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Pakistan Journal of Medical Sciences Jul 2024To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME).
OBJECTIVE
To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME).
METHODS
We retrospectively reviewed the clinical data of 118 patients with DME admitted to The Affiliated Eye Hospital of Nanchang University from May 2021 to March 2023. Among them, 38 patients received LP alone (Laser-group), 39 patients received ranibizumab alone (Ranibizumab-group), and 41 patients received LP combined with ranibizumab (Combined-group). The improvement of macular edema (ME), visual acuity, and complications between the groups were compared.
RESULTS
The time of ME regression, exudation absorption and fundus hemorrhage absorption in the Combined-group was shorter than in the Laser-group and the Ranibizumab-group (P<0.05). After treatment, the CMT and RNV of the three groups decreased compared to pretreatment levels and were lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). BCVA increased after the treatment in all groups, and was markedly higher in the Combined-group than in the Laser and the Ranibizumab-groups (P<0.05). NO were higher in the Combined-group compared to the Laser-group and the Ranibizumab-group. The post-treatment VEGF levels decreased in all groups, and were significantly lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). The incidence of complications in the Combined-group was lower than in the Laser-group and the Ranibizumab-group (P<0.05).
CONCLUSIONS
Compared to ranibizumab or LP alone, ranibizumab combined with LP is more effective in reducing ME in patients with DEM, and is associated with fewer complications.
PubMed: 38952520
DOI: 10.12669/pjms.40.6.9213 -
Heliyon Jun 2024Resveratrol is a natural phenolic compound widely found in plants. Previous studies have suggested its neuroprotective role in cerebral ischemia due to its...
BACKGROUND
Resveratrol is a natural phenolic compound widely found in plants. Previous studies have suggested its neuroprotective role in cerebral ischemia due to its anti-oxidative, anti-inflammatory, and anti-apoptotic effects. Intranasal administration of resveratrol enhances its capacity to penetrate the blood-brain barrier, increasing therapeutic efficacy and safety.
OBJECTIVE
We aimed to examine the therapeutic potential of intranasal administration of resveratrol treatment in rats exposed to cerebral ischemia.
METHODS
Sixty-four male rats were divided into three groups: the sham group, which was exposed to only surgical stress; the vehicle and resveratrol groups, which received intranasal vehicle or 50 mg/kg resveratrol for 7 days following middle cerebral artery occlusion, respectively. We assessed the modified neurologic severity scores, wire hanging tests, blood-brain barrier disruption, brain water content, and infarct volume. Levels of matrix metalloproteinase-9, nuclear factor-kappa B, B-cell lymphoma protein 2, and B-cell lymphoma protein 2-associated X messenger RNA expression were examined.
RESULTS
At 3- and 7-days post-ischemia, rats receiving intranasal resveratrol had lower modified neurological severity scores and a smaller brain infarct volume than the rats receiving vehicle. Additionally, the intranasal resveratrol-treated rats showed significantly prolonged wire-hanging performance at the 7-day mark post-ischemia compared to the vehicle group. The blood-brain barrier disruption and brain water content were significantly lower in the resveratrol group than in the vehicle group. Furthermore, the resveratrol-treated group displayed lower expression of Matrix Metalloproteinase-9 and Nuclear Factor-Kappa B in contrast to the vehicle group, while the difference in expression levels of B-cell lymphoma protein 2-associated X and B-cell lymphoma protein 2 were not significant.
CONCLUSION
Intranasal administration of resveratrol showed neuroprotective effects on ischemic stroke by improving neurobehavioral function, reducing blood-brain barrier disruption, cerebral edema, and infarct volume. This treatment also downregulated Matrix Metalloproteinase-9 and Nuclear Factor-Kappa B expression, indicating its potential as a therapeutic option for ischemic stroke.
