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2.
Cells ; 13(18)2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39329752

RÉSUMÉ

Cardiotonic steroids are known to bind to Na+/K+-ATPase and regulate several biological processes, including the immune response. The synthetic cardiotonic steroid γ-Benzylidene Digoxin 8 (BD-8) is emerging as a promising immunomodulatory molecule, although it has remained largely unexplored. Therefore, we tested the immunomodulatory potential of BD-8 both in vitro and in vivo. Hence, primary mouse macrophages were incubated with combinations of BD-8 and the pro-inflammatory fungal protein zymosan (ZYM). Nitric oxide (NO) production was determined by Griess reagent and cytokines production was assessed by enzyme-linked immunosorbent assay. Inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), p-nuclear factor kappa B p65 (NF-κB p65), p-extracellular signal-regulated kinase (p-ERK), and p-p38 were evaluated by flow cytometry. Macrophages exposed to BD-8 displayed reduced phagocytic activity, NO levels, and production of the proinflammatory cytokine IL-1ß induced by ZYM. Furthermore, BD-8 diminished the expression of iNOS and phosphorylation of NF-κB p65, ERK, and p38. Additionally, BD-8 exhibited anti-inflammatory capacity in vivo in a carrageenan-induced mouse paw edema model. Taken together, these findings demonstrate the anti-inflammatory activity of BD-8 and further reinforce the potential of cardiotonic steroids and their derivatives as immunomodulatory molecules.


Sujet(s)
Anti-inflammatoires , Digoxine , Macrophages , Animaux , Souris , Anti-inflammatoires/pharmacologie , Digoxine/pharmacologie , Macrophages/métabolisme , Macrophages/effets des médicaments et des substances chimiques , Nitric oxide synthase type II/métabolisme , Monoxyde d'azote/métabolisme , Mâle , Cytokines/métabolisme , Espèces réactives de l'oxygène/métabolisme , Cardiotoniques/pharmacologie , Facteur de transcription RelA/métabolisme , Interleukine-1 bêta/métabolisme , Zymosan , Oedème/traitement médicamenteux , Oedème/anatomopathologie , Inflammation/traitement médicamenteux , Inflammation/anatomopathologie
3.
J Mol Cell Cardiol ; 195: 73-82, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39142438

RÉSUMÉ

Sepsis-induced myocardial dysfunction (SIMD), also known as sepsis-induced cardiomyopathy (SICM), is linked to significantly increased mortality. Despite its clinical importance, effective therapies for SIMD remain elusive, largely due to an incomplete understanding of its pathogenesis. Over the past five decades, research involving both animal models and human studies has highlighted several pathogenic mechanisms of SICM, yet many aspects remain unexplored. Initially thought to be primarily driven by inflammatory cytokines, current research indicates that these alone are insufficient for the development of cardiac dysfunction. Recent studies have brought attention to additional mechanisms, including excessive nitric oxide production, mitochondrial dysfunction, and disturbances in calcium homeostasis, as contributing factors in SICM. Emerging clinical evidence has highlighted the significant role of myocardial edema in the pathogenesis of SICM, particularly its association with cardiac remodeling in septic shock patients. This review synthesizes our current understanding of SIMD/SICM, focusing on myocardial edema's contribution to cardiac dysfunction and the critical role of the bradykinin receptor B1 (B1R) in altering myocardial microvascular permeability, a potential key player in myocardial edema development during sepsis. Additionally, this review briefly summarizes existing therapeutic strategies and their challenges and explores future research directions. It emphasizes the need for a deeper understanding of SICM to develop more effective treatments.


Sujet(s)
Cardiomyopathies , Inflammation , Myocarde , Sepsie , Humains , Sepsie/complications , Sepsie/métabolisme , Animaux , Myocarde/métabolisme , Myocarde/anatomopathologie , Inflammation/métabolisme , Inflammation/anatomopathologie , Cardiomyopathies/métabolisme , Cardiomyopathies/étiologie , Oedème/métabolisme , Oedème/anatomopathologie , Oedème cardiaque/métabolisme , Oedème cardiaque/étiologie
4.
Pediatr Blood Cancer ; 71(10): e31234, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39086111

RÉSUMÉ

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman's disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome. Despite differences in presentation and treatment responses, all patients experienced excellent outcomes. This multi-institutional case series highlights the need to work toward earlier diagnosis and improved long-term management recommendations for patients with TAFRO syndrome.


