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1.
BMC Complement Med Ther ; 24(1): 186, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734604

RESUMEN

BACKGROUND: Cepharanthin® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin®. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. METHODS: Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. RESULTS: CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 µM of CEP significantly inhibited P-glycoprotein efflux function of CD4+ cells, CD8+ cells, and lymphocytes (P<0.05). 0.03~3 µM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 µM of CEP did not influence P-glycoprotein expression. 0.03~0.3 µM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4+, CD4+CD25+ and CD4+CD25+Foxp3+ T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 µM decreased the percentage of CD4+ T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ. CONCLUSIONS: CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin® alone or in combination with GC for the management of chronic ITP.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Bencilisoquinolinas , Sinergismo Farmacológico , Leucocitos Mononucleares , Metilprednisolona , Receptores de Glucocorticoides , Humanos , Bencilisoquinolinas/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Metilprednisolona/farmacología , Receptores de Glucocorticoides/metabolismo , Benzodioxoles
3.
BMJ Case Rep ; 17(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697684

RESUMEN

Acute eosinophilic pneumonia (AEP) is a rare cause of acute respiratory failure. Clinical presentations can range from dyspnoea, fever and cough, to rapidly progressive and potentially fulminant respiratory failure. While its exact cause is often unknown, associations with inhalational injuries and exposures to new medications have been described.We report a case of a middle-aged, non-smoking man with a history of alcohol use disorder. He presented with 4 days of shortness of breath that started hours after taking injectable naltrexone (Vivitrol). The patient had rapidly worsening hypoxaemia, necessitating emergent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage which showed 66% eosinophils. The patient was intubated for the procedure and unable to get extubated due to worsening hypoxaemic respiratory failure with high fractional inspired oxygen requirements. Chest radiograph showed worsening lung infiltrates and with a high index of suspicion for AEP, he was started empirically on methylprednisolone. He had rapid improvement in his respiratory status and was extubated on day 5 of admission then discharged on day 8. Histopathological examination confirmed acute/subacute eosinophilic pneumonia. A 3-week post-discharge follow-up chest radiograph confirmed the full resolution of pulmonary infiltrates.Naltrexone-induced AEP is rare, with only six other cases reported in the literature. Careful history taking and prompt evaluation for AEP are important given the potential for rapid progression to acute hypoxic respiratory failure and the excellent response to steroid treatment.


Asunto(s)
Naltrexona , Eosinofilia Pulmonar , Humanos , Masculino , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/diagnóstico , Naltrexona/uso terapéutico , Naltrexona/efectos adversos , Persona de Mediana Edad , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/administración & dosificación , Metilprednisolona/uso terapéutico , Insuficiencia Respiratoria/inducido químicamente , Broncoscopía , Enfermedad Aguda , Disnea
4.
BMJ Case Rep ; 17(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697686

RESUMEN

A girl in middle childhood was referred to the paediatric surgical team with acute colicky abdominal pain and bile-stained vomiting. This was preceded by a viral illness. Investigations revealed raised inflammatory markers, and imaging of the abdomen demonstrated ileal and jejunal thickening. Concerns were raised regarding whether she had inflammatory bowel disease. Endoscopy revealed gastritis and duodenitis, and colonoscopy was unremarkable. Video capsule endoscopy demonstrated ulcers in the jejunum and ileum.On day 8 of admission, she developed a symmetrical purpuric rash over both ankles leading to the diagnosis of Henoch-Schonlein-related ileitis. Multidisciplinary team working led to appropriate management of the patient and avoided surgery. Video capsule endoscopy enabled visualisation of the small bowel. She was managed with 5 days of methylprednisolone followed by oral steroids. She made a good recovery with no sequelae. This case highlighted that terminal ileitis is a rare complication of IgA vasculitis with a good prognosis.


