PMID- 30691808
OWN - NLM
STAT- MEDLINE
DCOM- 20191115
LR  - 20191115
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 235
DP  - 2019 Mar
TI  - Bladder-Drained Pancreas Transplantation: Urothelial Innate Defenses and Urinary 
      Track Infection Susceptibility.
PG  - 288-297
LID - S0022-4804(18)30651-6 [pii]
LID - 10.1016/j.jss.2018.09.028 [doi]
AB  - BACKGROUND: Pancreas transplantation restores insulin secretion in type 1 
      diabetes mellitus. The graft also produces exocrine secretions that can be 
      drained enterically (enteric drainage [ED]) or via the bladder (bladder drainage 
      [BD]). We suggest that in BD transplants, such secretions destroy bladder innate 
      immunity, specifically host defense peptides/proteins (HDPs), which increases 
      patient susceptibility to recurrent urinary tract infections (rUTIs). MATERIALS 
      AND METHODS: BD and ED patient records were reviewed retrospectively for UTIs. 
      Urine samples from ED and BD transplant recipients were analyzed for pH, the HDPs 
      beta-defensin 2 (HBD2) and lipocalin-2, and amylase concentrations. In vitro, 
      bacterial growth curves and antimicrobial assays were used to evaluate the 
      effects of pH, HBD2, and HBD2 + pancreatic digestive enzymes (pancreatin) on 
      uropathogenic Escherichia coli (UPEC) survival and growth. RESULTS: Urinalysis 
      revealed a significant difference in pH between the BD and ED cohorts (7.2 +/- 0.8 
      versus 6.7 +/- 0.8; P = 0.012). Urinary HDPs were measured and BD, but not ED, 
      lipocalin-2 concentrations were significantly decreased compared with those of 
      diabetics awaiting transplant (P < 0.05). In vitro, an alkaline environment, pH 
      8.0, concomitant with the urine of the patient who underwent BD transplantation, 
      significantly reduced UPEC growth (P < 0.05); addition of pancreatin to the 
      growth medium was associated with a significant increase (P < 0.001) in growth 
      rate. Antimicrobial data suggested significant UPEC killing in the presence of 
      HBD2 (P < 0.01), but not in the presence of HBD2 + pancreatin (>12,500 amylase 
      units). CONCLUSIONS: These in vivo and in vitro data suggest that BD pancreatic 
      exocrine secretions inactivate the bladder innate defenses, which facilitate UPEC 
      growth and underpins the increased susceptibility of patients who underwent BD 
      pancreas transplantation to rUTIs.
CI  - Crown Copyright (c) 2018. Published by Elsevier Inc. All rights reserved.
FAU - Byrne, Matthew
AU  - Byrne M
AD  - Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, 
      Newcastle upon Tyne, UK; Institute of Cell & Molecular Biosciences, Faculty 
      Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
FAU - Singh, Aminder
AU  - Singh A
AD  - Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, 
      Newcastle upon Tyne, UK; Institute of Cell & Molecular Biosciences, Faculty 
      Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
FAU - Mowbray, Catherine A
AU  - Mowbray CA
AD  - Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle 
      University, Newcastle upon Tyne, UK.
FAU - Aldridge, Phillip D
AU  - Aldridge PD
AD  - Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle 
      University, Newcastle upon Tyne, UK.
FAU - Drage, Lauren K L
AU  - Drage LKL
AD  - Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle 
      University, Newcastle upon Tyne, UK.
FAU - Ali, Ased S M
AU  - Ali ASM
AD  - Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, 
      Newcastle upon Tyne, UK.
FAU - Bates, Lucy
AU  - Bates L
AD  - Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, 
      Newcastle upon Tyne, UK; NIHR Blood and Transplant Research Unit 
      (Cambridge/Newcastle), The Institute of Transplantation, The Freeman Hospital, 
      Newcastle upon Tyne, UK.
FAU - Hall, Judith
AU  - Hall J
AD  - Institute of Cell & Molecular Biosciences, Faculty Medical Sciences, Newcastle 
      University, Newcastle upon Tyne, UK. Electronic address: Judith.Hall@ncl.ac.uk.
FAU - Wilson, Colin
AU  - Wilson C
AD  - Institute for Cellular Medicine, Faculty Medical Sciences, Newcastle University, 
      Newcastle upon Tyne, UK; NIHR Blood and Transplant Research Unit 
      (Cambridge/Newcastle), The Institute of Transplantation, The Freeman Hospital, 
      Newcastle upon Tyne, UK.
LA  - eng
PT  - Journal Article
DEP - 20181102
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (DEFB4A protein, human)
RN  - 0 (beta-Defensins)
RN  - 8049-47-6 (Pancreatin)
SB  - IM
MH  - Adult
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Immunity, Innate
MH  - Male
MH  - Middle Aged
MH  - Pancreas Transplantation/*adverse effects/methods
MH  - Pancreatin
MH  - Retrospective Studies
MH  - United Kingdom/epidemiology
MH  - Urinary Bladder/immunology
MH  - Urinary Tract Infections/epidemiology/*immunology
MH  - Urine/chemistry
MH  - beta-Defensins/physiology
OTO - NOTNLM
OT  - Bladder
OT  - Host defense
OT  - Pancreas
OT  - Pancreatin
OT  - Transplant
OT  - Uropathogenic Escherichia coli
EDAT- 2019/01/30 06:00
MHDA- 2019/11/16 06:00
CRDT- 2019/01/30 06:00
PHST- 2018/06/07 00:00 [received]
PHST- 2018/07/19 00:00 [revised]
PHST- 2018/09/11 00:00 [accepted]
PHST- 2019/01/30 06:00 [entrez]
PHST- 2019/01/30 06:00 [pubmed]
PHST- 2019/11/16 06:00 [medline]
AID - S0022-4804(18)30651-6 [pii]
AID - 10.1016/j.jss.2018.09.028 [doi]
PST - ppublish
SO  - J Surg Res. 2019 Mar;235:288-297. doi: 10.1016/j.jss.2018.09.028. Epub 2018 Nov 
      2.