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PubMedDate not supplied

Immunohistochemical demonstration of neuroactive substances in the inner ear of rat and guinea pig.

The presence and localization of different neuropeptides and other putative neurotransmitters or -modulators were examined by immunohistochemistry in the cochleovestibular end organs and in neurons innervating them in rats and guinea pigs. In the organ of Corti neural elements beneath inner hair cells showed immunoreactivity for enkephalin (ENK), calcitonin gene-related peptide (CGRP), L-glutamate decarboxylase (GAD), substance P (SP) and tyrosine hydroxylase (TH). Nerve chalices of type I vestibular hair cells contained SP and GAD, but not consistently. SP was only occasionally observed in neuronal cell bodies of the 8th cranial nerve but fine fibers with different neuroactive substances were seen in the nerve trunk in the following relative numbers: TH greater than SP greater than CGRP greater than ENK. The present data demonstrate the presence of several different neuroactive substances in the rat and guinea pig inner ear suggesting a multiplicity of neurotransmitters or -modulators in this system.

Animals↗
PubMed1999

Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation and recovery.

Multiple lines of evidence indicate that neurons within the pontomesencephalic tegmentum are critically involved in the generation of paradoxical sleep (PS). From single-unit recording studies, evidence suggests that unidentified but "possibly" cholinergic tegmental neurons discharge at higher rates during PS than during slow wave sleep or even waking and would thus play an active role, whereas "presumed" monoaminergic neurons cease firing during PS and would thus play a permissive role in PS generation. In the present study performed on rats, c-Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), or glutamic acid decarboxylase (GAD) for immunohistochemical identification of active neurons during PS recovery ( approximately 28% of recording time) as compared with PS deprivation (0%) and PS control (approximately 15%) conditions. With PS recovery, there was a significant increase in ChAT+/c-Fos+ cells, a significant decrease in Ser+/c-Fos+ and TH+/c-Fos+ cells, and a significant increase in GAD+/c-Fos+ cells. Across conditions, the percent PS was correlated positively with tegmental cholinergic c-Fos+ cells, negatively with raphe serotonergic and locus coeruleus noradrenergic c-Fos+ cells, and positively with codistributed and neighboring GABAergic c-Fos+ cells. These results support the hypothesis that cholinergic neurons are active, whereas monoaminergic neurons are inactive during PS. They moreover indicate that GABAergic neurons are active during PS and could thus be responsible for inhibiting neighboring monoaminergic neurons that may be essential in the generation of PS.

Acetylcholine↗
PubMed2003

Intervention of GI neuropeptides in pancreatic growth and regeneration: comparison with cholecystokinin.

The pancreatic gland has an enormous potential for growth and regeneration, mainly in rodents. These processes remain mostly under the control of the GI hormone cholecystokinin (CCK). The human pancreas however does not show proliferative properties after partial pancreatectomy, but research in this field has been scarce. Recent studies indicate that CCK might not be the expected trophic agent since its two receptors CCK(A) and CCK(B) were not found on human exocrine pancreas. Therefore, if human pancreas grows and regenerates, it has to be under the influence of some unknown trophic factors. Neuropeptides receiving much attention lately as regulators of pancreatic functions could be among the searched trophic agents. This presentation focus on neuropeptides growth potential: GRP-Bombesin, GABA, PP, PYY, Neurotensin, SP, VIP, PACAP, CGRP and galanin. Some neuropeptides have moderate effects on pancreatic enzymes and electrolytes secretion: SP, VIP, PACAP. However, their trophic effects remain unexplored except for GRP-bombesin and PACAP. PACAP preferentially exhibits its mitogenic and proliferative effects on the pancreatic acinar cells AR4-2J via tyrosine kinase, phospholipase D and ornithine decarboxylase activation but not through adenylate cyclase. The growth promoting action of GRP-bombesin is well documented on rodent's pancreas. However, recent studies indicate that this neuropeptide is potentially trophic for larger mammals' pancreas. Indeed, investigators recently documented that bombesin induced pancreatic regeneration in the pig after partial pancreatectomy through mitogen-activated protein kinases activation as do CCK-8 and caerulein on rat pancreas. Have we found the magic pancreatic trophic factor in large mammals? Further investigations will tell.

