The aims of this study were to evaluate the implication of food allergy as a cause of paediatric constipation and to determine the diet period needed to tolerate the constipation-causing foods. Fifty-four children aged 6 months to 14 years (median, 42 months) suffering from chronic constipation (without anatomic abnormalities, cοeliac disease or hypothyroidism), unresponsive to a 3-month laxative therapy, were prospectively evaluated. All participants were evaluated for allergy to cow's milk, egg, wheat, rice, corn, potato, chicken, beef and soy, using skin tests (SPT), serum specific IgE and atopy patch test (APT). A withdrawal of the APT-positive foods was instructed. Thirty-two children had positive APT; 15 were positive to one; six, to two and 11, to three or more food allergens, wheat and egg being the commonest. After withdrawing the APT-positive foods for an 8-week period, constipation had improved in 28/32 children, but a relapse of constipation was noticed after an oral food challenge, so they continued the elimination diet. Tolerance to food allergens was achieved in only 6/28 after 6 months, compared to 25/28 after 12 months and to all after a 2-year-long elimination. Food allergy seems to be a significant etiologic factor for chronic constipation not responding to treatment, in infants and young children. APT was found to be useful in evaluating non-IgE allergy-mediated constipation, and there was no correlation of APT with IgE detection. Tolerance was adequately achieved after 12 months of strict food allergen elimination.

Celiac disease is increasingly recognized autoimmune enteropathy caused by a permanent gluten intolerance. Gluten is the main storage protein of wheat, in genetically predisposed individuals. Celiac disease risk in first degree relatives is about 10%. Diarrhea and changes of bowel movement, observed as well in celiac disease as in IBS, may lead to misdiagnosis of IBS basing on the Rome criteria or may be associated with coexistence of both diseases. The aim of the study was to assess the celiac disease prevalence in patients with irritable bowel syndrome. The study group comprised 200 patients (120 women and 80 men) aged 18-78 years (mean: 46.7 years) with diarrhoeal form of irritable bowel syndrome (IBS), according to the Rome criteria II. At the beginning and after a three month period anti tissue transglutaminase antibodies (IgA tTG) were estimated. Gastroscopy with biopsy where performed in those with IgA tTG titre above 1/200. 40 patients were immunologically positive and 14 of them have histopathologically proven celiac disease. In the group of patients with detected celiac disease, gluten free diet was applied besides the treatment with trimebutin or mebewerin, recommended for IBS. After 6 months the decrease of IgA tTG titre in the serum was observed. In 5 of these patients IgA tTG level was negative. It was associated with the significant decrease of clinical symptoms, such as diarrhea and flatulence. The remaining symptoms, such as abdominal pain, feeling of incomplete defecation demanded continuation of IBS treatment. With regard to often atypical celiac disease symptoms--adult active searching should be performed to differentiate from irritable bowel syndrome.

BACKGROUND:Prospective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person.

METHODS:We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED ('PREvención con DIeta MEDiterránea') study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess theassociation between yearly repeated measurements of nut consumption and mortality.

RESULTS:During a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend<0.05, all). Compared to non-consumers, subjects consuming nuts>3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts>3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66).

CONCLUSIONS:Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165.

TRIAL REGISTRATION:Clinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

BACKGROUND:Garlic capsule (GAR) and/or selenium- vitamin A, C, E (S-VACE) might be useful in the treatment of lung diseases. The present study evaluated the toxicity of lisinopril (LIS) in the lungs of male rats and the reversal effect of GAR and/or selenium-vitamins A, C, and E (S-VACE).

METHODS:Group I served as the control, whereas animals in groups II, III, IV, and V received 28 mg of LIS/kg body weight by gavage. Group III was co-treated with GAR at a therapeutic dosage of 250 mg/kg body weight per day. Group IV was co-treated with S-VACE at dosage of 500 mg/kg body weight per day. Lastly, group V was co-treated with GAR and S-VACE at dosages of 250 and 500 mg/kg body weight per day, respectively. The experiment lasted for 8 days (sub-acute exposure).

