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1.
J Ethnopharmacol ; 300: 115727, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36116611

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cousinia thomsonii is traditionally known for treating various diseases including joint pain, swelling, body ache, asthma, dermatitis, cough and arthritis. AIM OF THE STUDY: This study employs lipopolysaccharide induced inflammatory wistar-rat model to evaluate efficacy of Cousinia thomsonii active-extracts on the expression of crucial inflammatory markers viz. iNOS, PPAR-γ, Rel-A, COX-2 and serum analysis of CRP. MATERIALS AND METHODS: Methanol and aqueous extracts were administered orally at 25, 50, 100 mg/kg doses for 21 days. Serum was collected on 22nd day and rats were sacrificed to extract paw tissues. Dexamethasone (0.5 mg/kg) served as positive control. Immunoblotting and qPCR was used for expression analysis of iNOS, PPAR-γ, Rel-A, COX-2 respectively. ELISA was employed for evaluating CRP levels. Discovery-studio and Auto-Dock-Vina were used to check docking interactions of various identified compounds. RESULTS: Both extracts caused dose-dependent decline in iNOS, Rel-A, COX-2 and CRP levels, while there was a dose-dependent increase in PPAR-γ expression. Methanol extract dominated immunomodulatory potential as compared with the aqueous extract. The results of the GCMS revealed the presence of ten compounds. Some of these compounds include 1-Octacosanol, Ethyl Linoleate, 1-Heptacosanol, 1-Hexadecanol, 1-Dodecanol and Behenic alcohol having strong anti-inflammatory, antimicrobial, anti-acne and anti-viral activities. Molecular Docking scores were calculated between each target protein and selected compounds. The best affinity/interactions were observed between 1-Octacosanol towards iNOS, PPAR-γ, Rel-A, COX-2 and CRP with binding energy of -10.4, -11.1, -8.6, -9.9 and -7.9 (kcal/mol) respectively. These compounds may act as strong inhibitors for iNOS, Rel-A, COX-2 and CRP or as agonists for PPAR-γ; thereby inducing anti-inflammatory/immuno-modulatory activities. CONCLUSIONS: The results indicate that Cousinia thomsonii contains therapeutically active compounds and thus could serve as potential therapeutic regimen against diverse inflammatory diseases.


Assuntos
Anti-Infecciosos , Asteraceae , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Dexametasona , Dodecanol , Álcoois Graxos , Lipopolissacarídeos , Metanol , Simulação de Acoplamento Molecular , Receptores Ativados por Proliferador de Peroxissomo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos
2.
J Ethnopharmacol ; 301: 115785, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36223847

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Viridiflorol was identified and isolated from the essential oil of Allophylus edulis leaves (EOAE). A. edulis was used as "tereré", which is a drink made by the infusion of herbs in cold water, to treat pain (toothache and headache). All anti-nociceptive (analgesic) and anti-arthritic properties of EOAE and viridiflorol have not been completely scientifically clarified. AIM OF THE STUDY: The aim of the present study was to investigate the analgesic (anti-hyperalgesic and anti-nociceptive) and anti-arthritic properties of EOAE and viridiflorol using in vivo models. MATERIALS AND METHODS: The oral administration (p.o.) of EOAE (30, 100 and 300 mg/kg), viridiflorol (30, 100 and 200 mg/kg), morphine (1 mg/kg, subcutaneous route (s.c.)) and the intraplantar (local) administration (i.pl.) of viridiflorol (100 µg/paw) were tested using formalin model in Swiss mice. EOAE (100 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, s.c.) were tested by zymosan-articular inflammation and in open-field models. Viridiflorol (0.3, 20 and 200 µg/paw) was also tested in carrageenan model, and viridiflorol (200 µg/paw) was also tested in tumor necrosis factor-α (TNF-α), and dopamine (DOPA) models. RESULTS: The oral administration of EOAE (100 and 300 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), morphine (1 mg/kg, s.c.) (MOR) and local administration of viridiflorol (100 µg/paw) significantly inhibited edema and nociception in formalin model. Oral treatments with EOAE and viridiflorol (200 mg/kg) did not cause motor impairment in the open field test since they did not reduce locomotor activity. EOAE, viridiflorol and dexamethasone significantly reduced mechanical hyperalgesia, edema, total leukocytes, polymorphonuclear cells, nitric oxide and protein exudation in the zymosan-induced articular inflammation model. The local administration of viridiflorol (200 µg/paw, i.pl.) significantly inhibited mechanical hyperalgesia and edema induced by carrageenan, TNF-α and DOPA. CONCLUSIONS: This study confirms the potential anti-arthritic, anti-nocicepttive and anti-hyperalgesic properties of EOAE and viridiflorol. These properties could explain, at least in part, the folk use of A. edulis against including pain (toothache and headache). Viridiflorol could be partially responsible for the EOAE anti-hyperalgesic, anti-nociceptive and anti-arthritic properties and its mechanism of action could involve the inhibition of TNF-α and DOPA pathways.


