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.

Escritura, comunicación científica y acceso abierto: un proyecto internacional y multidisciplinario-NECOBELAC / Scientific writing, scientific communication and open access: an international, multidisciplinary project NECOBELAC

Una red de colaboración entre seis países de Europa, América latina y El Caribe ha iniciado un proyecto para mejorar la comunicación y la diseminación científica en salud pública. El proyecto apunta a fomentar la comunicación científica en aspectos de valor actual y futuro como son la escritura científica y el acceso abierto a la información en salud. El proyecto NECOBELAC (www.necobelac.eu) es auspiciado por la Comunidad Europea (7th Framework Programme) y tiene una duración de tres años. Como un reto, el proyecto reconoce las diferencias socio culturales entre los países que participan y se ocupará de generar redes de instituciones en colaboración estrecha para realizar programas de entrenamiento e intercambio de saberes en producción de información y difusión (incluyendo los aspectos técnicos y éticos). El proyecto NECOBELAC incluye al Istituto Superiore di Sanità (ISS) de Italia, coordinador del mismo, el Consejo Superior de Investigaciones Científicas (CSIC) de España, la Universidad de Nottingham (SHERPA) del Reino Unido, BIREME de Brasil, el Instituto de Salud Pública (ISP) de Colombia y la Universidade de Minho, de Portugal.

A collaboration network involving 6 countries in Europe, Latin-America and the Caribbean has embarked on a project (Network of Collaboration Between Europe and Latin American Caribbean Countries-NECOBELAC; www.necobelac.eu) aimed at improving scientific writing open access and scholarly communication to spread know-how regarding current and future issues and information related to health. The NECOBELAC project is sponsored by the European Community (7th Framework Programme) and will last for 3 years. The project recognises the challenge arising from socio-cultural differences between the participating countries and will deal with generating networks involving institutions working in close collaboration for carrying out training and know-how exchange programmes aimed at producing open access information and spreading it (including technical and ethical aspects). The NECOBELAC project currently involves the Istituto Superiore di Sanità - ISS from Italy (coordinating the project), the Consejo Superior de Investigaciones Científicas (CSIC) from Spain, the University of Nottingham (SHERPA) from the United Kingdom, BIREME from Brazil, the Instituto de Salud Pública (ISP) from Colombia and the Universidade de Minho from Portugal.

[Importance of microlithiasis in testicular germ cell tumor ultrasound]. / Importancia de microlitiasis en ultrasonido de neoplasias de células germinales de testículo.

INTRODUCTION: Testicular microlithiasis (TM) is an infrequent finding in testicular ultrasound and its clinical importance has not been completely defined. We analyzed the ultrasounds of patients with testicular germ cell tumors in order to analyze the correlation between TM, histological findings and clinical variables. METHODS AND MATERIALS: Fifty-seven patients with germ cell tumors and radical orchiectomy were included. Clinical, pathological, and echographic data were analyzed. RESULTS: TM was observed in 27 men (48.27%) and was absent in 30 (52.6%). Patients with TM had a greater likelihood of nonseminomatous germ cell tumors (NSGCT) vs seminomatous (55.6% vs 30%, p=0.05), stage II/III testicular cancer (51.8% vs 16.7%, p=0.005), positive surgical margins (18.5% vs 0%, p=0.021), and spermatic cord invasion (14.8% vs 0%, p=0.048). No significant difference was found in respect to other histopathological variables. CONCLUSION: This study showed that TM in testicular tumors is associated to NSGCT, advanced clinical stage, positive surgical margins, and spermatic cord invasion.

Importancia de microlitiasis en ultrasonido de neoplasias de células germinales de testículo / Importance of microlithiasis in testicular germ cell tumor ultrasound

Introducción: La microlitiasis testicular (MT) es un hallazgo poco frecuente en el ultrasonograma cuyo significado clínico no se ha definido. El presente estudio se realizó en pacientes con tumores de células germinales de testículo para analizar la relación entre MT, los hallazgos histológicos y las variables clínicas. Material y métodos: Se incluyeron 57 pacientes sometidos a orquiectomía radical por neoplasia testicular germinal y se revisaron las variables clínico patológicas y ultrasonográficas. Resultados: Hubo 30 hombres (52,6%) sin MT y 27 hombres con MT (48,27%). Los pacientes con MT tuvieron mayor proporción de tumor germinal no seminomatoso (TGNS, 55,6% vs 30%, p=0,05),de cáncer testicular estadio II/III (51,8% vs 16,7%, p=0,005), de borde quirúrgico positivo (18,5% vs0%, p=0,021) y de invasión al cordón espermático (14,8% vs 0%, p=0,048). No se encontró diferencia significativa en relación a otras variables histopatológicas. Conclusión: En este estudio se demostró una asociación entre MT en tumores testiculares con el hallazgo de TGNS, estadio clínico avanzado, borde quirúrgico positivo e invasión al cordón (AU)