RESULTS:Administration of therapeutic dose of LIS to male rats depleted enzymatic antioxidants (superoxide dismutase and catalase) and cellular adenosine triphosphate content with concomitant increase in lipid peroxidation. Histopathology examination showed damage to the epithelial cells of the airways. These effects were prevented by both single and combination treatment of GAR and S-VACE in male rats with LIS-induced lung toxicity.

CONCLUSIONS:We therefore concluded that the combination of GAR and S-VACE can be a novel therapy for the management of lung diseases in humans.

BACKGROUND & AIMS:Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD).

METHODS:We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every 3 months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a subdimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains.

RESULTS:At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (P<.001). At baseline, 30.1% of CD patients had moderate to severe GERD (score>3) compared with 5.7% of controls (P<.01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%; P<.03). A rapid improvement was evidenced at 3 months after initial treatment with a GFD (P<.0001) with reflux scores comparable to healthy controls from this time point onward.

CONCLUSIONS:GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.

A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4-76.8mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.

Biological immunomodulators are routinely evaluated as a natural source of molecules with profound effects on the immune system. They belong to a group of physiologically active compounds, collectively termed biological response modifiers. Most of the studies were focused on immune system stimulation. Recently, they have become the focus of studies seeking molecules that are able to overcome negative effects of various immunotoxins. This paper concentrates on the effects of a glucan/resveratrol/vitamin C combination on immunosuppressive effects of mercury and perfluorinated hydrocarbons. Effects described in this review have strong clinical potential, as environmental contaminants have adverse effects on all aspects of the immune system and represent a serious threat to the health of both humans and animals.

Oxaliplatin, a platinum-based anti-cancer drug, induces peripheral neuropathy as a side effect and causes cold hyperalgesia in cancer patients receiving anti-cancer chemotherapy. In oxaliplatin-treated mice, aluminum was accumulated in the dorsal root ganglia (DRG), and accumulated aluminum in DRG or other organs aggravated oxaliplatin-induced neuropathic pain. To investigate whether aluminum oxalate, which is the compound of aluminum and oxaliplatin, might be the peripheral neuropathy inducer, the withdrawal responses of mice to coldness, the expression of transient receptor potential ankyrin 1 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays in DRG were analyzed in mice administered with aluminum oxalate. In addition, the concentrations of aluminum in aluminum oxalate-treated mice were significantly increased compared to those of mice treated with aluminum chloride. To alleviate neuropathic pain, glutathione (GSH), known as an antioxidant and a metal chelator, was injected into oxaliplatin-treated mice. The concentrations of aluminum in the DRG were decreased by the chelation action of GSH. Taken together, behavioral and molecular analyses also supported that aluminum accumulation on the DRG might be a factor for neuropathic pain. This result also suggested that the aluminum chelation by GSH can provide an alleviatory remedy of neuropathic pain for cancer patients with oxaliplatin-induced neuropathic pain.

OBJECTIVES/HYPOTHESIS: Wheat is one of the most common food allergens found in patients with Meniere's disease (MD). Gluten from wheat has been identified to have a etiopathogenetic role in celiac disease, IgE hypersensitivity to wheat disease, and recently to gluten sensitivity. The aim of this study was to verify the incidence of gliadin prick test response in patients affected by MD. STUDY DESIGN: Prospective individual case-control study. METHODS: There were 58 adult patients with definite MD, 25 healthy volunteers, and 25 patients with grass pollen rhinoconjunctivitis tested with skin prick test to gliadin. RESULTS: A total of 33 MD patients (56.9%) proved to be sensitive to gliadin, eight of whom were positive to prick test after 20 minutes, 13 after 6 hours, 11 after 12 hours, and one after 24 hours. CONCLUSIONS: This is the first report of gliadin skin test response in MD. Further studies are needed to define the relationship between immune response to wheat proteins and MD symptoms.