Assuntos
Óleos Voláteis , Animais , Camundongos , Analgésicos , Anti-Inflamatórios , Carragenina , Dexametasona/uso terapêutico , Di-Hidroxifenilalanina , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Formaldeído , Cefaleia/tratamento farmacológico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Derivados da Morfina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Odontalgia/tratamento farmacológico , Fator de Necrose Tumoral alfa , Zimosan
3.
Theriogenology ; 195: 46-54, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36283226

RESUMO

This study aimed to investigate the effect of dexamethasone (DEX) on chemotaxis and phagocytic activity of neutrophils for spermatozoa and semen quality of preserved boar semen. The different concentrations of dexamethasone were added to boar semen dilutions to detect its effects on the chemotaxis of neutrophils and phagocytosis of neutrophils and sperm motility sperm malformation rate, plasma membrane integrity, mitochondrial activity, and spermatozoa motility parameters. The study results showed that the experimental groups of DEX significantly inhibited the phagocytosis and chemotaxis of PMNs for spermatozoa. With the increased concentration of DEX, there was an inhibition effect on PMNs activity. In addition, under 17 °C storage conditions, the addition of DEX 1 × 10-6 mol/mL concentration has the best preservation effect on boar semen, which can effectively improve the sperm motility, movement parameters, plasma membrane integrity, mitochondrial activity, T-AOC activity, and significantly reduce the sperm malformation rate and H2O2 content. Therefore, the most suitable concentration of DEX to preserve boar semen at 17 °C is 1 × 10-6 mol/mL. The significant increase of conception rate of sows and litter size of piglets proved that DEX has practical application value. Thus, it is shown that the use of DEX to inhibit uterine inflammation is effective and feasible for sperm damage providing new methods for developing low-dose artificial insemination technology.


Assuntos
Preservação do Sêmen , Sêmen , Suínos , Animais , Masculino , Feminino , Sêmen/fisiologia , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Motilidade Espermática , Quimiotaxia , Neutrófilos , Peróxido de Hidrogênio/farmacologia , Espermatozoides/fisiologia , Dexametasona/farmacologia
4.
Food Chem ; 403: 134473, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358083

RESUMO

Milk fat globule membrane (MFGM) protein is a complex milk protein system with antioxidant property, which can alleviate skeletal muscle dysfunction caused by oxidative stress. In this study, peptide products of MFGM protein obtained through in vitro digestion were isolated and purified, and the composition and antioxidant activities of MFGM peptides (MFGMP) were identified and assessed using LC-MS/MS combined with molecular docking and in vitro approach. Three novel antioxidant peptides TGIIT, YAR and YYK were identified from MFGMPF1, among which TGIIT and YAR exhibited excellent antioxidant effects and protected dexamethasone (Dex)-induced L6 cells by enhancing mitochondrial function and biogenesis involving modulating Sirt-1/PGC-1α signaling pathway. Furthermore, YAR and TGIIT also significantly decreased expression of pro-apoptotic factors such as cyt-c, cleaved caspase-3 and caspase-9. Therefore, YAR and TGIIT, two novel antioxidant peptides, are expected to be utilized in functional food or medicine, providing an emerging role of MFGMP in maintaining anti-oxidant/oxidant status.


