Supplementing preservation solution with mitochondria‐targeted H2S donor AP39 protects cardiac grafts from prolonged cold ischemia–reperfusion injury in heart transplantation

Heart transplant has been accepted as the standard treatment for end‐stage heart failure. Because of its susceptibility to ischemia–reperfusion injury, the heart can be preserved for only 4 to 6 hours in cold static preservation solutions. Prolonged ischemia time is adversely associated with primary graft function and long‐term survival. New strategies to preserve donor hearts are urgently needed. We demonstrate that AP39, a mitochondria‐targeting hydrogen sulfide donor, significantly increases cardiomyocyte viability and reduces cell apoptosis/death after cold hypoxia/reoxygenation in vitro. It also decreases gene expression of proinflammatory cytokines and preserves mitochondria function. Using an in vivo murine heart transplant model, we show that preserving donor hearts with AP39‐supplemented University of Wisconsin solution (n = 7) significantly protects heart graft function, measured by quantitative ultrasound scan, against prolonged cold ischemia–reperfusion injury (24 hours at 4°C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP39 protects cardiac grafts from prolonged ischemia, highlighting its therapeutic potential in preventing ischemia–reperfusion injury in heart transplant.     

Clinical,radiological and histopathological characteristics of surgically removed orbital hematic cysts: A case series

Background

Hematic cyst is a rare orbital condition that has a wide range of clinical presentation and is characterized pathologically by lack of endothelial lining.

Unilateral amblyopia: Optical coherence tomography findings

Purpose

This study was performed to measure the macular and the retinal nerve fiber layer (RNFL) thicknesses using optical coherence tomography (OCT) in patients with unilateral amblyopia.

Methods

Measurement of the Retinal nerve fiber layer and Macular Retinal Layer thickness for both amblyopic and normal fellow eyes by (OCT) was carried out at king Abdulaziz University Hospital, Riyadh, Saudi Arabia.

Results

Ninety-three patients with unilateral amblyopia between the ages of 5 years and 12 years were included. The macular retinal thickness and the RNFL thickness were measured using OCT. The mean macular retinal thickness was 259.3 μm and 255.6 μm, and the mean RNFL thickness was 112.16 μm and 106 μm, in the amblyopic eye and the normal eye, respectively. OCT assessment of RNFL thickness revealed a significantly thicker RNFL in amblyopic eye (P < 0.0001), but no statistically significant difference was found in macular retinal thickness (P = 0.195).

Conclusion

The amblyopic process may involve the RNFL, but not the macula. However, further evaluation is needed.     

Combination of levetiracetam with sodium selenite prevents pentylenetetrazole-induced kindling and behavioral comorbidities in rats

IntroductionThe pentylenetetrazol (PTZ)-induced kindling model acts through the antagonism of central GABA_A receptors and is one of the most widely used experimental animal models to study the characteristics of seizure development, behavioral manifestations and evaluation of antiseizure effects of existing and new drug candidates.MethodologyIn the current study, we investigated the impact of chronically administered levetiracetam (50 mg/kg) and sodium selenite (Sod.Se: 0.25 and 0.5 mg/kg) alone and in combination during the kindling process (21 days) in rats. Moreover, the behavioral changes (through the integration of a wide array of behavioral tests) and markers of oxidative stress in isolated brain homogenates were assessed in PTZ- kindled rats.ResultsThe outcomes from the fully kindled rats revealed the increased seizure score and severity over time with marked behavioral deficits. However, the animals treated with the selected dose of LEV alone showed partial protection from epileptogenesis and amelioration (P < 0.05) of anxiety-like behavior (open filed, light/dark, elevated plus maze tests), cognitive impairment (y-maze, novel object recognition and water maze tests) and depression (sucrose preference test). Moreover, combining the LEV with sodium selenite resulted in a significant neuroprotective effect in comparison to monotherapy by reducing the disease progression and ameliorating behavioral outcomes. The combination of Sod.Se in a dose-dependent manner with LEV produced additive effects as maximum animals remained seizure-free compared to kindled rats (P < 0.05). The attenuation of PTZ induced oxidative stress was evident from the reduced malondialdehyde and elevated superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) level with P < 0.05, as compared to control epileptic rats. These observed results of combination therapy might be due to the antioxidant and neuroprotective properties of Sod.Se, thus augmenting the seizure-modifying potentials of levetiracetam.ConclusionOverall, the current findings support the prominence of combining the Sod.Se with LEV, over monotherapy to deal with prevailing challenges of drug resistance and neuropsychiatric sufferings common in epileptic patients.     

Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization,antibacterial activity against uropathogens,and in vivo reno-protective effect in cisplatin induced nephrotoxicity

Epigallocatechin-3-gallate (EGCG) was isolated from Cycas thouarsii leaves for the first time and encapsulated in aqueous core poly(lactide-co-glycolide) (PLGA) nanocapsules (NCs). This work investigates antimicrobial activity and in vivo reno-protective effects of EGCG-PLGA NCs in cisplatin-induced nephrotoxicity. A double emulsion solvent evaporation process was adopted to prepare PLGA NCs loaded with EGCG. Particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (%EE), structural morphology, and in vitro release platform were all studied in vitro. The optimum formula (F2) with particle size (61.37 ± 5.90 nm), PDI (0.125 ± 0.027), zeta potential (–11.83 ± 3.22 mV), %EE (85.79 ± 5.89%w/w), initial burst (36.85 ± 4.79), and percent cumulative release (87.79 ± 9.84) was selected for further in vitro/in vivo studies. F2 exhibited an enhanced antimicrobial activity against uropathogens as it had lower minimum inhibitory concentration (MIC) values and a more significant impact on bacterial growth than free EGCG. Forty male adult mice were randomly allocated into five groups: control vehicle, untreated methotrexate, MTX groups treated with a daily oral dose of free EGCG, placebo PLGA NCs, and EGCG PLGA NCs (F2) for 10 days. Results showed that EGCG PLGA NCs (F2) exerted promising renoprotective effects compared to free EGCG. EGCG PLGA NCs group induced a significant decrease in kidney index, serum creatinine, kidney injury molecule-1 (KIM-1), NGAL serum levels, and pronounced inhibition of NLPR-3/caspase-1/IL/1β inflammasome pathway. It also significantly ameliorated oxidative stress and decreased NFκB, Bax expression levels. Aqueous core PLGA NCs are a promising formulation strategy that provides high polymeric protection and sustained release pattern for hydrophilic therapeutic agents.