Background Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol, an active form of vitamin D, plays an important role in renal, endothelial and cardiovascular protection. We evaluated the anti-inflammatory and histologic effects of a GLP-1 analogue (liraglutide) and of calcitriol in a db/db mouse diabetes model and in endothelial cells exposed to a diabetes-like environment.
Objectives: Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients. Methods: All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed. Results: Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52–76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD. Conclusions: Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.
HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.
The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.
Background
Emerging evidence demonstrates the involvement of Janus tyrosine kinase/signal transducer and transcription activator (JAK/STAT) proteins in the pathophysiology of diabetic kidney disease (DKD). The JAK/STAT pathway is involved in the inflammatory response and endothelial cell dysfunction observed in DKD. The glucagon‐like peptide‐1 (GLP‐1) analog liraglutide is an effective treatment for type 2 diabetes because it improves the inflammatory changes observed in experimental models of DKD. This study used db/db mice and endothelial cells (ECs) to determine the effect of diabetic environment on the JAK/STAT pathway and to assess the potential effect of liraglutide (200 μg/kg) in both models.
Methods
Diabetic db/db mice (12 weeks old) were treated with liraglutide for 14 weeks. The kidneys were then perfused with saline and removed for mRNA, protein, and immunohistochemical analyses. Endothelial cells were stimulated advanced glycation end products (AGEs) (200 μg/μL) glucose (200 mg/dL) and liraglutide (100 nM) for 24 hours. Total RNA and protein were extracted and analyzed for expression of JAK/STAT signaling.
Results
Phosphorylated (p‐) STAT3 was significantly upregulated in db/db mice compared with non‐diabetic mice. Liraglutide significantly downregulated p‐STAT3 protein expression in db/db mice. In db/db mice, p‐STAT3 was primarily expressed in the glomeruli, whereas p‐JAK2 was also expressed in kidney tubules. In ECs, liraglutide treatment prevented increased expression of p‐STAT3 and p‐JAK2. Liraglutide inhibited the target gene suppressor of cytokine signaling 3 (SOCS3) and sirtuin 1 (SIRT1) in db/db mice and in cultured EC.
Conclusions
This study suggests that the GLP‐1 analog liraglutide inhibits the JAK/STAT pathway, which participates in intracellular processes in experimental models of diabetes.
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