RAGE: a new frontier in chronic airways disease

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous inflammatory disorders of the respiratory tract characterized by airflow obstruction. It is now clear that the environmental factors that drive airway pathology in asthma and COPD, including allergens, viruses, ozone and cigarette smoke, activate innate immune receptors known as pattern-recognition receptors, either directly or indirectly by causing the release of endogenous ligands. Thus, there is now intense research activity focused around understanding the mechanisms by which pattern-recognition receptors sustain the airway inflammatory response, and how these mechanisms might be targeted therapeutically. One pattern-recognition receptor that has recently come to attention in chronic airways disease is the receptor for advanced glycation end products (RAGE). RAGE is a member of the immunoglobulin superfamily of cell surface receptors that recognizes pathogen- and host-derived endogenous ligands to initiate the immune response to tissue injury, infection and inflammation. Although the role of RAGE in lung physiology and pathophysiology is not well understood, recent genome-wide association studies have linked RAGE gene polymorphisms with airflow obstruction. In addition, accumulating data from animal and clinical investigations reveal increased expression of RAGE and its ligands, together with reduced expression of soluble RAGE, an endogenous inhibitor of RAGE signalling, in chronic airways disease. In this review, we discuss recent studies of the ligand–RAGE axis in asthma and COPD, highlight important areas for future research and discuss how this axis might potentially be harnessed for therapeutic benefit in these conditions.     

A preliminary risk assessment of potential exposure to naturally occurring estrogens from Beijing (China) market milk products

This study was conducted to determine the occurrence of the natural steroid hormones estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2) and estriol (E3) in 38 commercial milk samples obtained from markets in Beijing, China. Liquid Chromatography coupled with tandem mass spectrometry (LC–MS/MS) was employed to determine estrogens levels. The concentrations of E1, αE2, βE2 and E3 in different milk products varied from 0–146.12 ng/L, 0–70.12 ng/L, 0–31.85 ng/L to 0–2.18 ng/L, respectively. We compared exposures to estrogens through milk consumption with acceptable daily intakes (ADIs) and threshold for toxicological concern (TTC) to determine whether estrogen intakes from milk consumption are larger or smaller than the toxicity-based benchmarks. The combined margin of safety MOS (MOS_T) for total estrogens are about 72–99, 118–161, 539–1104, for 2–4, 4–7 year-old residential children, and adults, respectively. The lowest MOS_T for children of 2–4 years old result from comparing total of estrogens with the lowest TTC value (0.15 μg/person/day) (MOS = 3.5). The MOS values suggest that the individual and total estrogens that may present in milk are not causing a health risk for the local residents, including young children.     

Antimicrobial activity of Buchenavia tetraphylla against Candida albicans strains isolated from vaginal secretions

Context: Buchenavia tetraphylla (Aubl.) RA Howard (Combretaceae: Combretoideae) is an ethnomedicinal plant with reported antifungal action.

Objective: This study evaluates the antimicrobial activity of B. tetraphylla leaf extracts against clinical isolates of Candida albicans. The morphological alterations, combinatory effects with fluconazole and the cytotoxicity of the active extract were analyzed.

Materials and methods: Extracts were obtained using different solvents (hexane: BTHE; chloroform: BTCE; ethyl acetate: BTEE; and methanol: BTME). Antimicrobial activity was determined by the broth microdilution method using nine strains of C. albicans isolated from vaginal secretions and one standard strain (UFPEDA 1007).

Results: All extracts showed anti-C. albicans activity, including against the azole-resistant strains. The MIC values ranged from 156 to 2500?μg/mL for the BTHE; 156 to 1250?μg/mL for the BTCE; 625 to 1250?μg/mL for the BTME and 625?μg/mL to 2500?μg/mL for the BTEE. BTME showed the best anti-C. albicans activity. This extract demonstrated additive/synergistic interactions with fluconazole. Scanning electron microscopy analysis suggested that the BTME interferes with the cell division and development of C. albicans. BTME showed IC₅₀ values of 981 and 3935?μg/mL, against J774 macrophages and human erythrocytes, respectively. This extract also enhanced the production of nitric oxide by J774 macrophages.

Discussion and conclusion: Buchenavia tetraphylla methanolic extract (BTME) is a great source of antimicrobial compounds that are able to enhance the action of fluconazole against different C. albicans strains; this action seems related to inhibition of cell division.     