Asunto(s)
Vasculitis por IgA , Ileítis , Humanos , Femenino , Ileítis/diagnóstico , Ileítis/complicaciones , Niño , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/complicaciones , Endoscopía Capsular , Metilprednisolona/uso terapéutico , Inmunoglobulina A/inmunología
5.
Wiad Lek ; 77(3): 608-612, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38691808

RESUMEN

A case report of Jarisch-Herxheimer (JHR) reaction on a 10th day of Leptospirosis caused by Leptospira Pomona. JHR occurs as a complication of an antibiotic treatment of various spirochetes and may lead to respiratory distress syndrome, renal failure, hepatic insufficiency, and multiple organ failure. This case represents a skin and cardio-vascular form of JHR with no lung involvement. The patient was treated with benzylpenicillin and low dexamethasone doses for 5th day of the disease with a shift to ceftriaxone and high doses of methylprednisolone. The fastest diagnosis of a sporadic zoonotic disease, early start of antibiotic therapy, and adequate doses of corticosteroids are key to the successful treatment of leptospirosis.


Asunto(s)
Antibacterianos , Leptospirosis , Humanos , Leptospirosis/tratamiento farmacológico , Leptospirosis/complicaciones , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Masculino , Leptospira/aislamiento & purificación , Ceftriaxona/uso terapéutico , Ceftriaxona/efectos adversos , Adulto , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/efectos adversos
6.
Can Vet J ; 65(5): 462-472, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694734

RESUMEN

Objective: To determine the complications, outcomes, and patency of a permanent epidural catheter and subcutaneous access port system (ECAPS) as part of conservative management of degenerative lumbosacral stenosis in dogs. Animals and procedure: Medical records of 11 client-owned dogs that underwent an ECAPS insertion were evaluated retrospectively. Clinical signs, complications related to the procedure, and system patency are reported. Results: All dogs had lumbosacral pain at their initial neurological assessment, with comfort levels adequately controlled following epidural infiltrations. None suffered from complications related to the ECAPS procedure. In 10 dogs, there were no malfunctions for the duration of the study. However, in 1 dog, there was a suspected leak at Day 814. The longest duration of patency reported in this study was 870 d (at the time of writing). Conclusion: Placement of an ECAPS is a feasible technique and a viable option to permit repeated epidural injections of steroids in dogs with degenerative lumbosacral stenosis that is managed conservatively. Further studies are required to evaluate complication rates.


Évaluation préliminaire d'un cathéter épidural permanent (à demeure) pour l'administration répétée de méthylprednisolone lors de sténose lombosacrée dégénérative chez le chien. Objectif: Décrire la technique, les complications, les résultats et la perméabilité d'un système composé d'un cathéter épidural et d'un port d'injection sous-cutanée (ECAPS) pour le traitement médical de la sténose lombosacrée dégénérative chez le chien. Animaux et protocole: Les dossiers médicaux de 11 chiens appartenant à des clients ayant subi l'implantation d'un ECAPS ont été évalués de façon rétrospective. Cette étude décrit les signes cliniques, les complications reliées à la procédure et la perméabilité du système. Résultats: Tous les patients inclus présentaient de la douleur lombosacrée à l'examen initial. Le niveau de confort de tous les patients suite aux injections épidurales fut maitrisé de façon adéquate. Aucun des patients n'a subi de complications reliées à l'implantation du système. Le système n'a pas démontré de dysfonctionnement dans le cas de dix patients. Chez un des patients, une fuite fut suspectée au jour 814. La durée maximale de perméabilité enregistrée dans cette étude est de 870 jours (au moment de la rédaction). Conclusion: L'implantation d'un système ECAPS représente une option faisable et viable pour l'administration additionnelle de stéroïdes pour une gestion conservatrice de sténose lombosacrée dégénérative chez les chiens atteints. Des recherches supplémentaires sont requises pour l'évaluation des taux de complications.(Traduit par les auteurs).


Asunto(s)
Catéteres de Permanencia , Enfermedades de los Perros , Metilprednisolona , Estenosis Espinal , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Inyecciones Epidurales/veterinaria , Estudios Retrospectivos , Masculino , Femenino , Estenosis Espinal/veterinaria , Estenosis Espinal/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Catéteres de Permanencia/veterinaria , Catéteres de Permanencia/efectos adversos , Región Lumbosacra
7.
Front Immunol ; 15: 1375943, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765005

