Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.

Effects of Ginkgo biloba extract on brain oxidative condition after cisplatin exposure.

PURPOSE: The purpose of this study was to evaluate the efficacy of Ginkgo biloba extract (EGb 761) on oxidative events of brain in cisplatin-administrated rats. METHODS: Rats were divided into four experimental groups: 1) control (n=6); 2) cisplatin (8 mg/kg, intraperitoneally one dose, n=6); 3) EGb 761 (100 mg/kg intraperitoneally for 15 days, n=6); and 4) cisplatin + EGb 761 (n=6). After drug administration, rats were sacrificed and brain tissues were removed. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in brain tissues. RESULTS: Single dose cisplatin administration significantly increased NO and GSH levels, but decreased MDA levels in brain tissue samples. EGb 761 treatment reversed the effects of cisplatin on NO and GSH levels, but did not affect the decreased MDA levels. CONCLUSION: Results of the study indicate that oxidative stress can be an important pathogenetic mechanism of cisplatin-induced neurotoxicity. EGb 761, an standardized extract of G. biloba leaves that has antioxidant properties, may improve the oxidative stress-related neurological side effects of cisplatin.

Protective effects of Ankaferd blood stopper on aspirin-induced oxidative mucosal damage in a rat model of gastric injury.

The exposure of gastric mucosa to damaging factors, such as ethanol and some therapeutic drugs, produces pathological changes: inflammatory process, hemorrhagic erosions and even acute ulcers. Ankaferd blood stopper (ABS) comprises a standardized mixture of five different plant extracts. The purpose of our present investigations is to explain the participation of reactive oxygen species in acute gastric mucosal damage by acetylsalicylic acid (ASA) and the effects of new hemostatic agent ABS. Experiments were carried out on 23 male Wistar rats. To assess gastric mucosal damage, biochemical and histopathological data were used. The colorimetric assays were used to determine the malondialdehyde (MDA) and superoxide dismutase (SOD) activity. The level of myeloperoxidase (MPO) activity, the level of nitric oxide (NO) and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay technique. We demonstrated that the biological effects of ROS were estimated by measuring the tissue and plasma levels of MDA, the products of lipid peroxidation, as well as the activity of SOD and the scavenger of ROS produced by ASA in the experiment group. Moreover, it was found that MPO activity as well as NO and TNF-α levels also demonstrated significant improvement by ABS treatment. The pathogenesis of experimental ASA-induced mucosal damage in rat stomach includes the generation of ROS that seems to play an important role, due to the generation of lipid peroxides, accompanied by the impairment of antioxidative enzyme activity of cells. ABS appeared to attenuate the oxidative and inflammatory changes caused by ASA-induced gastric mucosal damage in rats.

Effects of pretreatment with esmolol and lidocaine on injection pain and rocuronium-induced withdrawal response.

BACKGROUND/AIM: We aimed to compare the effectiveness of esmolol 1 mg/kg and lidocaine 1 mg/kg for injection pain and for the prevention of rocuronium-induced withdrawal response. MATERIALS AND METHODS: We enrolled a total of 81 patients in the study. Patients were randomly assigned to receive either 10 mL of 0.9% NaCl (Group P), esmolol 1 mg/kg (Group E), or lidocaine 1.0 mg/kg (Group L). A subparalyzing dose of rocuronium 0.05 mg/ kg was administered to all patients and its effects were recorded. Anesthesia was induced with intravenous propofol and intravenous rocuronium 0.5 mg/kg in all groups. The withdrawal movements of the patient groups were subsequently graded. RESULTS: There was a statistically significant difference in overall incidence of pain in group E and L compared to the placebo group after administrating the subparalyzed dose (no pain response: Group E = 81.5%, Group L = 77.8%, Group P = 14.8%) (P < 0.001). After intravenous administration of an intubating dose of rocuronium, the esmolol group had a significantly lower incidence of withdrawal movement than the other groups (no response: Group E = 81.5%, Group L = 63%, Group P = 22.2%) (P < 0.001). CONCLUSION: We found that esmolol significantly attenuates rocuronium-induced withdrawal movement and also reduces pain when used at subparalyzing doses.

Caffeic acid phenethyl ester: its protective role against certain major eye diseases.

As an effective compound found mainly in the honeybee product propolis, caffeic acid phenethyl ester (CAPE) has been commonly utilized as a medicine and remedial agent, in a number of countries. Specifically, it might inhibit nuclear factor kappa B at micromolar concentrations and demonstrate antioxidant, antineoplastic, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and anti-inflammatory features. This review article summarizes the recent progress regarding the favorable effects of CAPE on a number of eye disease models, including cataract and posterior capsule opacification, corneal diseases, retina and optic nerve-related diseases, ischemia/reperfusion injury of retina, inflammation and infection-related diseases. CAPE has been found to exhibit promising efficacy, with minimal adverse effects, in animal and cell culture studies of several eye diseases.