Sujet(s)
Hyperplasie lymphoïde angiofolliculaire , Thrombopénie , Adolescent , Femelle , Humains , Nourrisson , Mâle , Hyperplasie lymphoïde angiofolliculaire/anatomopathologie , Hyperplasie lymphoïde angiofolliculaire/diagnostic , Hyperplasie lymphoïde angiofolliculaire/thérapie , Oedème/anatomopathologie , Oedème/étiologie , Fièvre/étiologie , Syndrome , Thrombopénie/thérapie , Thrombopénie/diagnostic , Thrombopénie/anatomopathologie
5.
Sci Rep ; 14(1): 18900, 2024 08 14.
Article de Anglais | MEDLINE | ID: mdl-39143315

RÉSUMÉ

To investigate whether peritumoral edema (PE) could enhance deep learning radiomic (DLR) model in predicting axillary lymph node metastasis (ALNM) burden in breast cancer. Invasive breast cancer patients with preoperative MRI were retrospectively enrolled and categorized into low (< 2 lymph nodes involved (LNs+)) and high (≥ 2 LNs+) burden groups based on surgical pathology. PE was evaluated on T2WI, and intra- and peri-tumoral radiomic features were extracted from MRI-visible tumors in DCE-MRI. Deep learning models were developed for LN burden prediction in the training cohort and validated in an independent cohort. The incremental value of PE was evaluated through receiver operating characteristic (ROC) analysis, confirming the improvement in the area under the curve (AUC) using the Delong test. This was complemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics. The deep learning combined model, incorporating PE with selected radiomic features, demonstrated significantly higher AUC values compared to the MRI model and the DLR model in the training cohort (n = 177) (AUC: 0.953 vs. 0.849 and 0.867, p < 0.05) and the validation cohort (n = 111) (AUC: 0.963 vs. 0.883 and 0.882, p < 0.05). The complementary analysis demonstrated that PE significantly enhances the prediction performance of the DLR model (Categorical NRI: 0.551, p < 0.001; IDI = 0.343, p < 0.001). These findings were confirmed in the validation cohort (Categorical NRI: 0.539, p < 0.001; IDI = 0.387, p < 0.001). PE improved preoperative ALNM burden prediction of DLR model, facilitating personalized axillary management in breast cancer patients.


Sujet(s)
Aisselle , Tumeurs du sein , Apprentissage profond , Noeuds lymphatiques , Métastase lymphatique , Imagerie par résonance magnétique , Humains , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du sein/imagerie diagnostique , Imagerie par résonance magnétique/méthodes , Adulte d'âge moyen , Métastase lymphatique/imagerie diagnostique , Études rétrospectives , Noeuds lymphatiques/anatomopathologie , Noeuds lymphatiques/imagerie diagnostique , Oedème/imagerie diagnostique , Oedème/anatomopathologie , Adulte , Sujet âgé , Courbe ROC ,
7.
Niger J Clin Pract ; 27(6): 716-722, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38943295

RÉSUMÉ

BACKGROUND: Rhinoplasty is a common surgical procedure used in nose esthetics and pathologies. Shaping the nasal bones is a crucial step in achieving successful rhinoplasty surgery. However, complications such as excessive bleeding, edema, mucosal damage, and periosteal damage may occur during osteotomy for nose shaping. AIM: To investigate the damage to soft tissue and the effects on oxidative stress and proinflammatory cytokines in the blood caused by osteotomy performed on rabbits, using different osteotomy methods. Methods: Thirty-two albino New Zealand rabbits were divided into four groups. Group A was the sham group (n = 8), Group B the piezoelectric device group (n = 8), Group C the manual saw group (n = 8), and Group D the classical osteotomy group (n = 8). About 3 ml of blood was drawn to compare preoperative and postoperative interleukin-1ß (IL-1ß), thiobarbituric acid-reactive substances (TBARS), tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO), interleukin-10 (IL-10), and glutathione (GSH) levels. A 1 mm3 piece of soft tissue from the nasal bone of each animal in the study groups was sent for histopathological examination. The Chi-square test was used to analyze the incidence of postoperative necrosis, inflammation, and edema in the groups. RESULTS: Histopathologically, edema was significantly higher in Group C and Group D compared to Group B. Inflammation was increased in all groups. The necrosis was significantly higher in Group B compared to Group C and Group D. Except for two parameters, no significant changes were found in the biochemical markers for all groups. CONCLUSIONS: The piezoelectric device was found to be a better option for reducing edema and inflammation, while manual saws and classical osteotomy may lead to more tissue damage.