Assuntos
Antioxidantes , Hidrolisados de Proteína , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/metabolismo , Cromatografia Líquida , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Glicolipídeos/química , Proteínas do Leite/metabolismo , Gotículas Lipídicas/metabolismo , Mitocôndrias/metabolismo , Dexametasona/farmacologia
5.
Autoimmunity ; 56(1): 1-7, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36343159

RESUMO

Dexamethasone (Dex) is a type of glucocorticoid drug. Long term use can induce growth plate chondrocytes (GPCs) apoptosis, impair differentiation, and inhibit cell proliferation and bone growth. It has been reported that Krüppel-like factor 2 (KLF2) inhibits osteoblast damage induced by Dex, but the role in Dex-induced GPCs remains unclear. Dex was used to construct a model of growth plate injury in vitro. CCK-8 and TUNEL kits were used to determine cell viability and apoptosis. A model of growth plate injury was established by intraperitoneal injection of Dex. Immunohistochemistry was used to investigate the expression of KLF2 in rats. The results showed that KLF2 expression of rat tibial GPCs was down-regulated after Dex stimulation. Overexpression of KLF2 promoted cell viability and cell cycle, while inhibited apoptosis of growth plate Dex-induced chondrocytes. Moreover, KLF2 inhibited Runx2-mediated PI3K/AKT and ERK signalling pathways. And PI3K/AKT and ERK signalling pathways, which were involved in the regulation of KLF2 on GPCs. Further studies showed that KLF2 alleviated growth plate injury in vivo. In conclusion, our study found that KLF2 promoted proliferation and inhibited apoptosis of Dex-induced GPCs by targeting the Runx2-mediated PI3K/AKT and ERK signalling pathways.


Assuntos
Condrócitos , Fraturas Salter-Harris , Ratos , Animais , Condrócitos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Lâmina de Crescimento/metabolismo , Fraturas Salter-Harris/metabolismo , Dexametasona/efeitos adversos , Fatores de Transcrição/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo
6.
Ann Pharmacother ; 57(1): 5-15, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35590468

RESUMO

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , COVID-19/tratamento farmacológico , SARS-CoV-2 , Estudos Retrospectivos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Respiração Artificial , Corticosteroides/uso terapêutico , Dexametasona/uso terapêutico , Oxigênio
7.
Adv Wound Care (New Rochelle) ; 12(1): 1-14, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35081741

RESUMO

Objective: Although the use of dexamethasone as an adjunct agent is associated with alleviating pain and prolonging analgesic duration in local wound infiltration (LWI), efficacy and safety of dexamethasone infiltration have not been fully explored. The study sought to quantify the pooled effects of dexamethasone infiltration on postoperative pain, analgesic consumption, and side effects through a review of randomized controlled trials (RCTs). Approach: RCTs comparing dexamethasone + LWI with LWI alone were retrieved from seven electronic databases. Co-primary outcomes were rest pain scores and cumulative morphine equivalent consumption within 24 h postoperatively. The study followed PRISMA, AMSTAR, and the Cochrane Collaboration. Results: Eight trials comprising 609 patients were included in the final analysis. Results indicated that dexamethasone infiltration effects were only statistical but not clinically significant at individual time points of rest pain and patient satisfaction scores. Notably, the effect of dexamethasone infiltration therapy on other pain-related parameters, including cumulative morphine consumption (mean difference, -9.05 mg; 95% CI: -22.47 to 4.37), was not significantly different compared with the control group. Analysis showed no significant differences in safety indicators between the two groups. The overall quality of evidence was high to very low. Innovation: Although statistically significant effects of dexamethasone infiltration were observed for some outcomes of postoperative wound pain, the overall benefits were below the expected minimal clinically important difference. Conclusions: In summary, the current evidence does not support routine clinical use of dexamethasone in LWI. However, further studies should explore the clinical value of preemptive analgesia and safety of a combination of dexamethasone with ropivacaine for LWI.


