Polyunsaturated Fatty Acids Attenuate Diet Induced Obesity and Insulin Resistance, Modulating Mitochondrial Respiratory Uncoupling in Rat Skeletal Muscle.

OBJECTIVES: Omega (ω)-3 polyunsaturated fatty acids (PUFA) are dietary compounds able to attenuate insulin resistance. Anyway, the precise actions of ω-3PUFAs in skeletal muscle are overlooked. We hypothesized that PUFAs, modulating mitochondrial function and efficiency, would ameliorate pro-inflammatory and pro-oxidant signs of nutritionally induced obesity. STUDY DESIGN: To this aim, rats were fed a control diet (CD) or isocaloric high fat diets containing either ω-3 PUFA (FD) or lard (LD) for 6 weeks. RESULTS: FD rats showed lower weight, lipid gain and energy efficiency compared to LD-fed animals, showing higher energy expenditure and O2 consumption/CO2 production. Serum lipid profile and pro-inflammatory parameters in FD-fed animals were reduced compared to LD. Accordingly, FD rats exhibited a higher glucose tolerance revealed by an improved glucose and insulin tolerance tests compared to LD, accompanied by a restoration of insulin signalling in skeletal muscle. PUFAs increased lipid oxidation and reduced energy efficiency in subsarcolemmal mitochondria, and increase AMPK activation, reducing both endoplasmic reticulum and oxidative stress. Increased mitochondrial respiration was related to an increased mitochondriogenesis in FD skeletal muscle, as shown by the increase in PGC1-α and -ß. CONCLUSIONS: our data strengthened the association of high dietary ω3-PUFA intake with reduced mitochondrial energy efficiency in the skeletal muscle.

Gut microbiota as potential therapeutic target for the treatment of cow's milk allergy.

Cow's milk allergy (CMA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with about 80% naturally acquiring tolerance by the age of four years. However, recent studies suggest that the natural history of CMA is changing, with an increasing persistence until later ages. The pathogenesis of CMA, as well as oral tolerance, is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by CMA and healthy infants. These findings prompt the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells. The aim of this paper is to review what is currently known about the use of probiotics as dietary supplements in CMA.

Crenotherapy modulates the expression of proinflammatory cytokines and immunoregulatory peptides in nasal secretions of children with chronic rhinosinusitis.

BACKGROUND: The effect of crenotherapy on major mucosal markers of inflammation, TNF alpha, human beta-defensins 2 (hBD-2), and calprotectin, are largely unexplored in pediatric chronic rhinosinusitis (CRS). The aim of this study was to investigate the effects of crenotherapy with sulfate-sodium-chloride water on mucosal markers of inflammation in children with CRS. METHODS: Children with CRS received 15-day crenotherapy consisting of sulfate-sodium-chloride thermal water inhalations by nasal aerosol (15 minutes/day). Concentrations of nasal mucosal markers of inflammation (TNF alpha, hBD-2, and calprotectin) were measured before and after crenotherapy. Presence of specific symptoms (nasal obstruction, nasal discharge, facial pain, sense of smell, and cough), value of symptoms score sino-nasal 5 (SN5), quality of life (QoL) score (1 [worse] to 10 [optimal]) were also assessed. RESULTS: After crenotherapy a significant reduction was observed in TNF alpha (from 0.14 ± 0.02 to 0.08 ± 0.01; p < 0.001), calprotectin (from 2.9 ± 1.0 to 1.9 ± 0.5; p < 9.001), and hBD-2 (from 2.0 ± 0.1 to 0.9 ± 0.6; p < 0.001) concentrations. A significant (p < 0.05) reduction in number of subjects presenting symptoms of nasal obstruction (100% versus 40%), nasal discharge (33% versus 13%), facial pain (30% versus 10%), and sense of smell (60% versus 20%) was observed. A significant improvement of SN5 (from 3.07 ± 0.76 to 2.08 ± 0.42; p < 0.001) was observed after the crenotherapy. QoL also improved after crenotherapy (from 4.2 ± 1.1 to 6.6 ± 1.0; p < 0.001). CONCLUSION: Crenotherapy induced a down-regulation of nasal mucosal inflammatory mediators in children with CRS.