Introduction: Testicular microlithiasis (TM) is an infrequent finding in testicular ultrasound and its clinical importance has not been completely defined. We analyzed the ultrasounds of patients with testicular germ cell tumors in order to analyze the correlation between TM, histological findings and clinical variables. Methods and materials: Fifty-seven patients with germ cell tumors and radical orchiectomy were included. Clinical, pathological, and echographic data were analyzed. Results: TM was observed in 27 men (48.27%) and was absent in 30 (52.6%). Patients with TM had a greater likelihood of non seminomatous germ cell tumors (NSGCT) vs seminomatous (55.6% vs 30%,p=0.05), stage II/III testicular cancer (51.8% vs 16.7%, p=0.005), positive surgical margins (18.5% vs0%, p=0.021), and spermatic cord invasion (14.8% vs 0%, p=0.048). No significant difference was found in respect to other histopathological variables. Conclusion: This study showed that TM in testicular tumors is associated to NSGCT, advanced clinical stage, positive surgical margins, and spermatic cord invasion (AU)

Oral (gavage), in utero and postnatal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical chemistry.

Tributyltin (TBT) is a biocide that contaminates foods, especially shellfish. TBT is an endocrine disrupter in several marine species and is neurotoxic and immunotoxic in mammals. We have examined the effects of exposure to low doses of tributyltin chloride (TBTC) from day 8 of gestation until adulthood. Pregnant rats were gavaged daily with 0, 0.025, 0.25 or 2.5 mg TBTC/kg body weight from day 8 of gestation until weaning. Stomach contents of suckling pups contained undetectable levels of TBT and dibutyltin (DBT) levels were detectable only in the highest TBTC dose used, indicating negligible lactational transfer to pups. Post weaning, pups were gavaged daily with the same dose of TBTC administered to their mothers and sacrificed on post-natal days (PND) 30 (males and females), 60 (females) and 90 (males). TBTC had no effects on dams' body weights, food consumption, litter size, sex ratio or survival of pups to weaning. However, all doses of TBTC significantly affected parameters of the growth profile of the pups (mean body weights, average slope, curvature) and the ratio of weekly food consumption to weekly body weight gain indicated enhanced food conversion to body mass in females but a decreased conversion in males. Liver, spleen and thymus weights were also affected by TBTC. In male pups dosed at 2.5 mg/kg/day, reduced serum thyroxine levels were evident, indicating that the thyroid is a target for TBTC toxicity. No histopathological lesions were seen in the liver but elevated serum alanine aminotransferase, gamma-glutamyl transferase and amylase indicated hepatotoxicity. Significant decreases in liver weights in female pups exposed to 0.025 mg/kg/day TBTC were observed at PND 60. Decreases in spleen and thymus weights also pointed towards toxic effects of TBTC on the immune system. The 0.025 mg/kg/day TBTC should have been a no affect dose and yet this dose caused significant effects on growth profiles, decreased liver weights and elevated serum GGT levels in females.

Oral (gavage), in utero and post-natal exposure of Sprague-Dawley rats to low doses of tributyltin chloride. Part II: effects on the immune system.

