Because of its structural similarity to polyunsaturated fatty acids, anandamide could serve as substrate for enzymes such as lipoxygenases and cyclooxygenases, which metabolize polyunsaturated fatty acids to potent bioactive metabolites. Here the ability of recombinant human cyclooxygenase-1 (hCOX-1) and cyclooxygenase-2 (hCOX-2) to metabolize anandamide was studied. Baculovirus-expressed and -purified hCOX-2, but not hCOX-1, effectively oxygenated anandamide. Reverse phase high pressure liquid chromatography analysis of the products derived from 1-14 C-labeled anandamide showed that the products formed are similar to those formed with arachidonic acid as substrate. The major prostanoid product derived from anandamide was determined by mass spectrometry to be prostaglandin E 2 ethanolamide. Incubation of anandamide with lysates and the intact cell line expressing COX-2 but not that of COX-1 produced prostaglandin E 2 ethanolamide. These results demonstrate the existence of a COX-2-mediated pathway for anandamide metabolism, and the metabolites formed represent a novel class of prostaglandins.Anandamide (arachidonoyl ethanolamide, AEA) 1 is a polyunsaturated fatty acyl amide that was identified from porcine brain lipids as an endogenous ligand for brain cannabinoid receptor (1). Although structurally different from cannabinoids, AEA by its ability to activate the central CB1 receptor displays pharmacological properties similar to cannabinoids (2, 3). In addition to its central action via the CB1 receptor, AEA displays potent immunomodulatory and anti-inflammatory activities by interacting with peripheral CB1 and/or CB2 receptors (4 -6).Free AEA is present in both central and peripheral tissues (see Ref. 7 for a review) and could interact with CB receptors to display some of its immunomodulatory and anti-inflammatory activities. In addition, AEA is also stored esterified to phosphatidylethanolamines and is released by the action of phospholipase D in response to various stimuli (7). The AEA thus released inside the cell could participate in signal transduction as a second messenger and display some of its immunomodulatory and anti-inflammatory activities independent of its interaction with the CB receptors. In fact, AEA has been shown to antagonize CB2 receptors, and it is not clear how this antagonism results in immunomodulatory activities observed in cells only expressing CB2 receptors (8). It is possible that a metabolite of AEA rather than AEA itself could account for all or some of these properties. Furthermore, because of its structural similarities to polyunsaturated fatty acids, endogenously released AEA could serve as substrate for lipoxygenases and cyclooxygenases (COX) that metabolize polyunsaturated fatty acids to potent bioactive molecules. It has been demonstrated that lipoxygenase could metabolize AEA, and the metabolites have potent biological activities (9, 10). However, it is not known whether COX can metabolize AEA. Arachidonic acid (AA) is the substrate for both COX-1 and COX-2. AEA is structur...

rGLP-1 has antihypertensive and cardiac and renoprotective effects in Dahl S rats fed a high salt diet. The antihypertensive effect of rGLP-1 in Dahl S rats is due mainly to its diuretic and natriuretic effects, rather than an effect to improve insulin-resistance.

Background: Medical care workers experienced unprecedented levels of workload and pressure since the outbreak of coronavirus disease 2019 (COVID-19). Little is known about its exact impact on medical care workers and related factors in China. This study aims to identify the psychological impact of COVID-19 on medical care workers in China. Methods: From February 23 to March 5, 2020, a cross-sectional survey was conducted among 863 medical care workers from seven provinces in China using standard questionnaires measuring adverse psychological outcomes including Impact of Event Scale-6 (IES-6), Depression, Anxiety and Stress Scale(DASS)and related psychosocial factors like perceived threat, social support and coping strategies. Exploratory Factor analysis was performed to identify the dimensions of perceived threat by study participants. Multivariate regression was used to examine the determinants of adverse psychological outcomes. Results: Posttraumatic stress (PTS) were prevalent in this sample of health care professionals, and 40.2% indicated positive screens for significant posttraumatic stress disorder symptoms. The proportion of having mild to extremely severe symptoms of depression, anxiety and stress were 13.6, 13.9 and 8.6%, respectively. Perceived threat and passive coping strategies were positively correlated to PTS and DASS scores, while perceived social support and active coping strategies were negatively correlated to DASS scores. Nurses were more likely to be anxious than others among medical care workers during the COVID-19 epidemic. Conclusions: Adverse psychological symptoms were prevalent among medical care workers in China during the COVID-19 epidemic. Screening for adverse psychological outcomes and developing corresponding preventive measures would be beneficial in decreasing negative psychological outcomes.

Garlic has been claimed to be effective against diseases, in the pathophysiology of which oxygen free radicals (OFRs) have been implicated. Effectiveness of garlic could be due to its ability to scavenge OFRs. However, its antioxidant activity is not known. We investigated the ability of allicin (active ingredient of garlic) contained in the commercial preparation Garlicin to scavenge hydroxyl radicals (.OH) using high pressure liquid chromatographic (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). H2O2 produced a concentration-dependent .OH as estimated by .OH adduct products 2,3-DHBA and 2,5-DHBA. Allicin equivalent in Garlicin (1.8, 3.6, 7.2, 14.4, 21.6, 28.8 and 36 micrograms) produced concentration-dependent decreases in the formation of 2,3-DHBA and 2,5-DHBA. The inhibition of formation of 2,3-DHBA and 2,5-DHBA with 1.8 micrograms/ml was 32.36% and 43.2% respectively while with 36.0 micrograms/ml the inhibition was approximately 94.0% and 90.0% respectively. The decrease in .OH adduct products was due to scavenging of .OH and not by scavenging of formed .OH adduct products. Allicin prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner. These results suggest that allicin scavenges .OH and Garlicin has antioxidant activity.