RESUMEN

Introduction: Brain death (BD) is known to compromise graft quality by causing hemodynamic, metabolic, and hormonal changes. The abrupt reduction of female sex hormones after BD was associated with increased lung inflammation. The use of both corticoids and estradiol independently has presented positive results in modulating BD-induced inflammatory response. However, studies have shown that for females the presence of both estrogen and corticoids is necessary to ensure adequate immune response. In that sense, this study aims to investigate how the association of methylprednisolone (MP) and estradiol (E2) could modulate the lung inflammation triggered by BD in female rats. Methods: Female Wistar rats (8 weeks) were divided into four groups: sham (animals submitted to the surgical process, without induction of BD), BD (animals submitted to BD), MP/E2 (animals submitted to BD that received MP and E2 treatment 3h after BD induction) and MP (animals submitted to BD that received MP treatment 3h after BD induction). Results: Hemodynamics, systemic and local quantification of IL-6, IL-1ß, VEGF, and TNF-α, leukocyte infiltration to the lung parenchyma and airways, and adhesion molecule expression were analyzed. After treatment, MP/E2 association was able to reinstate mean arterial pressure to levels close to Sham animals (p<0.05). BD increased leukocyte infiltration to the airways and MP/E2 was able to reduce the number of cells (p=0.0139). Also, the associated treatment modulated the vasculature by reducing the expression of VEGF (p=0.0616) and maintaining eNOS levels (p=0.004) in lung tissue. Discussion: Data presented in this study show that the association between corticoids and estradiol could represent a better treatment strategy for lung inflammation in the female BD donor by presenting a positive effect in the hemodynamic management of the donor, as well as by reducing infiltrated leukocyte to the airways and release of inflammatory markers in the short and long term.


Asunto(s)
Muerte Encefálica , Estradiol , Metilprednisolona , Neumonía , Ratas Wistar , Animales , Femenino , Estradiol/farmacología , Metilprednisolona/farmacología , Ratas , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Pulmón/inmunología , Modelos Animales de Enfermedad , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
8.
Transfus Apher Sci ; 63(3): 103920, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38570214

RESUMEN

Emergent Red Blood Cell (RBC) exchange is indicated in sickle cell disease (SCD) patients with severe acute chest syndrome. However, fully matched RBC units may not be available for patients with multiple RBC antibodies. Intravenous immunoglobulin (IVIG) and steroids were reported for preventing potential delayed hemolytic transfusion reaction (HTR) in simple transfusion of antigen-positive RBCs. We investigated the efficacy and safety of IVIG and steroids in two SCD patients presented with acute chest syndrome receiving RBC exchange with multiple incompatible units. The first patient had multiple historical alloantibodies, including anti-Jsb, although none of them were reactive. IVIG (1 g/kg) was given before and after RBC exchange with methylprednisolone (500 mg IV) one hour before exchange. Her sickle hemoglobin (HbS) was reduced from 89.4% to 17.4% after the exchange with five Jsb-positive units. The patient improved clinically without acute or delayed hemolysis. The second patient had reactive anti-Jsb on two different admissions 18 months apart. Only one of the sixteen units used in the exchanges was Jsb negative. He received the same IVIG regimen during both admissions but 100 mg IV hydrocortisone instead of methylprednisolone. His HbS was reduced from 63.4% to 22.4% after the first exchange. Significant clinical improvements were achieved after both exchanges. No delayed HTR was observed. Our experience of these two patients suggested that IVIG and steroids may be used in preventing potential delayed HTR in some SCD patients with rare antibodies receiving large amounts of antigen-positive RBC products.


Asunto(s)
Anemia de Células Falciformes , Transfusión de Eritrocitos , Inmunoglobulinas Intravenosas , Humanos , Anemia de Células Falciformes/terapia , Anemia de Células Falciformes/sangre , Inmunoglobulinas Intravenosas/uso terapéutico , Femenino , Masculino , Transfusión de Eritrocitos/métodos , Adulto , Reacción a la Transfusión/prevención & control , Esteroides/uso terapéutico , Hemólisis , Isoanticuerpos , Metilprednisolona/uso terapéutico
9.
Target Oncol ; 19(3): 343-357, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38643346