Animals↗
PubMed2005

[Clinical and immunological characteristics in rapid-onset type 1 diabetes with hyperamylasemia].

OBJECTIVE: To investigate the clinical characteristics and different status of islet autoantibodies of rapid-onset type 1 diabetes in China with elevated serum pancreatic enzymes. METHODS: In accordance with the criteria Imagawa reported, 40 cases of acute-onset type 1 diabetics with ketosis or ketoacidosis were selected and 4 fell into the criteria of rapid-onset type 1 diabetes. Compared the clinical characteristics between fulminant (group F, n = 4) and nonfulminant (group NF, n = 36) type 1 diabetics. Same parameters were compared between the patients with diabetic symptoms within 1 week (group A, n = 11) and those beyond 1week (group B, n = 29). The percentage of elevated serum amylase were compared between patients with and without severe ketoacidosis. Islet autoantibodies, including glutamic acid decarboxylase antibody (GAD-Ab), protein tyrosine phosphatase antibody (IA-2Ab) and insulin autoantibody (IAA),, were detected by radioligand assays. RESULTS: We found 4 cases of rapid-onset type 1 diabetes in Chinese, accounted for 10% of acute-onset type 1 diabetes. Among 4 rapid-onset type 1 diabetics, 2 patients detected GAD-Ab positive. Patients with duration of diabetic symptoms within 1 week (group A) were found all with severe ketoacidosis and 10 of 11 patients were found serum amylase elevated and this group appeared higher blood glucose, lower PH and CO(2)CP, nearly normal HbA(1c) and more severe ketoacidosis, more patients with elevated amylase (P < 0.05) than those with duration of symptoms more than 1 week (group B). Patients with severe ketoacidosis (n = 20) owned higher percentage of elevated serum amylase than those with mild or moderate ketoacidosis (n = 20) (60% vs 20%, P < 0.05). CONCLUSION: (1) Rapid-onset type 1 diabetes cases are also observed in China. (2) Rapid-onset type 1 diabetes may be a group of syndromes with different etiology which immune and non-immune factors may both involved in. (3) Elevated pancreatic enzymes are not specific markers for rapid-onset type 1 diabetes, it may result from severe ketoacidosis and metabolic derangements.

Autoantibodies↗
PubMedDate not supplied

Do tyrosine hydroxylase-immunoreactive neurons in the ventrolateral arcuate nucleus produce dopamine or only L-dopa?

Dopamine (DA) was early demonstrated in the arcuate nucleus by means of the formaldehyde-induced histofluorescence method. In the present study we have investigated the distribution of cell bodies in the arcuate nucleus with antisera against tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC) and DA. The results indicate that TH-immunoreactive cells in the dorsomedial part of the arcuate nucleus also contain immunoreactivity for both AADC and DA. However, TH-positive cells in the ventrolateral arcuate nucleus lacked AADC- and DA-immunoreactivity with the sensitivity of the present methods. The findings raise the question whether the ventrolateral cells synthesize L-DOPA or DA as endproducts.

Animals↗
PubMed1998

In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector.

An adeno-associated virus (AAV) vector, expressing genes for human tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC), demonstrated significantly increased production of dopamine in 293 (human embryonic kidney) cells. This bicistronic vector was used to transduce striatal cells of six asymptomatic but dopamine-depleted monkeys which had been treated with the neurotoxin MPTP. Striatal cells were immunoreactive for the vector-encoded TH after stereotactic injection for periods up to 134 days, with biochemical effects consistent with dopamine biosynthetic enzyme expression. A subsequent experiment was carried out in six more severely depleted and parkinsonian monkeys. Several TH/aadc-treated monkeys showed elevated levels of dopamine near injection tracts after 2.5 months. Two monkeys that received a beta-galactosidase expressing vector showed no change in striatal dopamine. Behavioral changes could not be statistically related to the vector treatment groups. Toxicity was limited to transient fever in several animals and severe hyperactivity in one animal in the first days after injection with no associated histological evidence of inflammation. This study shows the successful transfection of primate neurons over a period up to 2.5 months with suggestive evidence of biochemical phenotypic effects and without significant toxicity. While supporting the idea of an in vivo gene therapy for Parkinson's disease, more consistent and longer lasting biochemical and behavioral effects will be necessary to establish the feasibility of this appraoch in a primate model of parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1977

Studies on the depletion of brain amines by m-tyrosine.

