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1.
Int J Cardiol ; : 132403, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39089479

RESUMEN

BACKGROUND: Coronary artery dissection is managed primarily conservatively with serial imaging or percutaneous coronary intervention (PCI). Exposure to contrast in either modality could potentially result in acute tubular necrosis (ATN). However, no data compares ATN incidence in these management strategies. This study compares the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. METHODS: A retrospective analysis was performed using data from the National Inpatient Sample database, including patients with coronary artery dissection between 2016 through 2020. We analyzed the incidence of ATN and associated mortality of PCI and conservative management of coronary artery dissection. RESULTS: We found that the odds of developing ATN were 22% lower in patients managed with PCI than those managed conservatively. There was no difference in the in-hospital mortality or hospital length of stay between the two groups but the mortality rate in patients with ATN was double that of those who did not develop ATN in both PCI and conservatively managed groups. CONCLUSIONS: The higher incidents of ATN in patients with coronary dissection being managed with conservative measures compared to PCI suggest that the use of CTA may be harmful. Additionally, persons who developed ATN may have higher mortality. Therefore, more studies in the management of coronary artery dissection need to be done which would allow further steps to be taken to reduce this harm.

2.
Sci Rep ; 14(1): 17860, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090223

RESUMEN

This study aimed to analyse the treatment and outcomes of traumatic hip dislocation (THD) in children. Clinical data of children with THD were collected at our clinical centre from 1 June 2012 to 1 January 2023. Demographic data, injury mechanism, type of dislocation, combined injuries, reduction time, reduction method, and radiographs were analysed. The Merle d'Aubigné-Postel hip score was used to evaluate hip function and complications at the final follow-up. A total of 19 children with THD were enrolled, including 12 male and seven female patients, with an average age of 8.28 ± 0.99 years. Posterior dislocation was the main type of dislocation (89.47%). Fifteen patients (78.95%) had experienced high-energy injuries and traffic accidents were the main causes of injury (47.37%). Closed reduction was performed as soon as possible, and open reduction was performed if necessary. The hip scores of 18 patients (94.74%) were excellent. One patient had osteonecrosis of the femoral head, with a hip function score of 10 (moderate). High-energy injuries, such as traffic accidents, have gradually become the main cause of injury. The prognosis for THD in children is generally good.


Asunto(s)
Luxación de la Cadera , Humanos , Masculino , Femenino , Niño , Luxación de la Cadera/terapia , Luxación de la Cadera/etiología , Estudios Retrospectivos , Accidentes de Tránsito , Resultado del Tratamiento , Preescolar
3.
Pharmacoepidemiol Drug Saf ; 33(8): e5878, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39090766

RESUMEN

PURPOSE: To present the main findings of a post-authorization safety study assessing pregnancy and infant outcomes after prenatal golimumab exposure in a real-world setting. METHODS: This observational population-based cohort study included data from pregnancies ending in 2006-2018 (Finland) or 2019 (Denmark, Sweden). Infants born to women with rheumatic diseases or ulcerative colitis diagnoses were identified. Based on prescription fills from 90 days prior to pregnancy until delivery, infants were assigned to one of the four drug-exposure cohorts: golimumab, other anti-TNF biologics, other biologics, and nonbiologic systemic therapy, and the general population. Prevalence of adverse pregnancy outcomes, mortality, diagnoses of major congenital anomalies (MCA), and inpatient infections in the infants' first year of life were assessed. Odds ratios and 95% CIs were calculated for MCA and infection. RESULTS: Among 134 infants in the golimumab cohort, none were stillborn or died in the first year of life. MCA were diagnosed in 4.5% of the infants in the golimumab cohort, versus 6.8%, 10.9%, 5.5%, and 4.6% in the other anti-TNF biologics, other biologics, nonbiologic systemic therapy and general population cohorts, respectively. Inpatient infections were diagnosed in 11% of golimumab-exposed infants, compared with 9%-11% of infants in the other cohorts. Unadjusted and selected adjusted comparisons showed no association between prenatal golimumab exposure and MCA or infection compared with the other exposure cohorts or general population. CONCLUSIONS: The number of infants with prenatal golimumab exposure was low, but results are reassuringly consistent with the evidence available for other anti-TNF biologics. Continued monitoring is needed.


