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.

[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.

An immunohistochemical method for the localization of N-acetylserotonin (NAS) in the central nervous system. Description, validation, and application of the technique.

Antisera to N-acetylserotonin (NAS) were raised in rabbits by coupling NAS to bovine serum albumin (BSA) through a p-carboxybenzyl (PCB) bridge at the indole N. The specificity and applicability of these antisera in immunohistochemistry is reported. The anti-NAS antiserum and a fluorescein-labeled immunoglobulin were employed to investigate the topographic distribution of immunoreactive NAS (INAS) in the hindbrain (mesencephalon, cerebellum, pons, and medulla oblongata). Positive identification of INAS was confirmed in the granular layer of the cerebellum, the tractus spinalis nervi trigemini and the reticular formation. INAS was also identified in Purkinje cells, cerebellar nuclei, nucleus principalis nervi trigemini, nucleus tractus mesencephali, cochlear and vestibular nuclei, the locus coeruleus, and other brain stem regions. The pattern of INAS distribution is independent of serotonin (5-HT) and norepinephrine (NE), although certain loci could contain both INAS and serotonin or INAS and norepinephrine.

Age-associated changes in the circadian rhythm of retinal N-acetylserotonin and melatonin in rats with pigmented eyes.

Using a semiquantitative immunohistochemical procedure, we have evaluated the 24 hour circadian rhythm of N-acetylserotonin- and melatonin-like immunoreactivity in the retina of male hooded rats that have pigmented eyes. Three and twenty months old Long Evans rats were used. Animals were kept under a 14 light (L): 10 dark (D) lighting cycle and were sacrificed during the month of June. Four time points were assessed in the 24 hour light/dark cycle. Retinal N-acetylserotonin and melatonin were assessed by immunohistochemistry and microphotometric procedures as previously used by us. In young animals, the intensity of retinal N-acetylserotonin and melatonin immunofluorescence was significantly different (P less than 0.005, DF = 17) in animals killed during the light vs the dark period with peak values during the dark period. In contrast, retinal N-acetylserotonin and melatonin-immunofluorescence in old animals showed a flattened 24 hour rhythm, with light values as high as those observed during the dark period. The age-associated bluntness of the 24 hour rhythm was more noticeable for N-acetylserotonin than for melatonin immunofluorescence.

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.

N-Acetylserotonin in the central nervous system.

N-acetylserotonin has been identified by immunohistochemistry in specific brain areas separate from melatonin and serotonin. N-acetylserotonin is widely distributed within the brain stem, cerebellum and hippocampus and in the brain stem it is contained within the reticular formation nuclei and motor nuclei. Like serotonin, N-acetylserotonin appears to be derived from tryptophan as tryptophan hydroxylase inhibition leads to a lowering in immunoreactive N-acetylserotonin in brain and blood. Beta adrenergic drugs influence N-acetylserotonin neurons with beta adrenergic agonists causing a rise in immunoreactive N-acetylserotonin. The presence of N-acetylserotonin in brain has been confirmed by gas chromatography, mass spectrometry and radioimmunoassay. At this point little is known of the possible role of N-acetylserotonin in the brain. In the hippocampus N-acetylserotonin is present in granule cells and its appearance parallels the appearance of those cells. High affinity binding of tritiated N-acetylserotonin is found in brain and in various brain areas and this radioligand appears to label serotonergic receptors. Preliminary iontophoretic studies performed on hippocampal slices indicate an inhibitory action of N-acetylserotonin on glutamate induced firing of pyramidal cells. Taken together these findings suggest that N-acetylserotonin may have a role in the central nervous system distinct from that of being a precursor for melatonin. If this hypothesis is correct it would suggest that indoleamines have certain similarities to catecholamines. Thus for the catecholamines, dopamine, norepinephrine and epinephrine form a synthetic sequence and yet have independent roles as neurotransmitters and/or hormones. The three indoleamines serotonin, N-acetylserotonin and melatonin also form a synthetic sequence and these three substances may also have independent roles as neurotransmitters and/or hormones.

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.

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.

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.

B-adrenergic regulation of N-acetylserotonin (NAS) synthesis in the rat cerebellum.

The synthesis of N-acetylserotonin (NAS) in the pineal gland is dependent upon the activity of the enzymes tryptophan-hydroxylase, 1-aromatic amino acid decarboxylase and N-acetyltransferase. Pineal N-acetyltransferase activity is regulated by the level of B-adrenergic activation. N-acetylserotonin (NAS) has also been identified in extra-pineal brain tissue. In order to investigate whether extra-pineal brain NAS levels are regulated by tryptophan hydroxylase and B-adrenergic activity, the effects of tryptophan hydroxylase inhibitors (parachlorophenylalanine and 6-fluoro-tryptophan) and adrenergic drugs (l-isoproterenol and propranolol) were examined. NAS was evaluated in the cerebellum of the rat using quantitative NAS-immunohistochemistry. A significant decrease in NAS-immunofluorescence was observed after tryptophan hydroxylase inhibition. Treatment with l-isoproterenol, a B-adrenergic agonist, resulted in a significant increase in NAS-immunofluorescence intensity. This effect was blocked by propranolol, a B-adrenergic blocking agent. These data indicate that the synthesis of NAS, in the cerebellum utilizes the established serotonin pathway and that NAS synthesis in the cerebellum is regulated by a B-adrenergic mechanism similar to that in the pineal gland.

Subchronic toxicity study of domoic acid in the rat.

Male and female Sprague-Dawley rats were dosed by gavage for 64 days with 0, 0.1 or 5 mg/kg/day domoic acid. Treated animals showed no clinical abnormalities. Terminal values in haematology and clinical chemistry did not reveal differences between treated and control groups. Findings in histopathology and immunohistochemistry were unremarkable. The 24-hr urinary excretion rate for domoic acid determined at three time points was approximately 1.8% of the dose and remained unchanged during the study.

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.

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.

[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.

[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.

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.