Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0030305 (
pancreatitis
)
16,014
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
1. We recently demonstrated that hypertonic saline reduces inflammation and mortality in acute pancreatitis. The present study investigated the effects of hypertonic saline in metalloproteinase (
MMP
) regulation and
pancreatitis
-associated hepatic injury. 2. Wistar rats were divided into four groups: (i) control, not subjected to insult or treatment; (ii) no treatment (NT), induction of
pancreatitis
(retrograde infusion of 2.5% sodium taurocholate (1.0 mL/kg)), but no further treatment; (iii) normal saline (NS), induction of
pancreatitis
and treatment with normal saline (0.9% NaCl, 34 mL/kg, i.v. bolus, 1 h after the induction of
pancreatitis
); and (iv) hypertonic saline (HS), induction of
pancreatitis
and treatment with hypertonic saline (7.5% NaCl, 4 mL/kg administered over a period of 5 min, 1 h after the induction of
pancreatitis
). In all four groups, 4, 12 and 24 h after the induction of
pancreatitis
, liver tissue samples were assayed to determine levels of MMP-2, MMP-9, 47 kDa heat shock protein (HSP47) and collagen (Type I and III). 3. Compared with the control group, MMP-9 expression and activity was increased twofold in the NS and NT groups 4 and 12 h after the induction of
pancreatitis
, but remained at basal levels in the HS group. In contrast, MMP-2 expression was increased twofold 12 h after the induction of
pancreatitis
only in the NS group, whereas the expression of HSP47 was increased 4 h after the induction of
pancreatitis
in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups compared with the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. 4. In conclusion, the results of the present study indicate that hypertonic saline is hepatoprotective and reduces hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during
pancreatitis
. Hypertonic saline-mediated regulation of
MMP
expression may have clinical relevance in
pancreatitis
-associated liver injury.
...
PMID:Hypertonic saline reduces metalloproteinase expression in liver during pancreatitis. 1951 67
Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowel Disease thought it appropriate to review the present indications for use of TPMT and TP metabolite testing. Substantial evidence demonstrates that TP therapy is useful for both Crohn disease and ulcerative colitis. Review of the existing data yielded the following recommendations. TPMT testing is recommended before initiation of TPs to identify individuals who are homozygote recessive or have extremely low TPMT activity, with the latter having more reliability than the former. Individuals who are homozygous recessive or have extremely low TPMT activity should avoid the use of TPs because of concerns for significant leukopenia. TMPT testing does not predict all cases of leukopenia and has no value to predict hypersensitivity adverse effects such as
pancreatitis
. Any potential value to reduce the risk of malignancy has not been studied. All individuals taking TPs should have routine monitoring with complete blood cell count and white blood cell count differential to evaluate for leukopenia regardless of TPMT testing results. Metabolite testing can be used to determine adherence with TP therapy. Metabolite testing can be used to guide dose increases or modifications in patients with active disease. Consideration would include either increasing the dose, changing therapy or for those with elevated transaminases or an elevated 6-
MMP
, using adjunctive allopurinol to help raise 6-thioguanine metabolites and suppress formation of 6-
MMP
. Routine and repetitive metabolite testing has little or no role in patients who are doing well and taking an acceptable dose of a TP.
...
PMID:Role of thiopurine metabolite testing and thiopurine methyltransferase determination in pediatric IBD. 2328 4