The immunotoxic effects of tributyltin chloride (TBTC) were examined in the offspring of Sprague-Dawley rats exposed in utero from day 8 of gestation, through lactation and post-weaning until pups reached the age of 30 days (male and female), 60 days (female) and 90 days (male). Daily oral (gavage) doses of 0.025, 0.25 and 2.5 mg/kg body weight/day were administered in olive oil 7 days/week. Immunologic endpoints were investigated at the termination of each study. Statistically significant results (P<0.05) included the following: At 30 days, the mean percent and absolute natural killer (NK) cell numbers were increased in male and female rats treated with the high TBTC dose. At 60 days, female rats had increased mean serum IgM levels at the low and high TBTC doses, increased mean percentage CD4(+)8(+) (immature) T lymphocytes at the middle and high doses, a non-linear dose-response increase in NK cell activity at the 50:1 and 100:1 effector:target cell ratios (pairwise comparisons significant at the low dose compared with control), and increased mean numbers of L. monocytogenes colony-forming bacteria on Day 2 post-infection (significant for trend) and Day 3 post infection (pairwise comparisons significant only in the middle dose). The 90-day male rats had decreased mean serum IgA levels at the middle dose group; increased IgM levels at the high dose group, increased IgG levels at the middle and high doses; decreased IgG2(a) in the high dose compared to the control; a dose-related increase in the mean percentage NK cell numbers (pairwise comparisons significant at the high dose compared with the control) and increased mean NK cell activity (pairwise comparisons significant at all dose groups compared with the control). The delayed-type hypersensitivity response to oxazolone was increased in the low and middle doses and decreased in the high dose. Thymus atrophy was observed in the high TBTC dose across all ages. Thus, in utero and post-natal treatment of F1 rats with low levels of TBTC affected some aspects of humoral and cell mediated immunity as well as the number and function of cells which are involved in the host's immunosurveillance mechanisms against tumours and viral infections.

[Hemorrhagic stroke associated to neurocysticercosis]. / Accidente cerebrovascular hemorrágico asociado a neurocisticercosis.

A well-known complication of neurocysticercosis is cerebral arteritis, which is usually manifested by cerebral ischemia. Only anecdotal cases of hemorrhagic stroke associated to this parasitosis have been described. Previously there are only two reported cases of this association. One of these cases had an intracystic hemorrhage confirmed by autopsy without cerebrovascular risk factors. Autopsy revealed an inflammatory arteriopathy adjacent to the cyst intracystic hemorrhage. The second case had a subarachnoidal hemorrhage secondary to the rupture of an aneurysm in the right anteroinferior cerebellar artery. At surgery, the aneurysm was found to be surrounded by a thickened-leptomeninges, which histologically showed the presence of cysticercous with dense inflammation. Our first patient was a 32 year-old female developed a lenticulo-capsular hemorrhage around a cysticercotic lesion. The second patient was a 34 year-old male developed an intracystic hemorrhage. As cerebral angiography was normal in both patients, cerebral hemorrhages were considered to be related to cysticercotic arteritis of small penetrating vessels. We conclude that cysticercosis is associated with differenttypes of intracranial hemorrhage, as documented the present cases. In neurocysticercosis endemic areas, cysticercotic arteritis should be added to the list of causes of intracranial hemorrhage in young people.

[Peripheral neuropathy during a second cycle of treatment with high doses of interferon-alpha in a patient with hepatitis C, and a review of the literature]. / Neuropatía periférica durante un segundo ciclo de tratamiento con dosis altas de interferón alfa en un paciente con hepatitis C y revisión de la bibliografía.

INTRODUCTION: Alpha interferons (IFN a) have been shown to be effective in patients with chronic active hepatitis C. IFN a treatment may be associated with neurologic complications, including peripheral neuropathy. CASE REPORT: We describe a patient with active hepatitis C treated with IFN a, who developed peripheral neuropathy after a second cicle of treatment with interferon. He received a first cicle of treatment with IFN a during 22 weeks (6 MU/day 3 times a week). Afther that he did not received treatment during one year and then he received the second cycle (6 MU/day 3 times a week). After 3 months of therapy the patient complained about paresthesias of both legs. CONCLUSIONS: IFN a related neuropathy is probably rare; however, some cases may be misdiagnosed. Diagnosis of IFN a related neuropathy should be considered by physicians, particularly in patients given longterm treatment and high IFN a dosage. In this case we think that the patient had an acumulative efectt of interferon though he did not received treatment with interferon during one year.

Neuropatía periférica durante un segundo ciclo de tratamientocon dosis altas de interferón alfa en un paciente con hepatitis Cy revisión de la bibliografía / Peripheral neuropathy during a second cycle of treatment with high doses of interferon-alpha in a patient with hepatitis C, and a review of the literature

