Immune-mediated thrombotic thrombocytopenic purpura is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibodies against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient outcomes are yet to be identified. Seventy-three unique patients with a confirmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical information, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers associated with endothelial injury (e.g. von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g. human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activation of the complement alternative pathway (e.g. factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls who did not have a hematological disease; moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality; so were the prolonged activated partial thromboplastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management; the findings may also provide a framework for future multicenter studies to identify valuable prognostic markers for immune-mediated thrombotic thrombocytopenic purpura.

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA), a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease mouse models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts that characterize the respiratory phenotype of Pompe mouse models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease mouse models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, higher-order respiratory control centers, phrenic and hypoglossal motor nuclei, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

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Background Cardiotonic steroids (CTS), Na/K‐ATPase (NKA) ligands, have potential neuroprotective effects. Despite the importance of the NKA and CTS in the brain physiology, their roles in Alzheimer’s disease (AD) pathology are not fully elucidated. Bufadienolide CTS, marinobufagenin (MBG), was lower in 15‐month old double‐mutant Alzheimer’s mice (APPswe/PS1dE9; AD) compared to age‐matched wild type (WT) controls. The present study examined whether the treatment with MBG affects behavioral and other parameters in the mouse AD model. Methods Fifteen‐month old male AD and WT mice were administered MBG (100 µg/day/kg body weight; AD‐MBG, n=8; WT‐MBG, n=4) or vehicle (control: AD‐C, n=8; WT‐C, n=4) using subcutaneous ALZET osmotic minipumps for 3‐month. Systolic blood pressure (SBP; by tail cuff plethysmography), open field test (OFT), home cage activity (HCA), plasma and brain cortex were collected in 18‐mo old mice. SBP was assessed because MBG may increase blood pressure. Statistical analysis: 2‐way ANOVA, t‐test; data presented as mean±SEM. Results SBP and heart rate did not differ between WT‐C and AD‐C. MBG administration did not affect SBP, and increase heart rate in WT‐MBG vs. WT‐C. Plasma MBG was lower in AD‐C vs. WT‐C and increased in both WT‐MBG and AD‐MBG (Table). No differences were found in HCA, and in OFT for total distance traveled, nor for time spent in the center between AD‐C and WT‐C, and between AD‐C and AD‐MBG. MBG caused a greater reduction in distance traveled in the center for WT mice than it did for AD mice (Table). AD‐C mice had 1.6‐fold higher expression of inflammatory marker interleukin‐6 (IL6) mRNA in cortex vs. WT‐C; MBG treatment reversed this expression in AD‐MBG (Table). Conclusion AD mice had lower endogenous plasma MBG and higher brain pro‐inflammatory mRNA marker IL6 vs. WT mice. Treatment with MBG significantly reduced levels of this inflammatory marker. WT mice exhibited more exploratory behavior than AD mice in the OFT; MBG decreased exploratory behavior. The additional behavioral tests may be needed to assess the MBG effects on different cognitive components. The association of the brain inflammatory response, cognitive functions and MBG will be further explored in this AD mouse model. Supported by the NIH/NIA Intramural Research Program.