We also incorporated inpatient and outpatient diagnosis files to ascertain the history of cardiovascular disease, peripheral vascular disease, cerebrovascular MK-8669 manufacturer disease, retinopathy, nephropathy, neuropathy, depression, chronic kidney disease, chronic liver disease, and chronic lung disease based on ICD-9-CM codes. Patients were classified as having chronic liver disease if they had at least one hospital admission or outpatient

visit with a diagnostic code of hepatitis B virus infection (ICD-9-CM codes 070.2x, 070.3x, V02.61), hepatitis C virus infection (070.41, 070.44, 070.51, 070.54, V02.62), chronic hepatitis (571.4), liver cirrhosis (571.2, 571.5, 571.6),

or alcoholic liver disease (571.0x, 571.1x, 571.2, 571.3x). A previous validation study using hospital administrative database reported a positive predictive value of 90% with this definition. 23 Covariate information included age, gender, and socioeconomic status (i.e., using monthly income as a proxy). Conditional logistic regression was used to estimate the crude and adjusted odds ratio (OR) and 95% confidence interval (CI) for the association between rosiglitazone/pioglitazone and cancer occurrence with “nonuse” as the reference group. Potential covariates, including socioeconomic status (monthly income level), this website diabetes complications and comorbidities at cancer diagnosis, other antidiabetic agents, antihypertensive medications, statin, and aspirin were examined. In the multivariate analysis, we adjusted for the use of short-acting human insulin, sulfonylurea, metformin, as these 上海皓元医药股份有限公司 antidiabetic agents were reported to be associated with cancer risks and could potentially confound the association. Other variables were chosen by using stepwise selection with P values < 0.10 for model entry and > 0.05 for removal. The association

between rosiglitazone/pioglitazone and individual cancer incidence was separately estimated after adjustment for potential confounders specific to that cancer type. In the dose- and duration-response analyses, we calculated the ORs for higher (≥120 DDD) and lower cumulative dose (<120 DDD) use, and for cumulative treatment duration ≥3, 2-3, 1-2, and ≤1 years. A two-sided P value < 0.05 was considered statistically significant. Approximately 15% participants claimed at lease one prescription for pioglitazone. Assuming a correlation coefficient for pioglitazone use between case and control was 0.5 and an ORs was 0.8, a study of 2,500 cases and 4 controls for each case would have a power ≥80% at α = 0.05.

5 The authors suggest earlier antiretroviral therapy initiation in coinfected patients in whom HCV has not been eradicated. Our

results provide a potential physiological rationale for this approach. In conclusion, our study provides a link between HIV and hepatic fibrosis through direct effects on HSCs and broadens PLX3397 our understanding of the mechanisms underlying liver disease in patients coinfected with HIV/HCV. Furthermore, these findings provide a rationale to examine whether HAART should be initiated in coinfected patients earlier than current guidelines recommend. The authors wish to thank Drs. Cathy Fan, Sasan Roayaie, and M. Isabel Fiel for providing liver resection specimens and Goar Mosoyan for technical assistance with p24 assays.

“
“Mounting epidemiological evidence supports a role for insulin-signaling deregulation and diabetes mellitus in human hepatocarcinogenesis. However, the underlying molecular mechanisms remain unknown. To study the oncogenic effect of chronically elevated insulin on hepatocytes in the presence of mild hyperglycemia, we developed a model of pancreatic islet transplantation into the liver. In this model, islets of a donor rat are transplanted into the liver of a recipient diabetic rat, with resulting local hyperinsulinism that leads http://www.selleckchem.com/products/ABT-263.html to the development of preneoplastic lesions and hepatocellular carcinoma (HCC). Here, medchemexpress we investigated the metabolic and growth properties of the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (AKT/mTOR) pathway, a major downstream effector of insulin signaling, in this model of insulin-induced hepatocarcinogenesis. We found that activation of insulin signaling triggers a strong induction of the AKT/mTOR

