(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/re

(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/reperfusion (I/R) represents a highly complex cascade of events leading to hepatocellular injury after liver transplantation

(LT). These events are triggered when the liver is transiently Metabolism inhibitor exposed to hypoxic and hypothermic conditions and is reperfused with warm and oxygenated blood. The procedure is unavoidable during transplantation surgery, and every liver graft suffers from some degree of I/R injury. Liver I/R injury represents a serious problem in LT and significantly affects patient and graft outcomes.1, 2 In a large series of living donor and deceased donor LT patients, a longer cold ischemia time was associated with a higher frequency of early graft failure and with a higher rate of acute cellular rejection.3 Moreover, I/R injury contributes to the donor organ shortage because of the higher susceptibility of marginal livers to ischemic insults. To date, there is no specific treatment available to prevent or reduce hepatic I/R injury, and the current treatment is based merely on supportive care. Thus, extensive SB203580 in vivo research efforts to better understand the mechanisms of hepatic I/R injury after LT are warranted. B7 homolog 1 (B7-H1), which is also called CD274 and programmed death 1 (PD-1) ligand, is a recently

identified member of the B7 family with important regulatory functions in cell-mediated immune responses.4, 5 Together with the PD-1 receptor, B7-H1 is known to play an important role in regulating TGF-beta inhibitor local immune responses to infection,6, 7 autoimmunity,8, 9 and alloimmunity.10-;12 PD-1 is a member of the CD28 family, which is expressed by activated CD4 and CD8 T cells, B cells, and myeloid cells.13, 14 In

contrast, B7-H1 is expressed by antigen-presenting cells (APCs), such as dendritic cells (DCs), monocytes, and B cells, upon stimulation.15 Moreover, B7-H1 can be detected in the parenchymal cells of nonlymphoid organs, including hepatocytes.16 A growing number of reports suggest a crucial role for B7-H1 expression in the regulation of local immune responses in the liver. It has been reported that interactions with B7-H1 in the liver selectively delete activated CD8+ T cells.17 Moreover, the spontaneous acceptance of mouse liver grafts is prevented when the grafts lack B7-H1 expression because of the reduced apoptosis of graft-infiltrating host CD8+ T cells.18 In this study, we hypothesized that the hepatic expression of B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) mice, we tested this hypothesis directly in the mouse LT model with prolonged cold preservation (24 hours).

(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/re

(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/reperfusion (I/R) represents a highly complex cascade of events leading to hepatocellular injury after liver transplantation

(LT). These events are triggered when the liver is transiently selleck kinase inhibitor exposed to hypoxic and hypothermic conditions and is reperfused with warm and oxygenated blood. The procedure is unavoidable during transplantation surgery, and every liver graft suffers from some degree of I/R injury. Liver I/R injury represents a serious problem in LT and significantly affects patient and graft outcomes.1, 2 In a large series of living donor and deceased donor LT patients, a longer cold ischemia time was associated with a higher frequency of early graft failure and with a higher rate of acute cellular rejection.3 Moreover, I/R injury contributes to the donor organ shortage because of the higher susceptibility of marginal livers to ischemic insults. To date, there is no specific treatment available to prevent or reduce hepatic I/R injury, and the current treatment is based merely on supportive care. Thus, extensive Venetoclax research buy research efforts to better understand the mechanisms of hepatic I/R injury after LT are warranted. B7 homolog 1 (B7-H1), which is also called CD274 and programmed death 1 (PD-1) ligand, is a recently

identified member of the B7 family with important regulatory functions in cell-mediated immune responses.4, 5 Together with the PD-1 receptor, B7-H1 is known to play an important role in regulating Etomidate local immune responses to infection,6, 7 autoimmunity,8, 9 and alloimmunity.10-;12 PD-1 is a member of the CD28 family, which is expressed by activated CD4 and CD8 T cells, B cells, and myeloid cells.13, 14 In