Assuntos
Analgesia , Dor Pós-Operatória , Humanos , Ropivacaina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Morfina/farmacologia , Morfina/uso terapêutico , Analgesia/métodos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Int J Nanomedicine ; 17: 5153-5162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36348765

RESUMO

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by arthrocele, cartilage damage and disability. Although several anti-RA drugs have been developed for long-term treatment, they require frequent local injection and lead to multiple adverse effects such as osteoporosis and myelosuppression. Purpose: Reducing the amount and frequency of anti-RA drugs methotrexate (MTX) and dexamethasone sodium phosphate (DSP) by local injection of phospholipid-based phase separation gel (PPSG) coloaded the two drugs, which presented PPSG-(+). Methods: First, We characterized PPSG-(+). And we used UV spectrophotometry and high performance liquid chromatography (HPLC) to detect drug concentration, which can clarify the drug release in vitro and in vivo, respectively. We also injected PPSG-(+) into the joint cavity of healthy rabbits to prove the safety of PPSG-(+). Then, we injected PPSG-(+) into the joint cavity of RA modeled rabbits to demonstrate the effect in anti-RA of PPSG-(+) including the thickness of joints, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß detection, hematoxylin-eosin (H&E) staining and computed tomography (CT) of joints. Results: Suspended particles show a tight and uniform arrangement in PPSG-(+). The gel underwent a phase transition at 20 min in vitro and 8 h in vivo, and vesicular structures reflecting its degradation and phase transition were observed in vivo. PPSG-(+) released both drugs in a sustained and fixed ratio for more than 14 days, while it proved to be safe for intra-articular injection and did not induce inflammation in a rabbit. Eventually, PPSG-(+) showed a good anti-RA effect and its potency can be maintained for 3 weeks. Conclusion: PPSG-(+) is a drug delivery system offering good biocompatibility and sustained release of MTX and DSP, leading to long-lasting anti-RA effect.


Assuntos
Artrite Reumatoide , Metotrexato , Animais , Coelhos , Fosfolipídeos/química , Géis/química , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Injeções Intra-Articulares , Fator de Necrose Tumoral alfa/uso terapêutico , Dexametasona/uso terapêutico
9.
Nat Commun ; 13(1): 7171, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36418322

RESUMO

Anthracyclines, widely used to treat breast cancer, have the potential for cardiotoxicity. We have previously identified and validated a germline single nucleotide polymorphism, rs28714259, associated with an increased risk of anthracycline-induced heart failure. We now provide insights into the mechanism by which rs28714259 might confer increased risk of cardiac damage. Using hiPSC-derived cardiomyocyte cell lines with either intrinsic polymorphism or CRISPR-Cas9-mediated deletion of rs28714259 locus, we demonstrate that glucocorticoid receptor signaling activated by dexamethasone pretreatment prior to doxorubicin exposure preserves cardiomyocyte viability and contractility in cardiomyocytes containing the major allele. Homozygous loss of the rs28714259 major allele diminishes dexamethasone's protective effect. We further demonstrate that the risk allele of rs28714259 disrupts glucocorticoid receptor and rs28714259 binding affinity. Finally, we highlight the activation of genes and pathways involved in cardiac hypertrophy signaling that are blocked by the risk allele, suggesting a decreased adaptive survival response to doxorubicin-related stress.