RESUMEN

BACKGROUND: Ruxolitinib (RUX), an orally administered selective Janus kinase 1/2 inhibitor, has received approval for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. We have previously demonstrated the anti-multiple myeloma effects of RUX alone and in combination with the immunomodulatory agent lenalidomide (LEN) and glucocorticosteroids both pre-clinically and clinically. OBJECTIVE: This study aims to evaluate whether LEN can achieve clinical activity among patients with multiple myeloma progressing on the combination of RUX and methylprednisolone (MP). METHODS: In this part of a phase I, multicenter, open-label study, we evaluated the safety and efficacy of RUX and MP for patients with multiple myeloma with progressive disease who had previously received a proteasome inhibitor, LEN, glucocorticosteroids, and at least three prior regimens; we also determined the safety and efficacy of adding LEN at the time of disease progression from the initial doublet treatment. Initially, all subjects received oral RUX 15 mg twice daily and oral MP 40 mg every other day. Those patients who developed progressive disease according to the International Myeloma Working Group criteria then received LEN 10 mg once daily on days 1-21 within a 28-day cycle in addition to RUX and MP, which were administered at the same doses these patients were receiving at the time progressive disease developed. RESULTS: Twenty-nine subjects (median age 64 years; 18 [62%] male) were enrolled in this part of the study and initially received the two-drug combination of RUX and MP. The median number of prior therapies was six (range 3-12). The overall response rate from this two-drug combination was 31% and the clinical benefit rate was 34%. The best responses were 1 very good partial response, 8 partial responses, 1 minor response, 12 stable disease, and 7 progressive disease. The median progression-free survival was 3.5 months (range  0.5-36.2 months). The median time to response was 3.0 months. The median duration of response was 12.5 months (range 2.8-36.2 months). Twenty (69%) patients who showed progressive disease had LEN added to RUX and MP; all patients had prior exposure to LEN and all but one patient was refractory to their last LEN-containing regimen. After the addition of LEN, the overall response rate was 30% and the clinical benefit rate was 40%. The best responses of patients following the addition of LEN were 2 very good partial responses, 4 partial responses, 2 minor responses, 8 stable disease, and 4 progressive disease. The median time to response was 2.6 months (range 0.7-15.0 months). The median duration of response was not reached. The median progression-free survival following the addition of LEN was 3.5 months (range 0.3-25.9 months). CONCLUSIONS: For patients with multiple myeloma, treatment with RUX and MP is effective and well tolerated, and LEN can be used to extend the benefit of this RUX-based treatment. CLINICAL TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT03110822, and is ongoing.


Asunto(s)
Lenalidomida , Metilprednisolona , Mieloma Múltiple , Nitrilos , Pirazoles , Pirimidinas , Humanos , Mieloma Múltiple/tratamiento farmacológico , Masculino , Lenalidomida/uso terapéutico , Lenalidomida/farmacología , Femenino , Anciano , Pirazoles/uso terapéutico , Pirazoles/farmacología , Nitrilos/uso terapéutico , Pirimidinas/uso terapéutico , Pirimidinas/farmacología , Persona de Mediana Edad , Metilprednisolona/uso terapéutico , Metilprednisolona/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Anciano de 80 o más Años , Progresión de la Enfermedad , Adulto
10.
BMC Med ; 22(1): 176, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664766

RESUMEN

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Metotrexato , Metilprednisolona , Humanos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Femenino , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Adulto , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto Joven , Resultado del Tratamiento , Quimioterapia Combinada , Anciano , Adolescente , Enfermedad Aguda
11.
BMJ Open ; 14(4): e078137, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38670610

RESUMEN

OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.


Asunto(s)
COVID-19/complicaciones , Inmunoglobulinas Intravenosas , Metilprednisolona , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Niño , Suiza , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoglobulinas Intravenosas/administración & dosificación , Adolescente , Hospitales Pediátricos , Tratamiento Farmacológico de COVID-19 , Femenino , Masculino , Antiinflamatorios/uso terapéutico , Preescolar , Resultado del Tratamiento
12.
Bone ; 183: 117094, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38582289

