Metabolic Bone Disease

There is increasing evidence that cardiorespiratory fitness (CRF) is an important health marker already in youth. This study aimed to determine the ability of five VO(2max) equations to discriminate between low/high Metabolic Risk in 450 Portuguese adolescents aged 10-18. We measured waist and hip circumferences, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and blood pressure. For each of these variables, a Z-score was computed. The HDL-cholesterol was multiplied by -1. A metabolic risk score was constructed by summing the Z scores of all individual risk factors. High risk was considered when the individual had ≥1 SD of this score. Cardiorespiratory fitness (CRF) was measured with the 20-m shuttle run test. We estimated VO(2max) from the CRF tests using five equations. ROC analyses showed a significant discriminatory accuracy for the Matsuzaka and Barnett(a) equations in identifying the low/high metabolic risk in both genders (Matsuzaka girls: AUC=0.654, 95%CI: 0.591-0.713, p<0.001, VO(2max)=39.5 mL kg⁻¹min⁻¹; boys: AUC=0.648, 95%CI: 0.576-0.716, p<0.001, VO(2max)=41.8 mL kg⁻¹min⁻¹; Barnett(a) girls: AUC=0.620, 95%CI: 0.557-0.681, p<0.001, VO(2max)=46.4 mL kg⁻¹min⁻¹; boys: AUC=0.628, 95%CI: 0.555-0.697, p=0.04, VO(2max)=42.6 mL kg⁻¹min⁻¹), and the Ruiz equation in boys (AUC=0.638, 95%CI: 0.565-0.706,…

Knockout mouse models allow preparation of primary neuronal cultures from distinct brain regions in order to investigate the underlying neuronal pathomechanisms of human metabolic diseases associated with severe, regionally distinct brain pathologies (e.g. Zellweger syndrome, the most severe form of a peroxisomal biogenesis disorder). However, homozygous mouse pups with Zellweger syndrome usually die shortly after birth. Therefore, in this study, we established optimized protocols for the simultaneous preparation and cultivation of serum-free primary neuronal cultures from distinct brain regions (medial neocortex, hippocampus and cerebellum) from individual newborn (P0.5) C57Bl/6J mice. For each of the three types of neuronal cultures, we have optimized the isolation procedures and cultivation conditions including coating substrates, enzyme digestion, mode of trituration, seeding density and composition of the culture medium. As indicated by indirect immunofluorescence using antibodies against NeuN, GFAP and CNPase, the purity of the distinct neuronal cultures was high. The percentage of oligodendrocytes was less than 1% in all neuronal cultures. Only 5% astrocytes were present in cortical, 7% in hippocampal and 10% in cerebellar cultures. Cytosine arabinofuranoside (AraC) treatment reduced the percentage of astrocytes only significantly in hippocampal cultures, however, increased the percentage of apoptotic neurons in hippocampal and cortical cultures.

Resumo – Diabetes Mellitus tipo 2 (DM2) é uma doença metabólica caracterizada por hiperglicemia e disfunções cardiovasculares, as quais podem ser controladas com exercícios físicos, controle dietético e tratamento farmacológico. Pesquisas recentes têm demonstrado associações ...

We present evidence that a 480G-->A transition in the coding region of the beta-glucuronidase gene, which results in an aspartic-acid-to-asparagine substitution at amino acid position 152 (D152N), produces a pseudodeficiency allele (GUSBp) that leads to greatly reduced levels of beta-glucuronidase activity without apparent deleterious consequences. The 480G-->A mutation was found initially in the pseudodeficient mother of a child with mucopolysaccharidosis VII (MPSVII), but it was not on her disease-causing allele, which carried the L176F mutation. The 480G-->A change was also present in an unrelated individual with another MPSVII allele who had unusually low beta-glucuronidase activity, but whose clinical symptoms were probably unrelated to beta-glucuronidase deficiency. This individual also had an R357X mutation, probably on his second allele. We screened 100 unrelated normal individuals for the 480G-->A mutation with a PCR method and detected one carrier. Reduced beta...

The aim of this study was to determine serum lecithin:cholesterol acyltransferase (LCAT) activity in parallel with HDL2 and HDL3 amounts and composition in pregnancy induced hypertension (PIH) and chronic hypertensive (CH) mothers and in their small for gestational age (SGA) newborns. LCAT activity was assayed by conversion of [3H] cholesterol to labelled cholesteryl ester. HDL2 and HDL3 were separated by ultracentrifugation. At term, cholesterol values were similar in PIH, CH and controls. However, higher levels of triglycerides were observed in PIH and CH (+20% and +21%, respectively) as compared with normotensive control mothers (NC). HDL2 and HDL3-phospholipids, HDL2-cholesterol concentrations and LCAT activity were lower in PIH and CH mothers than in NC mothers. Similar changes were also observed in SGA newborns of PHI mothers and in SGA newborns of CH mothers when compared to appropriate for gestational age newborns of control mothers (AGA-NC). In addition, SGA newborns showed low HDL2 and HDL3 apoA-I contents. Maternal hypertension and foetal intrauterine growth retardation are associated with profound abnormalities in HDL metabolism, consistent with an atherogenic risk. SGA lipoprotein profiles appear to implicate later metabolic diseases.

Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of the mitochondrial beta-oxidation of long-chain fatty acids. It is a rare multiorgan disease which includes hypoketotic hypoglycemia, severe hepatomuscular symptoms, cardiac abnormalities, seizures and lethargy, as well as dysmorphic features. Until now, only 22 affected families have been described in the literature. An increasing number of mutations are being identified in the CPT2 gene, with a distinct genotype-phenotype correlation in most cases. Herein we report a new case of neonatal CPT II deficiency associated with Dandy-Walker syndrome and sudden death at 13 days of life. CPT II deficiency was suggested by acylcarnitine analysis of dried-blood on filter paper in the expanded newborn screening. Genetic analysis of the CPT2 gene identified the presence of a previously described mutation in homozygosity (c.534_558del25bpinsT). All lethal neonatal CPT II de...

SUMMARY Introduction. The homocysteinuria is an inherited metabolic disease caused by deficiency of some of the enzymes that work in the catabolism of methionine, such as methylenetetrahydrofolate reduc- tase (MTHFR) or cystathionine b syn- thase (CbS). The CbS deficiency is the most common biochemical defect found for this disease and 104 mutations have been found for this enzyme. Objetive. To