Local autocrine plasticity signaling in single dendritic spines by insulin-like growth factors.

The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1 and 2 (IGF1 and IGF2) are differentially expressed in hippocampal neurons and released in an activity-dependent manner. Using a new fluorescence resonance energy transfer sensor for IGF1 receptor (IGF1R) with two-photon fluorescence lifetime imaging, we find that the release of IGF1 triggers rapid local autocrine IGF1R activation on the same spine and more than several micrometers along the stimulated dendrite, regulating the plasticity of the activated spine in CA1 pyramidal neurons. In CA3 neurons, IGF2, instead of IGF1, is responsible for IGF1R autocrine activation and synaptic plasticity. Thus, our study demonstrates the cell type-specific roles of IGF1 and IGF2 in hippocampal plasticity and a plasticity mechanism mediated by the synthesis and autocrine signaling of IGF peptides in pyramidal neurons.

Simultaneous Ligand and Cation Exchange of Colloidal CdSe Nanoplatelets toward PbSe Nanoplatelets for Application in Photodetectors.

Cation exchange emerged as a versatile tool to obtain a variety of nanocrystals not yet available via a direct synthesis. Reduced reaction times and moderate temperatures make the method compatible with anisotropic nanoplatelets (NPLs). However, the subtle thermodynamic and kinetic factors governing the exchange require careful control over the reaction parameters to prevent unwanted restructuring. Here, we capitalize on the research success of CdSe NPLs by transforming them into PbSe NPLs suitable for optoelectronic applications. In a two-phase mixture of hexane/N-methylformamide, the oleate-capped CdSe NPLs simultaneously undergo a ligand exchange to NH4I and a cation exchange reaction to PbSe. Their morphology and crystal structure are well-preserved as evidenced by electron microscopy and powder X-ray diffraction. We demonstrate the successful ligand exchange and associated electronic coupling of individual NPLs by fabricating a simple photodetector via spray-coating on a commercial substrate. Its optoelectronic characterization reveals a fast light response at low operational voltages.

Guanosine and GMP increase the number of granular cerebellar neurons in culture: dependence on adenosine A2A and ionotropic glutamate receptors.

The guanine-based purines (GBPs) have essential extracellular functions such as modulation of glutamatergic transmission and trophic effects on neurons and astrocytes. We previously showed that GBPs, such as guanosine-5'-monophosphate (GMP) or guanosine (GUO), promote the reorganization of extracellular matrix proteins in astrocytes, and increase the number of neurons in a neuron-astrocyte co-culture protocol. To delineate the molecular basis underlying these effects, we isolated cerebellar neurons in culture and treated them with a conditioned medium derived from astrocytes previously exposed to GUO or GMP (GBPs-ACM) or, directly, with GUO or GMP. Agreeing with the previous studies, there was an increase in the number of ß-tubulin III-positive neurons in both conditions, compared with controls. Interestingly, the increase in the number of neurons in the neuronal cultures treated directly with GUO or GMP was more prominent, suggesting a direct interaction of GBPs on cerebellar neurons. To investigate this issue, we assessed the role of adenosine and glutamate receptors and related intracellular signaling pathways after GUO or GMP treatment. We found an involvement of A2A adenosine receptors, ionotropic glutamate N-methyl-D-aspartate (NMDA), and non-NMDA receptors in the increased number of cerebellar neurons. The signaling pathways extracellular-regulated kinase (ERK), calcium-calmodulin-dependent kinase-II (CaMKII), protein kinase C (PKC), phosphatidilinositol-3'-kinase (PI3-K), and protein kinase A (PKA) are also potentially involved with GMP and GUO effect. Such results suggest that GMP and GUO, and molecules released in GBPs-ACM promote the survival or maturation of primary cerebellar neurons or both via interaction with adenosine and glutamate receptors.

A novel assay reveals preferential binding between Rabs, kinesins, and specific endosomal subpopulations.

