setting: Primary Care of São Carlos - São Paulo - Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. INTERVENTION AND COMPARATOR: Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. MAIN OUTCOMES: The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. RANDOMISATION: The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool ( http://www.random.org/lists ). BLINDING (MASKING): The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). TRIAL STATUS: Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. TRIAL REGISTRATION: COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm ) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
/terapia , Homeopatia/métodos , Materia Medica/administração & dosagem , Atenção Primária à Saúde/métodos , Cloreto de Sódio na Dieta/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , /virologia , Método Duplo-Cego , Feminino , Seguimentos , Homeopatia/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Adulto Jovem
11.
Nat Commun ; 12(1): 836, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547321

RESUMO

Dynamic regulation of intestinal cell differentiation is crucial for both homeostasis and the response to injury or inflammation. Sprouty2, an intracellular signaling regulator, controls pathways including PI3K and MAPKs that are implicated in differentiation and are dysregulated in inflammatory bowel disease. Here, we ask whether Sprouty2 controls secretory cell differentiation and the response to colitis. We report that colonic epithelial Sprouty2 deletion leads to expanded tuft and goblet cell populations. Sprouty2 loss induces PI3K/Akt signaling, leading to GSK3ß inhibition and epithelial interleukin (IL)-33 expression. In vivo, this results in increased stromal IL-13+ cells. IL-13 in turn induces tuft and goblet cell expansion in vitro and in vivo. Sprouty2 is downregulated by acute inflammation; this appears to be a protective response, as VillinCre;Sprouty2F/F mice are resistant to DSS colitis. In contrast, Sprouty2 is elevated in chronic colitis and in colons of inflammatory bowel disease patients, suggesting that this protective epithelial-stromal signaling mechanism is lost in disease.


Assuntos
Colite/genética , Glicogênio Sintase Quinase 3 beta/genética , Homeostase/genética , Interleucina-33/genética , Proteínas de Membrana/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Criança , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Feminino , Regulação da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Células HT29 , Homeostase/efeitos dos fármacos , Humanos , Interleucina-33/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Dodecilsulfato de Sódio/administração & dosagem
12.
Cardiovasc Ther ; 2021: 2680107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552234

RESUMO

Background: The probable impact of growth hormone (GH) as a heart failure (HF) treatment strategy is still less investigated. Therefore, we aimed to evaluate the relation of 3-month GH prescription on left ventricular ejection fraction (LVEF), interventricular septum (IVS), posterior left ventricle (LV) thickness, end systolic and end diastolic diameters (ESD and EDD), and pulmonary arterial pressure (PAP) among Iranian individuals suffering from HF due to MI attack. Methods: A total of 16 clinically stable participants with HF diagnosis and LVEF < 40% were selected for enrollment in this pilot randomized double-blinded study. They were randomly assigned equally to groups received 5 IU subcutaneous GH or placebo. Injections were done every other day for a total of 3-month duration. After termination of intervention and nine months afterwards, cardiac outcomes were assessed. Results: Baseline and 12-month posttrial participants' characteristics were similar. LVEF was increased significantly by three months started from baseline in individuals receiving GH (32 ± 3.80% to 43.80 ± 4.60%, P = 0.002). During the next 9 months of follow-up concurrent with cessation of injections, LVEF was declined (43.80 ± 4.60% to 32.20 ± 6.97%, P = 0.008). LVEF and ESD were remarkably higher and lower in GH group compared with controls by the end date of injections (43.80 ± 4.60% vs. 33.14 ± 4.84%, P = 0.02 and 39.43 ± 3.45 mm vs. 33 ± 3.16 mm, P = 0.03, respectively). No other considerable association was found in terms of other predefined variables in neither GH nor placebo groups. Conclusions: GH administration in HF patients was associated with increased LVEF function. Several randomized clinical trials are necessary proving this relation. This trial is registered with IRCT201704083035N1.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Infarto do Miocárdio/complicações , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Injeções Subcutâneas , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Projetos Piloto , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
13.
J Hand Surg Asian Pac Vol ; 26(1): 84-91, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33559584

RESUMO

Background: With the emergence of the COVID-19 pandemic, most health-care personnel and resources are redirected to prioritize care for seriously-ill COVID patients. This situation may poorly impact our capacity to care for critically injured patients. We need to devise a strategy to provide rational and essential care to hand trauma victims whilst the access to theatres and anaesthetic support is limited. Our center is a level 1 trauma center, where the pandemic preparedness required reorganization of the trauma services. We aim to summarise the clinical profile and management of these patients and highlight, how we modified our practice to optimize their care. Methods: This is a single-centre retrospective observational study of all patients with hand injuries visiting the Department of Plastic Surgery from 22nd March to 31st May 2020. Patient characteristics, management details, and outcomes were analysed. Results: A total of 102 hand injuries were encountered. Five patients were COVID-19 positive. The mean age was 28.9 ± 14.8 years and eighty-two (80.4%) were males. Thirty-one injuries involved fractures/dislocations, of which 23 (74.2%) were managed non-operatively. Seventy-five (73.5%) patients underwent wound wash or procedure under local anaesthetic and were discharged as soon as they were comfortable. Seventeen cases performed under brachial-plexus block, were discharged within 24 hours except four cases of finger replantation/ revascularisation and one flap cover which were discharged after monitoring for four days. At mean follow-up of 54.4 ± 21.8 days, the rates of early complication and loss to follow-up were 6.9% and 12.7% respectively. Conclusions: Essential trauma care needs to continue keeping in mind, rational use of resources while ensuring safety of the patients and health-care professionals. We need to be flexible and dynamic in our approach, by utilising teleconsultation, non-operative management, and regional anaesthesia wherever feasible.


