Transthyretin monomers: a new plasma biomarker for pre-symptomatic transthyretin-related amyloidosis.

BACKGROUND: Genotyping and amyloid fibril detection in tissues are generally considered the diagnostic gold standard in transthyretin-related amyloidosis. Patients carry less stable TTR homotetramers prone to dissociation into non-native monomers, which rapidly self-assemble into oligomers and, ultimately, amyloid fibrils. Thus, the initial event of the amyloid cascade produces the smallest transthyretin species: the monomers. This creates engineering opportunities for diagnosis that remain unexplored. METHODS: We hypothesise that molecular sieving represents a promising method for isolating and concentrating trace TTR monomers from the tetramers present in plasma samples. Subsequently, immunodetection can be utilised to distinguish monomeric TTR from other low molecular weight proteins within the adsorbed fraction. A two-step assay was devised (ImmunoSieve assay), combining molecular sieving and immunodetection for sensing monomeric transthyretin. This assay was employed to analyse plasma microsamples from 10 individuals, including 5 pre-symptomatic carriers of TTR-V30M, the most prevalent amyloidosis-associated TTR variant worldwide, and 5 healthy controls. RESULTS: The ImmunoSieve assay enable sensitive detection of monomeric transthyretin in plasma microsamples. Moreover, the circulating monomeric TTR levels were significantly higher in carriers of amyloidogenic TTR mutation. CONCLUSIONS: Monomeric TTR can function as a biomarker for evaluating disease progression and assessing responses to therapies targeted at stabilising native TTR.

Serum amyloid A and muscle activity biomarkers in horses submitted to equestrian show jumping / Biomarcadores de amilóide sérica A e de atividade muscular em cavalos submetidos a salto equestre

The aim of this study was to evaluate the serum amyloid A (SAA) and biomarkers of muscle activity of horses submitted to show jumping activity. To do this, the variables SAA, glucose, lactate and the biomarkers creatine kinase (CK) and aspartate amino transferase (AST) were evaluated in 10 horses submitted to the show jumping exercise in a tournament for beginners. The evaluations occurred before exercise (T0), immediately after (T1), 30 minutes (T2), 60 minutes (T3) and 24 hours after the end (T4). Data were evaluated using analysis of variance for repeated measures. The statistical software SAEG 9.1 was used to verify the level of significance between the moments for P<0.05. Glucose presented a difference between the moments T0 (97.7±13.3mg/dL) and T1 (79.7±14.1mg/dL). Lactate presented elevation in T1 (15.3±6.1mmol/L) compared to the others T0 (3.8±0.8mmol/L), T2 (6.5±3.9mmol/L), T3 (5.3±2.2mmol/L) and T4 (5.1±1.6mmol/L). The CK showed a significant difference between T0 (82.8±51.2U/L) and T1 (140.1±58.5U/L) and between T4 (74.4±43.1U/L) with T1 (140.1±58.5U/L). The AST presented no difference between moments. The show jumping activity with one-meter obstacles did not induce changes in the SAA protein between the moments.(AU)

O objetivo deste estudo foi avaliar a amilóide sérica A (SAA) e biomarcadores de atividade muscular de equinos submetidos a atividade de salto, ou hipismo clássico. Para tanto, foram avaliadas as variáveis SAA, glicose, lactato e os biomarcadores creatina quinase (CK) e aspartatoaminotransferase (AST) em 10 equinos submetidos ao exercício de saltos em torneio para iniciantes. As avaliações ocorreram antes do exercício (T0), imediatamente após (T1), 30 minutos (T2), 60 minutos (T3) e 24 horas após o término (T4). Os dados foram avaliados utilizando análise de variância para medidas repetidas. O software estatístico SAEG 9.1 foi utilizado para verificar o nível de significância entre os momentos para P<0,05. A glicose diferenciou-se entre os momentos T0 (97.7±13.3mg/dL) e T1 (79.7±14.1mg/dL). O lactado apresentou elevação comparada com o momento T1(15.3±6.1mmol/L) e os demais T0 (3.8±0.8mmol/L), T2 (6.5±3.9mmol/L), T3 (5.3±2.2mmol/L) e T4 (5.1±1.6mmol/L). A CK mostrou diferença significativa entre T0 (82.8±51.2U/L) e T1 (140.1±58.5U/L) e entre T4 (74.4±43.1U/L) com T1 (140.1±58.5U/L). A AST não apresentou diferença entre os momentos. A atividade de hipismo clássico com obstáculos de um metro não induziu alterações na proteína SAA entre os momentos.(AU)