BackgroundTo assess the influence of diabetes mellitus (DM), glycemic control, and diabetes-related comorbidities on manifestations and outcome of treatment of pulmonary tuberculosis (TB).Methodology/Principal FindingsCulture positive pulmonary TB patients notified to health authorities in three hospitals in Taiwan from 2005–2010 were investigated. Glycemic control was assessed by glycated haemoglobin A1C (HbA1C) and diabetic patients were categorized into 3 groups: HbA1C<7%, HbA1C 7–9%, HbA1C>9%. 1,473 (705 with DM and 768 without DM) patients were enrolled. Of the 705 diabetic patients, 82 (11.6%) had pretreatment HbA1C<7%, 152 (21.6%) 7%–9%, 276 (39.2%) >9%, and 195 (27.7%) had no information of HbA1C. The proportions of patients with any symptom, cough, hemoptysis, tiredness and weight loss were all highest in diabetic patients with HbA1C>9%. In multivariate analysis adjusted for age, sex, smoking, and drug resistance, diabetic patients with HbA1C>9% (adjOR 3.55, 95% CI 2.40–5.25) and HbA1C 7–9% (adjOR 1.62, 95% CI 1.07–2.44) were significantly more likely to be smear positive as compared with non-diabetic patients, but not those with HbA1C<7% (adjOR 1.16, 95% CI 0.70–1.92). The influence of DM on outcome of TB treatment was not proportionately related to HbA1C, but mainly mediated through diabetes-related comorbidities. Patients with diabetes-related comorbidities had an increased risk of unfavorable outcome (adjOR 3.38, 95% CI 2.19–5.22, p<0.001) and one year mortality (adjOR 2.80, 95% CI 1.89–4.16). However, diabetes was not associated with amplification of resistance to isoniazid (p = 0.363) or to rifampicin (p = 0.344).Conclusions/SignificancePoor glycemic control is associated with poor TB treatment outcome and improved glycemic control may reduce the influence of diabetes on TB.

Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca 2ϩ ([Ca 2ϩ ]i) in response to methacholine (10 M) and histamine (10 M) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 M)-induced increases in [Ca 2ϩ ]i were unaffected. Methacholineinduced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) for 3 days prevented impaired [Ca 2ϩ ]i signaling response to methacholine and histamine and restored methacholineinduced NO production in aortas from rats on a HS diet. Adding Tempol (500 M) to the tissue bath to scavenge superoxide anions increased NO release and caused N -nitro-L-arginine methyl estersensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca 2ϩ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca 2ϩ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca 2ϩ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca 2ϩ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca 2ϩ signaling, and reduced NO production in the endothelium. endothelium; sodium; dietary salt intake; vascular relaxation; nitric oxide A VARIETY OF AGENTS, including muscarinic agonists such as ACh, dilate blood vessels by stimulating the synthesis of nitric oxide (NO) by endothelial NO synthase. Endothelial cell activation in response to agonists and autacoids leads to NO formation via receptor-mediated increases in intracellular calcium ion concentration ([Ca 2ϩ ] i ). However, emerging evidence indicates that endothelial NO synthase activity can be affected by a variety of other mechanisms that are independent of [Ca 2ϩ ] i (7,12,21,26,27). This raises the possibility that changes in NO production under some physiological conditions may be independent of changes in endothelial [Ca 2ϩ ] i . Endothelium-dependent relaxation in response to ACh is impaired in the aorta, resistance arteries, and microvessels of rats fed a high-salt (HS) diet (2-5, 15, 16, 18, 28). Elevated dietary salt intake causes suppression of plasma ANG II levels (8, 9), and previous studies (18,30,31) have demonstrated that the impaired vascular relaxation in Sprague-Dawley rats fed a HS diet can be prevented by a continuous intravenous infusion of a low dose of ANG II to maintain normal circulating levels of ANG II.In the present study, we tested the hypothesis that receptormediated increases in [Ca 2ϩ ] i and/or...

Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50 ~ 60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12-3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.

The 81-bp region of the rpoB gene in 66 Rif r Mycobacterium tuberculosis isolates from China, Japan, Korea, and Taiwan was analyzed. Twelve single-nucleotide substitutions in the rpoB gene were detected. The most prevalent mutations were at Ser-531 (52%), Asp-516 (17%), and His-526 (11%). Mutations were not found in seven (11%) of the isolates. Higher mutation rates in 50 Beijing family isolates were found than in other isolates for mutations at Asp-516 (18 and 12.5%, respectively) and His-526 (12 and 6.3%, respectively). The different rates of mutation may reflect the choice of rifamycin analogs.