Assuntos
/epidemiologia , Traumatismos da Mão/epidemiologia , Traumatismos da Mão/terapia , Adolescente , Adulto , Anestesia Geral/estatística & dados numéricos , Anestésicos Locais/administração & dosagem , Bloqueio do Plexo Braquial/estatística & dados numéricos , Feminino , Acesso aos Serviços de Saúde , Humanos , Índia/epidemiologia , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Pandemias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Centros de Traumatologia , Adulto Jovem
14.
Pan Afr Med J ; 38: 9, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520078

RESUMO

In this paper, we report two cases of induced thrombocytopenia after the infusion of glycoprotein (GP) IIb/IIIa receptors antagonists, following a coronary angioplasty. The first patient is a 65-year-old woman, admitted with acute coronary syndrome requiring percutaneous angioplasty with stenting. The patient was given tirofiban + unfractionated heparin (UFH). Ten hours later, the patient revealed very severe thrombocytopenia and went into hemorrhagic shock (hematemesis and hematoma at the injection site). The patient was transfused with nine units of red blood cells (RBCs), 24 platelets pellets and 4 units of fresh frozen plasma (FFP). The second patient is a 76-year-old woman. She was admitted to hospital for acute coronary syndrome necessitating percutaneous angioplasty with stenting and a glycoprotein IIb/IIIa receptor antagonists, tirofiban + unfractionated (UFH). Four hours later, the patient presented with gingivorrhagia associated thrombocytopenia. She received six platelet pellets transfusion with well clinical and biological improvement. These two observations raise the significance of a close monitoring of platelet count after the initiation of GP IIb/IIIa antagonists infusion, which are sometimes responsible for life-threatening adverse events.


Assuntos
Inibidores da Agregação de Plaquetas/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Tirofibana/efeitos adversos , Idoso , Angioplastia Coronária com Balão , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Plasma , Inibidores da Agregação de Plaquetas/administração & dosagem , Transfusão de Plaquetas , Trombocitopenia/terapia , Tirofibana/administração & dosagem
15.
Medicine (Baltimore) ; 100(4): e23753, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530174

RESUMO

ABSTRACT: To evaluate the utility of low-concentration nitrous oxide (N2O) anesthesia in ptosis surgeryThis study was a retrospective consecutive case series that included 54 successive patients with blepharoptosis who underwent bilateral levator aponeurosis advancement and on whom skin resection performed by the same surgeon between August 2016 and July 2017. Among these patients, 27 were operated with a local anesthesia injection (air group) and 27 with a local anesthesia injection and low-concentration N2O anesthesia (N2O group). All N2O cases used a total of 6 L of gas comprising 70% oxygen and 30% N2O. Preoperative and postoperative blood pressure (BP) and heart rate (HR) and intraoperative pain, anxiety, nausea, and memory were measured immediately after surgery using visual analog scale score (VASS). Additionally, perioperative side effects were examined.There was no significant difference in age, sex, and preoperative and postoperative margin reflex distance (MRD) between the 2 groups (all P > .05). The intraoperative mean peripheral oxygen saturation was significantly higher (97.5% ±â€Š1.6% vs 99.5% ±â€Š.6%, P < .001), intraoperative HR was significantly lower (78.2 ±â€Š12.8 vs 70.7 ±â€Š11.6 bpm, P = .02), and operation time was significantly shorter (33.1 ±â€Š8.1 vs 29.4 ±â€Š10.3 minutes, P = .03) in the N2O group than in the air group.Difference between intraoperative and preoperative systolic BP (BPs) (+15.8 ±â€Š18.0 vs + 3.1 ±â€Š21.7 mm Hg, P = .02), diastolic BP (BPd) (+7.0 ±â€Š17.4 vs -2.3 ±â€Š13.6 mm Hg, P = .04), and HR (3.2 ±â€Š8.5 vs -3.9 ±â€Š9.4 bpm, P = .01) was significantly lower in the N2O group than in the air group.VASS of intraoperative pain was significantly lower in the N2O group than in the air group (49.5 ±â€Š24.7 vs 22.6 ±â€Š14.9, P < .001), whereas intraoperative anxiety and memory did not present significant differences between the groups (P = .09 and P = .45, respectively). Intraoperative nausea score was 0 for all cases in both groups. There was no other side effect.Ptosis surgery with anesthesia using 30% N2O may effectively suppress intraoperative BP and HR along with pain and shorten the operation time without side effects such as nausea.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Blefaroplastia/métodos , Blefaroptose/cirurgia , Óxido Nitroso/administração & dosagem , Óxido Nitroso/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anestésicos Locais/administração & dosagem , Ansiedade/prevenção & controle , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Período Intraoperatório , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Duração da Cirurgia , Manejo da Dor , Estudos Retrospectivos , Sinais Vitais
16.
Medicine (Baltimore) ; 100(4): e23880, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530182

