MẤT PROTEIN QUA RUỘT – MỘT BIẾN CHỨNG NẶNG CỦA NHIỄM GIUN MÓC: BÁO CÁO CA BỆNH

Mục tiêu: Mô tả đặc điểm lâm sàng, cận lâm sàng và kết quả điều trị trường hợp nhiễm giun móc có biến chứng giảm protein máu nặng. Đối tượng và phương pháp: Báo cáo ca bệnh có biến chứng nặng của giun móc tại khoa Cấp cứu và Chống độc, Bệnh viện Nhi Trung ương. Kết quả: Trẻ gái 20 tháng tuổi, dân tộc Mường nhập viện vì li bì và tiêu chảy. Xét nghiệm cho thấy trẻ thiếu máu rất nặng, bạch cầu ưa acid tăng cao và protein máu giảm nặng. Bệnh nhân được điều trị tình trạng cấp cứu và xác định những căn nguyên gây giảm protein máu; loại trừ bệnh lý: suy dinh dưỡng, gan và thận,... Dựa vào yếu tố dịch tễ và các triệu chứng gợi ý, chúng tôi đã chỉ định xét nghiệm tìm kí sinh trùng trong đó có tìm trứng giun móc đồng thời định lượng nồng độ alpha 1 antitrypsin (A1AT) trong phân. Kết quả mẫu phân có rất nhiều trứng giun móc (+++) và tăng nồng độ A1AT (106,2 mg/dL). Chẩn đoán xác định là mất protein qua ruột (PLE) do nhiễm giun móc. Điều trị bằng albendazol trong 3 ngày. Sau 16 ngày chẩn đoán và điều trị, bệnh nhân đại tiện bình thường, hết phù, protein máu không giảm lại và được xuất viện. Kết luận: Mặc dù nhiễm giun móc là bệnh tương đối phổ biến ở các nước đang phát triển nhưng biến chứng nặng như mất protein qua ruột thường hiếm gặp vì vậy cần được chẩn đoán và điều trị kịp thời để tránh tình trạng nguy kịch đến tính mạng.

Detection of Novel Biomarkers in Saliva of Rheumatoid Arthritis Model Mice by Proteomics and Pathological Analysis

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

Diagnostic sensitivity of arginase, alpha-1 antitrypsin and alpha-fetoprotein in hepatitis patients

Chronic hepatitis C virus (HCV) and hepatocellular carcinoma (HCC) are common liver diseases that lead to death in Egypt, especially in men. The current study aimed to evaluate the diagnostic sensitivity of arginase (ARG) activity, alpha-1 antitrypsin (AAT), and alpha-fetoprotein (AFP) in the sera of patients with HCV (with & without viremia) and HCC. A total of 190 men classified as 40 healthy used as control (G1), 100 infected with HCV (subdivided into 50 with viremia (G2) and 50 without viremia (G3), and 50 with HCC (G4). The activity of ARG significantly decreased in HCV and HCC groups along with significant elevation in the level of AAT and AFP as compared with the control. Although a non-significant variation was scored in AST/ALT, significant differences were observed among AST/ARG and ARG/ALT in the pathogenic groups as compared with the healthy group. Moreover, significant variations in ARG, AAT, AFP, AST/ARG, and ARG/ALT were observed between viremia and non-viremia. Although AFP scored significant change among the viremia and HCC, the rest parameters scored non-significant changes between both groups. Furthermore, a receiver operating characteristic curve (ROC) showed the diagnostic ability for the selected parameters with high sensitivity and multiple linear regressions exhibited good associations between those parameters. These findings suggest the using possibility of ARG, AAT, and AFP in the diagnosis and/or follow-up of patients with HCV or HCC.