contrast, B7-H1 is expressed by antigen-presenting cells (APCs), such as dendritic cells (DCs), monocytes, and B cells, upon stimulation.15 Moreover, B7-H1 can be detected in the parenchymal cells of nonlymphoid organs, including hepatocytes.16 A growing number of reports suggest a crucial role for B7-H1 expression in the regulation of local immune responses in the liver. It has been reported that interactions with B7-H1 in the liver selectively delete activated CD8+ T cells.17 Moreover, the spontaneous acceptance of mouse liver grafts is prevented when the grafts lack B7-H1 expression because of the reduced apoptosis of graft-infiltrating host CD8+ T cells.18 In this study, we hypothesized that the hepatic expression of B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) mice, we tested this hypothesis directly in the mouse LT model with prolonged cold preservation (24 hours).

(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/re

(HEPATOLOGY 2011;) Liver damage caused by liver graft ischemia/reperfusion (I/R) represents a highly complex cascade of events leading to hepatocellular injury after liver transplantation

(LT). These events are triggered when the liver is transiently Panobinostat manufacturer exposed to hypoxic and hypothermic conditions and is reperfused with warm and oxygenated blood. The procedure is unavoidable during transplantation surgery, and every liver graft suffers from some degree of I/R injury. Liver I/R injury represents a serious problem in LT and significantly affects patient and graft outcomes.1, 2 In a large series of living donor and deceased donor LT patients, a longer cold ischemia time was associated with a higher frequency of early graft failure and with a higher rate of acute cellular rejection.3 Moreover, I/R injury contributes to the donor organ shortage because of the higher susceptibility of marginal livers to ischemic insults. To date, there is no specific treatment available to prevent or reduce hepatic I/R injury, and the current treatment is based merely on supportive care. Thus, extensive Selumetinib research efforts to better understand the mechanisms of hepatic I/R injury after LT are warranted. B7 homolog 1 (B7-H1), which is also called CD274 and programmed death 1 (PD-1) ligand, is a recently

identified member of the B7 family with important regulatory functions in cell-mediated immune responses.4, 5 Together with the PD-1 receptor, B7-H1 is known to play an important role in regulating Branched chain aminotransferase local immune responses to infection,6, 7 autoimmunity,8, 9 and alloimmunity.10-;12 PD-1 is a member of the CD28 family, which is expressed by activated CD4 and CD8 T cells, B cells, and myeloid cells.13, 14 In

contrast, B7-H1 is expressed by antigen-presenting cells (APCs), such as dendritic cells (DCs), monocytes, and B cells, upon stimulation.15 Moreover, B7-H1 can be detected in the parenchymal cells of nonlymphoid organs, including hepatocytes.16 A growing number of reports suggest a crucial role for B7-H1 expression in the regulation of local immune responses in the liver. It has been reported that interactions with B7-H1 in the liver selectively delete activated CD8+ T cells.17 Moreover, the spontaneous acceptance of mouse liver grafts is prevented when the grafts lack B7-H1 expression because of the reduced apoptosis of graft-infiltrating host CD8+ T cells.18 In this study, we hypothesized that the hepatic expression of B7-H1 plays crucial roles during innate immune responses induced by hepatic I/R injury, and using B7-H1 knockout (KO) mice, we tested this hypothesis directly in the mouse LT model with prolonged cold preservation (24 hours).

9 months (95% CI, 194-456) and 244 months (95% CI, 186-381)

9 months (95% CI, 19.4-45.6) and 24.4 months (95% CI, 18.6-38.1) for BCLC stage A (including three sorafenib patients in the noncensored cohort), 19.0 months (95% CI, 12.8-25.0) and 16.9 months (95% CI, 12.8-22.8) for BCLC stage B (including 11 sorafenib patients in the noncensored cohort), and 10.0 months (95% CI, 8.0-10.9) and 10.0 months (95% CI, 7.7-10.9) for BCLC stage C (including