Identifying the proteins that regulate vesicle trafficking is a fundamental problem in cell biology. In this paper, we introduce a new assay that involves the expression of an FKBP12-rapamycin-binding domain-tagged candidate vesicle-binding protein, which can be inducibly linked to dynein or kinesin. Vesicles can be labeled by any convenient method. If the candidate protein binds the labeled vesicles, addition of the linker drug results in a predictable, highly distinctive change in vesicle localization. This assay generates robust and easily interpretable results that provide direct experimental evidence of binding between a candidate protein and the vesicle population of interest. We used this approach to compare the binding of Kinesin-3 family members with different endosomal populations. We found that KIF13A and KIF13B bind preferentially to early endosomes and that KIF1A and KIF1Bß bind preferentially to late endosomes and lysosomes. This assay may have broad utility for identifying the trafficking proteins that bind to different vesicle populations.

Axonal transport plays a crucial role in mediating the axon-protective effects of NmNAT.

Deficits in axonal transport are thought to contribute to the pathology of many neurodegenerative diseases. Expressing the slow Wallerian degeneration protein (Wld(S)) or related nicotinamide mononucleotide adenyltransferases (NmNATs) protects axons against damage from a broad range of insults, but the ability of these proteins to protect against inhibition of axonal transport has received little attention. We set out to determine whether these proteins can protect the axons of cultured hippocampal neurons from damage due to hydrogen peroxide or oxygen-glucose deprivation (OGD) and, in particular, whether they can reduce the damage that these agents cause to the axonal transport machinery. Exposure to these insults inhibited the axonal transport of both mitochondria and of the vesicles that carry axonal membrane proteins; this inhibition occurred hours before the first signs of axonal degeneration. Expressing a cytoplasmically targeted version of NmNAT1 (cytNmNAT1) protected the axons against both insults. It also reduced the inhibition of transport when cells were exposed to hydrogen peroxide and enhanced the recovery of transport following both insults. The protective effects of cytNmNAT1 depend on mitochondrial transport. When mitochondrial transport was inhibited, cytNmNAT1 was unable to protect axons against either insult. The protective effects of mitochondrially targeted NmNAT also were blocked by inhibiting mitochondrial transport. These results establish that NmNAT robustly protects the axonal transport system following exposure to OGD and reactive oxygen species and may offer similar protection in other disease models. Understanding how NmNAT protects the axonal transport system may lead to new strategies for neuroprotection in neurodegenerative diseases.

Amyloid-ß oligomers induce tau-independent disruption of BDNF axonal transport via calcineurin activation in cultured hippocampal neurons.

Disruption of fast axonal transport (FAT) is an early pathological event in Alzheimer's disease (AD). Soluble amyloid-ß oligomers (AßOs), increasingly recognized as proximal neurotoxins in AD, impair organelle transport in cultured neurons and transgenic mouse models. AßOs also stimulate hyperphosphorylation of the axonal microtubule-associated protein, tau. However, the role of tau in FAT disruption is controversial. Here we show that AßOs reduce vesicular transport of brain-derived neurotrophic factor (BDNF) in hippocampal neurons from both wild-type and tau-knockout mice, indicating that tau is not required for transport disruption. FAT inhibition is not accompanied by microtubule destabilization or neuronal death. Significantly, inhibition of calcineurin (CaN), a calcium-dependent phosphatase implicated in AD pathogenesis, rescues BDNF transport. Moreover, inhibition of protein phosphatase 1 and glycogen synthase kinase 3ß, downstream targets of CaN, prevents BDNF transport defects induced by AßOs. We further show that AßOs induce CaN activation through nonexcitotoxic calcium signaling. Results implicate CaN in FAT regulation and demonstrate that tau is not required for AßO-induced BDNF transport disruption.

The clathrin adaptor complex responsible for somatodendritic protein sorting.

Neuronal proteins contain "address labels" that govern their localization. In this issue of Neuron, Farías et al. (2012) identify the machinery that recognizes one class of dendritic localization signals and establish its role in the polarization of dendritic proteins, including several postsynaptic receptors.

A novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations.