Sujet(s)
Ostéotomie , Stress oxydatif , Rhinoplastie , Animaux , Lapins , Ostéotomie/méthodes , Rhinoplastie/méthodes , Marqueurs biologiques/sang , Marqueurs biologiques/métabolisme , Monoxyde d'azote/métabolisme , Monoxyde d'azote/sang , Cytokines/sang , Cytokines/métabolisme , Inflammation/sang , Interleukine-1 bêta/sang , Interleukine-1 bêta/métabolisme , Facteur de nécrose tumorale alpha/sang , Substances réactives à l'acide thiobarbiturique/métabolisme , Glutathion , Oedème/anatomopathologie , Interleukine-10/sang , Interleukine-10/métabolisme , Piézochirurgie/méthodes , Nez/chirurgie
8.
Eur J Dermatol ; 34(2): 158-162, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38907546

RÉSUMÉ

For herpes zoster (HZ) infection, early diagnosis and treatment are important in order to shorten the course of the disease and reduce sequelae, however, there is a lack of non-invasive diagnostic methods. Reflectance confocal microscopy (RCM) is a non-invasive technique often used to diagnose dyspigmented dermatosis, skin tumours, human papillomavirus infectious dermatosis, etc. To evaluate the clinical value of RCM for the early diagnosis of HZ. We collected RCM images from 30 HZ patients with typical vesicles in order to analyse their features. We then utilized RCM to analyse early lesions of another 12 HZ patients, who presented with localized erythema or papules, but not typical vesicles. In addition, we recruited one patient with HZ and observed the lesions over 14 days also using RCM. RCM images showed that the typical lesions of HZ mainly involved oedema of the spinous layer, intraepidermal blister formation, ballooning multinucleated giant (BMG) cells, and dermal papillary oedema. Among them, BMG cells were of specific diagnostic value. Early lesions of HZ patients without typical vesicles showed BMG cells under RCM. A few BMG cells were observed during the early stage of HZ. However, the number of BMG cells increased significantly as typical clustered blisters gradually appeared in the lesions. With the regression of the lesions, the number of BMG cells decreased gradually. RCM, with the advantages of being non-invasive, rapid, and convenient, has an important role in monitoring the evolution of HZ.


Sujet(s)
Diagnostic précoce , Zona , Microscopie confocale , Humains , Microscopie confocale/méthodes , Zona/anatomopathologie , Zona/diagnostic , Femelle , Mâle , Adulte d'âge moyen , Sujet âgé , Adulte , Cellules géantes/anatomopathologie , Cloque/imagerie diagnostique , Cloque/anatomopathologie , Cloque/virologie , Oedème/imagerie diagnostique , Oedème/anatomopathologie , Sujet âgé de 80 ans ou plus
9.
Am J Dermatopathol ; 46(9): 617-619, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-38842357

RÉSUMÉ

ABSTRACT: Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.


Sujet(s)
Oedème , Hémangiosarcome , Sclérodermie systémique , Tumeurs cutanées , Humains , Femelle , Hémangiosarcome/anatomopathologie , Hémangiosarcome/complications , Adulte d'âge moyen , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/complications , Sclérodermie systémique/complications , Sclérodermie systémique/anatomopathologie , Oedème/anatomopathologie , Pseudolymphome/anatomopathologie , Face/anatomopathologie
10.
Clin Radiol ; 79(8): e1003-e1009, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38763808

