Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Metodologias de avaliação do valor nutricional do farelo de arroz desengordurado para suínos

O objetivo deste trabalho foi comparar o método de substituição com o de análise de regressão, na determinação do valor nutricional do farelo de arroz desengordurado, em dietas para suínos, nas fases de crescimento e terminação. Foram conduzidos dois ensaios de digestibilidade com 16 suínos machos castrados na fase de crescimento, com peso vivo inicial de 50,0±3,1 kg, e 16 suínos machos castrados na fase de terminação, com peso vivo inicial de 95,0±3,8 kg, alojados em gaiolas metabólicas. Utilizou-se o delineamento inteiramente casualizado com quatro tratamentos − 0, 15, 30 e 45% de substituição da dieta‑referência por farelo de arroz desengordurado − e quatro repetições, com um animal como unidade experimental. A análise de regressão foi mais precisa para estimar o valor nutricional do farelo de arroz desengordurado do que o método de substituição. Por esta análise, os coeficientes de digestibilidade aparente da matéria seca, matéria orgânica, proteína bruta e o valor de energia metabolizável do farelo de arroz desengordurado foram, respectivamente: 57,7, 64,8, 56,6% e 2.429 kcal kg‑1, na fase de crescimento, e 57,7, 64,7, 62,6% e 2.233 kcal kg‑1, na fase de terminação.The objective of this work was to compare the substitution method and the regression analysis method to determine the nutritional value of defatted rice bran in diets for swines at growing and finishing phases. Two digestibility bioassays were carried out with 16 barrows with initial body weight of 50.0±3.1 kg, in the growing phase, and 16 barrows with initial body weight of 95.0±3.8 kg, in the finishing phase, housed in metabolic cages. A completely randomized design was used with four treatments − 0, 15, 30 and 45% of substitution of the reference diet by defatted rice bran − and four replications, with one animal as the experimental unit. The regression analysis was more accurate than the method of substitution to assess the nutritional value of defatted rice bran. Throught this analyse, the apparent digestibility coefficients of dry matter, organic matter, crude protein and metabolizable energy of defatted rice bran were, respectively, 57.7, 64.8, 56.6% and 2,429 kcal kg‑1 on growing phase, and 57.7, 64.7, 62.6% and 2,233 kcal kg‑1 on finishing phase