cascade that is paralleled by increased synthesis of fatty acids, cholesterol, and triglycerides, induction of glycolysis, and decrease of fatty acid oxidation and gluconeogenesis in rat preneoplastic and neoplastic liver lesions, when compared with the healthy liver. AKT/mTOR metabolic effects on hepatocytes, after insulin stimulation, were found to be mTORC1 dependent and independent in human HCC cell lines. In these cells, suppression of lipogenesis, glycolysis, and the pentose phosphate pathway triggered a strong growth restraint, despite insulin administration. Noticeably, metabolic abnormalities and proliferation driven by insulin were effectively reverted using the dual PI3K/mTOR inhibitor, NVP-BEZ235, both in vitro and in vivo. Conclusions: The present results indicate that activation of the AKT/mTOR cascade by unconstrained insulin signaling induces a defined module of metabolic alterations in hepatocytes contributing to aberrant cell growth. Thus, inhibition of AKT/mTOR and related metabolic changes might represent a novel preventive and therapeutic approach to effectively inhibit insulin-induced hepatocarcinogenesis.

001) (Fig. 3). The cumulative incidence rates at 1, 2, and 3 years were 0.17%, 1.12%, and 1.58% in patients with LSM value ≤8 kPa (0.54% per 1 person-year); 1.05%, 2.51%, and 6.28% in patients with 8 kPa< LSM value ≤13 kPa (1.75% per 1 person-year); 2.33%, 5.63%, and 8.77% in patients with 13kPa< LSM value ≤18 kPa (2.94 % per 1 person-year); 0%, 7.86%, and 19.07% in patients with 18 kPa< LSM value ≤23 kPa (7.04% per 1 person-year); 4.48%, 16.8%, and 24.76% in patients with 23 kPa> LSM value (9.80% per 1 person-year). We investigated the discordance that could occur when diagnosing cirrhosis using LSM and clinical criteria, and evaluated any

differences in the risk of HCC development. For this subanalysis, we assessed 1,110 patients without baseline liver histology at enrollment (Fig. 4).22 Overall, 874 (78.7%) patients had LSM ≤13 kPa and 236 (21.3%) had LSM >13 kPa. In patients with LSM ≤13 kPa, the incidence this website of HCC estimated using person-years was not significantly different between patients with cLC (n = 45, 5.1%) and patients without cLC (n = 829, 94.9%) (0.87% versus 0.89% per 1 person-year; P = 0.518). By contrast, among patients with LSM >13 kPa, Selleckchem Metformin HCC developed more frequently when liver cirrhosis was diagnosed according to clinical criteria (n = 132, 55.9%) than when it was not (n = 104, 44.1%) (5.84% versus 3.26% per 1 person-year;

P < 0.001). One hundred forty-nine (13.4%) patients showed discordance in the diagnosis of cirrhosis when comparing LSM and clinical criteria. The incidence of HCC was higher in 104 patients who showed LSM >13 kPa and no cLC than 45 who showed LSM ≤13 kPa with cLC (3.26% versus 0.87% per 1 person-year) (Fig. 4). After excluding two patients who underwent follow-up LSM after HCC development, 822 patients underwent a second LSM after a median of 18.2 months (range, 11.9-23.0 months), and HCC developed in 26 (3.2%) patients. To estimate the incidence of HCC according to the LSM change, we stratified the patients into four groups as follows: both initial and follow-up MCE公司 LSM ≤13

kPa (group 1), initial LSM >13 kPa and follow-up LSM ≤13 kPa (group 2), initial LSM ≤13 kPa and follow-up LSM >13 kPa (group 3), and both initial and follow-up LSM >13 kPa (group 4) (Fig. 5). In patients with initial LSM ≤13 kPa (groups 1 and 3), the patients in group 3 who had an elevated follow-up LSM had a significantly higher incidence of HCC than those in group 1 (2.05% [2 of 34 patients] versus 0.44% [7 of 598 patients] per 1 person-year; P < 0.001), whereas in the patients with an initial LSM >13 kPa (groups 2 and 4), patients in group 2 who had a decreased follow-up LSM had a significantly lower incidence of HCC than those in group 4 (1.96% [3 of 71 patients] per 1 person-year versus 4.31% [14 of 119 patients] per 1 person-year; P < 0.001) (Fig. 5). A chi-square test (Fisher’s exact test) revealed that the overall incidence of HCC differed significantly among the four groups (P < 0.001).