BACKGROUND:It has been suggested that peptides from gluten and casein may have a role in the origins of autism and that the physiology and psychology of autism might be explained by excessive opioid activity linked to these peptides. Research has reported abnormal levels of peptides in the urine and cerebrospinal fluid of persons with autism. If this is the case, diets free of gluten and /or casein should reduce the symptoms associated with autism.

OBJECTIVES:To determine the efficacy of gluten- and/or casein- free diets as an intervention to improve behaviour, cognitive and social functioning in individuals with autism.

SEARCH STRATEGY:Electronic searching of abstracts from the Cochrane Library (Issue 3, 2003), PsycINFO (1971- May 2003), EMBASE (1974- May 2003), CINAHL (1982- May 2003), MEDLINE (1986- May 2003), ERIC (1965-2003), LILACS (to 2003) and the specialist register of the Cochrane Complementary Medicine Field (January 2004). Review bibliographies were also examined to identify potential trials.

SELECTION CRITERIA:All randomised controlled trials involving programmes which eliminated gluten, casein or both gluten and casein from the diets of individuals diagnosed with autistic spectrum disorder.

DATA COLLECTION AND ANALYSIS:Abstracts of studies identified in searches of electronic databases were read and assessed to determine whether they might meet the inclusion criteria. The authors independently selected the relevant studies from the reports identified in this way. As only one trial fitted the inclusion criteria, no meta-analysis is currently possible and data are presented in narrative form.

MAIN RESULTS:The one trial included reported results on four outcomes. Unsurprisingly in such a small-scale study, the results for three of these outcomes (cognitive skills, linguistic ability and motor ability) had wide confidence intervals that spanned the line of nil effect. However, the fourth outcome, reduction in autistic traits, reported a significant beneficial treatment effect for the combined gluten- and casein- free diet.

REVIEWERS' CONCLUSIONS:This is an important area of investigation and large scale, good quality randomised controlled trials are needed.

Gluten exclusion (protein complex present in many cereals) has been proposed as an option for the prevention of diseases other than coeliac disease. However, the effects of gluten-free diets on obesity and its mechanisms of action have not been studied. Thus, our objective was to assess whether gluten exclusion can prevent adipose tissue expansion and its consequences. C57BL/6 mice were fed a high-fat diet containing 4.5% gluten (Control) or no gluten (GF). Body weight and adiposity gains, leukocyte rolling and adhesion, macrophage infiltration and cytokine production in adipose tissue were assessed. Blood lipid profiles, glycaemia, insulin resistance and adipokines were measured. Expression of the PPAR-α and γ, lipoprotein lipase (LPL), hormone sensitive lipase (HSL), carnitine palmitoyl acyltransferase-1 (CPT-1), insulin receptor, GLUT-4 and adipokines were assessed in epidydimal fat. Gluten-free animals showed a reduction in body weight gain and adiposity, without changes in food intake or lipid excretion. These results were associated with up-regulation of PPAR-α, LPL, HSL and CPT-1, which are related to lipolysis and fatty acid oxidation. There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ. Moreover, intravital microscopy showed a lower number of adhered cells in the adipose tissue microvasculature. The overexpression of PPAR-γ is related to the increase of adiponectin and GLUT-4. Our data support the beneficial effects of gluten-free diets in reducing adiposity gain, inflammation and insulin resistance. The data suggests that diet gluten exclusion should be tested as a new dietary approach to prevent the development of obesity and metabolic disorders.

Eight adult female patients suffering from abdominal pain and chronic diarrhea which was often incapacitating and frequently nocturnal, had dramatic relief on a gluten-free diet and return of symptoms after gluten challenge. Previous nonspecific measures and a milk-free diet were ineffective. Multiple jejunal biopsies showed minor, but significant changes in cellularity which returned to normal on the gluten-free diet. Apart from a slight increase in jejunal cellularity, no immunological abnormalities were found after gluten challenge. Steatorrhea or other biochemical defects, common in celiac disease, were not found. It was concluded that these patients had a gluten-sensitive diarrhea, but had no evidence of celiac disease.

