Efficacy of a Mediterranean diet supplemented with fatty fish in ameliorating inflammation in paediatric asthma: a randomised controlled trial.

BACKGROUND: Childhood asthma is the most common respiratory disorder worldwide, being associated with increased morbidity and a decreased quality of life. Omega-3 fatty acids have anti-inflammatory and immunomodulating properties; however, their efficacy in asthma is controversial. The present study aimed to examine the efficacy of a Mediterranean diet supplemented with a high omega-3 'fatty' fish intake in Greek asthmatic children. METHODS: A single-centred, 6-month, parallel randomised controlled trial compared the consumption of a Mediterranean diet supplemented with two meals of 150 g of cooked fatty fish weekly (intervention) with the usual diet (control) with respect to pulmonary function in children (aged 5-12 years) with mild asthma. Pulmonary function was assessed using spirometry and bronchial inflammation by fractional exhaled nitric oxide analysis. RESULTS: Sixty-four children (52% male, 48% female) successfully completed the trial. Fatty fish intake increased in the intervention group from 17 g day-1 at baseline to 46 g day-1 at 6 months (P < 0.001). In the unadjusted analysis, the effect of the intervention was of borderline significance (P = 0.06, ß = -11.93; 95% confidence interval = -24.32 to 0.46). However, after adjusting for age, sex, body mass index and regular physical activity, a significant effect was observed (P = 0.04, ß = -14.15 ppb; 95% confidence interval = -27.39 to -0.91). No difference was observed for spirometry, asthma control and quality of life scores. CONCLUSIONS: A Mediterranean diet supplemented with two fatty fish meals per week might be a potential strategy for reducing airway inflammation in childhood asthma. Future robust clinical trials are warranted to replicate and corroborate these findings.

The role of fish intake on asthma in children: A meta-analysis of observational studies.

BACKGROUND: The evidence is mixed on the use of long chain Omega-3 fatty acids in the prevention and management of childhood asthma. METHODS: We conducted a systematic search and meta-analysis investigating the role of fish intake, the main dietary source of long chain omega-3 fatty acids, on asthma in children. RESULTS: A total of 1119 publications were identified. Twenty-three studies on fish intake in association with childhood asthma were included in the final review. In 15 of 23 studies, early introduction of fish (6-9 months) and regular consumption (at least once a week) improved asthma symptoms and reduced risk in children 0-14 years as compared to no fish consumption; 6 of 23 showed no effect and 2 of 23 studies suggest adverse effects. Meta-analysis revealed an overall "beneficial effect" for "all fish" intake on "current asthma" [OR: 0.75; 95%CI: 0.60-0.95] and "current wheeze" [OR: 0.62; 95%CI: 0.48-0.80] in children up to 4.5 years old. An overall protective effect of "fatty fish" intake as compared to "no fish" intake in children 8-14 years old was also observed [OR: 0.35; 95%CI: 0.18-0.67]. CONCLUSION: This meta-analysis suggests that introduction of fish early in life (6-9 months) and regular consumption of all fish (at least once a week) reduces asthma and wheeze in children up to 4.5 years old, while fatty fish intake may be beneficial in older children. Future well-designed clinical trials are recommended to confirm the promising findings documented in this literature analysis.

Temperature effects on the viscosity and the wavelength-dependent refractive index of imidazolium-based ionic liquids with a phosphorus-containing anion.

A systematic study on the viscosity and refractive index of 1-alkyl-3-methylimidazolium based ionic liquids (alkyl = methyl, butyl and hexyl) combined with three phosphorus containing anions, i.e. dimethylphosphate, methyl methylphosphonate and methylphosphonate, is reported. Experimental measurements account for temperature effects, while the refractive index is determined at multiple wavelengths in the visible and near infrared region. Despite the structural similarity of these anions, significant differences in the physical properties of the resulting ILs are identified, along with the clear trend of viscosity increase - and refractive index decrease - with increasing alkyl chain length on the cation. Ab initio theoretical calculations are carried out to support and rationalise the observed behaviour.

Feeding and macronutrient selection patterns in rats: adrenalectomy and chronic corticosterone replacement.

To analyze further the role of corticosterone (CORT) in the control of feeding behavior, we examined the impact of adrenalectomy (ADX) and chronic CORT implants on the food intake and macronutrient self-selection patterns of adult male rats at different periods of the diurnal cycle. Consistent with a separate study of acute CORT injection in ADX rats (Kumar and Leibowitz, 1988), the present findings indicate that ADX significantly attenuated the rats' daily (24 hr) ingestion of all three macronutrients, namely, protein, carbohydrate and fat. However, food intake in the dark cycle, specifically during the first few hours after dark onset, was significantly more affected (-70%) than feeding in the later dark and light periods (-25%). Moreover, during this early dark time when circulating CORT level normally peaks, ADX appeared to have its strongest suppressive effect on carbohydrate ingestion. Chronic subcutaneous CORT implants in the ADX animals reversed these effects of surgery and generally restored the rats' eating patterns to that of the cholesterol-implanted SHAM animals. These findings suggest that CORT exerts a decisive influence on caloric intake, on the diurnal pattern of feeding, and on appetite for specific macronutrients. The impact of CORT on carbohydrate intake is apparent specifically during the active eating period, particularly at dark onset when endogenous CORT levels normally peak and carbohydrate is exhibited as the preferred macronutrient.