5 g/dL, and prothrombin time >50%); and (7) adequate renal function (serum creatinine <1.5 times the upper limit of the normal range). Exclusion criteria were: (1) myocardial infarction in the past year or active ischemic heart disease; (2) acute variceal bleeding in the past month; 3) severe peripheral arterial disease; (4) cardiac arrhythmia under treatment with drugs other than beta-blockers or digoxin; (5) uncontrolled ascites; (6) encephalopathy; or (7) inability to fulfill the follow-up schedule. All patients provided written informed consent before enrolment. The study was approved by the Institutional Review

Board and complied with the provisions of the Good Clinical Practice guidelines and the Declaration learn more AZD3965 clinical trial of Helsinki. TTP was defined as the time from the date of starting sorafenib to disease progression. Radiologic evaluation of response during follow-up

was done by computed tomography (CT) scan according to the response evaluation criteria in solid tumors (RECIST) v.1.1[12] with the amendments were implemented in the pivotal SHARP trial that ultimately were reflected in the mRECIST proposal.[3, 13] We registered the cause of progression (patterns of progression): ≥20% increase in tumor size against a known baseline lesion (intrahepatic growth [IHG] or extrahepatic

growth [EHG]), new intrahepatic lesion (NIH), or new extrahepatic lesion and/or vascular invasion (NEH). Radiology assessment was blinded to the evolution and outcome of the patients. Those patients who died before the first imaging assessment were classified as progressors. 上海皓元医药股份有限公司 OS was measured from the date of starting sorafenib until the date of death. PPS was measured from the date of detecting progression at radiology until the date of death or last follow-up. The relationship of OS with TTP and with OS predictors was determined in the whole cohort. We also assessed the impact of progression pattern on OS and PPS in patients with radiologic progression. Moreover, we did a subanalysis of patients who, because of adequate liver function and preserved PS, were still fit for second-line treatment in research trials. This subgroup of patients represents the population where a competing risk due to liver function impairment is excluded, as occurred in the pivotal sorafenib trials[1, 14] (Fig. 1). Sorafenib was initiated at full dose (800 mg/day), which was modified upon development of adverse events according to the manufacturer’s recommendations. Treatment was continued until symptomatic progression, unacceptable adverse events, or death.

S. Food and Drug Administration (FDA) insist that therapeutic studies in HRS use current definitions, when this puts new therapeutic trials at risk of premature failure. The current article by Parikh et al. sets the scene for the future.6 They studied 192 patients with cirrhosis who developed acute kidney injury. In all, 44% of patients progressed in their stage of AKI, and nearly 50% of patients developed stage 3 AKI. Importantly, the authors observed that 60% of patients

had evidence of AKI click here on admission to hospital, with the remaining 40% developing AKI during their hospitalization. Interestingly, mortality was significantly higher in those patients who developed AKI subsequent to admission than in those who presented with AKI, 36% versus 21%, respectively (P = 0.01). This clearly presents an opportunity to intervene in these patients earlier and thus decrease mortality. The severity of AKI worsened following the initial fulfillment of AKIN criteria in 85 (44%) of patients. In all, 12% had proteinuria which is roughly consistent with recent reports of chronic AZD6738 cell line kidney disease in some patients with cirrhosis.6 It has become increasingly apparent over the years that bacterial infection plays a major role in all decompensating episodes such as variceal bleeding, hepatic encephalopathy. If we look at the underlying reasons associated with AKI in the patients with

cirrhosis we see in the article by Belcher et al. that ∼20% have bacteremia, 20% have pneumonia, 30% have a urinary tract infection, and 25% have a gastrointestinal bleed.7 Thus, most patients MCE have bacterial infection as a precipitating cause. While the role of endotoxemia and presumably infection as a cause of hepatorenal syndrome has been with us since the 1970s with work done by Steve Wilkinson and others,8,

9 it has taken us a long time to acknowledge this role. This study shows clearly how as one progresses from stage 1 (2% mortality) to stage 2 (15% mortality) to stage 3 (44% mortality), that the development or AKI is important for prognosis for patients with cirrhosis who develop AKI.6 In an article in press, Tsien and colleagues studied 90 patients with ascites over about 14 months with the objective of determining the prevalence of AKI in cirrhosis with ascites and the impact of AKI on patient outcomes. They observed that 82 episodes of AKI occurred in 49 patients, with the majority of episodes precipitated by a disturbance in systemic hemodynamics. AKI occurred in >50% patients with cirrhosis and ascites. In fact, for all the AKI episodes, there was a significant negative correlation between the peak serum creatinine and the simultaneous mean arterial pressure, and the development of AKI was accompanied by a transient fall in the mean arterial pressure from 89 ± 3 mm Hg to 76 ± 3 mmHg, which returned to baseline upon resolution of the AKI episodes.9 So what have we learned and where do we go from here? It is clear that AKI or HRS have major implications for survival.