PubMed: 38952360
DOI: 10.1016/j.heliyon.2024.e32592 -
Periodontology 2000 Jul 2024Radiographic examination has been an essential part of the diagnostic workflow in periodontology and implant dentistry. However, radiographic examination unavoidably... (Review)
Review
Radiographic examination has been an essential part of the diagnostic workflow in periodontology and implant dentistry. However, radiographic examination unavoidably involves ionizing radiation and its associated risks. Clinicians and researchers have invested considerable efforts in assessing the feasibility and capability of utilizing nonionizing imaging modalities to replace traditional radiographic imaging. Two such modalities have been extensively evaluated in clinical settings, namely, ultrasonography (USG) and magnetic resonance imaging (MRI). Another modality, optical coherence tomography (OCT), has been under investigation more recently. This review aims to provide an overview of the literature and summarize the usage of USG, MRI, and OCT in evaluating health and pathology of periodontal and peri-implant tissues. Clinical studies have shown that USG could accurately measure gingival height and crestal bone level, and classify furcation involvement. Due to physical constraints, USG may be more applicable to the buccal surfaces of the dentition even with an intra-oral probe. Clinical studies have also shown that MRI could visualize the degree of soft-tissue inflammation and osseous edema, the extent of bone loss at furcation involvement sites, and periodontal bone level. However, there was a lack of clinical studies on the evaluation of peri-implant tissues by MRI. Moreover, an MRI machine is very expensive, occupies much space, and requires more time than cone-beam computed tomography (CBCT) or intraoral radiographs to complete a scan. The feasibility of OCT to evaluate periodontal and peri-implant tissues remains to be elucidated, as there are only preclinical studies at the moment. A major shortcoming of OCT is that it may not reach the bottom of the periodontal pocket, particularly for inflammatory conditions, due to the absorption of near-infrared light by hemoglobin. Until future technological breakthroughs finally overcome the limitations of USG, MRI and OCT, the practical imaging modalities for routine diagnostics of periodontal and peri-implant tissues remain to be plain radiographs and CBCTs.
PubMed: 38951932
DOI: 10.1111/prd.12591 -
Neurobiology of Disease Jun 2024The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders...
OBJECTIVE
The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema.
METHODS
A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation.
RESULTS
During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level.
CONCLUSION
AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.
PubMed: 38950712
DOI: 10.1016/j.nbd.2024.106586 -
Neuropharmacology Jun 2024Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the...
Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-minute blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.
PubMed: 38950691
DOI: 10.1016/j.neuropharm.2024.110054 -
Fitoterapia Jun 2024Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established...
Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.
PubMed: 38950636
DOI: 10.1016/j.fitote.2024.106098 -
Cornea Jun 2024Descemet Stripping Only (DSO) is a promising surgical option for select patients with Fuchs endothelial dystrophy (FED). There is growing support for the use of topical...
PURPOSE
Descemet Stripping Only (DSO) is a promising surgical option for select patients with Fuchs endothelial dystrophy (FED). There is growing support for the use of topical Rho-associated protein kinase inhibitors (ROCKi) to optimize DSO outcomes. However, in many settings, ROCKi are either unavailable or not approved to treat corneal diseases. This study sought to characterize patient outcomes after DSO in the absence of ROCKi and potentially broaden the settings where DSO can be offered to patients.
METHODS
Single-center retrospective case series of 15 eyes/11 patients (66 years; 52-74) that underwent DSO, alone or combined with cataract surgery, by one surgeon between August 2020 and January 2023. Patients included in analyses had FED with central guttae, no clinical evidence of corneal edema, and a clinically healthy peripheral corneal endothelium.
RESULTS
Mean follow-up time was 14 months (2-34). Fourteen of 15 eyes achieved corneal clearance (93.3%). Mean time to clearance was 8.5 weeks (3-23). Eleven eyes (73%) achieved corrected distance visual acuity of ≤0.2 with a significant postoperative improvement at 4 to 8 months (P < 0.05) and sustained improvements at >12 months. No significant astigmatism was introduced by the procedure. Two eyes developed cystoid macular edema postoperatively. A trend toward earlier clearance was observed in the <65 years old group.
CONCLUSIONS
Despite a longer time to corneal clearance in this cohort compared with the few studies using ROCKi, the overall success rate and visual outcomes for the patients in our cohort supports the use of DSO in settings where ROCKi are not readily available.
PubMed: 38950069
DOI: 10.1097/ICO.0000000000003619 -
The American Journal of Case Reports Jul 2024BACKGROUND Cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) is a rare noninfectious chronic inflammatory disease of the digestive tract confined to the...