RESUMEN

The present study aimed to establish and evaluate a preclinical model of steroid-associated osteonecrosis (SAON) in mice. Sixteen 24-week-old male C57BL/6 mice were used to establish SAON by two intraperitoneal injections of lipopolysaccharide (LPS), followed by three subcutaneous injections of methylprednisolone (MPS). Each injection was conducted on working day, with an interval of 24 h. Six cycles of injections were conducted. Additional twelve mice (age- and gender-matched) were used as normal controls. At 2 and 6 weeks after completing induction, bilateral femora and bilateral tibiae were collected for histological examination, micro-CT scanning, and bulk RNA sequencing. All mice were alive until sacrificed at the indicated time points. The typical SAON lesion was identified by histological evaluation at week 2 and week 6 with increased lacunae and TUNEL+ osteocytes. Micro-CT showed significant bone degeneration at week 6 in SAON model. Histology and histomorphometry showed significantly lower Runx2+ area, mineralizing surface (MS/BS), mineral apposition rate (MAR), bone formation rate (BFR/BS), type H vessels, Ki67+ (proliferating) cells, and higher marrow fat fraction, osteoclast number and TNFα+ areas in SAON group. Bulk RNA-seq revealed changed canonical signaling pathways regulating cell cycle, angiogenesis, osteogenesis, and osteoclastogenesis in the SAON group. The present study successfully established SAON in mice with a combination treatment of LPS and MPS, which could be considered a reliable and reproducible animal model to study the pathophysiology and molecular mechanism of early-stage SAON and to develop potential therapeutic approaches for the prevention and treatment of SAON.


Asunto(s)
Lipopolisacáridos , Osteonecrosis , Masculino , Ratones , Animales , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Osteonecrosis/tratamiento farmacológico , Esteroides , Osteogénesis , Metilprednisolona/uso terapéutico
13.
Mol Biol Rep ; 51(1): 559, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643306

RESUMEN

BACKGROUND: Methylprednisolone (MP) is a pharmaceutical agent employed in the management of Leukemia, which is a systemic malignancy that arises from abnormalities in the hematological system. Numerous investigations in the field of cancer research have directed their attention towards propolis, a natural substance with significant potential as a treatment-supportive agent. Its utilization aims to mitigate the potential adverse effects associated with chemotherapy medications. The objective of this study was to examine the impact of olive oil-based propolis (OEP) and caffeic acid phenethyl ester (CAPE) on the treatment of acute myeloid leukemia, as well as to determine if they exhibit a synergistic effect when combined with the therapeutic support product methylprednisolone. METHODS AND RESULTS: The proliferation of HL-60 cells was quantified using the WST-8 kit. The PI Staining technique was employed to do cell cycle analysis of DNA in cells subjected to OEP, CAPE, and MP, with subsequent measurement by flow cytometry. The apoptotic status of cells was determined by analyzing them using flow cytometry after staining with the Annexin V-APC kit. The quantification of apoptotic gene expression levels was conducted in HL-60 cells. In HL-60 cells, the IC50 dosages of CAPE and MP were determined to be 1 × 10- 6 M and 5 × 10- 4 M, respectively. The HL-60 cells were subjected to apoptosis and halted in the G0/G1 and G2/M phases of the cell cycle after being treated with MP, CAPE, and OEP. CONCLUSIONS: Propolis and its constituents have the potential to serve as effective adjunctive therapies in chemotherapy.


Asunto(s)
Ácidos Cafeicos , Leucemia Mieloide Aguda , Alcohol Feniletílico/análogos & derivados , Própolis , Humanos , Própolis/farmacología , Aceite de Oliva , Metilprednisolona/farmacología , Apoptosis
14.
Zhonghua Er Ke Za Zhi ; 62(5): 467-472, 2024 May 02.
Artículo en Chino | MEDLINE | ID: mdl-38623016

RESUMEN

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.


Asunto(s)
Asparaginasa , Infecciones por Virus de Epstein-Barr , Etopósido , Linfohistiocitosis Hemofagocítica , Terapia Recuperativa , Humanos , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/complicaciones , Estudios Retrospectivos , Terapia Recuperativa/métodos , Niño , Lactante , Preescolar , Etopósido/administración & dosificación , Asparaginasa/administración & dosificación , Doxorrubicina/administración & dosificación , Metilprednisolona/administración & dosificación , Mutación , Proteínas de la Membrana/genética , Resultado del Tratamiento , Perforina/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Liposomas , Herpesvirus Humano 4/genética
15.
J Cell Physiol ; 239(5): e31224, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38481029