Epigenetic mechanisms elicited by nutrition in early life.

A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

Results from the pediatric European register for treatment of Helicobacter pylori (PERTH).

BACKGROUND AND AIM: Data on the eradication treatment for childhood Helicobacter pylori are scanty. A register was established on the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) website to collect data on treatment performed by European pediatricians to ascertain what is practiced in the field. SUBJECTS: From January 2001 to December 2002, information on 597 children were entered by 23 European Centers, but only data of 518 treated children were completed and analyzed (86.7%, 262 male subjects, median age 9 years, range 1-14). According to their nationality, 226 children were from Southern Europe, 132 from Eastern Europe, 68 from Western Europe, and 4 from northern Europe, 68 from North Africa, and 20 from Asia. At endoscopy, 454 children had gastritis and 64 had ulcer (12.3%). Antibiotic sensitivity, tested in 361 cases, revealed 18% clarithromycin-resistant and 19% metronidazole-resistant H. pylori strains. RESULTS: Treatment was performed for 1 week in 388 and for 2 weeks in 130 children. Antibiotics were associated with proton pump inhibitors (PPI) in 345 and with bismuth in 121 children. Triple therapy was given to 485 children, dual therapy to 26, quadruple to 7. Follow-up data, by (13)C-Urea-Breath Test or histology or both, were available for 480 children. Overall eradication rate was 65.6%, significantly higher in children with ulcer (79.7%) than without (63.9%, p = .001). When given as first treatment, bismuth-containing triple therapies were more efficacious than PPI-containing ones (77% versus 64%, p = .02, OR 1.88, 95% CI 1.1-3.3). Twenty-seven different treatment regimens were used, but only six were administered to at least 18 children (range 18-157). There was no difference between treatments given for 1 or 2 weeks, or given as first or second therapies. CONCLUSION: European pediatricians entering data in the register used 27 different regimens. Bismuth-containing therapies resulted in higher eradication rate. Omeprazole-containing triple therapies were the most used although their efficacy was low. Therapies recommended for adults do not appear to be suitable for children.

Zinc fights diarrhoea in HIV-1-infected children: in-vitro evidence to link clinical data and pathophysiological mechanism.

Diarrhoea-related morbidity is reduced by zinc supplementation in HIV-1-infected children. The mechanisms of this effect are largely undefined. We provide evidence for role for Tat (transactivating peptide produced by HIV-1) in the pathogenesis of diarrhoea in AIDS patients. In this study we showed that zinc, preventing Tat-induced fluid secretion, directly limits a specific mechanism of HIV-1-related diarrhoea. Our data support a 'zinc approach' in adjunct to specific antiretroviral therapy in HIV-1-infected children.

Zinc inhibits cholera toxin-induced, but not Escherichia coli heat-stable enterotoxin-induced, ion secretion in human enterocytes.

BACKGROUND: Because zinc deficiency in malnourished children is associated with severe diarrhea, use of zinc supplementation has been proposed as an adjunct to oral rehydration. However, the effects of zinc on enterocyte ion transport are largely unknown. The objective of the present study was to investigate the effects of zinc on transepithelial ion transport under basal conditions and under conditions of enterotoxin-induced ion secretion. METHODS: Ion transport was investigated by monitoring electrical parameters in human intestinal Caco-2 cells that were mounted in Ussing chambers and exposed to increasing concentrations of zinc, both in the absence and presence of either cholera toxin (CT) or Escherichia coli heat-stable enterotoxin (ST). Intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) concentrations were also determined. RESULTS: The addition of zinc to the luminal or basolateral side of enterocytes induced a chloride-dependent, dose-related decrease in short-circuit current, indicating ion absorption. It also resulted in a substantial reduction in CT-induced ion secretion and in cAMP concentration. E. coli ST-induced ion secretion and cGMP concentration were not affected. Ion absorption peaked at 35 mu mol/L zinc, whereas excess zinc load induced active ion secretion. CONCLUSIONS: By causing a decrease in cAMP concentration, zinc directly promotes ion absorption and substantially reduces CT-induced, but not E. coli ST-induced, ion secretion.