S. Food and Drug Administration (FDA) insist that therapeutic studies in HRS use current definitions, when this puts new therapeutic trials at risk of premature failure. The current article by Parikh et al. sets the scene for the future.6 They studied 192 patients with cirrhosis who developed acute kidney injury. In all, 44% of patients progressed in their stage of AKI, and nearly 50% of patients developed stage 3 AKI. Importantly, the authors observed that 60% of patients

had evidence of AKI Stem Cell Compound Library on admission to hospital, with the remaining 40% developing AKI during their hospitalization. Interestingly, mortality was significantly higher in those patients who developed AKI subsequent to admission than in those who presented with AKI, 36% versus 21%, respectively (P = 0.01). This clearly presents an opportunity to intervene in these patients earlier and thus decrease mortality. The severity of AKI worsened following the initial fulfillment of AKIN criteria in 85 (44%) of patients. In all, 12% had proteinuria which is roughly consistent with recent reports of chronic Cyclopamine concentration kidney disease in some patients with cirrhosis.6 It has become increasingly apparent over the years that bacterial infection plays a major role in all decompensating episodes such as variceal bleeding, hepatic encephalopathy. If we look at the underlying reasons associated with AKI in the patients with

cirrhosis we see in the article by Belcher et al. that ∼20% have bacteremia, 20% have pneumonia, 30% have a urinary tract infection, and 25% have a gastrointestinal bleed.7 Thus, most patients MCE have bacterial infection as a precipitating cause. While the role of endotoxemia and presumably infection as a cause of hepatorenal syndrome has been with us since the 1970s with work done by Steve Wilkinson and others,8,

9 it has taken us a long time to acknowledge this role. This study shows clearly how as one progresses from stage 1 (2% mortality) to stage 2 (15% mortality) to stage 3 (44% mortality), that the development or AKI is important for prognosis for patients with cirrhosis who develop AKI.6 In an article in press, Tsien and colleagues studied 90 patients with ascites over about 14 months with the objective of determining the prevalence of AKI in cirrhosis with ascites and the impact of AKI on patient outcomes. They observed that 82 episodes of AKI occurred in 49 patients, with the majority of episodes precipitated by a disturbance in systemic hemodynamics. AKI occurred in >50% patients with cirrhosis and ascites. In fact, for all the AKI episodes, there was a significant negative correlation between the peak serum creatinine and the simultaneous mean arterial pressure, and the development of AKI was accompanied by a transient fall in the mean arterial pressure from 89 ± 3 mm Hg to 76 ± 3 mmHg, which returned to baseline upon resolution of the AKI episodes.9 So what have we learned and where do we go from here? It is clear that AKI or HRS have major implications for survival.

S. Food and Drug Administration (FDA) insist that therapeutic studies in HRS use current definitions, when this puts new therapeutic trials at risk of premature failure. The current article by Parikh et al. sets the scene for the future.6 They studied 192 patients with cirrhosis who developed acute kidney injury. In all, 44% of patients progressed in their stage of AKI, and nearly 50% of patients developed stage 3 AKI. Importantly, the authors observed that 60% of patients

had evidence of AKI http://www.selleckchem.com/products/gsk1120212-jtp-74057.html on admission to hospital, with the remaining 40% developing AKI during their hospitalization. Interestingly, mortality was significantly higher in those patients who developed AKI subsequent to admission than in those who presented with AKI, 36% versus 21%, respectively (P = 0.01). This clearly presents an opportunity to intervene in these patients earlier and thus decrease mortality. The severity of AKI worsened following the initial fulfillment of AKIN criteria in 85 (44%) of patients. In all, 12% had proteinuria which is roughly consistent with recent reports of chronic buy Ceritinib kidney disease in some patients with cirrhosis.6 It has become increasingly apparent over the years that bacterial infection plays a major role in all decompensating episodes such as variceal bleeding, hepatic encephalopathy. If we look at the underlying reasons associated with AKI in the patients with

cirrhosis we see in the article by Belcher et al. that ∼20% have bacteremia, 20% have pneumonia, 30% have a urinary tract infection, and 25% have a gastrointestinal bleed.7 Thus, most patients MCE公司 have bacterial infection as a precipitating cause. While the role of endotoxemia and presumably infection as a cause of hepatorenal syndrome has been with us since the 1970s with work done by Steve Wilkinson and others,8,