RÉSUMÉ

OBJECTIVE: To determine whether preoperative classification of breast edema on T2-weighted imaging (T2WI) is useful for predicting sentinel lymph node (SLN) metastasis and biological behavior in patients with early-stage breast cancer. METHODS: This retrospective study involved 341 women with breast cancer who underwent breast MRI from January 2019 to March 2022. Breast edema was scored on a scale of 1-4 on T2WI (1, no edema; 2, peritumoral edema; 3, prepectoral edema; and 4, subcutaneous edema). A logistic regression model was employed for univariate and multivariate analyses. A clinicopathological model was established using independent influencing factors identified in the multivariate analyses, excluding breast edema score (BES). Subsequently, BES was incorporated into this model to establish a combined BES model. The AUC and Delong test were used to examine the additional predictive value of the BES. RESULTS: Logistic regression analysis showed that breast edema was an independent risk factor for SLN metastasis. The combined BES model significantly improved the predictive performance of SLN metastasis compared with the clinicopathological model alone (AUC, 0.77 vs. 0.71; p=0.005). In addition, the BES was significantly positively correlated with the tumor diameter (p<0.001), histologic grade (p=0.001), Ki-67 index (p<0.001), and non-luminal subtypes (p<0.001). CONCLUSION: The BES on T2WI is useful for predicting SLN metastasis. A higher grade of breast edema is associated with breast cancer aggressiveness and increases the probability of SLN metastasis.


Sujet(s)
Tumeurs du sein , Oedème , Métastase lymphatique , Imagerie par résonance magnétique , Noeud lymphatique sentinelle , Humains , Tumeurs du sein/anatomopathologie , Tumeurs du sein/imagerie diagnostique , Femelle , Adulte d'âge moyen , Études rétrospectives , Métastase lymphatique/imagerie diagnostique , Métastase lymphatique/anatomopathologie , Imagerie par résonance magnétique/méthodes , Oedème/imagerie diagnostique , Oedème/anatomopathologie , Noeud lymphatique sentinelle/anatomopathologie , Noeud lymphatique sentinelle/imagerie diagnostique , Adulte , Sujet âgé , Valeur prédictive des tests , Région mammaire/imagerie diagnostique , Région mammaire/anatomopathologie , Biopsie de noeud lymphatique sentinelle
11.
NEJM Evid ; 3(5): EVIDmr2300299, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38815159

RÉSUMÉ

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case.This report examines the story of a 73-year-old man who sought evaluation for 1 month of shortness of breath, bilateral lower-extremity edema, and weight gain of 14 kg. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.


Sujet(s)
Dyspnée , Oedème , Prise de poids , Humains , Mâle , Sujet âgé , Oedème/diagnostic , Oedème/anatomopathologie , Dyspnée/étiologie , Dyspnée/diagnostic , Diagnostic différentiel
12.
Int J Oral Implantol (Berl) ; 17(2): 189-198, 2024 May 27.
Article de Anglais | MEDLINE | ID: mdl-38801332

RÉSUMÉ

Maxillary sinus grafting is a predictable regenerative technique to facilitate maxillary posterior implant placement when there is insufficient vertical bone height inferior to the maxillary sinuses to allow placement of implants of adequate dimensions. It enables an increase in vertical bone height, which makes implant placement easier. Maxillary sinus mucosal membrane perforation is one of the most common intraoperative complications during maxillary sinus grafting and may result in extrusion of graft material into the sinus. When this occurs, the mucociliary function of the maxillary sinus may expel the extruded graft material through its natural ostium, though graft particles may remain in the sinus or possibly occlude the natural ostium. After grafting, transient maxillary sinus mucosal oedema may occur. A postoperative CBCT scan may reveal varying degrees of sinus opacification, namely partial, subtotal or total. Although it is always possible to identify graft material, which may enter the sinus as a result of membrane perforation that might not even be visible to the implantologist during the surgical procedure, it is challenging to assess whether sinus opacification is due to mucosal thickening or mucus accumulation. The aim of the present case series was to offer a pragmatic approach to managing asymptomatic patients whose CBCT scans demonstrated partial, subtotal or total maxillary sinus opacification with bone graft particles that seemed to have been extruded into the sinus.


Sujet(s)
Tomodensitométrie à faisceau conique , Sinus maxillaire , Rehaussement du plancher du sinus , Humains , Transplantation osseuse/méthodes , Transplantation osseuse/effets indésirables , Pose d'implant dentaire endo-osseux/effets indésirables , Pose d'implant dentaire endo-osseux/méthodes , Oedème/étiologie , Oedème/imagerie diagnostique , Oedème/anatomopathologie , Études de suivi , Sinus maxillaire/chirurgie , Sinus maxillaire/imagerie diagnostique , Muqueuse nasale/imagerie diagnostique , Muqueuse nasale/anatomopathologie , Complications postopératoires/imagerie diagnostique , Complications postopératoires/étiologie , Rehaussement du plancher du sinus/effets indésirables , Rehaussement du plancher du sinus/méthodes
13.
Neuroscience ; 549: 84-91, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38460904