20 sorafenib patients in the noncensored cohort). A considerable amount of information has been published in the last decade regarding the use of radioembolization with 90Y-loaded microspheres for the treatment of HCC.28 Median survivals, however, vary widely (between 7 and 27 months) between phase II studies, depending on performance status, extent of disease buy Talazoparib involvement, degree of hepatic functional reserve, and presence or absence of cirrhosis.13, 14, 19, 20, 29 Very recently, Salem et al.17 reported a large prospective study in 291 patients treated with glass-based 90Y microspheres (TheraSphere; MDS Nordion, Ottawa, Ontario, Canada) showing Doxorubicin cell line that liver function and portal vein thrombosis were main predictors of survival. However, a consistent analysis of safety and survival

according to the BCLC staging system has yet to be published. In this study, we present the largest series of HCC patients receiving radioembolization and the first large, multicenter evaluation. Data were analyzed in a way that allows comparison with other treatment options, taking into account the natural course of the disease across different well-established prognostic groups. This analysis may help to better understand

the potential effect of radioembolization on survival and to aid in the design of future clinical studies. It should be noted that the outcomes of this evaluation reveal a high degree of concordance with those of 90Y-glass microspheres in patients with unresectable HCC.17 Taken together, the results of these two series provide reliable data regarding the potential use of radioembolization for the treatment of HCC. Overall, a low incidence of severe (grade >3) adverse events was observed with radioembolization in a cohort with a high incidence of cirrhosis. The procedure not itself was well tolerated, with mild-to-moderate nausea and/or vomiting, abdominal pain, and fever of limited duration occurring in less than one-third of patients. As would be expected in a population of patients with underlying chronic liver disease, many patients had grade 1 or 2 abnormal values in liver-associated parameters such as INR, bilirubin, platelets, and alanine aminotransferase prior to radioembolization, and the majority experienced no change in grade at 3 months posttreatment. In contrast with other liver function tests, a grade 3 or higher increase in bilirubin was observed in 5% of patients, suggesting a potential for radioembolization-induced liver disease in a small number of patients.

5A) Little to no SAc-conjugate-purified and rPDC-E2-purified ant

5A). Little to no SAc-conjugate-purified and rPDC-E2-purified antibodies were detected against SAc-conjugated proteins using anti-IgG secondary antibodies. However, when SAc-conjugate-purified antibodies were tested against rPDC-E2 the binding population was found to be predominantly IgG (P < 0.0001).

When an anti-IgM was used as a developing antibody, SAc-conjugate affinity-purified antibodies displayed reactivity against SAc-conjugates at levels that were significantly higher (SAc-BSA-purified selleck products antibodies, P < 0.001; SAc-RSA-purified antibodies, P < 0.0001) than did rPDC-E2-purified antibodies (Fig. 5B). rPDC-E2-purified antibodies reactivity to SAc-conjugates (0.074 ± 0.020 against SAc-BSA; 0.095 ± 0.024 against SAc-RSA) was negligible. SAc-RSA-purified antibodies and rPDC-E2-purified antibodies reacted to rPDC-E2 to a similar degree, but SAc-BSA-purified antibodies bound rPDC-E2 significantly less than rPDC-E2-purified antibodies (P < 0.05). Of the 100 studied PBC sera, 50 were stage 1-2

and 50 were stage 3-4. selleck inhibitor In these two groups, there were seven AMA-negative sera each and in all AMA-negative cases we confirmed the absence of reactivity to both SAc-BSA and to PDC-E2. Importantly, 30/43 early stage and 33/43 reacted to both SAc and recombinant PDC-E2. Interestingly, however, there was a slight and statistically significant increase in IgM reactivity when comparing early PBC (OD 0.164 ± 0.025) and late PBC (OD 0.205 ± 0.027) with respect