Identifying the kinesin motors that interact with different vesicle populations is a longstanding and challenging problem with implications for many aspects of cell biology. Here we introduce a new live-cell assay to assess kinesin-vesicle interactions and use it to identify kinesins that bind to vesicles undergoing dendrite-selective transport in cultured hippocampal neurons. We prepared a library of "split kinesins," comprising an axon-selective kinesin motor domain and a series of kinesin tail domains that can attach to their native vesicles; when the split kinesins were assembled by chemical dimerization, bound vesicles were misdirected into the axon. This method provided highly specific results, showing that three Kinesin-3 family members-KIF1A, KIF13A, and KIF13B-interacted with dendritic vesicle populations. This experimental paradigm allows a systematic approach to evaluate motor-vesicle interactions in living cells.

An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease- associated Aß oligomers.

Defective brain insulin signaling has been suggested to contribute to the cognitive deficits in patients with Alzheimer's disease (AD). Although a connection between AD and diabetes has been suggested, a major unknown is the mechanism(s) by which insulin resistance in the brain arises in individuals with AD. Here, we show that serine phosphorylation of IRS-1 (IRS-1pSer) is common to both diseases. Brain tissue from humans with AD had elevated levels of IRS-1pSer and activated JNK, analogous to what occurs in peripheral tissue in patients with diabetes. We found that amyloid-ß peptide (Aß) oligomers, synaptotoxins that accumulate in the brains of AD patients, activated the JNK/TNF-α pathway, induced IRS-1 phosphorylation at multiple serine residues, and inhibited physiological IRS-1pTyr in mature cultured hippocampal neurons. Impaired IRS-1 signaling was also present in the hippocampi of Tg mice with a brain condition that models AD. Importantly, intracerebroventricular injection of Aß oligomers triggered hippocampal IRS-1pSer and JNK activation in cynomolgus monkeys. The oligomer-induced neuronal pathologies observed in vitro, including impaired axonal transport, were prevented by exposure to exendin-4 (exenatide), an anti-diabetes agent. In Tg mice, exendin-4 decreased levels of hippocampal IRS-1pSer and activated JNK and improved behavioral measures of cognition. By establishing molecular links between the dysregulated insulin signaling in AD and diabetes, our results open avenues for the investigation of new therapeutics in AD.

N-methyl-D-aspartate receptors are required for synaptic targeting of Alzheimer's toxic amyloid-ß peptide oligomers.

Soluble amyloid-ß peptide (Aß) oligomers, known to accumulate in Alzheimer's disease brains, target excitatory post-synaptic terminals. This is thought to trigger synapse deterioration, a mechanism possibly underlying memory loss in early stage Alzheimer's disease. A major unknown is the identity of the receptor(s) targeted by oligomers at synapses. Because oligomers have been shown to interfere with N-methyl-d-aspartate receptor (NMDAR) function and trafficking, we hypothesized that NMDARs might be required for oligomer binding to synapses. An amplicon vector was used to knock-down NMDARs in mature hippocampal neurons in culture, yielding 90% reduction in dendritic NMDAR expression and blocking neuronal oxidative stress induced by Aß oligomers, a pathological response that has been shown to be mediated by NMDARs. Remarkably, NMDAR knock-down abolished oligomer binding to dendrites, indicating that NMDARs are required for synaptic targeting of oligomers. Nevertheless, oligomers do not appear to bind directly to NMDARs as indicated by the fact that both oligomer-attacked and non-attacked neurons exhibit similar surface levels of NMDARs. Furthermore, pre-treatment of neurons with insulin down-regulates oligomer-binding sites in the absence of a parallel reduction in surface levels of NMDARs. Establishing that NMDARs are key components of the synaptic oligomer binding complex may illuminate the development of novel approaches to prevent synapse failure triggered by Aß oligomers.

Impaired astrocytic extracellular matrix distribution under congenital hypothyroidism affects neuronal development in vitro.