The biochemical basis of the well-known physiological and pharmacological actions of m-tyrosine was examined by a detailed study of its effect on the brain biogenic amines. m-Tyrosine was injected i.p. and rat brain monoamine levels were measured. Endogenous levels of dopamine, norepinephrine and serotonin all showed approximately 50% reductions 1 h after the administration of L-m-tyrosine at 150 mg/kg. These actions of L-m-tyrosine could be blocked by the inhibition of the central dopa decarboxylase. Depletion of brain monoamines was also observed with the D-isomer of m-tyrosine, although this effect was less pronounced than that of the L-isomer. In vitro experiments with rat brain homogenates showed that L-m-tyrosine, m-tyramine and m-octopamine enhanced in efflux of exogenous labeled monamines from brain particles, whereas D-m-tyrosine was completely ineffective. From these results it is concluded that the observed decreased in brain monamine levels by L-m-tyrosine may be due to a m-tyramine-enhanced release of the amines which are quickly metabolized in vivo.

Animals↗
PubMed2000

Retinal cholinergic and dopaminergic deficits of aged rats are improved following treatment with GM1 ganglioside.

Selected cholinergic and dopaminergic markers were compared in the retina of aged (20-22-months-old) and young (3-months-old) rats before and after treatment with GM1 ganglioside. The dopaminergic markers, tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were comparable in the young and aged animals and GM1 treatment did not alter them. In contrast, mazindol binding, a marker for the dopamine transporter, was diminished in the aged retina and treatment with GM1 restored binding to values found in the young animals. The cholinergic markers choline acetyltransferase and hemicholinium-3 binding, a marker for the high-affinity choline transport, were depressed in aged rats and GM1 corrected the deficits.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Role of dopamine in the neurotoxic effects of methamphetamine.

Multiple administrations of high doses of methamphetamine to rats cause long-term depression of both dopamine and serotonin synthesis. Coadministration of the catecholamine synthesis inhibitor, alpha-methyl-p-tyrosine, antagonizes this effect of methamphetamine on both neurotransmitter systems. However, when catecholamine synthesis was maintained by the administration of L-dopa and the peripheral decarboxylase inhibitor R04-4602, alpha-methyl-p-tyrosine no longer prevented the effects of methamphetamine on either dopamine or serotonin synthesis. In addition, the administration of the specific dopamine uptake blocker, amfonelic acid, significantly attenuated the changes in the serotonin synthesizing enzyme, tryptophan hydroxylase, resulting from multiple high doses of methamphetamine. The ability of a single administration of methamphetamine to depress tryptophan hydroxylase was also dependent on catecholamine synthesis. These results suggest that dopamine plays an important role in the changes mediated by the administration of methamphetamine in both the dopaminergic and serotonergic systems.

Animals↗
PubMed2000

Islet cell antibody frequency differs from that of glutamic acid decarboxylase antibodies/IA2 antibodies after diagnosis of diabetes.

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency.

Adolescent↗
PubMed1996

Diurnal rhythm in ornithine decarboxylase activity and noradrenergic and cholinergic markers in rat submaxillary lymph nodes.