Introducción. La utilización de interferón alfa (IFN) ha mostrado su efectividad en el tratamiento de la infección por el virus de la hepatitis C. Se han descrito efectos secundarios del uso de interferón en el sistema nervioso, entre ellos la neuropatía. Caso clínico. En este artículo describimos un caso de neuropatía periférica asociada al uso de IFN-alfa en un paciente con hepatitis C, quien recibió un primer ciclo de tratamiento durante 22 semanas en dosis de 6 millones UI tres veces a la semana. Tras permanecer un año sin recibir ninguna terapia, recibió un segundo ciclo de IFN-alfa en dosis de 6 millones UI tres veces por semana. Después de tres meses de tratamiento el paciente desarrolló datos de neuropatía periférica. Los estudios de electrofisiología mostraron una polineuropatía axonal. Conclusiones. La neuropatía asociada al uso de IFN-alfa es una manifestación rara; sin embargo, hay que considerar que puede estar subdiagnosticada, ya que en la mayoría de los pacientes no se sospecha esta patología. El diagnóstico debe considerarse en pacientes que reciben tratamiento a largo plazo y en los que reciben dosis altas. Pensamos que en nuestro caso pudo haber un efecto acumulativo de la dosis de IFN-alfa , aunque el paciente había estado un año sin recibir IFN-alfa (AU)

Altered islet homeostasis before classic insulitis in BB rats.

Young diabetes-prone BioBreeding (BBdp) rats fed a diabetes-promoting, cereal-based, NIH-07 (NIH) diet have decreased islet area compared with rats fed a diabetes-retardant diet at a time when classic insulitis is minimal. This finding raised the possibility that islet homeostasis in BBdp rats may be abnormal. To investigate this possibility further, comparisons were made between BBdp and BB control (BBc) rats fed a diabetes-promoting NIH diet for 22 days after weaning. Pancreatic sections were fixed in Bouin's solution and evaluated using immunohistochemistry and image analysis by staining with antibodies for islet hormones: insulin, glucagon; cell proliferation markers: PCNA, BrdU; markers of islet neogenesis: PDX-1, cytokeratin 20; apoptosis was assessed by morphological changes and TUNEL staining. Body weight of BBdp rats was significantly smaller than BBc rats. Although the total number of islets was higher in BBdp compared with BBc, both islet and beta-cell fraction were similar. BBdp rats had a lower beta-cell mass than BBc rats, although this was not statistically significant. Alpha-cell fraction and beta-cell size were similar. Apoptotic bodies were rare in beta-cells but more frequent in acinar tissue of BBdp rats. When the day-night cycle was reversed to synchronize the apoptotic process, the number of apoptotic bodies in islets and in acinar cells was increased. Apoptotic bodies and BrdU+ or PCNA+ beta-cells were more frequently encountered in islets of BBdp rats. Although the frequency of CK20+ islets in BBdp rats was not different, CK20+ area fraction was smaller in BBdp. The number of extra-islet insulin+ and glucagon+ clusters (<4 cells) was significantly greater in BBdp rats. These data are consistent with an enhanced compensatory or "repair" process in the pancreas of BBdp rats that attempts to maintain islet cell mass by altering homeostasis through increased islet neogenesis.

Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females. On a daily basis, each monkey's feed and water consumption was determined, its health was monitored and the females were swabbed to evaluate menstrual status. On a weekly basis, each monkey's body weight was determined and a detailed clinical evaluation was performed. At 4-week intervals, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. Also, a local anaesthetic was administered to the nuchal fat pad area of each monkey, and adipose samples were obtained for toxaphene analysis. 1 day prior to the biopsies, a 24-h urine and faecal collection was obtained for toxaphene analysis. After 34 weeks of treatment, the immune system of the monkeys was evaluated. After 52 weeks of dosing, all treated and two control animals were necropsied. Liver samples were obtained and microsomal fractions were prepared immediately. A portion of liver and kidney was taken for toxaphene analysis. All of the major internal organs were weighed and bone marrow evaluations were conducted. Organ and tissue samples were fixed in 10% formalin and processed for light microscopy. There was no effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters. Two major clinical findings were inflammation and/or enlargement of the tarsal gland and impacted diverticulae in the upper and lower eye lids. At necropsy, the relative spleen and thymus weights were greater for the treated monkeys than the controls. Toxaphene administration produced an increase in metabolism of aminopyrene, methoxyresorufin and ethoxyresorufin, three substrates that are altered specifically by cytochrome P450-based hepatic monooxygenase enzymes. Histopathological examination of tissues was unremarkable by light microscopy. Tissue analysis for toxaphene and immunology findings have been published elsewhere.

[Guillain-Barre syndrome. Experience in a third level hospital]. / Síndrome de Guillain-Barré. Experiencia en un hospital de tercer nivel.