Asunto(s)
Anticuerpos Monoclonales , Resultado del Embarazo , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Suecia/epidemiología , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Recién Nacido , Resultado del Embarazo/epidemiología , Adulto , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Finlandia/epidemiología , Lactante , Estudios de Cohortes , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Dinamarca/epidemiología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Anomalías Inducidas por Medicamentos/epidemiología , Adulto Joven
4.
ADMET DMPK ; 12(3): 553-580, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39091899

RESUMEN

Introduction: Berberine is a poorly water-soluble alkaloid compound showing significant anti-inflammatory characteristics. It reduces the levels of pro-inflammatory and inflammatory cytokines, including tumour necrosis factor (TNF-α, IFN-γ) and interleukin (IL-23, IL-12, and IL-23). Diacerein significantly reduces the splenomegaly associated with psoriasis. It downregulates the production of TNF-α and IL-12. Method: This study reported the development of transferosomes containing berberine HCl and diacerein using a film hydration method followed by optimization using a Box-Behnken design. Sodium deoxycholate was used as an edge activator. The impact of independent variables (amount of phosphatidylcholine, amount of edge activator, and sonication cycles) on dependent variables (particle size and entrapment efficiency) was examined. The optimized formulation was characterized for polydispersity index, vesicle size, entrapment efficiency, ζ potential, spectral analysis like Fourier transform infrared, thermal analysis, X-ray diffraction, deformability, transmission electron microscopy, antioxidant assay, in-vitro release, and ex-vivo skin permeation studies. Results: The optimized formulation had a particle size of 110.90±2.8 nm with high entrapment efficiency (89.50±1.5 of berberine HCl and 91.23±1.8 of diacerein). Deformability, polydispersity index, ζ potential, and antioxidant activity of the optimized formulation were 2.44, 0.296, -13.3, and 38.36 %, respectively. Optimized transferosomes exhibited 82.093±0.81 % and 85.02±3.81 % release of berberine HCl and diacerein after 24 h of dissolution study. The transdermal flux of optimized formulation was 0.0224 µg cm-2 h-1 (2.24 cm h-1 permeation coefficient) and 0.0462 µg cm-2 h-1 (4.62 cm h-1 permeation coefficient), respectively, for berberine HCl and diacerein. Raman analysis of treated pig skin confirmed that the transferosomes can permeate the skin. No change in the skin condition or irritation was observed in BALB/c mice. Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Conclusions: Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.

5.
Indian J Orthop ; 58(8): 1070-1078, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39087038

RESUMEN

Introduction: Avascular necrosis of the femoral head is common in routine orthopedic clinics. The challenge arises in managing early stages (I and II) without obvious radiological evidence. Authors explore this naïve research area by comparing surgical procedures in early AVN patients. Materials and Methods: A prospective multicentric study was performed from November 2020 to February 2023 on 82 patients treated with surgical decompression and adjuvants, concerning the defined inclusion and exclusion criteria. Radiopacity and intraosseous edema resolution and THA conversion rates were assessed. Hip pain VAS, groin/thigh pain, difficulty in sitting cross-legged incidence, pain-free walking distance, Harris hip scores, 30-s chair test, and complications were noted. Results: Among 82 patients, the mean age was 28.46 years. Male:female ratio of 3.9:1. 8.5% had bilateral affection and 48.78% had a positive family history. 93.90% presented with groin pain and difficulty in sitting cross-legged, restricted hip movements in 85.3%, and thigh pain in 54.87%. Harris hip scored worst in Group 3 followed by Group 2 and Group 1. 63.41% and 36.58% of patients had Grades 1 and 2 AVN, respectively. At 1 week post-operatively, 96.3% and 93.9% of patients were relieved from groin and thigh pain, respectively (p < 0.001); the trend being Group 3 > Group 2 > Group 1. Hip pain VAS followed a similar trend. At 4 weeks, Harris hip scores improved in Group 3 > Group 2 > Group 1. At 6 months, the trend was Group 2 > Group 3 > Group 1. Group 3 had better 30-s chair test results, pain-free walking distance, and longer cross-legged sitting time. Complication rate of 3.6%. 6.09% of patients underwent THA later. Sclerotic patch and marrow edema resolution early in Group 3, i.e., 46 and 31 days respectively, followed by Group 2 and Group 1. Conclusion: In Stages I and II AVN, biplanar core decompression (double) and intraosseous PRP injection is a promising salvage option; patients have better early hip scores (4 weeks), and early groin and thigh pain recovery. Patients treated early have better clinical and radiological recovery.

