Vinpocetine protects against chloroquine-induced cardiotoxicity by mitigating oxidative stress.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are classical antimalarial drugs, and recently have been used for other applications including coronavirus disease 2019 (COVID-19). Although they are considered safe, cardiomyopathy may associate CQ and HCQ applications particularly at overdoses. The goal of the present study was to evaluate the potential protective effect of the nootropic agent vinpocetine against CQ and HCQ adverse effects with a specific focus on the heart. For this purpose, a mouse model of CQ (0.5 up to 2.5 g/kg)/HCQ (1 up to 2 g/kg) toxicity was used, and the effect of vinpocetine was evaluated by survival, biochemical, as well as histopathological analyses. Survival analysis revealed that CQ and HCQ caused dose-dependent lethality, which was prevented by co-treatment with vinpocetine (100 mg/kg, oral or intraperitoneal). To gain deeper understanding, a dose of 1 g/kg CQ-which did not cause death within the first 24 h after administration-was applied with and without vinpocetine administration (100 mg/kg, intraperitoneal). The CQ vehicle group showed marked cardiotoxicity as evidenced by significant alterations of blood biomarkers including troponione-1, creatine phosphokinase (CPK), creatine kinase-myocardial band (CK-MB), ferritin, and potassium levels. This was confirmed at the tissue level by massive alteration of the heart tissue morphology and coincided with massive oxidative stress. Interestingly, co-administration of vinpocetine strongly ameliorated CQ-induced alterations and restored the antioxidant-defense system of the heart. These data suggest that vinpocetine could be used as an adjuvant therapy together with CQ/HCQ applications.

Defining the mechanisms of action and mosquito larva midgut response to a yeast-encapsulated orange oil larvicide.

BACKGROUND: Yeast-encapsulated orange oil (YEOO) is a novel, ingestible larvicide that combines the benefits of a low-cost essential oil with yeast, an attractive food source for mosquito larvae. In this work, we investigated the underlying mechanisms of action associated with YEOO ingestion by Aedes aegypti larvae. METHODS: Aedes aegypti third-stage larvae (L3) were treated with sublethal or lethal concentrations of YEOO. Genes associated with apoptosis, autophagy and innate immune responses were investigated by RT-qPCR in guts and carcasses dissected from treated and control larvae. Differential expression of cytochrome P450 genes in the CYP6 and CYP9 families were also investigated. Confocal and transmission electron microscopy were used to assess damage caused by YEOO throughout the larval alimentary canal. TUNEL was used to assess apoptosis via DNA fragmentation. RESULTS: The apoptosis genes IAP1 and IAP2 in larvae displayed opposing effects following exposure to lethal doses of YEOO, with a 26-fold induction of IAP1 at 8 h post YEOO ingestion. The effector caspase CASPS8 displayed a 6.7-fold induction in the gut and concomitant 70-fold induction in the carcass at 8 h post YEOO ingestion. The midgut epithelia regenerator, Vein, had an 11-fold induction in the gut after 4 h and was repressed 7.6-fold in the carcass at 24 h. Sublethal concentrations (< LC50) led to significant differential expression of CYP6 and CYP9 genes. Midgut epithelial damage was highlighted by the destruction of microvilli, vacuolization of midgut cells and damage to cell junctions and basal lamina as early as 30 min. Larval type 2 peritrophic matrix structural integrity and porosity remain unchanged. CONCLUSION: Our results strongly suggest that the robust larvicidal activity of YEOO is due to a generalized broad-acting mechanism combining epithelial damage and apoptosis, with concomitant expression of multiple innate response genes involved in epithelial regeneration and detoxification. YEOO's amenability for use as part of an integrated vector management program makes this novel larvicide a practical approach for mosquito larval control in the future.

Effects of Yunanan Baiyao adjunct therapy on postoperative recovery and clinical prognosis of patients with traumatic brain injury: A randomized controlled trial.