9 it has taken us a long time to acknowledge this role. This study shows clearly how as one progresses from stage 1 (2% mortality) to stage 2 (15% mortality) to stage 3 (44% mortality), that the development or AKI is important for prognosis for patients with cirrhosis who develop AKI.6 In an article in press, Tsien and colleagues studied 90 patients with ascites over about 14 months with the objective of determining the prevalence of AKI in cirrhosis with ascites and the impact of AKI on patient outcomes. They observed that 82 episodes of AKI occurred in 49 patients, with the majority of episodes precipitated by a disturbance in systemic hemodynamics. AKI occurred in >50% patients with cirrhosis and ascites. In fact, for all the AKI episodes, there was a significant negative correlation between the peak serum creatinine and the simultaneous mean arterial pressure, and the development of AKI was accompanied by a transient fall in the mean arterial pressure from 89 ± 3 mm Hg to 76 ± 3 mmHg, which returned to baseline upon resolution of the AKI episodes.9 So what have we learned and where do we go from here? It is clear that AKI or HRS have major implications for survival.

[21] Certain studies even suggest that the liver is the prime driver of adipose inflammation and atherogenesis.[22] The incidence of hepatocellular carcinoma (HCC) in NAFLD remains controversial, since the association see more of NASH with cryp togenic cirrhosis as cause of HCC is difficult to prove. Patients with NASH can develop HCC even in the absence of cirrhosis, influenced by risk factors that contribute to the development of HCC. A systematic review of epidemiology studies including a total of 35 cohort, case control, and cross-sectional studies,

as well as case reports, reported a cumulative HCC mortality rate during Selleck GSI-IX a follow-up of up to 20 years in non-cirrhotic

NASH below 3%.[23] In cirrhotic NASH, the cumulative incidence ranged from 2.4% to 12.8% in 3–12 years.[23] Overall, this is considerably lower compared with virus-associated HCCs. In Hepatitis B surface antigen-positive patients with compensated cirrhosis, the 5-year cumulative HCC risk reaches 15% in endemic areas.[24] Since only a subset of patients with NAFLD progresses to NASH, lifestyle and genetic predisposition remains the best defined disease determinants. Recently, high dietary cholesterol, an activator of liver x receptor,[25, 26] was shown to negatively affect the balance between storage and oxidation of fatty acids.[27] Thus, with excessive supply to the liver, either from de novo lipogenesis or from excess dietary fat, fatty acids are processed to non-triglyceride metabolites, including diacylglycerol (DG) and lysophosphatidyl choline, that drive lipotoxic injury of hepatocytes (Fig. 2).[28] The type of dietary fat contributes to the development of NASH, as MCE公司 shown in mice on a diet enriched in trans-saturated fats.[29] Moreover, fructose, which depletes intracellular ATP, is transformed to lipid in the absence of insulin, thus increasing

fat deposits and contributing to NAFLD and NASH, as also evidenced by the strong association of type 2 diabetes and NASH in individuals consuming high-fructose-containing soft drinks.[30] The depletion of hepatic ATP favors mitochondrial dysfunction, generation of reactive oxygen species and the resultant inflammation, and enhances endoplasmic reticulum stress, with subsequent activation of the stress-related Jun N-terminal kinase (JNK) which promotes hepatocyte apoptosis, the hallmark of NASH.[31] The amount of lipotoxic metabolites is influenced by peripheral lipolysis, hepatic de novo lipogenesis, and the oxidative disposal of triglycerides involving lysosomes and β-oxidation.

