Living with coeliac disease and a gluten-free diet: a Canadian perspective.

OBJECTIVE: Strict adherence to a gluten-free diet is the only treatment for coeliac disease. The gluten-free diet is complex, costly and impacts on all activities involving food, making it difficult to maintain for a lifetime. The purpose of this cross-sectional study was to evaluate the difficulties experienced, the strategies used and the emotional impact of following a gluten-free diet among Canadians with coeliac disease. METHODS: A questionnaire was mailed to all members (n = 10 693) of both the Canadian Celiac Association and the Fondation québécoise de la maladie cœliaque in 2008. RESULTS: The overall response rate was 72%. Results are presented for the 5912 respondents (≥18 years) reporting biopsy-confirmed coeliac disease and/or dermatitis herpetiformis. Two-thirds never intentionally consumed gluten. Women reported significantly greater emotional responses to a gluten-free diet but, with time, were more accepting of it than men. Difficulties and negative emotions were experienced less frequently by those on the diet for >5 years, although food labelling and eating away from home remained very problematic. Frustration and isolation because of the diet were the most common negative emotions experienced. CONCLUSIONS: The present study quantifies the difficulties experienced, the strategies used and the emotional impact of following a gluten-free diet. It highlights the need to improve the training and education of dietitians, other health providers and the food service industry workers about coeliac disease and a gluten-free diet, with the aim of better helping individuals improve their adherence to a gluten-free diet and their quality of life.

Glutamate receptors in peripheral tissues: current knowledge, future research, and implications for toxicology.

We illustrate the specific cellular distribution of different subtypes of glutamate receptors (GluRs) in peripheral neural and non-neural tissues. Some of the noteworthy locations are the heart, kidney, lungs, ovary, testis and endocrine cells. In these tissues the GluRs may be important in mediating cardiorespiratory, endocrine and reproductive functions which include hormone regulation, heart rhythm, blood pressure, circulation and reproduction. Since excitotoxicity of excitatory amino acids (EAAs) in the CNS is intimately associated with the GluRs, the toxic effects may be more generalized than initially assumed. Currently there is not enough evidence to suggest the reassessment of the regulated safety levels for these products in food since little is known on how these receptors work in each of these organs. More research is required to assess the extent that these receptors participate in normal functions and/or in the development of diseases and how they mediate the toxic effects of EAAs. Non-neural GluRs may be involved in normal cellular functions such as excitability and cell to cell communication. This is supported by the wide distribution in plants and animals from invertebrates to primates. The important tasks for the future will be to clarify the multiple biological roles of the GluRs in neural and non-neural tissues and identify the conditions under in which these are up- or down-regulated. Then this could provide new therapeutic strategies to target GluRs outside the CNS.

Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity.

Glutamate receptors (GluRs) are ubiquitously present in the central nervous system (CNS) as the major mediators of excitatory neurotransmission and excitotoxicity. Neural injury associated with trauma, stroke, epilepsy, and many neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases and amyotrophic lateral sclerosis may be mediated by excessive activation of GluRs. Neurotoxicity associated with excitatory amino acids encountered in food, such as domoic acid and monosodium glutamate, has also been linked to GluRs. Less is known about GluRs outside the CNS. Recent observations suggest that several subtypes of GluRs are widely distributed in peripheral tissues. Using immunochemical and molecular techniques, the presence of GluR subtypes was demonstrated in the rat and monkey heart, with preferential distribution within the conducting system, nerve terminals, and cardiac ganglia. GluR subtypes NMDAR 1, GluR 2/3, and mGluR 2/3 are also present in kidney, liver, lung, spleen, and testis. Further investigations are needed to assess the role of these receptors in peripheral tissues and their importance in the toxicity of excitatory compounds. Therefore, food safety assessment and neurobiotechnology focusing on drugs designed to interact with GluRs should consider these tissues as potential target/effector sites.

Immunochemical localization of the metabotropic glutamate receptors in the rat heart.

The localization of the glutamate receptor outside of the central nervous system is becoming more evident. These receptors have been implicated in brain function and pathology. It can also be envisioned that they play a vital role in the physiology of other organs and systems. We recently reported the presence of ionotropic glutamate receptors in the rat heart. These were distributed differentially in specific cardiac structures, including nerve terminals, ganglion cells, and the conducting system. In this study, we investigated the presence and localization of the metabotropic glutamate receptors (mGluRs) in the rat heart by immunohistochemistry. The experimental data show that the mGluR 1alpha, mGLuR 2/3, and mGluR 5 are present in the rat heart. Their preferential localization includes nerve terminals, ganglion cells, and elements of the conducting system. The mGluR 5 was the only receptor located in the intercalated disks of the cardiac muscle and in the endothelial lining of the blood vessels. This preferential localization to the different components of the conducting system and cardiac neural structures suggest that they play a role in the physiology of the heart.

Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart.

Excitatory amino acids (EAA) and glutamate receptors (GluRs) play a fundamental role in the central nervous system (CNS). Ionotropic glutamate receptors (iGluRs) are coupled to ion channels, which are classified according to their most selective agonists. These ligand-gated channels are permeable to Na+, K+, and Ca+. Interaction of EAA receptor is linked to Ca+2/Na+ influx. Influx changes lead to an action potential, which in the heart is transmitted along the cardiocyte membrane. Furthermore, the heart has a rich innervation and specialized conduction system for rapid conduction and regulation of cardiac rhythmicity. Availability of EAA receptors in the heart might be important for cardiac function. The following GluRs were cloned by isoform-specific RT-PCR from rat heart ribonucleic acid (RNA): GluR 1, GluR 3, GluR 4, GIuR 7, Ka 1, and Ka 2. Expression in cardiac tissue was confirmed by western (for anti-GluR 2/3) and northern blots (for GluR 3, NMDAR 1, and Ka 2). The anatomical distribution was investigated by immunohistochemistry. Antibodies to GluR 2/3, GluR 5/6/7, Ka 2, and NMDAR 1 showed the strongest signals. These signals were specifically localized to cardiac nerve terminals, ganglia, conducting fibers, and some to myocardiocytes particularly in the atrium. Each antibody had a specific pattern of distribution. This anatomical localization suggests that they might play a role in cardiac electrophysiology and pathology.

Age-related changes in GABA and benzodiazepine receptor binding in rat brain are influenced by sampling time.

1. This study examined the saturation binding of tritiated gamma-aminobutyric acid [( 3H]GABA) and [3H]diazepam in brain membranes from young (3 month-old) and aged (21-23 month-old) Long Evans male rats killed at two time points in the 24-hour cycle. 2. The daytime density of low-affinity GABA binding sites was significantly (p less than 0.05) lower in cortical membranes from aged animals. There were no differences between young and old rats in low-affinity GABA binding at night, or in high-affinity GABA binding at either time point. 3. Diazepam binding was significantly lower in the brains of aged animals killed during the daytime. There was no differences at night, when diazepam binding in young animals declined to match that of aged animals. 4. There were no differences in the affinities of either GABA or diazepam binding sites. 5. These findings indicate that sampling time significantly influences age-associated changes in the densities of low-affinity GABA and diazepam binding sites. Therefore, the effects of age on brain receptor binding parameters should be measured at several points in the 24-hour light/dark cycle in order to control for possible age-related changes in binding rhythmicity.

Identification and quantification of n-acetylserotonin (NAS) in the developing hippocampus of the rat.

1. A specific anti-NAS antibody and fluorescein-labelled second antibody were employed to investigate the presence of NAS in the dentate gyrus of the hippocampus as a function of age. 2. Immunoreactive NAS (INAS) was present in the granular cell layer of the dentate gyrus as early as 20 days postconception. 3. INAS appears to be present primarily in cell bodies. 4. Cross-reactivity and inhibition experiments confirm the positive identification of INAS. 5. INAS is age-dependent and increases with age reaching adult levels by day 30 post-conception/17 days after birth. 6. The appearance and subsequent increase in INAS correlates with the development of dentate granular cells and their subsequent synapse development suggesting a role for NAS in the normal functioning of these cells.

Intracellular pancreatic B cell serotonin and the dynamics of insulin release.

The role of intracellular pancreatic B cell serotonin in the dynamics of insulin release was investigated in an in situ perfused rat pancreas preparation. Animals were pretreated with 5-hydroxytryptophan (5-HTP) to increase the intracellular levels of serotonin (5-HT) as shown by fluorescence histochemistry. Despite a clear induction of intracellular 5-HT fluorescence in pancreatic islets neither the pattern nor the total amount of insulin released were significantly modified after perfusion with either glucose or tolbutamide. However, the L-amino acid decarboxylase inhibitor, RO 4--4602, significantly decreased both phases of glucose-mediated insulin release in normal animals as well as in those receiving 5-HTP.