BackgroundChanges in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms.MethodsWe assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls.ResultsWe identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these dataConclusionsOur analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.

Após leitura cuidadosa do artigo mencionado, apresento a contribuição que segue.Os autores relatam que nos últimos 10 anos apenas quatro trabalhos foram publicados referentes as calcificações dos gânglios da base na literatura nacional. Informo-lhe que existem outras publicações nacionais 1 -4 .Além das localizações cerebrais descritas no trabalho citado, é também freqüente ocorrer calcificações no cerebelo e, raramente, no tronco cerebral 5 .A ocorrência de calcificações dos gânglios da base tem sido cada vez mais descrita na literatura médica, principalmente após o uso rotineiro da TC em pacientes portadores de epilepsia e em casos de hipoparatireoidismo e pseudo-hipoparatireoidismo 4-6 . Dos casos de calcificação dos núcleos da base vistos na TC, cerca de 5 a 8% são secundários a hipoparatireoidismo 23 . RESPOSTA DA AUTORARecebi por escrito as observações cuidadosas do Dr. Pereira quanto ao referido artigo e gostaria de esclarecer apenas que há poucos estudos especificamente sobre pseudo-hipoparatireoidismo (PHP), sendo que na população sem distúrbio específico do metabolismo do cálcio, como mostram Ogata e col. 1 em 5897 pacientes que se submeteram a CT de crânio pelas mais diversas razões apenas um deles era portador de PHP. Contudo, sendo o hipoparatireoidismo uma doença muito mais comum e do ponto de vista fisiopatológico totalmente diferente do PHP, há maior número de estudos publicados quanto ao comprometimento neurológico, evidenciando incidência de calcificações dos gânglios da base e de outras localizações diferente do que ocorreria no PHP, objetivo do nosso relato de caso.Quanto as outras publicações na literatura nacional, agradeço a informação complementar fornecida. Cristiane Rocha Rua Santa Madalena 267103 01322-020 São Paulo SP CORRESPONDÊNCIA divulga opiniões e observações construtivas, particularmente acerca de artigos publicados nos últimos números de Arquivos de Neuro-Psiquiatria. São aceitas cartas assinadas, sucintas e precisas, desprovidas de caráter pessoal, abordando aspectos objetivos dos artigos e utilizando até cinco referências bibliográficas.

RESUMO -Descrevemos o caso de uma criança do sexo masculino, com 2 meses de idade, com tremor e hipertonia desde 15º dia de vida transferido para o nosso Serviço em que foi diagnosticado como tendo crises epilépticas. A investigação constatou hipocalcemia (4 mg/dL) e hipomagnesemia (1,6 mg/dL) e a correção intravenosa foi iniciada. Em todas as tentativas de suspensão da medicação intravenosa havia recidiva das crises. O diagnóstico de hipoparatireoidismo foi aventado e confirmado por investigação complementar. O exame neurológico mostrava uma criança irritada e em opistótono. A tomografia e a ressonância de encéfalo foram normais, mas o EEG evidenciou graves anormalidades. O tratamento oral com colecalciferol, cálcio e magnésio foi instituído. O paciente permaneceu internado durante 6 meses com dificuldade de controle das crises e infecções repetidas, vindo a falecer por esse motivo. Discutimos os achados clínicos, exames complementares, o diagnóstico diferencial e o tratamento instituído.PALAVRAS-CHAVE: epilepsia, hipocalcemia, hipoparatireoidismo.Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism Hypocalcemia and neonatal seizures: a rare case of congenital hypoparathyroidism ABSTRACT -We report the case of a white male infant, 2 months-old, with tremor and hypertonia since 15 th day of life transferred to our service and diagnosed as seizures. Investigation showed hypocalcaemia (4 mg/dl) and hypomagnesemia (1.6 mg/dL) and the infant's serum metabolic disturb was corrected by intravenous calcium gluconate and magnesium sulphate, but attempted to "wean" him from intravenous treatment led to a relapse of hypocalcemia. At this time hypoparathyroidism was suspected and the additional investigation confirmed this suspect ion. The neurologic examination revealed an irritable patient with marked extensor hypertonia and opisthotonos. Cranial CT and MRI scans were normal, but the EEG exam showed severe abnormalities. The infant was given the oral calcium gluconate, magnesium chloride and colecalciferol daily to maintain a normal calcium concentration, but the control was very difficult. The patient had an extend hospitalization of 6 months and death was due to repetitive infection. We discuss the clinical findings, imaging, EEG exam, differential diagnosis and treatment of this disorder.KEY WORDS: hypocalcemia, epilepsy, hypoparathyroidism. As crises epilépticas do período neonatal constituem fenômeno comum nesse período podendo ser decorrentes de diversas etiologias. O distúrbio metabólico é uma das principais causas das convulsões neonatais. A demora na realização do diagnóstico e no início do tratamento é fator decisivo na evolução clínica do recém-nascido. Descrevemos um caso de convulsão neonatal secundária a hipoparatireoidismo congênito, em que...

The authors describe the case of a 18-year-old man with short stature, epilepsy, mental deficiency and basal ganglia and central nervous system calcifications. The clinical and laboratorial findings have suggested pseudohypoparathyroidism which is a rare pathology with a peripheral resistance to parathormone, neuromuscular hyperexcitability, short stature and various clinical findings. This paper reviews the clinical form and treatment of pseudohypoparathyroidism and the neuroradiologic aspects of calcifications.

Introduction: Type 1 diabetes is characterized by the autoimmune destruction of insulin-secreting β-cells, mediated by T auto reactive infiltrating cells, inflammatory cytokines and immunological mechanisms. However, little is known about the expression of genes and pathways dysregulated in peripheral blood mononuclear cells of patients with T1D. Objective: to investigate the gene expression profiles of circulating PBMC in recent-onset T1D patients (up to 6 months of diagnosis) in comparison with controls in the context of putative disease-related pathobiological processes and pathways. Methods: expression of mRNA from PBMC of 20 T1D patients, 15.8±8.6 years and age-matched 20 healthy controls, 14.7±6.7 years, (p>0.05) was evaluated with the Whole Human Genome Microarray Agilent and analyzed by GeneSpring with a fold change cutoff of 1.5 and adjusted P value <0.05; pathways analysis was performed with the software IPA. Results: 326 genes were differentially expressed between T1D patients and controls, being 204 (63%) upregulated, and 122 (37%) downregulated in T1D. Interactions between the differentially expressed genes evidenced expression patterns of 24 networks. The most significantly enriched canonical pathways were namely ErbB (erythroblastic leukemia viral oncogene) signaling, micropinocytosis signaling, savage pathways of pyrimidine ribonucleotides and hepathocyte growth factor in descending order of significance. The up-regulated protein targets within these signaling pathways were NEK2, PLK1, ATM, PRKCD, CCND1, NRG2 and those down regulated were AREG, CDC42 and CDADC1. Conclusion: The majority of upregulated genes of patients with T1D was related to cell cycle control, mitotic progression, proliferation and DNA repair, probably related to changes in PBMC metabolism and function due to DNA damage associated with hyperglycemia. The lower expression of AREG and CDC42 can be related to reduce immunosuppressive activity of regulatory T cells and B cell functions. Disclosure A. Santos: None. C. Chevillard: None. N. Gonfinetti: None. F. Bertonha: None. C. Moreira-Filho: None. J. Kalil: None. E. Cunha-Neto: None. M. Silva: None. Funding European Foundation for the Study of Diabetes; São Paulo Research Foundation