Assuntos
Células-Tronco Pluripotentes Induzidas , Policetídeos , Humanos , Antraciclinas/toxicidade , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Estudo de Associação Genômica Ampla , Receptores de Glucocorticoides/metabolismo , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Inibidores da Topoisomerase II/farmacologia , Fenótipo , Policetídeos/metabolismo , Dexametasona/farmacologia
10.
BMJ Open ; 12(11): e063835, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396314

RESUMO

OBJECTIVE: Describe the population of babies who do and do not receive postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia (BPD). DESIGN: Retrospective cohort study using data held in the National Neonatal Research Database. SETTING: National Health Service neonatal units in England and Wales. PATIENTS: Babies born less than 32 weeks gestation and admitted to neonatal units from 1 January 2012 to 31 December 2019. MAIN OUTCOMES: Proportion of babies given postnatal corticosteroid; type of corticosteroid; age at initiation and duration, trends over time. SECONDARY OUTCOMES: Survival to discharge, treatment for retinopathy of prematurity, BPD, brain injury, severe necrotising enterocolitis, gastrointestinal perforation. RESULTS: 8% (4713/62019) of babies born <32 weeks and 26% (3525/13527) born <27 weeks received postnatal corticosteroids for BPD. Dexamethasone was predominantly used 5.3% (3309/62019), followed by late hydrocortisone 1.5%, inhaled budesonide 1.5%. prednisolone 0.8%, early hydrocortisone 0.3% and methylprednisolone 0.05%. Dexamethasone use increased over time (2012: 4.5 vs 2019: 5.8%, p=0.04). Median postnatal age of initiation of corticosteroid course was around 3 weeks for late hydrocortisone, 4 weeks for dexamethasone, 6 weeks for inhaled budesonide, 12 weeks for prednisolone and 16 weeks for methylprednisolone. Babies who received postnatal corticosteroids were born more prematurely, had a higher incidence of comorbidities and a longer length of stay. CONCLUSIONS: In England and Wales, around 1 in 12 babies born less than 32 weeks and 1 in 4 born less than 27 weeks receive postnatal corticosteroids to prevent or treat BPD. Given the lack of convincing evidence of efficacy, challenges of recruiting to and length of time taken to conduct randomised controlled trial, our data highlight the need to monitor long-term outcomes in children who received neonatal postnatal corticosteroids.


Assuntos
Displasia Broncopulmonar , Lactente , Criança , Recém-Nascido , Humanos , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , Estudos Retrospectivos , Hidrocortisona , Estudos de Coortes , Medicina Estatal , País de Gales , Corticosteroides/uso terapêutico , Budesonida , Dexametasona/uso terapêutico , Metilprednisolona
11.
Front Immunol ; 13: 1021928, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405732

RESUMO

ACE2 and TMPRSS2 are crucial for SARS-CoV-2 entry into the cell. Although ACE2 facilitates viral entry, its loss leads to promoting the devastating clinical symptoms of COVID-19 disease. Thus, enhanced ACE2/TMPRSS2 expression is likely to increase predisposition of target cells to SARS-CoV-2 infection. However, little evidence existed about the biological kinetics of these two enzymes and whether dexamethasone treatment modulates their expression. Here, we show that the expression of ACE2 at the protein and mRNA levels was significantly higher in the lung and heart tissues of neonatal compared to adult mice. However, the expression of TMPRSS2 was developmentally regulated. Our results may introduce a novel concept for the reduced susceptibility of the young to SARS-CoV-2 infection. Moreover, ACE2 expression but not TMPRSS2 was upregulated in adult female lungs compared to their male counterparts. Interestingly, the ACE2 and TMPRSS2 expressions were upregulated by dexamethasone treatment in the lung and heart tissues in both neonatal and adult mice. Furthermore, our findings provide a novel mechanism for the observed differential therapeutic effects of dexamethasone in COVID-19 patients. As such, dexamethasone exhibits different therapeutic effects depending on the disease stage. This was supported by increased ACE2/TMPRSS2 expression and subsequently enhanced infection of normal human bronchial epithelial cells (NHBE) and Vero E6 cells with SARS-CoV-2 once pre-treated with dexamethasone. Therefore, our results suggest that individuals who take dexamethasone for other clinical conditions may become more prone to SARS-CoV-2 infection.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Masculino , Feminino , Camundongos , Animais , Enzima de Conversão de Angiotensina 2/genética , COVID-19/tratamento farmacológico , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2 , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Serina Endopeptidases/genética
12.
BMC Gastroenterol ; 22(1): 470, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402985

