A case of pulmonary arterial hypertension complicated by anti-neutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis

Pulmonary arterial hypertension (PAH) is a rare complication of ANCA-associated vasculitis (AAV). We report a 37-year-old man with PAH complicated by both AAV and SSc who presented with dyspnea, cardiac enlargement, positive myeloperoxidase (MPO)-ANCA, anti-centromere antibodies, proteinuria, and urinary casts. Elevated pulmonary arterial pressure (58/22/34 mmHg) and low PAWP (2 mmHg) were confirmed by right heart catheterization. Treatment with glucocorticoids (GC) decreased urinary protein and serum MPO-ANCA; however, PAH did not respond to GC. Therefore, a combination of beraprost, bosentan, and tadalafil was needed. The differences in responses to GC suggest that the pathophysiology of nephropathy is different from that of PAH. We considered that nephropathy was associated with AAV but that PAH was associated with SSc in the present case. We discuss the pathophysiology and treatment response of PAH complicated by AAV, referring to nine past cases

X-ray structure of Galdieria Rubisco complexed with one sulfate ion per active site

AbstractRibulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the reactions of carboxylation and oxygenation of ribulose-1,5-bisphosphate. These reactions require that the active site should be closed by a flexible loop (loop 6) of the large subunit. Rubisco from a red alga, Galdieria partita, has the highest specificity for carboxylation reaction among the Rubiscos hitherto reported. The crystal structure of unactivated Galdieria Rubisco has been determined at 2.6 Å resolution. The electron density map reveals that a sulfate binds only to the P1 anion-binding site of the active site and the loop 6 is closed. Galdieria Rubisco has a unique hydrogen bond between the main chain oxygen of Val332 on the loop 6 and the ϵ-amino group of Gln386 of the same large subunit. This interaction is likely to be crucial to understanding for stabilizing the loop 6 in the closed state and to making a higher affinity for anionic ligands

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease

[Background] Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferatoractivated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. [Methods] We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27?81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. [Results] After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. [Conclusion] Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD

Chronic Active Epstein–Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report

Chronic active Epstein–Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/μg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable

Skeletal myoblast sheet transplantation improves the diastolic function of a pressure-overloaded right heart

ObjectiveThe development of right ventricular dysfunction has become a common problem after surgical repair of complex congenital heart disease. A recent study reported that tissue-engineered skeletal myoblast sheet transplantation improves left ventricular function in patients with dilated and ischemic cardiomyopathy. Therefore myoblast sheet transplantation might also improve ventricular performance in a rat model of a pressure-overloaded right ventricle.MethodsSeven-week-old male Lewis rats underwent pulmonary artery banding. Four weeks after pulmonary artery banding, myoblast sheet transplantation to the right ventricle was performed in the myoblast sheet transplantation group (n = 20), whereas a sham operation was performed in the sham group (n = 20).ResultsFour weeks after performing the procedure, a hemodynamic assessment with a pressure–volume loop showed a compensatory increase in systolic function in both groups. However, only the myoblast sheet transplantation group showed a significant improvement in the diastolic function: end-diastolic pressure (sham vs myoblast sheet transplantation, 10.3 ± 3.1 vs 5.0 ± 3.7 mm Hg; P < .001), time constant of isovolumic relaxation (11.1 ± 2.5 vs 7.6 ± 1.2 ms, P < .001), and end-diastolic pressure–volume relationship (16.1 ± 4.5 vs 7.6 ± 2.4/mL, P < .005). The right ventricular weight and cell size similarly increased in both groups. A histologic assessment demonstrated significantly suppressed ventricular fibrosis and increased capillary density in the myoblast sheet transplantation group in comparison with those in the sham group. Reverse transcription–polymerase chain reaction demonstrated an increased myocardial gene expression of hepatocyte growth factor and vascular endothelial growth factor in the myoblast sheet transplantation group but not in the sham group.ConclusionsSkeletal myoblast sheet transplantation improved the diastolic dysfunction and suppressed ventricular fibrosis with increased capillary density in a rat model of a pressure-overloaded right ventricle. This method might become a novel strategy for the myocardial regeneration of right ventricular failure in patients with congenital heart disease

Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.ArticleScientific reports 7(1) : 8630-(2017)journal articl