BACKGROUND: Effective therapies are needed to prevent the secondary injury and poor prognosis associated with emergency craniotomy of traumatic brain injury (TBI). HYPOTHESIS/PURPOSE: The wound-healing medicine Yunnan Baiyao (YB) and Xingnaojing (XNJ) adjunct-therapy may improve the outcome of orthodox mono-therapy (OT). STUDY DESIGN: Randomized controlled trial. METHODS: Eighty patients with moderate-to-severe TBI received emergency craniotomy (within 12 h after TBI) at the Chinese PLA General Hospital before being randomly assigned to 4 different treatments (n = 20) for 7 days: 1) OT; 2) OT+XNJ (i.v. 20 ml/daily); 3) OT+low dose-YB (oral, 1,000 mg/day); 4) OT+high dose-YB, 2,000 mg/day). RESULTS: GCS score was improved more quickly and became significantly higher in XNJ, l-YB, h-YB groups than in OT group (p<0.01). Serum S100B peaked higher but declined more slowly in OT group than in other groups (p<0.01). On postoperative Day 7, S100B was 20% below baseline in YB and XNJ groups but remained 19% above baseline in OT group which also lost 38% of superoxide dismutase (SOD) activity on Day 3 and recovered 69% of SOD on Day 7 whereas the YB and XNJ groups lost 16%∼23% of SOD activity on Day 3 and recovered 92%∼99% of SOD on Day 7 (p<0.01). Clinical prognosis (Glasgow Outcome Scale and Karnofsky Performance Scale) were significantly better (25%∼30%) in the XNJ, l-YB and h-YB groups than in OT group 3 months post-surgery and were correlated with serum S100B and SOD. CONCLUSIONS: YB and XNJ adjunct therapies improved postoperative recovery and clinical prognosis in patients with moderate-to-severe TBI partly through divergent regulation of S100B and SOD pathways. (The trial was registered at Chinese Clinical Trial Registry (ChiCTR) trial registration number: ChiCTR2000030280).

Chemical Composition and Antifungal Activity of Essential Oils from Flowers, Leaves, Rhizomes, and Bulbs of the Wild Iraqi Kurdish Plant Iris persica.

Essential oils-obtained by hydrodistillation of different parts of Iris persica L. were investigated for the first time by GC-FID and GC-MS; moreover, their antifungal activities were determined: 34,. 32, 27, and 17 compounds were identified in the oils from air-dried flowers, leaves, rhizomes and fresh. bulbs, respectively, representing ≥ 98% each oil. The major constituents of the flower essential oil were phenylethanol (24.8%) and furfural (13.8%), which, as the main component, constituted also 39.0% and 22.2% of the leaf and rhizome volatile fractions, respectively. Phenylacetaldehyde (37.1%) was the main constituent of the bulb volatile fraction. In in vitro tests, moderate antifungal activity was detected for the oils against strains of the human pathogenic fungal species Gandida albicans, Microsporum canis, and Trichophyton mentagrophytes, the plant-fungal pathogen Pyricularia oryzae, and the fungal food contaminant Aspergillus carbonarius,. The highest activity was exhibited by the essential oils from leaves and flowers, suggesting that they could be considered natural antimicrobial agents.

The effects of age and gender on the prevalence of insomnia in a sample of the Saudi population.

OBJECTIVES: The aim of this study was to determine the prevalence of insomnia among the Saudi adult population. STUDY DESIGN: A cross-sectional insomnia survey was conducted at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. The presence of insomnia was defined by difficulty initiating sleep, early morning awakening, or frequent awakening, in addition to the second-day effect in the form of fatigue, tiredness, or changes in the mode because of lack of sleep. RESULTS: The crude prevalence of insomnia was 77.7% (95% CI = 75.9-79.5%). The gender-adjusted prevalence of insomnia was higher for females, 88.7% (95% CI = 86.4-90.7%) than for males, 70.4% (95% CI = 67.8-72.9%), p-value = .001. The age-adjusted prevalence of insomnia was higher for the elderly, 93.7% (95% CI = 90.6-96.0%) than for the middle aged, 79.8% (95% CI = 77.4-82.1%), or for the young group, 64.2% (95% CI = 59.9-68.4%), p-value = .001. The Chi-square analyses revealed that (1) being elderly, widowed/divorced, females, or housewives, (2) having a lack of education, and (3) excessive tea consumption were significantly associated with elevated risks for insomnia (p-values < .05). CONCLUSIONS: Insomnia is most prevalent among Saudi females and the elderly Saudi population.

Deep brain stimulation for movement disorders.

Movement disorders remain the primary indication for the use of intracranial neurostimulation techniques. This review will discuss the history of this technology as well as the mechanisms of action, current clinical indications, and future prospects for the treatment of movement disorders.