6-Nitrobenzo[a]pyrene can be denitrated during mammalian metabolism

Nitropolycyclic aromatic hydrocarbons (nitroarenes), including 6-nitrobenzo[a]pyrene (6-NBap), occur in our environment and are mutagenic in bacterial mutagenesis assays. The mutagenicity of 6-NBaP is enhanced when rat liver S9 is added. To investigate the cause of this increased activity, the metabolism of 6-NBaP was carried out with a total rat liver homogenate obtained from 3-methylcholanthrene- (MC-) induced rats, a 9000 X g supernatant enzyme, and with both unwashed and washed microsomes. Ring-hydroxylated 6-NBaP was detected. On the basis of retention times for known standards in a high-performance liquid chromatographic system, benzo[a]pyrene (BaP) and 6-acetoxy-BaP (6-OAcBaP) were isolated as products. BaP was further characterized via ultraviolet (UV) and mass spectra and 6-OAcBaP by UV, mass, and nuclear magnetic resonance (NMR) spectra. 6-HydroxyBaP (6-OHBaP) was also detected by UV and mass spectra. It is suggested that BaP is formed via a nitroanion radical of 6-NBaP and undergoes metabolism, while the 6-OHBaP is acetylated to form 6-OAcBaP. The acetyl donor remains to be identified.     

Adhesion efficiency, platelet density and size

We have previously shown that adhesion of human platelets to immobilized collagen is extremely rapid, with initial rates approaching 3% of single particles adhering per 10 ms. Here, we have investigated adhesion efficiency to collagen as a function of platelet density. Platelet subpopulations: low-density (1.040 < d < 1.065 g/ml), intermediate-density (1.065 < d < 1.070 g/ml) and high-density (1.070 < d < 1.080 g/ml) were separated by Percoll density gradient centrifugation. They constituted 24%, 47% and 29% of the total platelet population and had mean volumes of 6.01, 7.37 and 8.21 fl, respectively. Using a continuous-flow, micro-affinity column, we found that the most dense (large) platelets exhibited initial rate of adhesion 4 times greater than the least dense (small) platelets. They were also less sensitive to inhibition by prostacyclin (PGI2). In contrast, there was no significant difference in aggregation induced by high doses of ADP and collagen, indicating that the most dense platelets were not preferentially involved in aggregation induced by high doses of agonists. These results suggest that normal circulating platelets can be distinctly heterogeneous in their ability to adhere to collagen under arterial-flow conditions. The greater efficiency of high-density platelets may be related to increased content of the glycoprotein Ia/IIa (GPIa/IIa) complex.     

Eugenol,a Component of Holy Basil (Tulsi) and Common Spice Clove,Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses

Journal of Neuroimmune Pharmacology - Spike S1 of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and...     

Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF)

Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF) is a relatively recent described entity. This article includes case reports of two patients who had bifrontal involvement during acute febrile encephalopathy. Case 1 describes a 1-y-old boy who presented with hyperpyrexia and dialeptic seizures. Imaging revealed significant bilateral frontal lobe involvement while serology proved presence of Influenza B infection. Over a period of one?wk, he recovered with significant cognitive decline and perseveratory behavior. Another 6-y-old boy presented with language and behavioral problems suggestive of frontal dysfunction after recovering from prolonged impairment of consciousness following a convulsive status epilepticus. Bilateral superior frontal lesions with gyral swelling was evident on neuroimaging. These cases are among the very few cases of AIEF described in recent literature and the article also reviews this unique subtype of acute encephalopathy.     

Flavonoids of Korean Citrus aurantium L. Induce Apoptosis via Intrinsic Pathway in Human Hepatoblastoma HepG2 Cells

Korean Citrus aurantium L. has long been used as a medicinal herb for its anti‐inflammatory, antioxidant, and anticancer properties. The present study investigates the anticancer role of flavonoids extracted from C. aurantium on human hepatoblastoma cell, HepG2. The Citrus flavonoids inhibit the proliferation of HepG2 cells in a dose‐dependent manner. This result was consistent with the in vivo xenograft results. Apoptosis was detected by cell morphology, cell cycle analysis, and immunoblot. Flavonoids decreased the level of pAkt and other downstream targets of phosphoinositide‐3‐kinase/Akt pathway – P‐4EBP1 and P‐p70S6K. The expressions of cleaved caspase 3, Bax, and Bak were increased, while those of Bcl‐2 and Bcl‐xL were decreased with an increase in the expression of Bax/Bcl‐xL ratio in treated cells. Loss of mitochondrial membrane potential was also observed in flavonoid‐treated HepG2 cells. It was also observed that the P‐p38 protein level was increased both dose and time dependently in flavonoid‐treated cells. Collectively, these results suggest that flavonoid extracted from Citrus inhibits HepG2 cell proliferation by inducing apoptosis via an intrinsic pathway. These findings suggest that flavonoids extracted from C. aurantium L. are potential chemotherapeutic agents against liver cancer. Copyright © 2015 John Wiley & Sons, Ltd.     