Diurnal variations in lymph node ornithine decarboxylase activity were examined in submaxillary lymph nodes of rats injected with Freund's complete adjuvant or its vehicle. After immunization, lymph node ornithine decarboxylase activity increased by about 10-fold. Both in immunized and non-immunized rats, a significant diurnal variation in ornithine decarboxylase activity was found, with a maximal activity at early (i.e. 13.00 h, vehicle) or late afternoon (i.e. 17.00 h, Freund's adjuvant). Injection of Freund's adjuvant during daylight or at night resulted in similar day-night differences in submaxillary lymph node ornithine decarboxylase activity. In rats subjected to the sympathetic postganglionic denervation (by ipsilateral superior cervical ganglionectomy) or the preganglionic parasympathetic decentralization (by chorda tympani section) of submaxillary lymph nodes, nyctohemeral variations in ornithine decarboxylase were still present, showing a maximum at 17.00 h. Superior cervical ganglionectomy augmented lymph node ornithine decarboxylase while chorda tympani section decreased it. When a unilateral superior cervical ganglionectomy plus chorda tympani section was performed, the diurnal changes in ornithine decarboxylase were abolished. [3H]Norepinephrine uptake and tyrosine hydroxylase activity attained their maxima in submaxillary lymph nodes at early night. After immunization, these two presynaptic indicators of sympathetic activity in submaxillary lymph nodes augmented significantly. Neuronal [3H]choline uptake and [3H]choline conversion into acetylcholine (two indicators of cholinergic activity) also augmented in lymph nodes of rats injected with Freund's adjuvant. In immunized rats, maxima in [3H]choline uptake and [3H]acetylcholine synthesis were found at 13.00-17.00 h while in non-immunized rats, a maximum in acetylcholine synthesis was found at 17.00 h. The results are compatible with the view that the autonomic nervous system plays a role in circadian changes of immune responsiveness in lymphoid tissue and that a significant augmentation of presynaptic autonomic activity takes place during immunization in lymphoid tissue.

Animals↗
PubMed1979

Effect of morphine on the accumulation of DOPA after decarboxylase inhibition in the rat.

Acute systemic administration of morphine (10 mg/kg s.c.) to rats increased in vivo tyrosine hydroxylation in the striatum measured as the accumulation of DOPA after decarboxylase inhibition. DOPA accumulation reached a maximum 30-60 min after morphine. The morphine antagonist naloxone (1, 10 or 100 mg/kg s.c.) did not significantly after DOPA accumulation. However, naloxone completely antagonized the effect of morphine. The DA agonist apomorphine decreased and the DA antagonist haloperidol increased DOPA accumulation. The effect of apomorphine (0.05 mg/kg) was counteracted by morphine. Naloxone did not significantly change the accumulation of DOPA after apomorphine or after haloperidol. In rats treated with gamma-butyrolactone (GBL) or with reserpine DOPA accumulation was not altered by treatment with morphine or naloxone. However, the inhibiting effect of apomorphine (0.5 mg/kg) on the accumulation of DOPA in rats treated with reserpine was weakly counteracted by morphine (0.5 mg/kg) on the accumulation of DOPA in rats treated with reserpine was weakly counteracted by morphine (10 mg/kg s.c.). Since the effects of morphine on the apomorphine-induced inhibition of DOPA accumulation were antagonized by naloxone, we suggest that the effects on striatal DOPA accumulation produced by morphine were mediated via opioid receptors and not directly via DA receptors.

4-Butyrolactone↗
PubMed1991

Preserved striatal tyrosine hydroxylase activity, assessed in vivo, following neonatal hypoxia-ischemia.

Previous in vitro studies have shown that biochemical indices of striatal dopaminergic systems are preserved following neonatal hypoxia-ischemia. There has been no previous assessment of these systems in vivo. Using the accumulation of striatal dopa following administration of a dopa decarboxylase inhibitor as an in vivo measure of tyrosine hydroxylase (TH) activity, we have found that baseline TH activity, and its regulation by both neuronal activity and presynaptic autoreceptors are also preserved following hypoxia-ischemia.

Animals↗
PubMed2005

Progesterone receptor and dopamine synthesizing enzymes in hypothalamic neurons of the guinea pig: an immunohistochemical triple-label analysis.