Astrocytes clearly play a role in neuronal development. An indirect mechanism of thyroid hormone (T3) in the regulation of neuronal development mediated by astrocytes has been proposed. T3 alters the production and organization of the extracellular matrix (ECM) proteins and proteoglycans, producing a high-quality substrate for neuronal differentiation. The present study investigated the effect of hypothyroidism on the astrocyte production of fibronectin (FN) and laminin (LN) as well as their involvement in neuronal growth and neuritogenesis. Our results demonstrated that the amount of both FN and LN were significantly reduced in cultures of hypothyroid astrocytes from rat cerebellum compared with normal cells. This effect was accompanied by reduced numbers of neurons and neuritogenesis. Similarly, the proportions of neurons and neurons with neurites were reduced in cultures on ECM prepared from hypothyroid astrocytes in comparison with normal cells. The proportion of both normal and hypothyroid neurons is strongly reduced in astrocyte ECM compared with cocultures on astrocyte monolayers, suggesting that extracellular factors other than ECM proteins are involved in this process. Moreover, treatment of hypothyroid astrocytic cultures with T3 restored the area of both FN and LN immunostaining to normal levels and partially reestablished neuronal survival and neuritogenesis. Taken together, our results demonstrated that hypothyroidism involves impairment of the astrocytic microenvironment and affects the production of ECM proteins. Thus, hypothyroidism is implicated in impaired neuronal development.

Amyloid-beta peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3beta in primary cultured hippocampal neurons.

Disruption of axonal transport is a hallmark of several neurodegenerative diseases, including Alzheimer's disease (AD). Even though defective transport is considered an early pathologic event, the mechanisms by which neurodegenerative insults impact transport are poorly understood. We show that soluble oligomers of the amyloid-beta peptide (AbetaOs), increasingly recognized as the proximal neurotoxins in AD pathology, induce disruption of organelle transport in primary hippocampal neurons in culture. Live imaging of fluorescent protein-tagged organelles revealed a marked decrease in axonal trafficking of dense-core vesicles and mitochondria in the presence of 0.5 microm AbetaOs. NMDA receptor (NMDAR) antagonists, including d-AP5, MK-801, and memantine, prevented the disruption of trafficking, thereby identifying signals for AbetaO action at the cell membrane. Significantly, both pharmacological inhibition of glycogen synthase kinase-3beta (GSK-3beta) and transfection of neurons with a kinase-dead form of GSK-3beta prevented the transport defect. Finally, we demonstrate by biochemical and immunocytochemical means that AbetaOs do not affect microtubule stability, indicating that disruption of transport involves a more subtle mechanism than microtubule destabilization, likely the dysregulation of intracellular signaling cascades. Results demonstrate that AbetaOs negatively impact axonal transport by a mechanism that is initiated by NMDARs and mediated by GSK-3beta and establish a new connection between toxic Abeta oligomers and AD pathology.

Biochemical alterations in caged Nile tilapia Oreochromis niloticus.

Joinville is an important industrial city in Santa Catarina, southern Brazil, and also a risk factor for the Babitonga drainage basin. Oxidative stress-related parameters were evaluated in caged tilapia (Oreochromis niloticus) exposed for 7 days (sites S1 and S2) in a Babitonga drainage basin tributary river. Site S1 showed enhanced levels of hepatic CYP1A, CYP2B-like and glutathione S-transferase activity, while site S2 showed decreased levels of glutathione and increased lipoperoxidation indexes, catalase, glutathione peroxidase and glutathione reductase activity. Correlation analyses revealed that oxidative stress-related parameters behaved like a group of interrelated variables, while CYPs and glutathione S-transferase seem to be independent. New putative biomarkers were evaluated in the tilapia brain. Caspase-3 activation (both sites), decreased in p38MAPK phosphorylation (site S2) and decreased expression in HSP70 (site S1) were observed. Data indicate that employed variables, when used as a group (oxidative stress-related parameters, CYP1A/2B-like, caspase-3, HSP70 and protein kinases) can be useful as predictors of pollution.

Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers.