Prevalence of primary angle-closure disease in retinitis pigmentosa

Purpose:To determine the prevalence of primary angle-closure disease (PACD) in patients with retinitis pigmentosa (RP).Methods: This was a retrospective review of the electronic medical records of all RP patients over the age of 10 years attending the Genetics Eye Clinic of a tertiary-care hospital during a 7-year period. Information regarding age, gender, vision, refraction, lens, intraocular pressure (IOP), type of RP, and inheritance pattern using pedigree charts for all patients were obtained. Patients with a shallow anterior chamber, high IOP, or glaucomatous optic discs were referred to the glaucoma department where they underwent additional IOP measurements, a gonioscopy, and disc evaluation by a glaucoma specialist. The prevalence of PACD was determined.Results: A total of 618 RP patients were examined during the study period, of which 95.1% had typical RP. The prevalence of primary angle-closure suspects was 2.9%, primary angle closure was 0.65%, and primary angle-closure glaucoma (PACG) was 2.27%. In contrast, the prevalence of primary open-angle glaucoma was 1.29%. The prevalence of PACG in those older than 40 years was 3.8% (95% confidence interval: 1.6–6.0).Conclusion: The prevalence of PACG in RP patients over 40 years was higher than that found in the general population of a similar age (3.8% vs. 0.8%). In our cohort of RP patients, 5.9% had PACD. Hence, gonioscopy is warranted in all RP patients to identify this condition and treat it appropriately.     

Molecular Alterations Caused by Alcohol Consumption in the UK Biobank: A Mendelian Randomisation Study

Alcohol consumption is associated with the development of cardiovascular diseases, cancer, and liver disease. The biological mechanisms are still largely unclear. Here, we aimed to use an agnostic approach to identify phenotypes mediating the effect of alcohol on various diseases. Methods: We performed an agnostic association analysis between alcohol consumption (red and white wine, beer/cider, fortified wine, and spirits) with over 7800 phenotypes from the UK biobank comprising 223,728 participants. We performed Mendelian randomisation analysis to infer causality. We additionally performed a Phenome-wide association analysis and a mediation analysis between alcohol consumption as exposure, phenotypes in a causal relationship with alcohol consumption as mediators, and various diseases as the outcome. Results: Of 45 phenotypes in association with alcohol consumption, 20 were in a causal relationship with alcohol consumption. Gamma glutamyltransferase (GGT; β = 9.44; 95% CI = 5.94, 12.93; P_fdr = 9.04 × 10⁻⁷), mean sphered cell volume (β = 0.189; 95% CI = 0.11, 0.27; P_fdr = 1.00 × 10⁻⁴), mean corpuscular volume (β = 0.271; 95% CI = 0.19, 0.35; P_fdr = 7.09 × 10⁻¹⁰) and mean corpuscular haemoglobin (β = 0.278; 95% CI = 0.19, 0.36; P_fdr = 1.60 × 10⁻⁶) demonstrated the strongest causal relationships. We also identified GGT and physical inactivity as mediators in the pathway between alcohol consumption, liver cirrhosis and alcohol dependence. Conclusion: Our study provides evidence of causality between alcohol consumption and 20 phenotypes and a mediation effect for physical activity on health consequences of alcohol consumption.     

Hypertensive encephalopathy as a complication of hyperdynamic therapy for vasospasm: report of two cases

OBJECTIVE AND IMPORTANCE: After developing subarachnoid hemorrhage, patients may deteriorate from a variety of well-known causes, including rebleeding, hydrocephalus, and vasospasm. Many patients now undergo empirical hyperdynamic vasospasm therapy with hypervolemia, induced hypertension, and nimodipine. CLINICAL PRESENTATION: We report two cases of iatrogenic hypertensive encephalopathy occurring during hyperdynamic therapy for cerebral vasospasm after subarachnoid hemorrhage. Hypertensive encephalopathy is a syndrome of rapidly evolving generalized or focal cerebral symptoms occurring in the setting of severe hypertension, which is reversible with antihypertensive therapy. INTERVENTION: The syndrome can be diagnosed in the appropriate clinical setting with computed tomographic or magnetic resonance imaging that demonstrates characteristic findings. In both cases, decreasing the blood pressure resulted in neurological improvement. CONCLUSION: In the setting of induced hypertensive/hypervolemic therapy for vasospasm, hypertensive encephalopathy should be considered as a potentially reversible cause of delayed neurological decline.