Proteomic Analysis of Exosomes Secreted from Human Alpha-1 Antitrypsin Overexpressing Mesenchymal Stromal Cells

Extracellular vesicles (EVs) mediate many therapeutic effects of stem cells during cellular therapies. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) were manufactured to overexpress the human antiprotease alpha-1 antitrypsin (hAAT) and studied to compare the EV production compared to lentivirus treated control MSCs. The goal of this study was to compare protein profiles in the EVs/exosomes of control and hAAT-MSCs using unbiased, high resolution liquid chromatography and mass spectrometry to explore differences. Nanoparticle tracking analysis (NTA) showed that the particle size of the EVs from control MSCs or hAAT-MSCs ranged from 30 to 200 nm. Both MSCs and hAAT-MSCs expressed exosome-associated proteins, including CD63, CD81, and CD9. hAAT-MSCs also expressed high levels of hAAT. We next performed proteomic analysis of EVs from three healthy donor cell lines. Exosomes collected from cell supernatant were classified by GO analysis which showed proteins important to cell adhesion and extracellular matrix organization. However, there were differences between exosomes from control MSCs and hAAT-MSCs in cytokine signaling of the immune system, stem cell differentiation, and carbohydrate metabolism (p < 0.05). These results show that hAAT-MSC exosomes contain a different profile of paracrine effectors with altered immune function, impacts on MSC stemness, differentiation, and prevention of cell apoptosis and survival that could contribute to improved therapeutic functions.

Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India: A Randomized Clinical Trial

This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500–2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention arm were supported to practice ciKMC until 28 days after birth, i.e., the neonatal period, or till the baby wriggled out of KMC position, if earlier. Infant stool specimens were collected during the first week of birth, and within 1 week after end of the neonatal period. Concentrations of fecal neopterin (nmol/L), myeloperoxidase (ng/mL), and alpha-1-antitrypsin (μg/mL) were determined using ELISA, and composite enteric enteropathy (EE) score at the end of the neonatal period was calculated by principal component analysis. We did not find any substantial difference in means between the ciKMC and control arm infants in the log-transformed values of neopterin (0.03; 95% CI −0.15 to 0.21), myeloperoxidase (0.28; 95% CI −0.05 to 0.61) and alpha-1-antitrypsin (0.02; 95% CI −0.30 to 0.34). The mean (SD) composite EE score was 13.6 (7.5) in the ciKMC and 12.4 (8.3) in the control arm infants, and the adjusted difference in means was negligible, 0.4 (95% CI −1.8 to 2.7). Our findings suggest that the promotion of ciKMC did not affect gut inflammation and permeability in our target population of LBW infants in North India.

C3d Elicits Neutrophil Degranulation and Decreases Endothelial Cell Migration, with Implications for Patients with Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by increased risk for emphysema, chronic obstructive pulmonary disease (COPD), vasculitis, and wound-healing impairment. Neutrophils play a central role in the pathogenesis of AATD. Dysregulated complement activation in AATD results in increased plasma levels of C3d. The current study investigated the impact of C3d on circulating neutrophils. Blood was collected from AATD (n = 88) or non-AATD COPD patients (n = 10) and healthy controls (HC) (n = 40). Neutrophils were challenged with C3d, and degranulation was assessed by Western blotting, ELISA, or fluorescence resonance energy transfer (FRET) substrate assays. Ex vivo, C3d levels were increased in plasma (p < 0.0001) and on neutrophil plasma membranes (p = 0.038) in AATD compared to HC. C3d binding to CR3 receptors triggered primary (p = 0.01), secondary (p = 0.004), and tertiary (p = 0.018) granule release and increased CXCL8 secretion (p = 0.02). Ex vivo plasma levels of bactericidal-permeability-increasing-protein (p = 0.02), myeloperoxidase (p < 0.0001), and lactoferrin (p < 0.0001) were significantly increased in AATD patients. In endothelial cell scratch wound assays, C3d significantly decreased cell migration (p < 0.0001), an effect potentiated by neutrophil degranulated proteins (p < 0.0001). In summary, AATD patients had increased C3d in plasma and on neutrophil membranes and, together with neutrophil-released granule enzymes, reduced endothelial cell migration and wound healing, with potential implications for AATD-related vasculitis.