RESUMO

PURPOSE: The aim of this study was to investigate the efficacy and safety of the combination of low-molecular-weight heparin + dexamethasone after partial splenic embolization in cirrhotic patients with massive splenomegaly. METHODS: This study included 116 patients with liver cirrhosis complicated with massive splenomegaly who underwent PSE in Union Hospital from January 2016 to December 2019, and they met the criteria. They were divided into two groups: PSE + Hep + Dex group (N = 54) and PSE group (N = 62). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients. RESULTS: The volume of splenic embolization was 622.34 ± 157.06 cm3 in the PSE + Hep + DEX group and 587.62 ± 175.33 cm3 in the PSE group (P = 0.306). There was no statistically difference in the embolization rate of the spleen between the two groups (P = 0.573). WBC peaked 1 week after PSE and PLT peaked 1 month after PSE in both groups; it gradually decreased later, but was significantly higher than the preoperative level during the 12-month follow-up period. The incidences of abdominal pain (46.3% vs 66.1%, P = 0.039), fever (38.9% vs 75.8%, P < 0.001), PVT (1.9% vs 12.9%, P = 0.026), refractory ascites (5.6% vs 19.4%, P = 0.027) were lower in the PSE + Hep + DEX group than in the PSE group. The VAS score of abdominal pain in PSE group was higher than that in PSE + Hep + DEX group on postoperative days 2-8 (P < 0.05). Splenic abscess occurred in 1(1.6%) patient in the PSE group and none (0.0%) in the PSE + Hep + DEX group (P = 0.349). CONCLUSIONS: The combined use of dexamethasone and low-molecular-weight heparin after PSE is a safe and effective treatment strategy that can significantly reduce the incidence of complications after PSE (such as post-embolization syndrome, PVT, refractory ascites).


Assuntos
Hiperesplenismo , Esplenopatias , Humanos , Hiperesplenismo/complicações , Hiperesplenismo/terapia , Heparina , Esplenomegalia/terapia , Esplenomegalia/complicações , Esplenopatias/etiologia , Estudos Retrospectivos , Ascite/complicações , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Dor Abdominal/complicações , Heparina de Baixo Peso Molecular/uso terapêutico , Dexametasona/uso terapêutico
13.
Curr Oncol ; 29(11): 8501-8512, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36354730

RESUMO

Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27-42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20-73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Bortezomib/uso terapêutico , Bortezomib/farmacologia , Talidomida/uso terapêutico , Talidomida/efeitos adversos , Lenalidomida/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Dexametasona/uso terapêutico , Dexametasona/farmacologia , Ciclofosfamida/uso terapêutico
14.
Vestn Otorinolaringol ; 87(5): 70-74, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36404694

RESUMO

Modern literature data are presented on the choice of a drug for hormonal therapy in acute neurosensory hearing loss of various origins, the doses used for systemic therapy, the features and methods of intratympanic administration of glucocorticosteroids, and the evaluation of the effectiveness of treatment with this group of drugs.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Humanos , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Dexametasona , Resultado do Tratamento , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/tratamento farmacológico , Administração Oral
15.
Front Endocrinol (Lausanne) ; 13: 971993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387847

