Varenicline Prevents LPS-Induced Inflammatory Response via Nicotinic Acetylcholine Receptors in RAW 264.7 Macrophages.

The cholinergic anti-inflammatory pathway plays an important role in controlling inflammation. This study investigated the effects of varenicline, an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, on inflammatory cytokine levels, cell proliferation, and migration rates in a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 murine macrophage cell lines. The cells were treated with increasing concentrations of varenicline, followed by LPS incubation for 24 h. Prior to receptor-mediated events, anti-inflammatory effects of varenicline on different cytokines and chemokines were investigated using a cytokine array. Nicotinic AChR-mediated effects of varenicline were investigated by using a non-selective nAChR antagonist mecamylamine hydrochloride and a selective α7nAChR antagonist methyllycaconitine citrate. TNFα, IL-1ß, and IL-6 levels were determined by the ELISA test in cell media 24 h after LPS administration and compared with those of dexamethasone. The rates of cellular proliferation and migration were monitored for 24 h after drug treatment using a real-time cell analysis system. Varenicline decreased LPS-induced cytokines and chemokines including TNFα, IL-6, and IL-1ß via α7nAChRs to a similar level that observed with dexamethasone. Varenicline treatment decreased LPS-induced cell proliferation, without any nAChR involvement. On the other hand, the LPS-induced cell migration rate decreased with varenicline via α7nAChR. Our data suggest that varenicline inhibits LPS-induced inflammatory response by activating α7nAChRs within the cholinergic anti-inflammatory pathway, reducing the cytokine levels and cell migration.

Therapeutic effects of melatonin on an ovalbumin-induced allergic rhinitis model in rats.

OBJECTIVE: We aimed to investigate the therapeutic effects of melatonin in an experimental AR model. METHODS: Thirty-two Wistar rats were randomised into four groups (n = 8 each). The experimental AR model was established in the saline (SF), ethanol, and melatonin groups via intraperitoneal (i.p.) injections and intranasal application of ovalbumin. The SF, ethanol, and melatonin groups received daily i.p. saline, 2% ethanol dissolved in saline, and 10 mg/kg melatonin dissolved in 2% ethanol and saline. The control group received the same amount of i.p. and intranasal saline. Total nasal symptom scores were recorded in all rats on days 1 (baseline), 15, 20, 25, and 30. Serum ovalbumin-specific IgE, IL-13, and melatonin levels were measured on days 1 (baseline), 15, and 30. The nasal mucosa of all rats was scored histopathologically. RESULTS: The total nasal symptom scores and serum ovalbumin-specific IgE values of the SF, ethanol, and melatonin groups were significantly higher on day 15 than those of the control group. On day 30, the scores and serum ovalbumin-specific IgE values of the melatonin group were similar to those of the control, whereas the SF and ethanol groups had statistically higher scores. The histological scores of the SF and ethanol groups were significantly higher than those of the control and melatonin groups, but no significant difference was found between the melatonin and control groups. CONCLUSION: Melatonin reduced total nasal symptom scores and serum ovalbumin-specific IgE levels and improved histological inflammation parameters in the ovalbumin-induced rat experimental AR model.

Towards patient-centred cancer care: cross-cultural validity and responsiveness of the Turkish Integrated Palliative care Outcome Scale.

BACKGROUND: A valid measure to describe the most important needs and concerns of people with life-threatening illnesses is missing in Cyprus. Our aim was to adapt and test the cross-cultural validity and responsiveness of the Integrated Palliative care Outcome Scale (IPOS) in a cohort of Turkish speaking cancer patients. METHODS: The IPOS (English) patient-reported measure was translated into Turkish following published guidelines including, 2 independent forward, 2 independent blind backward translations, expert panel review by 7 members and field testing with 11 cognitive interviews (5 patients and 6 specialists) and final approval of the copyright holder. Consecutive cancer patients (n = 234) seen by the community palliative care services were recruited from Help Those with Cancer Society (KHYD); of those 82 were followed-up. The instrument was administered by personal interview. Confirmatory Factor Analysis was used to validate the factor structure of Turkish IPOS. Internal consistency reliability of the subscales was evaluated by Cronbach's alpha and Intraclass Correlation Coefficient respectively. Validity was assessed by calculating Pearson's correlation coefficient (r) between Turkish IPOS scores and Turkish version of EQ-5D-3L - a validated generic measure of health status developed by the EuroQol Group. RESULTS: Turkish IPOS is conceptually and semantically equivalent to the English version and linguistically valid. The CFA was inconclusive for the three factor structure due to low sample size, as the SRMR and CFI tests only approached the defined minimums warranting further investigation. There were low levels of missing values, and no ceiling or floor effects. The Physical (α = 0.91) and the Social and Quality of Care Issues (α = 0.75) sub-scales showed good internal consistencies, however Emotional sub-scale showed poor internal consistency (α = 0.64). The reliability of the Physical (ICC = 0.51, 0.45-0.56 95% CI) and Social Quality of Care Issues (ICC = 0.50, 0.42-0.57 95% CI) were moderate. Poor internal consistency (α =0.64) and reliability (ICC = 0.31, 0.24-0.39, 95% CI) was obtained for Emotional Subscale. Construct validity was evidenced through significant correlations in the predicted directions and strength with EQ-5D. Turkish IPOS showed higher needs and concerns in participants at more advanced stages than those at earlier stages of cancer. The standardized response mean (SRM) of - 0.94 suggested large internal responsiveness to clinical change. CONCLUSION: Turkish IPOS is a clear, relevant, acceptable measure and responsive to the needs and concerns of cancer patients, observing regional differences, it may have implications for use in other Turkish speaking communities. Future studies are needed to clarify the factor structure, assess its external responsiveness and to improve the properties of its Emotional subscale.