RÉSUMÉ

We aimed to evaluate the role of the spinal lymphatic system in spinal cord injury and whether it has an impact on recovery after spinal cord injury. Flow cytometry was used to evaluate the changes in the number of microvesicles after spinal cord injury. Evans blue extravasation was used to evaluate the function of the lymphatic system. Evans blue extravasation and immunofluorescence were used to evaluate the permeability of blood spinal cord barrier. The spinal cord edema was evaluated by dry and wet weight.Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis after spinal cord injury. Nuclear factor-kappa B pathway was detected by Western blot. Behavioral tests were used to evaluate limb function. Microvesicles released after spinal cord injury can enter the thoracic duct and then enter the blood through the lymph around the spine. After ligation of the thoracic duct, it can aggravate the neuropathological manifestations and limb function after spinal cord injury. The potential mechanism may involve nuclear factor-kappa B pathway.


Sujet(s)
Récupération fonctionnelle , Traumatismes de la moelle épinière , Moelle spinale , Traumatismes de la moelle épinière/physiopathologie , Traumatismes de la moelle épinière/anatomopathologie , Traumatismes de la moelle épinière/métabolisme , Animaux , Récupération fonctionnelle/physiologie , Moelle spinale/métabolisme , Moelle spinale/anatomopathologie , Moelle spinale/physiopathologie , Facteur de transcription NF-kappa B/métabolisme , Mâle , Apoptose/physiologie , Rat Sprague-Dawley , Modèles animaux de maladie humaine , Système lymphatique/physiopathologie , Système lymphatique/anatomopathologie , Oedème/anatomopathologie , Conduit thoracique/physiopathologie , Femelle , Microparticules membranaires/métabolisme
14.
FEBS J ; 291(14): 3104-3127, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38487972

RÉSUMÉ

Intestinal edema is a common manifestation of numerous gastrointestinal diseases and is characterized by the accumulation of fluid in the interstitial space of the intestinal wall. Technical advances in laser capture microdissection and low-biomass proteomics now allow us to specifically characterize the intestinal edema proteome. Using advanced proteomics, we identify peptides derived from antimicrobial factors with high signal intensity, but also highlight major contributions from the blood clotting system, extracellular matrix (ECM) and protease-protease inhibitor networks. The ECM is a complex fibrillar network of macromolecules that provides structural and mechanical support to the intestinal tissue. One abundant component of the ECM observed in Salmonella-driven intestinal edema is the glycoprotein fibronectin, recognized for its structure-function interplay regulated by mechanical forces. Using mechanosensitive staining of fibronectin fibers reveals that they are tensed in the edema, despite the high abundance of proteases able to cleave fibronectin. In contrast, fibronectin fibers increasingly relax in other cecal tissue areas as the infection progresses. Co-staining for fibrin(ogen) indicates the formation of a provisional matrix in the edema, similar to what is observed in response to skin injury, while collagen staining reveals a sparse and disrupted collagen fiber network. These observations plus the absence of low tensional fibronectin fibers and the additional finding of a high number of protease inhibitors in the edema proteome could indicate a critical role of stretched fibronectin fibers in maintaining tissue integrity in the severely inflamed cecum. Understanding these processes may also provide valuable functional diagnostic markers of intestinal disease progression in the future.


Sujet(s)
Oedème , Fibronectines , Animaux , Fibronectines/métabolisme , Souris , Oedème/métabolisme , Oedème/anatomopathologie , Oedème/microbiologie , Matrice extracellulaire/métabolisme , Protéomique/méthodes , Souris de lignée C57BL , Salmonelloses/microbiologie , Salmonelloses/anatomopathologie , Salmonelloses/métabolisme , Intestins/microbiologie , Intestins/anatomopathologie , Salmonella typhimurium/pathogénicité , Salmonella typhimurium/métabolisme
15.
Circ Res ; 134(8): 954-969, 2024 Apr 12.
Article de Anglais | MEDLINE | ID: mdl-38501247