RESUMO

Context: High progesterone levels in the follicular stage interfere with the implantation window, causing infertility in women with 17-hydroxylase/17,20-lyase deficiency (17OHD). Dexamethasone can restore cortisol deficiency and suppress inappropriate mineralocorticoid secretion to control hypertension in 17OHD patients, but poses risks to the foetus if administered during pregnancy. Objective: We prospectively explored a rational glucocorticoid use protocol for assistive reproduction in a woman with non-classic 17OHD that reduced glucocorticoid side effects. Method: In this study, the treatment protocol for this 17OHD patient included the following steps. First, the appropriate type and dose of glucocorticoid for endogenous progesterone suppression was determined. Then, glucocorticoid was discontinued to increase endogenous progesterone levels for ovarian stimulation. Next, dexamethasone plus GnRHa were used to reduce progesterone levels in frozen embryos for transfer. Once pregnancy was confirmed, dexamethasone was discontinued until delivery. Results: Dexamethasone, but not hydrocortisone, reduced progesterone levels in the 17OHD woman. After endogenous progesterone-primed ovarian stimulation, 11 oocytes were retrieved. Seven oocytes were 2PN fertilised and four day-3 and two day-5 embryos were cryopreserved. After administering dexamethasone plus gonadotropin-releasing hormone agonist (GnRHa) to reduce progesterone levels to normal, hormone replacement therapy was administered until the endometrial width reached 9 mm. Exogenous progesterone (60 mg/day) was used for endometrial preparation. Two thawed embryos were transferred on day 4. Dexamethasone was continued until pregnancy confirmation on the 13th day post-transfer. Two healthy boys, weighing 2100 and 2000 g, were delivered at 36 weeks' gestation. Conclusion: Rational use of dexamethasone synchronised embryonic development with the endometrial implantation window, while not using in post-implantation avoided its side effects and promoted healthy live births in women non-classic 17OHD undergoing in vitro fertilisation.


Assuntos
Hiperplasia Suprarrenal Congênita , Dexametasona , Esteroide 17-alfa-Hidroxilase , Feminino , Humanos , Gravidez , Dexametasona/uso terapêutico , Fertilização In Vitro , Glucocorticoides/uso terapêutico , Progesterona , Hiperplasia Suprarrenal Congênita/tratamento farmacológico
16.
Cochrane Database Syst Rev ; 11: CD014963, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385229

RESUMO

BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated. OBJECTIVES: To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections. MAIN RESULTS: We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; ≥ 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease. AUTHORS' CONCLUSIONS: Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.


Assuntos
COVID-19 , Infecções Fúngicas Invasivas , Humanos , Idoso , Idoso de 80 Anos ou mais , COVID-19/tratamento farmacológico , Corticosteroides/efeitos adversos , Metilprednisolona , Dexametasona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Eur Rev Med Pharmacol Sci ; 26(21): 8087-8097, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394758

RESUMO

OBJECTIVE: Triplet regimens based on pomalidomide and dexamethasone have been applied to treat relapsed/refractory multiple myeloma, but the safety and efficacy are not yet very clear. This meta-analysis aimed at comparing the safety and efficacy of different triplet therapies and analyzing the best therapy regimen. MATERIALS AND METHODS: A comprehensive literature search identified a total of 615 studies, and 22 studies assessing 1,889 subjects met the inclusion criteria of this meta: phase II/III trial, over 2 median lines of prior therapy, and detailed efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival (PFS). All statistical analyses were performed by Revman version 5.3, and the heterogeneity was tested by I2 (25% indicating low heterogeneity, 50% moderate, and 75% high). For those with less heterogeneity, fixed-effect model was used. With a significant high heterogeneity, a random-effect model was used. RESULTS: Pooled analysis showed ORR 66.2% across all triplet regimens based on pomalidomide and dexamethasone. Among all triplet regimens, therapy containing bortezomib showed the highest ORR (90.3%), and the one containing elotuzumab showed the lowest ORR (41.2%). The pooled ORRs for the remaining treatment regimens are as follows: cyclophosphamide (70.1%), isatuximab (66.3%), daratumumab (61.2%), clarithromycin (60.0%), pembrolizumab (47.3%). A total of 21 adverse events appeared in the included studies, with neutropenia being the highest incidence of hematologic adverse events (32.1%) and cough being the highest incidence of non-hematologic adverse events (43.3.%). CONCLUSIONS: Three-drug regimens based on pomalidomide and dexamethasone could yield excellent overall response rate to relapsed/refractory multiple myeloma, but there are still various adverse events; therefore, consequent studies should address these adverse events.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Talidomida/efeitos adversos
18.
Medicine (Baltimore) ; 101(45): e31681, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397337

RESUMO

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort's characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ±â€…14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141-2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.