INTRODUCTION: Acute peripheral neuropathy represents a medical emergency. The causes of it are diverse and plentiful. The most common cause of acute paralytic peripheral neuropathy is the Guillain-Barré syndrome (GBS). As many as 85% of those affected can be expected to make an excellent recovery. OBJECTIVE: To describe the principal risk factors associated, clinical manifestations, treatment, evolution and complications of 28 cases of Guillain-Barré syndrome (GBS) in the "Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán". METHODS: We search in our computer records all files under diagnostic of GBS, during the last ten years. We found 28 cases that were available to study. RESULTS: Mean age was 37 years old (SD 17.2). Fifteen patients were female (54%) and 13 were male (46%). Nine patients (32%) were preceded by a superior via infection, 5 (18%) by a diarrhea illness and 14 patients had not a predisposing factor. The duration of symptoms before diagnostic has a median of 7 days (2-15). Twenty-six patients (93%) had an ascending paralysis and 18 had paresthesias (64%). The most frequent subtype was acute inflammatory-demyelinating polyneuropathy (AIDP) in 18 patients (64%), acute motor-sensory axonal neuropathy (AMSAN) in 5 (18%), acute motor axonal neuropathy (AMAN) in 3 (11%) and 2 patients (7%) had the Fisher-Miller syndrome. Fifteen patients (54%) developed respiratory involvement requiring mechanical ventilation. Twenty-four patients (86%) had cerebrospinal fluid proteins elevated. Twenty patients (72%) had a total recovery, 6 (21%) had a partial recovery and 2 had not any response (7%). DISCUSSION: GBS is a particularly highstakes illness in that its onset is sudden and paralysis is frequently extreme (requiring assisted respiration), however, as many as 85% of those affected can be expected to make an excellent recovery. In our study the majority of patients (54%) develop respiratory involvement requiring mechanical ventilation but in this group the majority had a favorable outcome (71%).

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.

Hydrolysed casein diet protects BB rats from developing diabetes by promoting islet neogenesis.

Feeding diabetes-prone BioBreeding (BBdp) rats a hydrolysed-casein (HC)-based semi-purified diet results in two-to-three-fold fewer diabetes cases compared with feeding cereal-based diets such as NIH-07 (NIH). We showed previously that young NIH-fed BBdp rats had decreased islet area at a time when classic insulitis was minimal. Rats fed an HC diet maintained near normal islet area followed 3-4 weeks later by a deviation of the pancreas cytokine pattern from Th1 to Th2/Th3. This finding raised the possibility that BBdp rats were more susceptible to diet-induced changes in islet homeostasis. To investigate this possibility further, BBdp rats were fed an NIH or HC diet from days 23 to 45. Bouin's fixed sections of pancreas were stained with H & E or antibodies for insulin and glucagon. Cell proliferation nuclear antigen (PCNA) was used as a marker of cell proliferation and cells were stained for putative markers of islet neogenesis, cytokeratin 20 (CK20) and Bcl-2. Apoptotic bodies were recognized by morphological features and by TUNEL-positive staining. BBdp rats fed an HC diet had a significantly higher beta-cell fraction than rats fed NIH, whereas alpha-cell fraction and beta-cell size were not affected by diet or rat type. Apoptotic bodies of beta-cells were rare and unaffected by diet. The number of PCNA(+)beta-cells was not affected by diet. CK20 expression was localized in the ductular system and at the periphery of islets in rats aged 7 and 45 days. There were more CK20(+)islets in BBdp rats fed NIH than in those fed HC but the CK20 area fraction was unaffected by diet. Bcl-2 expression was scattered among ducts and central acinar cells. The number of extra-islet insulin(+)and glucagon(+)clusters (

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.

30-day oral toxicity study of domoic acid in cynomolgus monkeys: lack of overt toxicity at doses approaching the acute toxic dose.

Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg for 15 days and then at 0.75 mg/kg for another 15 days. After the 30-day dosing period, the treated monkeys were killed. Parameters monitored as markers for toxicity included body weight, food and water consumption, clinical observations, hematology, serum chemistry, light microscopy of all major organs (including brain and retina), and glial fibrillary acid protein immunohistochemistry. Domoic acid in serum and 24-hour urine samples was measured at several time points. All parameters measured remained unremarkable. Domoic acid concentrations measured in the 24-hour urine samples indicated that gastrointestinal absorption in the monkey was approximately 4-7 percent of the administered dose, which is at least twice that previously reported for the rat.