6.
Indian J Orthop ; 58(8): 1053-1063, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39087043

RESUMEN

Introduction: Avascular Necrosis (AVN) of the femoral head, a condition characterized by the interruption of blood supply leading to bone tissue death, presents significant therapeutic challenges. Recent advancements in orthobiologics, including the use of Autologous Adult Live-Cultured Osteoblasts (AALCO), combined with core decompression, offer a novel approach for managing AVN. This study assesses the efficacy of this treatment modality in improving functional outcomes and hindering disease progression. Materials and methods: This retrospective observational study encompassed 30 patients treated between 2020 and 2023 for idiopathic AVN of the femoral head, grades I to III, who had not responded to conservative treatment. Patients were excluded based on specific criteria including age, secondary AVN causes, and certain health conditions. The treatment involved a two-stage surgical procedure under spinal anesthesia with OSSGROW® for AALCO generation. Post-operative care emphasized early mobilization, DVT prevention, and avoidance of NSAIDs. Outcome measures were evaluated using the Visual Analog Scale (VAS) for pain, modified Harris Hip Score, and annual MRI imaging for up to 36 months. Results: Among 26 patients (41 hips) completing the study, statistically significant improvements in pain and hip functionality were documented, alongside positive radiological signs of osteogenesis in the majority of cases. However, four instances required advancement to total hip replacement due to disease progression. Conclusion: The combination of core decompression and AALCO implantation shows promise as an effective treatment for AVN of the femoral head, with notable improvements in functional and radiological outcomes. This study supports the potential of orthobiologic approaches in AVN treatment, warranting further investigation through comprehensive randomized controlled trials.

7.
Oxf Med Case Reports ; 2024(7): omae080, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39087087

RESUMEN

Acute abdominal pathologies can cause electrocardiogram (ECG) changes mimicking an acute coronary syndrome (ACS), resulting in diagnostic uncertainty and delay. We report a 65-year-old male with multiple risk factors for ACS who presented with four hours of progressive epigastric and chest pain that resolved in the emergency department. ECG findings were concerning for new deeply inverted T-waves with normal troponins, raising concerns for Wellens Syndrome. Emergent heart catheterization was negative but abdominal computed tomography angiography showed occlusion of the superior mesenteric vessels. Subsequent exploratory laparotomy revealed a small bowel volvulus with extensive necrosis, resulting in a 430 cm resection.

8.
World J Gastrointest Surg ; 16(7): 2337-2342, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39087118

RESUMEN

BACKGROUND: Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department. Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply. In this case, we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer. CASE SUMMARY: A 28-year-old male patient sustained a knife stab wound to the right thigh, causing rupture of his femoral artery and leading to massive bleeding. He underwent cardiopulmonary resuscitation and received a large blood transfusion. Abdominal surgeries confirmed bowel necrosis, and jejunostomy was performed. The necrotic intestine was removed, the remaining intestine was anastomosed, and the right thigh was amputated. After three surgeries, the patient's overall condition gradually improved, and the patient was discharged from the hospital. However, one day after discharge, the patient was admitted again due to dizziness and melena, and a gastroduodenoscopy revealed a giant banded ulcer. After 2 weeks of treatment, the ulcer had decreased in size without bleeding. Six months after the last surgery, enterostomy and reintroduction surgery were completed. The patient was fitted with a right lower limb prosthesis one year after surgery. After 3 years of follow-up, the patient did not complain of discomfort. CONCLUSION: Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

9.
J Microencapsul ; : 1-16, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092777

RESUMEN

AIM: This study was aimed at investigating the cytotoxic effect of a novel combination of doxorubicin (DOX) and nano-formulation of Santolina chamaecyparissus L. essential oil (SCEO-NANO) on hepatic (HepG2) and colon (HT29) cancer cell lines. METHODS: A nano-emulsion was prepared by high-pressure homogenisation, then analysed by zetasizer and Fourier transform infrared spectroscopy. HepG2 and HT29 cells were used in in vitro tests for apoptosis detection. RESULTS: Formulated droplet size increased in DOX@SCEO-NANO/DOX to 11.54 ± 0.02 with uniform distribution (PDI = 0.13 ± 0.01), when compared with SCEO-NANO (size: 8.91 ± 0.02 nm; PDI = 0.1 ± 0.02). In both cells, DOX@SCEO-NANO/DOX led to a considerable reduction in colony formation. Compared to DOX, apoprotein proteins were overexpressed in HepG2 cells, showing increases of 8.66-fold for caspase-3 and 4.24-fold for the Bax/Bcl-2 ratio. In HT29 cells, ROS-dependent necrosis and apoptosis were seen. Comparing DOX@SCEO-NANO/DOX versus DOX, greater levels of caspase-3 and the Bax/Bcl-2 ratio were observed. CONCLUSION: The DOX@SCEO-NANO/DOX formulation showed potential for targeted eradication of colon adenocarcinoma and hepatocellular carcinoma cells.