We retrospectively evaluated a cohort XL765 solubility dmso of IBS patients who have been followed up for 10 years in one center. Methods: All consecutive

patients who were diagnosed with IBS in the year 2000 in one tertiary center were considered for analysis. Inclusion criteria: IBS without other significant comorbidities, diagnosed according to Rome II; at least 3 follow-up visits in the following 10 years in the same center; at least two normal colonoscopies during this interval; at least two psychological interviews available; exclusion criteria: missing data, patients lost to follow up, refusal to participate. Symptom severity (VAS: 0-10) and anxiety (STAI I and II) were recorded. Results: From a total of 252 IBS patients, only 46 (18%) were available for this analysis. They were 33 F, 13 M aged 42+12 yrs at baseline, with 22 C-IBS, 6 D-IBS, 18 M-IBS. These biographical features were representative for the full group of IBS patients. Median of follow-up visits was 6. The frequency of

the visits was higher in the first year of follow up (median 3 visits) and decreased in following interval. The second before last visit had the median 2 years. Symptom intensity (VAS) for pain, constipation, respectively diarrhea was similar Selinexor purchase at the start and at the end of the follow-up. Transitory improvement was seen only after the first visit (median by 8 weeks from the start) for diarrhea: from 6.6+2.9 to 4.5+2.3 (p < 0.01) but the effect was lost at follow-up visits. Intensity of pain and constipation were not significantly changed by the medical interventions. The anxiety level (STAI) did

not change during this interval. No malignant lesions were detected by colonoscopy, 上海皓元 22 pts presented new colonic polyps and 10 presented diverticula. Conclusion: Many patients with IBS are lost from the follow-up of a single specialized center, suggesting that IBS patients prefer to consult different healthcare providers; symptoms are stable in time, except anecdotal cases. The interaction with the patient is better at the beginning of the management as becomes more sporadic during the next 10 years follow-up interval. Diarrhea is transitorily improved at the beginning of the management. Symptoms do not change at 10 years despite conventional therapy. Key Word(s): 1. IBS; 2.

6). Hepatic IR caused massive hepatocyte apoptosis. Moreover, we determined that apoptotic hepatocytes can be detected in both necrotic and nonnecrotic areas after IR Dorsomorphin datasheet with significantly higher number of apoptotic cells in the necrotic zones of the liver. After hepatic IR, kidney and small intestine also showed severe capillary endothelial

apoptosis (insert expanded in Supporting Fig. 4B,C). Neutralization of IL-17A, deficiency in IL-17A receptor, or IL-17A significantly reduced apoptosis in all three organs (Supporting Figs. 4–6). Zinc depletion with dithizone treatment selectively and rapidly (within 1 hour) results in the loss of Paneth cell secretory granules in mice.11, 12 Accordingly, we treated mice with dithizone to deplete Paneth cell granules to test the effect of this pharmacological ablation on the response

to hepatic IR injury. Secretory Cobimetinib datasheet granules are evident and abundant in ileal Paneth cells from vehicle (lithium carbonate)-treated mice (Fig. 7A, left panel, arrows). In contrast, dithizone administration to mice almost completely depleted ileal Paneth cells of their granules within 6 hours of dithizone exposure (Fig. 7A, right panel, asterisk). We also stained small intestine crypts with lysozyme specific antibody as a marker of Paneth cell depletion after dithizone treatment. We demonstrate that Paneth cell granule depletion with dithizone treatment reduced lysozyme staining in small intestinal crypts after bilateral nephrectomy (Fig. 7B). Note that lysozyme staining was heavy in Paneth cells (arrows) of small intestinal crypts of mice treated with vehicle (Li2CO3). Paneth cell depletion with dithizone treatment

eliminated lysozyme staining in Paneth cells (asterisk). Treatment of Paneth cells with dithizone resulted in an approximately 64% reduction in plasma IL-17A levels 24 hours after liver IR (Fig. 7C). Furthermore, dithizone granule depletion drastically reduced IL-17A protein levels in the liver (76%), kidney (51%), and small intestine (67%) 24 hours after liver IR (Fig. 7C). Notably, Paneth cell depletion with dithizone caused the greatest reduction MCE公司 in IL-17A levels in isolated crypts after liver IR to near sham-operated values (Fig. 7C). Dithizone alone did not significantly affect IL-17A levels in sham-operated mice (data not shown). Depletion of Paneth cell granules with dithizone improved liver and kidney function after 60 minutes of liver ischemia and 24 hours of reperfusion (Fig. 7C). We also determined that Paneth cell granule depletion with dithizone significantly attenuated renal, hepatic and intestinal apoptosis (Supporting Figs. 5-7) and neutrophil infiltration (Supporting Fig. 8) after liver IR. In small intestine, we show that apoptotic cells are localized primarily to the tops of the villi and that dithizone treatment reduced intestinal apoptosis.