Synapse deterioration underlying severe memory loss in early Alzheimer's disease (AD) is thought to be caused by soluble amyloid beta (Abeta) oligomers. Mechanistically, soluble Abeta oligomers, also referred to as Abeta-derived diffusible ligands (ADDLs), act as highly specific pathogenic ligands, binding to sites localized at particular synapses. This binding triggers oxidative stress, loss of synaptic spines, and ectopic redistribution of receptors critical to plasticity and memory. We report here the existence of a protective mechanism that naturally shields synapses against ADDL-induced deterioration. Synapse pathology was investigated in mature cultures of hippocampal neurons. Before spine loss, ADDLs caused major downregulation of plasma membrane insulin receptors (IRs), via a mechanism sensitive to calcium calmodulin-dependent kinase II (CaMKII) and casein kinase II (CK2) inhibition. Most significantly, this loss of surface IRs, and ADDL-induced oxidative stress and synaptic spine deterioration, could be completely prevented by insulin. At submaximal insulin doses, protection was potentiated by rosiglitazone, an insulin-sensitizing drug used to treat type 2 diabetes. The mechanism of insulin protection entailed a marked reduction in pathogenic ADDL binding. Surprisingly, insulin failed to block ADDL binding when IR tyrosine kinase activity was inhibited; in fact, a significant increase in binding was caused by IR inhibition. The protective role of insulin thus derives from IR signaling-dependent downregulation of ADDL binding sites rather than ligand competition. The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis.

GMP prevents excitotoxicity mediated by NMDA receptor activation but not by reversal activity of glutamate transporters in rat hippocampal slices.

Glutamate is the main excitatory neurotransmitter in the mammalian nervous system and is essential for its normal functions. However, overstimulation of glutamatergic system due to hyperactivation of NMDA receptors and/or impairment of glutamate reuptake system has been implicated in many acute and chronic neurological diseases. Regulation of extracellular glutamate concentrations relies on the function of glutamate transporters which can be reversed in situations related to excitotoxicity. Guanosine-5'-monophosphate (GMP), a guanine nucleotide which displays important extracellular roles, such as trophic effects to neurons and astrocytes, behaves as antagonist of glutamate receptors and is neuroprotective in hippocampal slices against excitotoxicity or ischemic conditions. Hippocampal slices exposed to 1 or 10 mM glutamate, or 100 microM NMDA with 10 microM glycine for 1 h and evaluated after 6 or 18 h, showed reduced cell viability and DNA fragmentation, respectively. Glutamate- or NMDA-induced cell death was prevented by 50 microM MK-801, but only NMDA-induced cell damage was prevented by GMP (1 mM). Glutamate-induced cell viability impairment and glutamate-induced l-[(3)H]glutamate release were both prevented by adding DL-TBOA (10 microM). Otherwise, NMDA-induced cell viability loss was not prevented by 10 microM of DL-TBOA and NMDA did not induce l-[(3)H]glutamate release. Our results demonstrate that GMP is neuroprotective when acting selectively at NMDA receptors. Glutamate-induced hippocampal slice damage and glutamate release were blocked by glutamate transporter inhibitor, indicating that glutamate-induced toxicity also involves the reversal of glutamate uptake, which cannot be prevented by GMP.

Thyroid hormone increases astrocytic glutamate uptake and protects astrocytes and neurons against glutamate toxicity.