RÉSUMÉ

BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study's overall aim was to evaluate the therapeutic potential of novel MMP-9 (matrix metalloproteinase 9) ± LOX-1 inhibitors in combination with rt-PA to improve stroke outcomes. METHODS: A rat thromboembolic stroke model was utilized to investigate the impact of rt-PA delivered 4 hours poststroke onset as well as selective MMP-9 (JNJ0966) ±LOX-1 (BI-0115) inhibitors given before rt-PA administration. Infarct size, perfusion, and hemorrhagic transformation were evaluated by 9.4-T magnetic resonance imaging, vascular and parenchymal MMP-9 activity via zymography, and neurological function was assessed using sensorimotor function testing. Human brain microvascular endothelial cells were exposed to hypoxia plus glucose deprivation/reperfusion (hypoxia plus glucose deprivation 3 hours/R 24 hours) and treated with ±tPA and ±MMP-9 ±LOX-1 inhibitors. Barrier function was assessed via transendothelial electrical resistance, MMP-9 activity was determined with zymography, and LOX-1 and barrier gene expression/levels were measured using qRT-PCR (quantitative reverse transcription PCR) and Western blot. RESULTS: Stroke and subsequent rt-PA treatment increased edema, hemorrhage, MMP-9 activity, LOX-1 expression, and worsened neurological outcomes. LOX-1 inhibition improved neurological function, reduced edema, and improved endothelial barrier integrity. Elevated MMP-9 activity correlated with increased edema, infarct volume, and decreased neurological function. MMP-9 inhibition reduced MMP-9 activity and LOX-1 expression. In human brain microvascular endothelial cells, LOX-1/MMP-9 inhibition differentially attenuated MMP-9 levels, inflammation, and activation following hypoxia plus glucose deprivation/R. CONCLUSIONS: Our findings indicate that LOX-1 inhibition and ± MMP-9 inhibition attenuate negative aspects of ischemic stroke with rt-PA therapy, thus resulting in improved neurological function. While no synergistic effect was observed with simultaneous LOX-1 and MMP-9 inhibition, a distinct interaction is evident.


Sujet(s)
Encéphalopathie ischémique , Accident vasculaire cérébral ischémique , Accident vasculaire cérébral , Rats , Humains , Animaux , Activateur tissulaire du plasminogène , Matrix metalloproteinase 9/métabolisme , Accident vasculaire cérébral ischémique/traitement médicamenteux , Cellules endothéliales/métabolisme , Rat Sprague-Dawley , Accident vasculaire cérébral/traitement médicamenteux , Accident vasculaire cérébral/anatomopathologie , Hémorragie , Oedème/traitement médicamenteux , Oedème/anatomopathologie , Glucose/pharmacologie , Infarctus/traitement médicamenteux , Hypoxie
16.
Curr Med Imaging ; 20: 1-9, 2024.
Article de Anglais | MEDLINE | ID: mdl-38389340

RÉSUMÉ

BACKGROUND: Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is usually used for the semi-quantitative evaluation of joint changes in Rheumatoid Arthritis (RA). However, this method cannot evaluate early changes in bone marrow edema (BME). OBJECTIVE: To determine whether T1 mapping of wrist BME predicts early treatment response in RA. METHODS: This study prospectively enrolled 48 RA patients administered oral anti-rheumatic drugs. MRI of the most severely affected wrist was performed before and after 4 (48 patients) and 8 weeks of treatment (38 patients). Mean T1 values of BME in the lunate, triangular, and capitate bones; RAMRIS for each wrist; Erythrocyte-Sedimentation Rate (ESR); and 28-joint Disease Activity Score (DAS28)-ESR score were analyzed. Patients were divided into responders (4 weeks, 30 patients; 8 weeks, 32 patients) and non-responders (4 weeks, 18 patients; 8 weeks, 6 patients), according to EULAR response criteria. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 values. RESULTS: ESR and DAS28-ESR were not correlated with T1 value and RAMRIS at each examination (P > 0.05). Changes in T1 value and DAS28-ESR relative to the baseline were moderately positively correlated with each other at 4 and 8 weeks (r = 0.555 and 0.527, respectively; P < 0.05). At 4 weeks, the change and rate of change in T1 value significantly differed between responders and non-responders (-85.63 vs. -19.92 ms; -12.89% vs. -2.81%; P < 0.05). The optimal threshold of the rate of change in T1 value at 4 weeks for predicting treatment response was -5.32% (area under the ROC curve, 0.833; sensitivity, 0.900; specificity, 0.667). CONCLUSION: T1 mapping provides a new imaging method for monitoring RA lesions; changes in wrist BME T1 values reflect early treatment response.


