Pancreatitis-Induced Ascitic Fluid and Hepatocellular Dysfunction in Severe Acute Pancreatitis

Ueda, Takashi; Ho, Hung S.; Anderson, Steven E.; Takeyama, Yoshifumi

doi:10.1006/jsre.1998.5539

Cited by 24 publications

(10 citation statements)

References 34 publications

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“…It has been successfully used to assess the metabolic state of a variety of tissues under various conditions. [19][20][21] The ATP/DNA ratio suffers similar limitations, but DNA does not degrade as quickly in dead cells as either ATP or ADP. Because of this profound difference in the kinetics of degradation of DNA under conditions of stress, the ATP/DNA ratio permits the inclusion of dead cells into a viability estimate once the apoptotic process is fully executed.…”

Section: Discussionmentioning

confidence: 99%

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

Suszynski¹,

Wildey²,

Falde³

et al. 2008

Transplantation Proceedings

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Real-time, accurate assessment of islet viability is critical for avoiding transplantation of nontherapeutic preparations. Measurements of the intracellular ADP/ATP ratio have been recently proposed as useful prospective estimates of islet cell viability and potency. However, dead cells may be rapidly depleted of both ATP and ADP, which would render the ratio incapable of accounting for dead cells. Since the DNA of dead cells is expected to remain stable over prolonged periods of time (days), we hypothesized that use of the ATP/DNA ratio would take into account dead cells and may be a better indicator of islet cell viability than the ADP/ATP ratio. We tested this hypothesis using mixtures of healthy and lethally heat-treated (HT) rat insulinoma cells and human islets. Measurements of ATP/DNA and ADP/ATP from the known mixtures of healthy and HT cells and islets were used to evaluate how well these parameters correlated with viability. The results indicated that ATP and ADP were rapidly (within 1 hour) depleted in HT cells. The fraction of HT cells in a mixture correlated linearly with the ATP/DNA ratio, whereas the ADP/ADP ratio was highly scattered, remaining effectively unchanged. Despite similar limitations in both ADP/ADP and ATP/ DNA ratios, in that ATP levels may fluctuate significantly and reversibly with metabolic stress, the results indicated that ATP/DNA was a better measure of islet viability than the ADP/ATP ratio.Islet cell transplantation is emerging as a promising therapy for the treatment of type 1 diabetes. [1][2][3][4][5] Despite recent advances, the transplantation of islets poses a unique challenge with respect to achieving a consistent clinical outcome. Part of this challenge is being able to reliably and rapidly assess clinical islet quality through the quantification of viability and function before transplantation. Current viability assays are limited in their ability to accurately predict transplantation outcomes in vivo. 6 Consequently, to improve the clinical islet transplantation outcomes, it is imperative to develop more accurate viability assays.A proposed method to assess islet viability and potency before transplantation is quantification of the ADP/ATP ratio. 6 -10 This ratio has been specifically applied in discriminating islet preparations that are suitable for clinical transplantation from those that are not. 6 However, this application may be problematic under certain conditions. Intracellular ADP and ATP levels fluctuate rapidly because these high-energy phosphate molecules are rapidly produced and consumed in many intracellular biochemical reactions. It is widely known that viable cells turn over entire ATP stores on the order of minutes, and that dead cells are incapable of replenishing To better account for dead cells and to more accurately assess the viability of an islet preparation, we suggest the use of an ATP/DNA ratio. DNA does not degrade as rapidly as ADP or ATP in a dead cell. Therefore, using direct measurements of DNA, dead cells in an islet preparation...

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Section: Discussionmentioning

confidence: 99%

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

Suszynski¹,

Wildey²,

Falde³

et al. 2008

Transplantation Proceedings

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“…The ascites accompanying SAP can induce hepatic apoptosis; IL-1 converting enzyme inhibitor can relieve hepatic apoptosis and hepatic cell injury, and partial apoptosis could be prevented by neutralizing the transforming growth factor-β (TGF-β). Researchers believe the occurrence of hepatic apoptosis in SAP is related to TGF-β in ascites (Ueda et al, 1999;.…”

Section: Hepatic Apoptosismentioning

confidence: 99%

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Zhang

Wang

Zhang

2007

J. Zhejiang Univ. - Sci. B

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Study on the action mechanism of inflammatory mediators generated by the severe acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical field. In clinical practice, the main complicated organ dysfunctions are shock, respiratory failure, renal failure, encephalopathy, with the rate of hepatic diseases being closely next to them. The hepatic injury caused by SAP cannot only aggravate the state of pancreatitis, but also develop into hepatic failure and cause patient death. Its complicated pathogenic mechanism is an obstacle in clinical treatment. Among many pathogenic factors, the changes of vasoactive substances, participation of inflammatory mediators as well as OFR (oxygen free radical), endotoxin, etc. may play important roles in its progression.

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“…Recently, a number of researchers have reported that pancreatitis-associated ascitic fluid plays a major role in inducing hepatocyte damage and apoptosis (9,10 cretory block is subse quently followed by the lysosomal degradation of intercellular organelles within autophagic vacuoles in acinar cells and a marked interstitial edema. AP is considered to be an autodigestive disease.…”

Section: Introductionmentioning

confidence: 99%

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

Batçıoğlu

Gül

Uyumlu

et al. 2009

Braz J Med Biol Res

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The aim of this study was to evaluate the role of oxidative damage in pancreatitis-induced hepatic injury. Thirty-five rats were divided into five groups (each of 7 rats): control, cerulein (100 µg/kg body weight), cerulein and pentoxifylline (12 mg/kg body weight), cerulein plus L-NAME (10 mg/kg body weight) and cerulein plus L-arginine (160 mg/kg body weight). The degree of hepatic cell degeneration differed significantly between groups. Mean malondialdehyde levels were 7.00 ± 2.29, 20.89 ± 10.13, 11.52 ± 4.60, 18.69 ± 8.56, and 8.58 ± 3.68 nmol/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Mean catalase activity was 3.20 ± 0.83, 1.09 ± 0.35, 2.05 ± 0.91, 1.70 ± 0.60, and 2.85 ± 0.47 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively, and mean glutathione peroxidase activity was 0.72 ± 0.25, 0.33 ± 0.09, 0.37 ± 0.04, 0.34 ± 0.07 and 0.42 ± 0.1 U/mg protein for the control, cerulein, pentoxifylline, L-NAME, and L-arginine groups, respectively. Cerulein-induced liver damage was accompanied by a significant increase in tis sue malondialdehyde levels (P < 0.05) and a significant decrease in catalase (P < 0.05) and GPx activities (P < 0.05). L-arginine and pentoxifylline, but not L-NAME, protected against this damage. Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancre atitis-induced hepatic damage.

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Pancreatitis-Induced Ascitic Fluid and Hepatocellular Dysfunction in Severe Acute Pancreatitis

Cited by 24 publications

References 34 publications

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

The ATP/DNA Ratio Is a Better Indicator of Islet Cell Viability Than the ADP/ATP Ratio

Study progress on mechanism of severe acute pancreatitis complicated with hepatic injury

Liver lipid peroxidation and antioxidant capacity in cerulein-induced acute pancreatitis

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