to reactivity to SAc. IgG reactivity to SAc in both groups was insignificant. We do note, however, that in the early-stage group there were 6/43 patients with IgM reactivity to SAc that were higher than their IgM titers to PDC-E2; this pattern was not seen in any late-stage sera (Table 1). In this study we demonstrated that antibodies to the SAc-moiety are present in the majority of AMA-positive PBC patients. Two patterns of patient responsiveness are seen, one where AMAs crossreact with both SAc-conjugated proteins and rPDC-E2, and the other where AMAs show little Thymidylate synthase crossreactivity between the two antigens. Crossreactivity predominantly resides with SAc-conjugate affinity-purified antibodies and not rPDC-E2-affinity-purified antibodies. IgG from SAc-conjugate affinity-purified antibodies binds rPDC-E2 significantly more than SAc-conjugated proteins, whereas IgM from SAc-conjugate-purified antibodies binds both rPDC-E2 and SAc-conjugated proteins (Fig. 6). The presence of high amounts of IgM, a hallmark characteristic of PBC, leads us to speculate that these SAc-conjugate-purified IgM antibodies are footprints induced by xenobiotic exposure at the very early stages of development of PBC.

5A) Little to no SAc-conjugate-purified and rPDC-E2-purified ant

5A). Little to no SAc-conjugate-purified and rPDC-E2-purified antibodies were detected against SAc-conjugated proteins using anti-IgG secondary antibodies. However, when SAc-conjugate-purified antibodies were tested against rPDC-E2 the binding population was found to be predominantly IgG (P < 0.0001).

When an anti-IgM was used as a developing antibody, SAc-conjugate affinity-purified antibodies displayed reactivity against SAc-conjugates at levels that were significantly higher (SAc-BSA-purified NVP-AUY922 molecular weight antibodies, P < 0.001; SAc-RSA-purified antibodies, P < 0.0001) than did rPDC-E2-purified antibodies (Fig. 5B). rPDC-E2-purified antibodies reactivity to SAc-conjugates (0.074 ± 0.020 against SAc-BSA; 0.095 ± 0.024 against SAc-RSA) was negligible. SAc-RSA-purified antibodies and rPDC-E2-purified antibodies reacted to rPDC-E2 to a similar degree, but SAc-BSA-purified antibodies bound rPDC-E2 significantly less than rPDC-E2-purified antibodies (P < 0.05). Of the 100 studied PBC sera, 50 were stage 1-2

and 50 were stage 3-4. LDE225 molecular weight In these two groups, there were seven AMA-negative sera each and in all AMA-negative cases we confirmed the absence of reactivity to both SAc-BSA and to PDC-E2. Importantly, 30/43 early stage and 33/43 reacted to both SAc and recombinant PDC-E2. Interestingly, however, there was a slight and statistically significant increase in IgM reactivity when comparing early PBC (OD 0.164 ± 0.025) and late PBC (OD 0.205 ± 0.027) with respect

to reactivity to SAc. IgG reactivity to SAc in both groups was insignificant. We do note, however, that in the early-stage group there were 6/43 patients with IgM reactivity to SAc that were higher than their IgM titers to PDC-E2; this pattern was not seen in any late-stage sera (Table 1). In this study we demonstrated that antibodies to the SAc-moiety are present in the majority of AMA-positive PBC patients. Two patterns of patient responsiveness are seen, one where AMAs crossreact with both SAc-conjugated proteins and rPDC-E2, and the other where AMAs show little Megestrol Acetate crossreactivity between the two antigens. Crossreactivity predominantly resides with SAc-conjugate affinity-purified antibodies and not rPDC-E2-affinity-purified antibodies. IgG from SAc-conjugate affinity-purified antibodies binds rPDC-E2 significantly more than SAc-conjugated proteins, whereas IgM from SAc-conjugate-purified antibodies binds both rPDC-E2 and SAc-conjugated proteins (Fig. 6). The presence of high amounts of IgM, a hallmark characteristic of PBC, leads us to speculate that these SAc-conjugate-purified IgM antibodies are footprints induced by xenobiotic exposure at the very early stages of development of PBC.