Protein Oxidative Stress and Dyslipidemia in Dialysis Patients

Our aim was to investigate and determine the associations between oxidative stress (OS), dyslipidemia and inflammation in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) using observational cross‐sectional study. Twenty patients in CAPD and 48 in HD for at least 8 weeks and aged ≥18 years were included in the study. Individuals with malignant or acute inflammatory disease were excluded. A control group of 17 healthy individuals was also recruited. The biochemical parameter evaluations were analyzed using colorimetric kits for albumin, serum glucose, total cholesterol (TC) and lipid fractions. To determine the inflammatory status, CRP, IL‐6 and TNF‐α were analyzed by automated chemiluminescence kits. Plasma advanced oxidation protein products (AOPP) were determined by spectrophotometry. Mean AOPP levels were significantly higher for the HD group compared to the control, and there was no difference in AOPP concentrations between the control and CAPD groups. Dialysis patients had levels of inflammatory parameters higher than controls, and showed a high prevalence of patients with dyslipidemia, especially in CAPD. In the HD group, AOPP was positively correlated with triglycerides (TG) and inversely associated with HDL. Also the HD group was observed to have negative associations between TNF‐α and HDL, LDL and TC. In the CAPD group, CRP was inversely correlated with HDL. Hemodialysis patients had increased protein OS and associations of inflammation and dyslipidemia were also observed in these dialysis groups. A more detailed characterization of the relations between oxidative stress and other more traditional risk factors has therapeutic importance, since cardiovascular diseases are the leading cause of death among dialysis patients.     

The mutagenic,antimutagenic and antioxidant properties of Hypericum lydium

Context: There is a growing market demand for Hypericum sp., a pharmacologically active plant that has been traditionally used to treat various ailments. However, there have been limited studies on the extract or essential oil of Hypericum lydium Boiss (Hypericaceae).

Objective: This study investigates for the first time the antioxidant, mutagenic and antimutagenic activity of an ethanol extract of H. lydium.

Material and methods: Ethanol extract from aerial parts of H. lydium harvested from Turkey were tested for this mutagenic and antimutagenic activities (2.0–0.002?mg/plate) using Ames Salmonella/microsome test system. 4-Nitro-o-phenylenediamine (4-NPD) (3?μg/plate) for the Salmonella typhimurium TA98 and sodium azide (NaN₃) (8?μg/plate) for the S. typhimurium TA100 were used as positive controls. The antioxidant activity, total antioxidant activity and phenolic constituent of the extract (2.0–0.002?mg/mL) was determined by the inhibition of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), β-carotene-linoleic acid model and by means of Folin–Ciocalteu reagent, respectively.

Results: The extract showed no sign of mutagenicity at the tested concentrations (0.002–2.0?mg/mL), and showed concentration-dependent antimutagenic activity against NaN₃ and 4-NPD ranging from 26.8 to 81.5%. The extract was found to be an efficient scavenger of DPPH (IC₅₀ 0.165?±?0.23?mg/mL) and to inhibit β-carotene-linoleic acid bleaching (IC₅₀ 0.39?±?0.11?mg/mL).

Discussion and conclusion: These findings indicate ethanol extract of H. lydium to be a safe and effective agent that may be incorporated into new strategies for the prevention of cancer and mutagenesis.     

Associations Between Initial Subjective Experiences with Tobacco and Self-Reported Recent Use in Young Adulthood

Background: Youth tobacco use behaviors are predictive of patterns in adulthood and effect long-term health outcomes. Yet, few studies have examined the effect of initial subjective experiences (ISEs) during first tobacco use, which has been found to be an indicator of individuals. sensitivity to nicotine and vulnerability to dependence. Objective: The present study aimed to determine the prevalence of ISEs across a variety of tobacco products, evaluate the factor structure of ISEs by first tobacco product used, and examine the relationship between ISEs and recent (30-day) use of tobacco products across time, using a university sample. Methods: Exploratory factor analyses were conducted to identify latent factors present with respect to items measuring ISEs with tobacco, separately by tobacco product (e.g. cigarettes, cigars, hookah, e-cigarettes). Factor scores for positive and negative ISEs were calculated. Multiple logistic regression analyses were conducted to examine associations between ISEs and recent use of each tobacco product, adjusted for age at first use, sex, race/ethnicity, and cohort. Results: ISEs differ by the first tobacco product used. Associations between factor scores for positive and negative ISEs and recent use were found across a variety of tobacco products. Overall, positive ISEs were more strongly associated with recent use, relative to negative ISEs. Conclusions: Further research is needed to identify genetic and biological pathways and social contexts influencing initial subjective experiences with tobacco use, in efforts to delay the initiation for tobacco use and reduce risk for continued use among young adults.