Assuntos
COVID-19 , Influenza Humana , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Pandemias , Estudos Retrospectivos , Peso Corporal , Dexametasona/uso terapêutico
19.
BMC Microbiol ; 22(1): 268, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36348266

RESUMO

BACKGROUND: Infections affecting neonates caused by Staphylococcus aureus are widespread in healthcare facilities; hence, novel strategies are needed to fight this pathogen. In this study, we aimed to investigate the effectiveness of the FDA-approved medications ascorbic acid, dexamethasone, and sodium bicarbonate to reduce the virulence of the resistant Staphylococcus aureus bacteria that causes neonatal sepsis and seek out suitable alternatives to the problem of multi-drug resistance. METHODS: Tested drugs were assessed phenotypically and genotypically for their effects on virulence factors and virulence-encoding genes in Staphylococcus aureus. Furthermore, drugs were tested in vivo for their ability to reduce Staphylococcus aureus pathogenesis. RESULTS: Sub-inhibitory concentrations (1/8 MIC) of ascorbic acid, dexamethasone, and sodium bicarbonate reduced the production of Staphylococcus aureus virulence factors, including biofilm formation, staphyloxanthin, proteases, and hemolysin production, as well as resistance to oxidative stress. At the molecular level, qRT-PCR was used to assess the relative expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes regulating virulence factors production and showed a significant reduction in the relative expression levels of all the tested genes. CONCLUSIONS: The current findings reveal that ascorbic acid, dexamethasone, and sodium bicarbonate have strong anti-virulence effects against Staphylococcus aureus. Thus, suggesting that they might be used as adjuvants to treat infections caused by Staphylococcus aureus in combination with conventional antimicrobials or as alternative therapies.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Sepse Neonatal , Infecções Estafilocócicas , Recém-Nascido , Humanos , Staphylococcus aureus , Bicarbonato de Sódio/farmacologia , Bicarbonato de Sódio/uso terapêutico , Ácido Ascórbico/farmacologia , Biofilmes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fatores de Virulência/genética , Dexametasona/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
20.
J Ayub Med Coll Abbottabad ; 34(3): 427-430, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36377150

RESUMO

BACKGROUND: Immune thrombocytopenic purpura with multimodal incidence having peaks in each age groups is a chronic clinical syndrome in adults, with disease more predominant in females in adults. The aim of the study was to compare the efficacy (response rate) of high dose dexamethasone with conventional prednisolone in the treatment of newly diagnosed adult patients of Immune thrombocytopenic purpura. It was a prospective quasi-experimental study, conducted at the Department of Medicine of a tertiary care hospital from Jan to Dec 2019. METHODS: The sample population comprised of 130 cases of newly diagnosed ITP patients, having platelet count <30,000/ul with or without bleeding symptoms who received either dexamethasone (40 mg/day for 04 days) or prednisolone (0.5-1 mg/kg PSL for 01 week). Treatment response was measured at day 7. RESULTS: Out of 130 patients 65 patients were treated with dexamethasone and 65 patients with prednisolone .83.08% (n=54) cases in Group-A and 33.85% (n=22) in Group-B had response while remaining 16.92% (n=11) in Group-A and 66.15% (n=43) in Group-B had no response. The p value was calculated as 0.000 which shows a significant difference. CONCLUSIONS: We concluded that high dose of dexamethasone shows a significantly higher response when compared with conventional prednisolone in the treatment of newly diagnosed adult patients of Immune thrombocytopenia purpura.


Assuntos
Púrpura Trombocitopênica Idiopática , Humanos , Adulto , Feminino , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Prednisolona/uso terapêutico , Estudos Prospectivos , Contagem de Plaquetas , Dexametasona/uso terapêutico
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