Thyroid hormone (T(3)) regulates the growth and differentiation of rat cerebellar astrocytes. Previously, we have demonstrated that these effects are due, at least in part, to the increased expression of extracellular matrix molecules and growth factors, such as fibroblast growth factor-2. T(3) also modulates neuronal development in an astrocyte-mediated manner. In the mammalian central nervous system, excitatory neurotransmission is mediated mainly by glutamate. However, excessive stimulation of glutamate receptors can lead to excitotoxicity and cell death. Astrocytic glutamate transporters, GLT-1 and GLAST, play an essential role in the clearance of the neuronal-released glutamate from the extracellular space and are essential for maintaining physiological extracellular glutamate levels in the brain. In the present study, we showed that T(3) significantly increased glutamate uptake by cerebellar astrocytes compared with control cultures. Inhibitors of glutamate uptake, such as L-PDC and DL-TBOA, abolished glutamate uptake on control or T(3)-treated astrocytes. T(3) treatment of astrocytes increased both mRNA levels and protein expression of GLAST and GLT-1, although no significant changes on the distribution of these transporters were observed. The gliotoxic effect of glutamate on cultured cerebellar astrocytes was abolished by T(3) treatment of astrocytes. In addition, the neuronal viability against glutamate challenge was enhanced on T(3)-treated astrocytes, showing a putative neuroprotective effect of T(3). In conclusion, our results showed that T(3) regulates extracellular glutamate levels by modulating the astrocytic glutamate transporters. This represents an important mechanism mediated by T(3) on the improvement of astrocytic microenvironment in order to promote neuronal development and neuroprotection.

Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK signaling.

Glutamate excitotoxicity may culminate with neuronal and glial cell death. Glutamate induces apoptosis in vivo and in cell cultures. However, glutamate-induced apoptosis and the signaling pathways related to glutamate-induced cell death in acute hippocampal slices remain elusive. Hippocampal slices exposed to 1 or 10 mM glutamate for 1 h and evaluated after 6 h, showed reduced cell viability, without altering membrane permeability. This action of glutamate was accompanied by cytochrome c release, caspase-3 activation and DNA fragmentation. Glutamate at low concentration (10 microM) induced caspase-3 activation and DNA fragmentation, but it did not cause cytochrome c release and, it did not alter the viability of slices. Glutamate-induced impairment of hippocampal cell viability was completely blocked by MK-801 (non-competitive antagonist of NMDA receptors) and GAMS (antagonist of KA/AMPA glutamate receptors). Regarding intracellular signaling pathways, glutamate-induced cell death was not altered by a MEK1 inhibitor, PD98059. However, the p38 MAPK inhibitor, SB203580, prevented glutamate-induced cell damage. In the present study we have shown that glutamate induces apoptosis in hippocampal slices and it causes an impairment of cell viability that was dependent of ionotropic and metabotropic receptors activation and, may involve the activation of p38 MAPK pathway.

Guanine derivatives modulate extracellular matrix proteins organization and improve neuron-astrocyte co-culture.

Guanine derivatives (GD) have been shown to exert relevant extracellular effects as intercellular messengers, neuromodulators in the central nervous system, and trophic effects on astrocytes and neurons. Astrocytes have been pointed out as the major source of trophic factors in the nervous system, however, several trophic effects of astrocytic-released soluble factors are mediated through modulation of extracellular matrix (ECM) proteins. In this study, we investigated the effects of guanosine-5'-monophosphate (GMP) and guanosine (GUO) on the expression and organization of ECM proteins in cerebellar astrocytes. Moreover, to evaluate the effects of astrocytes pre-treated with GMP or GUO on cerebellar neurons we used a neuron-astrocyte coculture model. GMP or GUO alters laminin and fibronectin organization from a punctate to a fibrillar pattern, however, the expression levels of the ECM proteins were not altered. Guanine derivatives-induced alteration of ECM proteins organization is mediated by activation of mitogen activated protein kinases (MAPK), CA(2+)-calmodulin-dependent protein kinase II (CaMK-II), protein kinase C (PKC), and protein kinase A (PKA) pathways. Furthermore, astrocytes treated with GMP or GUO promoted an increased number of cerebellar neurons in coculture, without altering the neuritogenesis pattern. No proliferation of neurons or astrocytes was observed due to GMP or GUO treatment. Our results show that guanine derivatives promote a reorganization of the ECM proteins produced by astrocytes, which might be responsible for a better interaction with neurons in cocultures.