RESUMEN

With the prevalence of coronavirus disease 2019, the administration of glucocorticoids (GCs) has become more widespread. Treatment with high-dose GCs leads to a variety of problems, of which steroid-induced osteonecrosis of the femoral head (SONFH) is the most concerning. Since hypoxia-inducible factor 1α (HIF-1α) is a key factor in cartilage development and homeostasis, it may play an important role in the development of SONFH. In this study, SONFH models were established using methylprednisolone (MPS) in mouse and its proliferating chondrocytes to investigate the role of HIF-1α in cartilage differentiation, extracellular matrix (ECM) homeostasis, apoptosis and glycolysis in SONFH mice. The results showed that MPS successfully induced SONFH in vivo and vitro, and MPS-treated cartilage and chondrocytes demonstrated disturbed ECM homeostasis, significantly increased chondrocyte apoptosis rate and glycolysis level. However, compared with normal mice, not only the expression of genes related to collagens and glycolysis, but also chondrocyte apoptosis did not demonstrate significant differences in mice co-treated with MPS and HIF-1α inhibitor. And the effects observed in HIF-1α activator-treated chondrocytes were similar to those induced by MPS. And HIF-1α degraded collagens in cartilage by upregulating its downstream target genes matrix metalloproteinases. The results of activator/inhibitor of endoplasmic reticulum stress (ERS) pathway revealed that the high apoptosis rate induced by MPS was related to the ERS pathway, which was also affected by HIF-1α. Furthermore, HIF-1α affected glucose metabolism in cartilage by increasing the expression of glycolysis-related genes. In conclusion, HIF-1α plays a vital role in the pathogenesis of SONFH by regulating ECM homeostasis, chondrocyte apoptosis, and glycolysis.


Asunto(s)
Apoptosis , Condrocitos , Glucólisis , Homeostasis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Glucólisis/efectos de los fármacos , Apoptosis/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/patología , Ratones , Necrosis de la Cabeza Femoral/inducido químicamente , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/metabolismo , Necrosis de la Cabeza Femoral/genética , Cartílago/metabolismo , Cartílago/patología , Cartílago/efectos de los fármacos , Matriz Extracelular/metabolismo , Masculino , Modelos Animales de Enfermedad , Metilprednisolona/farmacología , Glucocorticoides/farmacología , Ratones Endogámicos C57BL , Cabeza Femoral/patología , Cabeza Femoral/metabolismo
16.
Injury ; 55(6): 111472, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38460480

RESUMEN

Spinal Cord Injury (SCI) is a condition leading to inflammation, edema, and dysfunction of the spinal cord, most commonly due to trauma, tumor, infection, or vascular disturbance. Symptoms include sensory and motor loss starting at the level of injury; the extent of damage depends on injury severity as detailed in the ASIA score. In the acute setting, maintaining mean arterial pressure (MAP) higher than 85 mmHg for up to 7 days following injury is preferred; although caution must be exercised when using vasopressors such as phenylephrine due to serious side effects such as pulmonary edema and death. Decompression surgery (DS) may theoretically relieve edema and reduce intraspinal pressure, although timing of surgery remains a matter of debate. Methylprednisolone (MP) is currently used due to its ability to reduce inflammation but more recent studies question its clinical benefits, especially with inconsistency in recommending it nationally and internationally. The choice of MP is further complicated by conflicting evidence for optimal timing to initiate treatment, and by the reported observation that higher doses are correlated with increased risk of complications. Thyrotropin-releasing hormone may be beneficial in less severe injuries. Finally, this review discusses many options currently being researched and have shown promising pre-clinical results.