RESUMO

ABSTRACT: Cervical spondylotic radiculopathy (CSR) is the most common type of cervical spondylosis, accounting for about 60% of the incidence of cervical spondylosis. Both cervical traction and traditional Chinese medicine hot compress are common and effective treatment for CSR. This study will be performed to investigate the effect of a combination of cervical traction and traditional Chinese medicine hot compress on CSR. In this non-blinded, randomized controlled trial, 100 eligible patients will be randomly divided into a treatment group (intermittent cervical traction combines with traditional Chinese medicine hot compress) and a control group (intermittent cervical traction combined with hot compresses). Before and after the intervention, the Visual Analog Scale score, Neck Disability Index score, and 20-score scale of symptoms will be evaluated at baseline and at 7, 14, 21, and 28 days. During the treatment period, any signs of acute adverse events, such as paralysis of aggravated pain, nausea, dizzy, and even syncope, will be recorded at each visit. Although intermittent cervical traction and traditional Chinese medicine hot compress have been used in the treatment of CSR in China for many years, there is no consensus on its effectiveness of combination therapy. This experiment will provide convincing evidence of the efficacy of intermittent cervical traction combined with traditional Chinese medicine hot compress in the treatment of CSR.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Radiculopatia/terapia , Espondilose/terapia , Tração , Terapia Combinada , Temperatura Alta , Humanos , Pressão , Estudos Prospectivos
18.
Nat Commun ; 12(1): 776, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536425

RESUMO

The rapid expansion of the COVID-19 pandemic has made the development of a SARS-CoV-2 vaccine a global health and economic priority. Taking advantage of versatility and rapid development, three SARS-CoV-2 mRNA vaccine candidates have entered clinical trials with a two-dose immunization regimen. However, the waning antibody response in convalescent patients after SARS-CoV-2 infection and the emergence of human re-infection have raised widespread concerns about a possible short duration of SARS-CoV-2 vaccine protection. Here, we developed a nucleoside-modified mRNA vaccine in lipid-encapsulated form that encoded the SARS-CoV-2 RBD, termed as mRNA-RBD. A single immunization of mRNA-RBD elicited both robust neutralizing antibody and cellular responses, and conferred a near-complete protection against wild SARS-CoV-2 infection in the lungs of hACE2 transgenic mice. Noticeably, the high levels of neutralizing antibodies in BALB/c mice induced by mRNA-RBD vaccination were maintained for at least 6.5 months and conferred a long-term notable protection for hACE2 transgenic mice against SARS-CoV-2 infection in a sera transfer study. These data demonstrated that a single dose of mRNA-RBD provided long-term protection against SARS-CoV-2 challenge.


Assuntos
/imunologia , /imunologia , /genética , /imunologia , /genética , Animais , Anticorpos Neutralizantes/imunologia , /genética , Linhagem Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pandemias/prevenção & controle , RNA Mensageiro/genética , RNA Mensageiro/imunologia , RNA Viral/genética , RNA Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/imunologia
19.
Mo Med ; 118(1): 68-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33551489

RESUMO

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.


Assuntos
/complicações , Síndrome da Liberação de Citocina/etiologia , Coagulação Intravascular Disseminada/etiologia , Doenças do Sistema Imunitário/etiologia , Deficiência de Magnésio/complicações , Deficiência de Vitamina D/complicações , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , /tratamento farmacológico , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Magnésio/administração & dosagem , Magnésio/farmacologia , Magnésio/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , /genética , Vitamina D/administração & dosagem , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitaminas/administração & dosagem , Vitaminas/farmacologia , Vitaminas/uso terapêutico
20.
Int J Nanomedicine ; 16: 609-621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531804

RESUMO

Objective: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection. Methods: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles' features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear's fluid at different time intervals after ocular application in albino rabbits. Results: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02±2.35%, particle size of 287.25±9.55 nm, polydispersity index of 0.46±0.01 and zeta potential of 36.15±1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes. Conclusion: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.


Assuntos
Sistemas de Liberação de Medicamentos , Olho/efeitos dos fármacos , Imidazóis/administração & dosagem , Terpenos/farmacologia , Administração Cutânea , Animais , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Masculino , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Coelhos , Suspensões
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