10.
J Orofac Orthop ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093345

RESUMEN

AIMS: To investigate the effect of tumor necrosis factor (TNF) on the growth of human periodontal ligament (PDL) cells, their osteogenic differentiation and modulation of their matrix secretion in vitro. METHODS: The influence of 10 ng/ml TNF on proliferation and metabolic activity of PDL cells was analyzed by cell counting (DAPI [4',6-diamidino-2-phenylindole] staining) and the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. In addition, cells were cultured under control conditions and osteogenic conditions (media containing 10 mM ß-glycerophosphate). Quantitative expression analysis of genes encoding the osteogenic markers alkaline phosphatase (ALP), collagen type I alpha 1 chain (COL1A1), osteoprotegerin (OPG), and osteopontin (OPN) was performed after 7 and 14 days of cultivation. Calcium deposits were stained with alizarin red. RESULTS: Our studies showed that 10 ng/ml TNF did not affect the survival and metabolic activity of PDL cells. Quantitative expression analysis revealed that long-term cultures with TNF impaired osteogenic cell fate at early and late developmental stages. Furthermore, TNF significantly reduced matrix secretion in PDL cells. CONCLUSION: The present data confirm TNF as a regulatory factor of proinflammatory remodeling that influences the differentiation behavior but not the metabolism and cell proliferation of the periodontium. Therefore, TNF represents an interesting target for the regulation of orthodontic remodeling processes in the periodontium.

11.
Curr Med Imaging ; 20: e15734056277516, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39087635

RESUMEN

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.


Asunto(s)
Necrosis de la Cabeza Femoral , Cuello Femoral , Fracturas por Estrés , Imagen por Resonancia Magnética , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Masculino , Femenino , Adulto , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Diagnóstico Diferencial , Fracturas por Estrés/diagnóstico por imagen , Cuello Femoral/diagnóstico por imagen , Adulto Joven , Curva ROC , Fracturas del Cuello Femoral/diagnóstico por imagen , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/lesiones , Radiografía/métodos , Persona de Mediana Edad
12.
Int J Infect Dis ; : 107170, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025201

RESUMEN

PURPOSE: Acute retinal necrosis (ARN) is a vision-threatening uveitis caused by herpesviruses reactivation, which has recently been suggested to be associated with COVID-19 infection and after vaccination against it. CASE DESCRIPTION: We present the case of a 58-year-old Japanese woman with ARN in the left eye due to herpes simplex virus 2 (HSV2) two days after receiving the fifth dose of the BNT162b2 mRNA COVID-19 vaccine. The patient demonstrated an ARN history in the right eye and had been treated for it. The patient was administered oral steroids and immunosuppressive drugs for mixed connective tissue disease and organizing pneumonia. The patient was treated with intravenous acyclovir and foscarnet, and a vitrectomy was performed for retinal detachment. The lesion took approximately two months to scar. CONCLUSION: This report suggests that patients with an ARN history might be at risk of ARN recurrence because of the reactivation of the herpes simplex virus induced by COVID-19 vaccination.

14.
Virus Res ; 348: 199436, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38996815

RESUMEN

RNA silencing is a prominent antiviral defense mechanism in plants. When infected with a virus, RNA silencing-deficient plants tend to show exacerbated symptoms along with increased virus accumulation. However, how symptoms are exacerbated is little understood. Here, we investigated the role of the copper chaperon for superoxide dismutase (CCS) 1, in systemic necrosis observed in Argonaute (AGO)2-silenced tomato plants infected with potato virus X (PVX). While infection with the UK3 strain of PVX induced mosaic symptoms in tomato plants, systemic necrosis occurred when AGO2 was silenced. The CCS1 mRNA level was reduced and micro RNA398 (miR398), which potentially target CCS1, was increased in AGO2-knockdown tomato plants infected with PVX-UK3. Ectopic expression of CCS1 using recombinant PVX attenuated necrosis, suggesting that CCS1 alleviates systemic necrosis by activating superoxide dismutases to scavenge reactive oxygen species. Previous reports have indicated a decrease in the levels of CCS1 and superoxide dismutases along with an increased level of miR398 in plants infected with other viruses and viroids, and thus might represent shared regulatory mechanisms that exacerbate symptoms in these plants.