Interactions among gonadal steroid hormones and the dopamine synthesizing enzymes, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC), participate in hypothalamic functions. Several findings suggest that the expression patterns of the progesterone receptor (PR), TH and AADC overlap in the guinea pig brain. However, it remained to be determined whether or not these two enzymes coexist in the same neurons which contain the PR. To test this hypothesis and quantify these colocalization relationships in the hypothalamus, we used a triple-labeling immunofluorescence procedure. Only PR/AADC-immunoreactive cells were seen in the preoptic area but no PR/TH cells and, therefore, no triple immunoreactive cells were found. An occasional colocalization between PR and the two enzymes was observed throughout the rostrocaudal extent of the arcuate nucleus with the greatest concentration of triple-labeled cells in the medial subdivision. In this region, quantitative estimation of cellular immunoreactivity showed that the triple immunoreactive cells represented about 29% of PR/TH cells, 9% of PR/AADC cells and 22% of TH/AADC cells in spite of a very low percentage in relation to total populations of neurons expressing only PR, TH or AADC. Thus, the PR are only present in monoenzymatic AADC expressing neurons in the preoptic area while they can be observed in neurons expressing both enzymes in the arcuate nucleus.

Animals↗
PubMed2005

Dehydroepiandrosterone sulfate and allopregnanolone directly stimulate catecholamine production via induction of tyrosine hydroxylase and secretion by affecting actin polymerization.

Adrenal cortical cells of zona reticularis produce the neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester dehydroepiandrosterone sulfate (DHEAS), and allopregnanolone (ALLO). An interaction between zona reticularis and adrenal medulla has been postulated based on their close proximity and their interwoven borders. The aim of this paper was to examine in vitro the possible paracrine effects of these steroids on catecholamine production from adrenomedullary chromaffin cells, using an established in vitro model of chromaffin cells, the PC12 rat pheochromocytoma cell line. We have found the following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10-30 min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels (norepinephrine and dopamine). 2) It appears that the acute effect of these steroids involved actin depolymerization/actin filament disassembly, a fast-response cellular system regulating trafficking of catecholamine vesicles. Specifically, 10(-6) m phallacidin, an actin filament stabilizer, completely prevented steroid-induced catecholamine secretion. 3) DHEAS and ALLO, but not DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased catecholamine levels at 24 h, an effect blocked by L-2-methyl-3-(-4-hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of tyrosine hydroxylase and L-aromatic amino acid decarboxylase, respectively, suggesting that this effect involved catecholamine synthesis. The latter hypothesis was confirmed by finding that DHEAS and ALLO increased both the mRNA and protein levels of tyrosine hydroxylase. In conclusion, our findings suggest that neuroactive steroids exert a direct tonic effect on adrenal catecholamine synthesis and secretion. These data associate the adrenomedullary malfunction observed in old age and neuroactive steroids.

Actins↗
PubMed1994

Progesterone suppresses tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nucleus on proestrus.

This study examined the intracellular mechanisms for the regulation of tyrosine hydroxylase in the tuberoinfundibular dopaminergic neurons of cycling female rats. It also evaluated the hormonal influences that contribute to the control of this enzyme on proestrus. Tyrosine hydroxylase messenger RNA (mRNA) levels in the arcuate nucleus of the hypothalamus were assessed by in situ hybridization. Tyrosine hydroxylase activity in the stalk-median eminence was determined from the in vitro or in vivo rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine or m-hydroxybenzylhydrazine, respectively. Tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation were similar on diestrous day 2 and proestrous mornings, but were reduced by 50% on estrus. Although circulating PRL concentrations were similar on the morning of each day of the estrous cycle, a broad preovulatory PRL surge was observed on the afternoon of proestrus. In vitro DOPA accumulation was similar at 1000 h before the PRL surge and at 1330 h during the peak phase of the PRL surge, but was reduced during the plateau phase of the PRL surge (1700 and 2200 h) coincident with the preovulatory progesterone rise and remained low on estrus. However, in vivo DOPA accumulation was transiently decreased only at 1700 h on proestrus. Tyrosine hydroxylase mRNA levels were similar at 1000, 1330, and 1700 h on proestrus, were reduced by 50% at 2200 h on proestrus subsequent to the decrease in enzyme activity, and remained low on the morning of estrus. Okadaic acid, a protein phosphatase-1 and -2A inhibitor, induced a similar increase in tyrosine hydroxylase activity in vitro at 1330 and 2200 h on proestrus and at 1100 h on estrus, indicating that tyrosine hydroxylase was capable of being activated in spite of decreased mRNA levels. Ovariectomy between 1100-1200 h on proestrus prevented the decrease in tyrosine hydroxylase mRNA levels and in vitro DOPA accumulation at 2200 h. The effects of ovariectomy were completely reversed by progesterone, whereas estradiol had no effect. Circulating PRL levels at 2200 h were suppressed to basal levels after ovariectomy, but were increased by progesterone treatment at 1530 h to levels similar to those in the plateau phase of the PRL surge in control rats. Administration of the progesterone antagonist RU486 at 1200 h on proestrus did not alter tyrosine hydroxylase activity, tyrosine hydroxylase mRNA levels, or circulating PRL concentrations at 2200 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