[13] In spite of the promising clinical efficacy data, telcagepan

[13] In spite of the promising clinical efficacy data, telcagepant development was discontinued because of concerns regarding liver toxicity. Elevations of hepatic enzymes were seen in some participants in a Phase IIa study where telcagepant was given twice daily for the prevention of migraine. Similar elevations were seen in a short-term study http://www.selleckchem.com/products/ensartinib-x-396.html of menstrual migraine.[13, 80] A third CGRP-RA, MK-3207, was 40- to 65-fold more potent than telcagepant[81] and was tested in an adaptive design exploring doses from 2.5 to 200 mg. The

100 and 200 mg doses yielded pain-free rates of 23.7% and 36.2% (placebo = 9.8%), and pain relief rates of 52.5% and 69% (placebo = 36.1%).[82] Similar to other compounds in the same class, tolerability was excellent but development was also discontinued because of concerns related to liver toxicity.[83] Finally, a Phase 2 trial

tested BI44370A in 341 patients. Doses ranged from 50 to 400 mg, and were compared with placebo and 40 mg eletriptan. The primary endpoint, 2-hour pain freedom, was achieved buy Panobinostat significantly more often by patients receiving the 400 mg dose (27.4%) and eletriptan (34.8%) than placebo (8.6%). Other doses were not significantly different from placebo for the primary endpoint. Tolerability was excellent.[84] In addition to demonstrating proof of efficacy, the CGRP-RA clinical trials also demonstrated the extraordinary tolerability of this class. The issue was best explored in the development of telcagepant, where in addition to the large pivotal studies, a distinct clinical trial was conducted specifically to evaluate its long-term tolerability for acute treatment of migraine attacks. The trial consisted of PIK-5 1068 patients. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Both regimens were well

tolerated but fewer drug-related adverse events (difference: –15.6%; 95% CI −22.2, −9.0) were reported for telcagepant vs rizatriptan.[85] Other CGRP-RAs are being developed and, at the time of this writing, clinicaltrial.gov lists 2 of them: BMS-927711 is listed in Phase 1,[86] and MK-1622 is in Phase 2B, with doses ranging from 1 to 100 mg, for the acute treatment of migraine attacks.[87] mAbs, or antibodies produced by a single clone of cells, were first shown to have therapeutic activity in 1982, when a patient with lymphoma experienced a complete response when given antibodies against his tumor cells produced in mice.[88] In the past 20 years, their clinical utility has expanded dramatically with more than 20 mAbs that are Food and Drug Administration (FDA)-approved for human use.

[13] In spite of the promising clinical efficacy data, telcagepan

[13] In spite of the promising clinical efficacy data, telcagepant development was discontinued because of concerns regarding liver toxicity. Elevations of hepatic enzymes were seen in some participants in a Phase IIa study where telcagepant was given twice daily for the prevention of migraine. Similar elevations were seen in a short-term study selleck products of menstrual migraine.[13, 80] A third CGRP-RA, MK-3207, was 40- to 65-fold more potent than telcagepant[81] and was tested in an adaptive design exploring doses from 2.5 to 200 mg. The

100 and 200 mg doses yielded pain-free rates of 23.7% and 36.2% (placebo = 9.8%), and pain relief rates of 52.5% and 69% (placebo = 36.1%).[82] Similar to other compounds in the same class, tolerability was excellent but development was also discontinued because of concerns related to liver toxicity.[83] Finally, a Phase 2 trial

tested BI44370A in 341 patients. Doses ranged from 50 to 400 mg, and were compared with placebo and 40 mg eletriptan. The primary endpoint, 2-hour pain freedom, was achieved selleckchem significantly more often by patients receiving the 400 mg dose (27.4%) and eletriptan (34.8%) than placebo (8.6%). Other doses were not significantly different from placebo for the primary endpoint. Tolerability was excellent.[84] In addition to demonstrating proof of efficacy, the CGRP-RA clinical trials also demonstrated the extraordinary tolerability of this class. The issue was best explored in the development of telcagepant, where in addition to the large pivotal studies, a distinct clinical trial was conducted specifically to evaluate its long-term tolerability for acute treatment of migraine attacks. The trial consisted of Temsirolimus mw 1068 patients. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Both regimens were well