Twenty selected patients with recurrent aphthous stomatitis in whom celiac disease had been specifically excluded were placed on a gluten-free diet. Five patients (25%) showed a favorable response to gluten withdrawal and a positive gluten challenge. Jejunal morphology was normal in all patients indicating gluten sensitivity without enteropathy. Gluten withdrawal provides a further method of treating some patients with recurrent aphthous stomatitis.

The use of vaccines including aluminum (Al)-based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher ( P<.001) in the lymph nodes of the vaccine group (82.65μg/g) compared with both adjuvant-only (2.53 μg/g) and control groups (0.96 μg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.

OBJECTIVE:Juvenile skin has been the subject of intense research efforts since ancient times. This article reports on synergistic complementarities in the biological actions of green tea and red light, which inspired the design of a green tea-assisted facial rejuvenation program.

BACKGROUND DATA:The approach is based on previous laboratory experiments providing insight into a mechanism by which visible light interacts with cells and their microenvironment.

METHODS:After 2 months of extreme oxidative stress, green tea-filled cotton pads were placed once per day for 20 minutes onto the skin before treatment with an array of light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm2).

RESULTS:Rejuvenated skin, reduced wrinkle levels, and juvenile complexion, previously realized in 10 months of light treatment alone were realized in 1 month.

CONCLUSION:The accelerated skin rejuvenation based on the interplay of the physicochemical and biological effects of light with the reactive oxygen species scavenging capacity of green tea extends the action spectrum of phototherapy. The duo opens the gate to a multitude of possible biomedical light applications and cosmetic formulas, including reversal of topical deterioration related to excess reactive oxygen species, such as graying of hair.

OBJECTIVE:Juvenile skin has been the subject of intense research efforts since ancient times. This article reports on synergistic complementarities in the biological actions of green tea and red light, which inspired the design of a green tea-assisted facial rejuvenation program.

BACKGROUND DATA:The approach is based on previous laboratory experiments providing insight into a mechanism by which visible light interacts with cells and their microenvironment.

METHODS:After 2 months of extreme oxidative stress, green tea-filled cotton pads were placed once per day for 20 minutes onto the skin before treatment with an array of light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm2).

RESULTS:Rejuvenated skin, reduced wrinkle levels, and juvenile complexion, previously realized in 10 months of light treatment alone were realized in 1 month.

CONCLUSION:The accelerated skin rejuvenation based on the interplay of the physicochemical and biological effects of light with the reactive oxygen species scavenging capacity of green tea extends the action spectrum of phototherapy. The duo opens the gate to a multitude of possible biomedical light applications and cosmetic formulas, including reversal of topical deterioration related to excess reactive oxygen species, such as graying of hair.

OBJECTIVE:Juvenile skin has been the subject of intense research efforts since ancient times. This article reports on synergistic complementarities in the biological actions of green tea and red light, which inspired the design of a green tea-assisted facial rejuvenation program.

BACKGROUND DATA:The approach is based on previous laboratory experiments providing insight into a mechanism by which visible light interacts with cells and their microenvironment.

METHODS:After 2 months of extreme oxidative stress, green tea-filled cotton pads were placed once per day for 20 minutes onto the skin before treatment with an array of light-emitting diodes (central wavelength 670 nm, dermal dose 4 J/cm2).

RESULTS:Rejuvenated skin, reduced wrinkle levels, and juvenile complexion, previously realized in 10 months of light treatment alone were realized in 1 month.

CONCLUSION:The accelerated skin rejuvenation based on the interplay of the physicochemical and biological effects of light with the reactive oxygen species scavenging capacity of green tea extends the action spectrum of phototherapy. The duo opens the gate to a multitude of possible biomedical light applications and cosmetic formulas, including reversal of topical deterioration related to excess reactive oxygen species, such as graying of hair.

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy.

CASE REPORT:In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient's teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86× 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely.

CONCLUSIONS:The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.