Glucose-dependent changes in alpha 2-noradrenergic receptors in hypothalamic nuclei.

Evidence indicates that hypothalamic norepinephrine (NE), acting via alpha 2-noradrenergic receptors, and also circulating glucose both have an important role in the control of normal feeding behavior in rats. In this report, we studied the relationship between glucose and the alpha 2-noradrenergic system, by manipulating blood glucose levels and analyzing changes in the binding of [3H]p-aminoclonidine [( 3H]PAC) to alpha 2-noradrenergic receptors in discrete hypothalamic areas. Brief periods (1-3 hr) of food deprivation, at the onset of the dark cycle, produced a significant decline in serum glucose levels and a simultaneous decrease in alpha 2-receptor binding sites, specifically in the hypothalamic paraventricular nucleus (PVN) as opposed to other hypothalamic areas. Restoration of circulating glucose levels, by refeeding for 0.5 hr after 2.5 hr food deprivation or by administration of glucose to 1 hr food-deprived rats, prevented this decline in serum glucose, as well as the reduction in PVN alpha 2-noradrenergic receptor density. In each of these experiments, a strong positive correlation between circulating glucose levels and PVN alpha 2-noradrenergic receptor sites was obtained. These findings suggest that blood glucose has direct impact upon alpha 2-noradrenergic receptor activity in the PVN and may affect feeding behavior, in part, through this neurochemical system.

The prognostic significance of immune changes in patients with renal cancer and melanoma treated with interferon-alpha 2b.

We evaluated the response rate and the immunorestorative properties of subcutaneously administered interferon-alpha 2b (IFN-alpha 2b) in patients with advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune status with clinical responses. Thirty-five patients with advanced RCC and 12 with MEL were treated with recombinant IFN-alpha 2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week and thereafter 15 x 10(6) IU subcutaneously. The response rate for RCC patients was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had stable disease, and (3) 20 patients progressed. The response rate for patients with MEL was as follows: (1) 4 patients experienced partial response and (2) 8 patients progressed. In all patients blood was withdrawn prior to IFN treatment and then monthly. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL-2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and interleukin-1 production (IL-1prod) by peripheral blood monocytes. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-alpha 2b. Patients with RCC experiencing a partial response showed a mean increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec and 76% in IL-1prod.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic significance of immune changes in patients with renal cancer, melanoma and colorectal cancer, treated with interferon alpha 2b.

In the present study we evaluated the response rate and the immunorestorative properties of interferon alpha 2b (IFn alpha 2b) administered to patients with advanced renal cell carcinoma (RCC), melanoma (MEL) or colorectal cancer (CC). We studied the immune status and correlated it with clinical responses. Thirty-five patients with advanced RCC, and 14 with MEL were treated with recombinant INF alpha 2b. The dose was increased progressively from 5 x 10(6) IU/day in the first week (three times every week) to 10 x 10(6) IU/day in the second week and thereafter to 15 x 10(6) IU/day subcutaneously. In patients with CC INF alpha 2b was given at 5 x 10(6) IU/day every other day (three times every week); these patients also received (together with INF) leucovorin 200 mg m-2 day-1 in a 1-h i.v. infusion every week, and mid-infusion 400 mg/m2 5-FU was administered as an intravenous bolus every week. The response rate was as follows: for RCC, 6 patients achieved partial response (PR), 10 stable disease (SD), and 21 progressed (PD); for MEL, 5 patients achieved PR and 9 PD; for CC, 6 achieved PR, 5 SD, and 9 PD. In all patients blood was withdrawn prior to INF alpha 2b treatment and then monthly. T lymphocytes, after isolation from peripheral blood, were tested for proliferation in the autologous mixed-lymphocyte reaction and allogeneic mixed-lymphocyte reaction, interleukin-2 (IL-2) production, expression of IL-2 receptors during the allogeneic-mixed-lymphocyte reaction, and the production of IL-1 by peripheral blood monocytes. Striking increases were demonstrated in all parameters 2 months after treatment with INF alpha 2b. In comparison to normal controls, all patients with the malignant neoplasms presented decreased (> 45%) mean values of the immunological parameters under investigation (P 0.0001). Responders (patients with RCC, MEL, and PR) presented lower mean values of all the parameters studied than did non-responders (P 0.0001). Patients with CC presented the lowest mean values of the parameters than did the other patients (RCC, MEL) (P 0.0001). After therapy with INF alpha 2b, patients with RCC experiencing PR showed a mean increase of more than 30% (P 0.0001). Patients with SD showed a mean increase of about 20% (P 0.0001), and those with PD showed a 6% increase in the immunological parameters under investigation. Patients with MEL experiencing PR showed a mean increase of more than 30% and patients with PD a decrease of more than 10% (P 0.0001). All patients, regardless of the clinical response, achieved an increase of more than 60% (P 0.0001). Administration of IFN alpha 2b resulted in a marked potentiation of a deficient cellular immune response in vitro in those patients with RCC and MEL who responded to the treatment. On the other hand, non-responders demonstrated a decrease in the examined parameters and, in some, deterioration of the already depressed immunological functions was observed. This observation can have prognostic significance regarding clinical response of INF. In contrast, our findings show that the immune stimulation associated with INF alpha treatment in all our CC patients did not predict an improved clinical outcome. There are several theoretical explanations for this discrepancy.