Sujet(s)
Polyarthrite rhumatoïde , Synovite , Humains , Synovite/diagnostic , Synovite/anatomopathologie , Polyarthrite rhumatoïde/imagerie diagnostique , Polyarthrite rhumatoïde/traitement médicamenteux , Imagerie par résonance magnétique/méthodes , Articulation du poignet/imagerie diagnostique , Articulation du poignet/anatomopathologie , Oedème/diagnostic , Oedème/anatomopathologie , Spectroscopie par résonance magnétique
17.
Int J Rheum Dis ; 27(3): e15046, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38414165

RÉSUMÉ

AIM: To assess the relationship between anatomical variants of sacroiliac joint (SIJ) and subchondral changes detected in magnetic resonance enterography (MRE) in patients with Crohn's disease (CD). METHODS: This was a retrospective study of 60 CD patients, who were divided into two groups: with (n = 16) and without SIJ (n = 44) involvement, depending on the presence of inflammatory (bone marrow edema) and structural changes (sclerosis and erosions) in MRE. Anatomical variants of SIJ were assessed in CT of the abdomen and/or pelvis, distinguishing typical form with convex iliac surface and atypical forms. Univariate and multivariate analyses were performed to reveal an association between joint changes and forms. RESULTS: Our study included 60 patients (38 males; mean age 38.72 years ± 13.33). Patients with SIJ changes were older (p = .044). No significant differences in CD localization and behavior were found. The most common SIJ lesions were structural changes (in 75% of patients); the main atypical form was the iliosacral complex. The univariate and multivariate analyses showed a significant association of atypical forms with total subchondral changes (odds ratio [OR]: 3.429, 95% confidence interval [CI] 1.043-11.268; p = .042; OR: 5.066, 95% CI: 1.273-20.167; p = .021, respectively), and with structural changes (OR: 4.185, 95% CI: 1.155-15.160; p = .029; OR: 5.986, 95% CI: 1.293-27.700; p = .022, respectively). CONCLUSION: Atypical forms of SIJ are a risk factor for the occurrence of structural joint changes in CD patients. An association between bone marrow edema and atypical forms was not found.


Sujet(s)
Maladies de la moelle osseuse , Maladie de Crohn , Mâle , Humains , Adulte , Articulation sacro-iliaque/imagerie diagnostique , Articulation sacro-iliaque/anatomopathologie , Maladie de Crohn/imagerie diagnostique , Études rétrospectives , Imagerie par résonance magnétique , Maladies de la moelle osseuse/imagerie diagnostique , Maladies de la moelle osseuse/étiologie , Oedème/imagerie diagnostique , Oedème/anatomopathologie
18.
Int J Mol Sci ; 25(3)2024 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-38339059

RÉSUMÉ

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.


Sujet(s)
Diclofenac , Zingiber officinale , Diclofenac/effets indésirables , Inflammation/traitement médicamenteux , Inflammation/induit chimiquement , Extraits de plantes/effets indésirables , Anti-inflammatoires/effets indésirables , Carragénane/effets indésirables , Facteur de nécrose tumorale alpha/usage thérapeutique , Cyclooxygenase 2 , Oedème/induit chimiquement , Oedème/traitement médicamenteux , Oedème/anatomopathologie
19.
Rheumatology (Oxford) ; 63(10): 2684-2693, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-38410065

RÉSUMÉ

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features. METHODS: New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics. RESULTS: Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, P = 0.005), perimysium (OR 6.0, P = 0.014) and fascia (OR 16.9, P < 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, P < 0.001) and Gottron sign (OR 8.05, P = 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, P = 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, P = 0.006) and malignancy (OR 8.49, P = 0.002). CONCLUSION: Muscle MRI holds promise in predicting muscle pathology, disease subtypes and clinical manifestations of IIMs.


Sujet(s)
Imagerie par résonance magnétique , Muscles squelettiques , Myosite , Humains , Myosite/imagerie diagnostique , Myosite/anatomopathologie , Myosite/immunologie , Femelle , Mâle , Imagerie par résonance magnétique/méthodes , Adulte d'âge moyen , Muscles squelettiques/anatomopathologie , Muscles squelettiques/imagerie diagnostique , Adulte , Sujet âgé , Biopsie , Autoanticorps/sang , Oedème/imagerie diagnostique , Oedème/anatomopathologie , Études rétrospectives
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