Anticorpos contra o citoplasma de neutrófilos / Antineutrophil cytoplasmic antibodies

Os auto-anticorpos antiantígenos citoplasmáticos de neutrófilos (ANCA) têm importante associação ao diagnóstico e possível monitoramento de uma significante parcela de doenças auto-imunes. A Proteinase 3 é o principal antígeno presente no tipo demarcação citoplasmática granular difusa (c-ANCA), e a Mieloperoxidase na marcação perinuclear (p-ANCA) em ensaios de imunofluorescência indireta (IFI) em neutrófilos fixados em etanol. A vasculite sistêmica compreende uma série de síndromes caracterizadas por dividir uma base histopatológica comum: inflamação nos vasos sangüíneos resultando em obstrução vascular com subseqüente isquemia e enfartamento tissular. A vasculite constitui um grupo heterogêneo de doenças que possuem como característica comum à inflamação destrutiva da parede de vasos sangüíneos. O papel potencializador de ANCA sobre as lesões é descrito em estágios iniciais de vasculite sistêmica pelo fato deste promover o recrutamento e adesões entre neutrófilos e células endoteliais.O presente trabalho teve como objetivo enfocar o papel do c-ANCA e p-ANCA no diagnóstico laboratorial de Vasculite Sistêmica e o levantamento de exames efetuados no período de 16/04/04 a 20/04/06 para estes mesmos marcadores no laboratório de ImunologiaClínica do Hospital Universitário Polydoro Ernani de São Thiago. Neste levantamento pudemos constatar uma reduzida parcela de resultados positivos para c-ANCA (15%) e p-ANCA (39%), fato este devido à larga gama de doenças com sintomatologias semelhantes às doenças relacionadas à ANCA, possuindo, porém ANCA negativo.A avaliação clínica é importante no manejo de doenças auto-imunes, mas o laboratório representa papel decisivo na avaliação dessas doenças. Testes laboratoriais auxiliam ao estabelecer o diagnóstico, na monitorização do curso da doença, na predição de sua evolução,na decisão acerca da terapêutica, na avaliação da resposta à terapia e também para o estudo da etiologia ou patogênese das doenças auto-imunes

Relação entre os níveis séricos de cálcio e paratormônio e a positividade da cintilografia das paratiróides com sestamibi: análise de 194 pacientes / The relation between serum levels of calcium and PTH and the positivity of parathyroid scintigraphy with sestamibi: analysis of 194 patients

Com o objetivo de correlacionar os níveis séricos de cálcio e PTH com a porcentagem de resultados positivos na cintilografia das paratiróides (CP), analisamos retrospectivamente 194 pacientes submetidos à CP. Avaliou-se visualmente a distribuição dos resultados das CP em um diagrama de dispersão cujos eixos eram os níveis de cálcio (eixo Y) e PTH (eixo X) séricos. Foram definidos 6 grupos de pacientes: 1) cálcio > 12mg/dL; 2) 11mg/dL < cálcio < 12mg/dL; 3) 9,9mg/dL < cálcio < 11mg/dL com PTH > 120pg/mL; 4) 9,9mg/dL < cálcio < 11mg/dL com 65pg/mL < PTH < 120pg/mL; 5) 9,9mg/dL < cálcio < 11mg/dL com PTH < 65pg/mL; e 6) cálcio < 9,9mg/dL. A porcentagem de exames positivos nestes 6 grupos foram respectivamente: 10/10 (100 por cento), 18/29 (62 por cento), 7/9 (78 por cento), 18/45 (40 por cento), 2/21 (10 por cento) e 1/80 (1 por cento). Em conclusão, nos pacientes com suspeita de hiperparatiroidismo primário, as CPs realizadas antes da cirurgia de paratiroidectomia naqueles com níveis de cálcio acima de 11mg/dL são, na maioria das vezes, positivas. Para pacientes com níveis de cálcio sérico entre 9,9mg/dL e 11mg/dL, a pertinência da realização da cintilografia vai depender dos níveis de PTH sérico, sendo esta pertinência alta para pacientes com níveis de PTH acima de 120pg/mL e muito baixa para pacientes com PTH abaixo de 65pg/mL. Pacientes com cálcio sérico abaixo de 9,9mg/dL raramente apresentam cintilografia das paratiróides positivas.