15.
Clin Endosc ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39044669

RESUMEN

Background/Aims: Coaxial placement of double pigtail plastic stents (DPPS) through lumen-apposing metal stents (LAMSs) is commonly performed to reduce the risk of LAMS obstruction, bleeding, and stent migration when used for the drainage of pancreatic fluid collections (PFCs). A systematic review and meta-analysis were performed to compare the outcomes of LAMS alone and LAMS with coaxial DPPS placement in the management of PFCs. Methods: A systematic review was conducted to identify studies comparing LAMS and LAMS/DPPS for PFC drainage. Primary outcomes included the rate of clinical success, overall adverse events (AEs), bleeding, infection, occlusion, and stent migration. The pooled effect size was summarized using a random-effects model and compared between LAMS and LAMS/DPPS by calculating odds ratios (ORs). Results: Nine studies involving 709 patients were identified (338 on LAMS and 371 on LAMS/DPPS). LAMS/DPPS was associated with a reduced risk of stent obstruction (OR, 0.59; p=0.004) and infection (OR, 0.55; p=0.001). No significant differences were observed in clinical success (OR, 0.96; p=0.440), overall AEs (OR, 0.57; p=0.060), bleeding (OR, 0.61; p=0.120), or stent migration (OR, 1.03; p=0.480). Conclusions: Coaxial DPPS for LAMS drainage of PFCs is associated with a reduced risk of stent occlusion and infection; however, no difference was observed in the overall AE rates or bleeding.

16.
Artículo en Inglés | MEDLINE | ID: mdl-39042221

RESUMEN

OBJECTIVES: Primary chronic Non-Bacterial Osteomyelitis of the jaw is a rare auto-inflammatory disease of unknown aetiology that bears pathophysiological resemblance to both the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children. Both SAPHO and CRMO respond to TNF-alpha blockade. Previously reported treatment regimens in CNOM including non-steroidal anti-inflammatory drugs, corticosteroids, antibiotics, anti-resorptive therapy, and surgery all bear disappointing results. TNF- α blockade is suggested as a treatment option by some experts but this is not backed by any clinical data.We sought to retrospectively and exhaustively report our experience of anti-TNF alpha therapy in refractory CNOM. METHODS: Fifteen patients with refractory CNOM and high disease burden were referred to our centre. TNF- α blockade was attempted in 10 cases, given its efficacy in neighbouring diseases, its good tolerance profile and failure of previous treatment strategiesWe herein retrospectively report detailed outcomes for all patients having received anti-TNF alpha therapy for this indication in our centre. RESULTS: TNF-α-targeting therapy resulted in a rapid and sustained remission in a majority of patients with CNOM, without serious adverse events. Treatment was tapered and stopped without relapse in some patients despite a refractory course of several years. Male sex seems to be associated with a poorer outcome. CONCLUSION: Our results suggest that blocking TNF-α is efficient and safe in CNOM.

17.
Front Immunol ; 15: 1435701, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39044828

RESUMEN

Ceramides generated by the activity of the neutral sphingomyelinase 2 (nSMase2) play a pivotal role in stress responses in mammalian cells. Dysregulation of sphingolipid metabolism has been implicated in numerous inflammation-related pathologies. However, its influence on inflammatory cytokine-induced signaling is yet incompletely understood. Here, we used proximity labeling to explore the plasma membrane proximal protein network of nSMase2 and TNFα-induced changes thereof. We established Jurkat cells stably expressing nSMase2 C-terminally fused to the engineered ascorbate peroxidase 2 (APEX2). Removal of excess biotin phenol substantially improved streptavidin-based affinity purification of biotinylated proteins. Using our optimized protocol, we determined nSMase2-proximal biotinylated proteins and their changes within the first 5 min of TNFα stimulation by quantitative mass spectrometry. We observed significant dynamic changes in the nSMase2 microenvironment in response to TNFα stimulation consistent with rapid remodeling of protein networks. Our data confirmed known nSMase2 interactors and revealed that the recruitment of most proteins depended on nSMase2 enzymatic activity. We measured significant enrichment of proteins related to vesicle-mediated transport, including proteins of recycling endosomes, trans-Golgi network, and exocytic vesicles in the proximitome of enzymatically active nSMase2 within the first minutes of TNFα stimulation. Hence, the nSMase2 proximal network and its TNFα-induced changes provide a valuable resource for further investigations into the involvement of nSMase2 in the early signaling pathways triggered by TNFα.