BACKGROUND Cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) is a rare noninfectious chronic inflammatory disease of the digestive tract confined to the small bowel. Chronic inflammatory wasting leads to protein loss and weight reduction, and some patients eventually develop small bowel stenosis. The etiopathogenesis of CMUSE remains unknown. CASE REPORT A thin 62-year-old man was admitted to the hospital with abdominal pain and distension accompanied by bilateral lower-extremity edema for 2 months. After a series of medical tests, rheumatic or immune-related diseases, hyperthyroidism, and tuberculosis were excluded, and common digestive system diseases were also excluded. Abdominal CT showed incomplete obstruction of the small bowel. Enteroscopy showed small-bowel luminal narrowing. The patient subsequently underwent partial resection of the small bowel with end-to-side anastomosis. The small-bowel stricture was about 120 cm from the ileocecal junction, and about 12 cm of small bowel was resected. Postoperative pathology of the resected material revealed multifocal ulceration of the mucosa with massive inflammatory cell infiltration and extensive hyperplastic fibrous tissue, consistent with the characteristics of CMUSE disease. At follow-up 6 months after surgery, he had no abdominal pain or distension, and his anemia and lower-extremity edema were improved. CONCLUSIONS CMUSE diagnosis requires a combination of patient history, imaging, endoscopy, pathology, and exclusion of other digestive disorders, such as Crohn's disease. It is a chronic wasting disease, often accompanied by weight loss, abdominal pain, melena, and hypoproteinemia. Surgery is an important treatment for intestinal strictures caused by CMUSE.
Topics: Humans; Male; Middle Aged; Intestinal Obstruction; Intestine, Small; Ulcer; Constriction, Pathologic
PubMed: 38949995
DOI: 10.12659/AJCR.944218 -
JAMA Jul 2024
PubMed: 38949806
DOI: 10.1001/jama.2024.6111 -
Medical Physics Jul 2024Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular...
BACKGROUND
Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular diffusivity changes during physiological alterations. Histological and molecular glioma classifications are essential for prognosis and treatment, with distinct water diffusion dynamics among subtypes.
PURPOSE
We developed a data-driven approach using a fully connected network (FCN) to enhance the speed and stability of calculating MDDs across varying SNRs, enable tumor microstructural mapping, and test its reliability in identifying MIB-1 labeling index (LI) levels and molecular status of gliomas.
METHODS
An FCN was trained to learn the mapping between the simulated diffusion decay curves and the ground truth MDDs. We performed 5 000 000 simulation curves with various diffusivity components and random SNR . Eighty percent of simulation curves were used for the FCN training, 10% for validation, and the others were external tests for the FCN performance evaluation. In vivo data were collected to evaluate its clinical reliability. One hundred one patients (44 years 14, 67 men) with gliomas and six healthy controls underwent a 3.0 T MRI examination with a spin echo-echo planar imaging (SE-EPI) diffusion-weighted imaging (DWI) sequence. The trained FCN was employed to calculate MDDs of each brain voxel by voxel. We used the Fuzzy C-means algorithm to cluster the MDDs of tumor voxels, facilitating the characterization of distinct glioma tissues. Quantitative assessments were conducted through sectional integrals of the MDDs, demarcated by six bands to derive signal fractions ( ) and diffusivities of the maximum peaks ( ). Cosine similarity scores (CSS) were used for MDD similarity. ANOVA and Mann-Whitney U test were used for difference analysis. Logistic regression and area under the receiver operator characteristic curve (AUC) were used for classification evaluation.
RESULTS
The simulation results showed that the FCN-based MDD approach (FCN-MDD) achieved higher CSS than non-negative least squares-based MDD (NNLS-MDD). For in vivo data, the spectra of ET and NET obtained by FCN-MDD are more distinguishable than NNLS-MDD. Fraction maps delineate the characteristics of different tumor tissues (enhancing and non-enhancing tumor, edema, and necrosis). showed a positive and negative correlation with MIB-1 respectively ( , all ). The AUC of for predicting MIB-1 LI levels was 0.900 (95% CI, 0.826-0.974), versus 0.781 (0.677-0.886) of ADC. The highest AUC of isocitrate dehydrogenase (IDH) mutation status, assessed by a logistic regression model ( ) was 0.873 (95% CI, 0.802-0.944).
CONCLUSION
The proposed FCN-MDD method was more robust to variations in SNR and less reliant on empirically set regularization values than the NNLS-MDD method. FCN-MDD also enabled qualitative and quantitative evaluation of the composition of gliomas.
PubMed: 38949565
DOI: 10.1002/mp.17280