Neonatal diet may influence the development of type 1 diabetes (T1D) in susceptible individuals through an intestinal mucosal inflammatory response, resulting in loss of self-tolerance. We tested the hypothesis that formula feeding during the neonatal period accelerates the development of T1D in diabetes-prone BioBreeding (BBDP) rats through regulation of CD4ϩCD25ϩ regulatory T lymphocytes (T reg ) and anti-inflammatory cytokines. BBDP rat pups fed rat milk substitute (RMS) via a "pup-in-the cup" system were compared with mother-fed (MF) rats. The spleen and thymus were analyzed for Foxp3-expressing CD4ϩ/CD25ϩ T cells. Multiplex enzyme-linked immunosorbent assays (ELISAs) were performed to measure cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor ␣ (TNF-␣), interferon-gamma (IFN-␥), interleukin (IL)-4, IL-10, and IL-18. Diabetes-free survival, time of disease onset, and T reg /total T lymphocyte ratios were not different. MF pups had higher ileal CINC (p Ͻ 0.001) and IL-18 (p ϭ 0.002), but no differences in the liver. There were no differences in ileal cytokine concentrations of 75-d-old rats, but the formula-fed rats had greater liver TNF-␣ (p Ͻ 0. T ype 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-secreting beta cells, resulting in insulin deficiency and hyperglycemia in genetically susceptible individuals. While genetic predisposition is clearly a major component of T1D, interactions between the environment and the immune system are thought to weigh heavily in disease development (1). Indeed, with evidence pointing to the pathogenesis of T1D beginning very early in life or perhaps in utero (2), more attention has recently been directed toward environmental exposures early in infancy, particularly that of diet.An underlying structural or developmental defect in the gastrointestinal tract may assist in the entry of dietary agents that have the potential to influence the T1D process (3,4). In healthy individuals, the small intestine acts as a gatekeeper between the external environment and the internal organ systems of the body, allowing the absorption of nutrients and preventing the passage of potential antigens. During infancy, especially in the first 2 mo of life, increased intestinal permeability allows dietary antigens greater access to the resident immune cells of the lamina propria (5). Increased gut permeability has also been reported in T1D patients who do not have associated celiac disease (6).BioBreeding diabetes-prone (BBDP) rats (Biomedical Research Models, Worcester, MA) are a well-studied model of T1D because at a predictable point in their life span (70 -120 d), a large majority (Ͼ90%) develops T1D manifested as overt glycosuria, hyperglycemia, and ketosis (7). The loss of tolerance that permits autoimmunity against the beta cell and the development of T1D (8) is largely mediated by CD4ϩCD25ϩ regulatory T lymphocytes T reg , which suppress the activity of effector T cells carrying destructive capacity. A decrease in T reg spleen cell...

No abstract

Purpose: To report our results and rationale for treating large bladder calculi in patients with neuropathic voiding dysfunction (NVD) using percutaneous cystolithalopaxy. Materials and Methods: Ten patients with a previously diagnosed NVD presenting with a large stone burden were identified from our department database and a retrospective review of case notes and imaging was performed. Results: Percutaneous access to remove bladder stones (range 8x7 to 3x2 cm) had a mean surgery length of 150 min and blood loss of 23 mL. Six of the seven patients treated percutaneously were discharged on the day of surgery and suffered no complications, while one patient experienced poor suprapubic tube drainage and required overnight admission with discharge the following day. Transurethral removal of stone burden (range 4x4 to 4x3 cm) had a mean surgery length of 111 min and blood loss of 8 mL. Each of these three patients were under our care for less than 23 hours, and one patient required a second attempt to remove 1x0.5 cm of stone fragments. There was no statistical difference between mean operative times and estimated blood loss, p = 0.5064 and p = 0.0944 respectively, for the two treatment methods. Conclusion: In this small series, percutaneous cystolithalopaxy was a safe, effective, and often preferred minimally invasive option for removal of large calculi in patients with NVD. We suggest possible guidelines for best endoscopic approach in this population, although a larger and prospectively randomized series will be ideal for definitive conclusions.