[IA-2 and anti-GAD antibodies in patients with newly diagnosed type 1 diabetes and their first degree relatives].

Antibodies recognising different pancreatic autoantigens (Abs) are detected many years before the clinical onset of insulin-dependent diabetes mellitus (IDDM). The humoral immune alterations, observed in the susceptible subjects, for example in first degree relatives of IDDM patients, could serve as predictive markers of IDDM development. It has recently been suggested that the predictive value of these humoral markers is associated with the number of the studied antibodies directed against different pancreatic antigens (ICA, GADA, IA-2,A IAA). The aim of the study was the estimation of the prevalence and titre of the antibodies directed against protein tyrosine phosphatase-2 (IA-2) and glutamic acid decarboxylase (GAD) in patients with newly diagnosed diabetes type 1 and their first degree relatives. The investigations were carried out in 52 diabetics (aged 5-25 years) and 136 first degree relatives. IA-2A and GADA were performed by radiobinding assay (RIA) using 2 microliters of serum and recombinant S35-labelled GAD65 and IA-2 antigens. The threshold of Abs detection was > or = 97.5 centile (of healthy schoolchildren). At least one of the antibody marker was detected in 92.7% of newly diagnosed IDDM patients, slightly more frequently observed were GADA (78.8%) than IA-2A (71.2%). The presence of 2 types of antibodies was found in 8.7% of parents and 9.4% of the siblings. The results of our study confirm high sensitivity and specificity of the combined measurement of IA-2A and GADA in recognising of autoimmune alterations in diabetes type 1 development. Taking into consideration small volume of the serum suitable for Abs measurement and possibility of the combined estimation of these Abs it seems that IA-2A and GADA combined measurement could actually serve as a screening marker for the detection of high risk of IDDM subjects also in the Polish population, but studies concerning their predictive value in the general population are suggested.

Adolescent↗
PubMed1999

Frequency of islet cell autoantibodies (IA-2 and GAD) in young Brazilian type 1 diabetes patients.

Type 1 diabetes, as an autoimmune disease, presents several islet cell-specific autoantibodies such as islet cell antibody (ICA), anti-insulin, anti-glutamic acid decarboxylase (GAD) and the antibody (Ab) against tyrosine phosphatase (PTP)-like protein known as ICA-512 (IA-2). In order to determine the frequency of the anti-GAD and anti-IA-2 autoantibodies in Brazilian type 1 diabetes patients we studied 35 diabetes mellitus (DM) type 1 patients with recent-onset disease (</=12 months) and 37 type 1 diabetes patients with long-duration diabetes (>12 months) who were compared to 12 children with normal fasting glucose. Anti-GAD65 and anti-IA-2 autoantibodies were detected with commercial immunoprecipitation assays. The frequency of positive results in recent-onset DM type 1 patients was 80.0% for GADAb, 62.9% for IA-2Ab and 82.9% for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1% for GADAb and IA-2Ab, and 67.5% for GAD and/or IA-2 antibodies. The control group showed no positive cases. Anti-GAD and IA-2 assays showed a high frequency of positivity in these Brazilian type 1 diabetes patients, who presented the same prevalence as a Caucasian population.

Adolescent↗