Asunto(s)
Esfingomielina Fosfodiesterasa , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Células Jurkat , Esfingomielina Fosfodiesterasa/metabolismo , Transducción de Señal , Membrana Celular/metabolismo
18.
Niger Med J ; 65(1): 92-100, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006181

RESUMEN

Background: Pulmonary tuberculosis may result in haematogenous and lymphatic extension in case of failure of early detection, or immunocompromised status, leading to extrapulmonary tuberculosis. Rare sites of extrapulmonary tuberculosis include the gastrointestinal tract, musculoskeletal system, genital tract, middle ear and pericardium. Histopathological findings of macro-confluent granuloma with or without caseous necrosis, along with detection of acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining, and GeneXpert for detection of Mycobacterium tuberculosis DNA, are key in establishing a diagnosis of tuberculosis. Methodology: Biopsy-proven extrapulmonary granulomatous lesions were included in this study. Histopathological evaluation of all extrapulmonary biopsy specimens sent to the Department of Pathology were done for the presence of granuloma and necrosis, and ZN staining for AFB was done in all the cases of granulomatous lesions with or without the presence of necrosis. The same cases, with biopsy specimens sent in normal saline, were re-evaluated in a molecular laboratory with the help of GeneXpert MTB to detect the DNA of Mycobacterium tuberculosis. All biopsy specimens from extrapulmonary sites which were sent to the Department of Pathology were used for DNA extraction. Results: Out of the 10 cases of extrapulmonary granulomatous lesions, 8 showed caseous necrosis on microscopy, and 7 showed the presence of acid-fast bacilli on Ziehl-Neelsen staining. GeneXpert detected DNA of Mycobacterium tuberculosis in 9 cases. Conclusion: Extrapulmonary tuberculosis rarely occurs as primary, and mostly spreads from lung parenchyma via a haematogenous route. Tuberculosis of the gastrointestinal tract, peritoneum, lymph nodes, and solid viscera are together termed abdominal tuberculosis. Entities like tuberculosis of the pericardium and ear are extremely rare. Extrapulmonary tuberculosis should be a differential in cases of chronic non-responding cases with diagnostic dilemmas. To avoid diagnostic delay, in cases of high suspicion, one should go for biopsy along with ZN staining for diagnostic confirmation as this is cost-effective, followed by GeneXpert for Mycobacterium tuberculosis in highly suspected cases with absent caseous necrosis and negative ZN staining.

19.
Cells ; 13(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38994956

RESUMEN

Clostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection.


Asunto(s)
Proteínas Bacterianas , Toxinas Bacterianas , Neuroglía , Fosfolípidos , Neuroglía/metabolismo , Neuroglía/efectos de los fármacos , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidad , Toxinas Bacterianas/farmacología , Fosfolípidos/metabolismo , Proteínas Bacterianas/metabolismo , Clostridioides difficile/metabolismo , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Lipidómica , Humanos
20.
Ultrasound J ; 16(1): 35, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995421

RESUMEN

BACKGROUND: Tracheal necrosis post endotracheal intubation is a rare life-threatening disease that can compromise airway patency. We demonstrated a novel usage of upper airway ultrasonography (USG) to diagnose tracheal necrosis. CASE PRESENTATION: A middle-aged smoking male presented with productive cough, noisy breathing and exertional dyspnea for 2 weeks. He was intubated one month prior due to a traumatic brain injury. Upper airway USG findings showed irregular air-mucosal interface (AMI) and comet tail artefacts over the 1st and 2nd tracheal ring. A direct laryngoscopy in the operating room showed thick mucopus inferior to the vocal cords, with necrotic tracheal cartilages and debris obstructing the airway. He was successfully treated with parenteral antibiotics, wound debridement and tracheostomy. CONCLUSION: Our case highlights the first documented USG findings of tracheal necrosis. Upper airway USG serves as a potential diagnostic modality in managing the condition.

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