Asunto(s)
Descompresión Quirúrgica , Metilprednisolona , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/complicaciones , Descompresión Quirúrgica/métodos , Metilprednisolona/uso terapéutico
17.
Mult Scler Relat Disord ; 85: 105554, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537510

RESUMEN

BACKGROUND: Detection of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is important for diagnosis of multiple sclerosis (MS). Previous studies reported that treatment with intravenous methylprednisolone (IVMP) before lumber puncture (LP) could suppress OCBs production. The aim of this study was to assess whether IVMP initiation prior to CSF collection affects OCBs results in patients with an acute demyelinating event. Additionally, we examined which clinical characteristics are associated with the presence of OCBs in the CSF. METHODS: We retrospectively evaluated patients admitted to the neurology department at rabin medical center (RMC) between 2010 and 2022 who underwent LP with OCBs analysis as part of their demyelinating attack workup. Patients were divided into OCB-positive and OCB-negative groups and demographical and clinical characteristics (including timing and duration of acute steroid treatment and history of prior demyelinating attacks) were analyzed for association with OCBs results. RESULTS: A total of 342 patients were included with a median age of 35 years (IQR, 27-46). Two hundred thirty-eight (69.6 %) were OCB-positive. Initiation of IVMP before LP was not associated with negative OCBs (11.8 % Vs. 13.5 %, P = 0.721), nor was it correlated with OCBs positivity (OR=0.86, P = 0.66). CSF cell count was higher in OCB-positive patients (5 Vs. 3, P = 0.001), and a history of prior demyelinating attacks was associated with- (33.6 % Vs. 20.2 %, P = 0.014) and predictive of OCBs positivity (OR=2, P = 0.013). CONCLUSIONS: Timing of steroids was not associated with OCB positivity. However, pleocytosis and a prior attack were associated with OCB positivity in this cohort. Our results suggest that steroid treatment is unlikely to affect OCBs results. Ideally, larger prospective studies would be needed to confirm our observations.


Asunto(s)
Metilprednisolona , Esclerosis Múltiple , Bandas Oligoclonales , Humanos , Bandas Oligoclonales/líquido cefalorraquídeo , Adulto , Femenino , Masculino , Estudios Retrospectivos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/líquido cefalorraquídeo , Persona de Mediana Edad , Metilprednisolona/administración & dosificación , Punción Espinal
18.
Neurosurg Rev ; 47(1): 132, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38546884

RESUMEN

This systematic review aims to summarize the findings from all clinical randomized trials assessing the efficacy of potential neuroprotective agents in influencing the outcomes of acute spinal cord injuries (SCI). Following the PRISMA guidelines, we conducted comprehensive searches in four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) up to September 5th, 2023. Our analysis included a total of 30 studies. We examined the effects of 15 substances/drugs: methylprednisolone, tirilazad mesylate, erythropoietin, nimodipine, naloxone, Sygen, Rho protein antagonist, granulocyte colony-stimulating factor, autologous macrophages, autologous bone marrow cells, vitamin D, progesterone, riluzole, minocycline, and blood alcohol concentration. Notable improvements in neurological outcomes were observed with progesterone plus vitamin D and granulocyte colony-stimulating factor. In contrast, results for methylprednisolone, erythropoietin, Sygen, Rho Protein, and Riluzole were inconclusive, primarily due to insufficient sample size or outdated evidence. No significant differences were found in the remaining evaluated drugs. Progesterone plus vitamin D, granulocyte colony-stimulating factor, methylprednisolone, Sygen, Rho Protein, and Riluzole may enhance neurological outcomes in acute SCI cases. It is worth noting that different endpoints or additional subgroup analyses may potentially alter the conclusions of individual trials. Therefore, certain SCI grades may benefit more from these treatments than others, while the overall results may remain inconclusive.


Asunto(s)
Eritropoyetina , Fármacos Neuroprotectores , Traumatismos de la Médula Espinal , Humanos , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Nivel de Alcohol en Sangre , Progesterona/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Eritropoyetina/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Vitamina D/uso terapéutico
19.
J Int Med Res ; 52(3): 3000605241233450, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38502002

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.


Asunto(s)
COVID-19 , Hepatitis Autoinmune , Femenino , Humanos , Adulto , COVID-19/complicaciones , Hepatitis Autoinmune/complicaciones , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , SARS-CoV-2 , Enfermedad Aguda , Metilprednisolona/uso terapéutico
20.
BMC Pediatr ; 24(1): 199, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515126

RESUMEN

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).


Asunto(s)
Púrpura Trombocitopénica Idiopática , Niño , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Inmunoglobulinas Intravenosas/efectos adversos , Glucocorticoides/uso terapéutico , Recuento de Plaquetas , Metilprednisolona/uso terapéutico
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