tolerated but fewer drug-related adverse events (difference: –15.6%; 95% CI −22.2, −9.0) were reported for telcagepant vs rizatriptan.[85] Other CGRP-RAs are being developed and, at the time of this writing, clinicaltrial.gov lists 2 of them: BMS-927711 is listed in Phase 1,[86] and MK-1622 is in Phase 2B, with doses ranging from 1 to 100 mg, for the acute treatment of migraine attacks.[87] mAbs, or antibodies produced by a single clone of cells, were first shown to have therapeutic activity in 1982, when a patient with lymphoma experienced a complete response when given antibodies against his tumor cells produced in mice.[88] In the past 20 years, their clinical utility has expanded dramatically with more than 20 mAbs that are Food and Drug Administration (FDA)-approved for human use.

Results SFTSV- RNA of all the 22 patients was positive SFTSV loa

Results SFTSV- RNA of all the 22 patients was positive. SFTSV load 1×107 (copies / ml) in 4 patients, 2 cases died; In the early stage of SFTSV-infection, serum ALT/AST/LDH/CK markedly elevated and WBC and PLT in peripheral blood decreased significantly. The level of ALT/AST/LDH/CK, WBC and PLT in 19 cured patients was gradually backed to normal with the reducing of viral load. The elevated level of serum AST/LDH/CK and SFTSV load positively correlated, PLT and SFTSV load negatively

correlated. At the same stage of infection process, ALT/AST/LDH/CK in incurable patients were significantly higher than in cured Rapamycin price patients; Compared with healthy population, the number of CD4+ cells was lower in the onset of the first 5 to 9 days; CD8+ cells was higher and NK cells was lower HDAC phosphorylation in 9 to 15 days. Lymphocyte subsets of most patients were normal with the viral load undetectable; The number of T cells of incurable patients significantly decreased, while NK cells increased. A variety of detection indicators could not recover with extension of disease course. Conclusion Liver may

be one of the target organs of SFTSV-infection injuries. Severity of tissue damage is closely related to serum SFTSV load. High viral load, decreasing of T cells, increasing of NK cells may be the important factors of poor prognosis. Disclosures: The following people have nothing to disclose: Jun Li, Yaping Han, Longfeng Jiang, Zuhu Huang Background: Conventional resuscitation (CR) from hemorrhagic shock (HS) that restores

central hemodynamic function nonetheless Etomidate results in gut and liver hypoperfusion and hypoxia, organ and cellular edema, and liver injury. This can lead to multi-system organ failure and death. Minocycline stabilizes mitochondrial membrane function inhibiting mitochondrial transition pore opening and cytochrome C release-mediated apoptosis. We hypothesized that minocycline might improve post-resuscitation (post-RES) hepatic function and, thus, prevent hepatic injury following hemorrhagic shock. Methods: Anesthetized male Sprague-Dawley rats were randomized to groups (n=7/group): 1) Sham (no HS); 2) Sham + Minocycline at time of RES (Sham + Min(0″)); 3) Sham + Min at 120″ min post-RES (Min(120″)); 4) HS + CR; 5) HS + CR + Min(0″); and 6) HS + CR + Min(120″). At 4 hours post-RES, we measured: 1) effective hepatic blood flow (EHBF) by galactose clearance; 2) hepatic injury (serum ALT); 3) CMP & CBC; 4) tissue edema (lung, liver, or ileum wet-dry weight ratios); and 5) lung, liver, and ileum histopathology. Results: Histopathology showed lung and liver injury in HS + CR at 4 hours post-RES. Serum ALT levels were increased in HS+CR but not in HS + CR + Min(0″) or HS + CR + Min(120″). During HS, all HS + CR groups had decreased EHBF that was restored by i.v. blood and saline RES.

Results SFTSV- RNA of all the 22 patients was positive SFTSV loa

Results SFTSV- RNA of all the 22 patients was positive. SFTSV load 1×107 (copies / ml) in 4 patients, 2 cases died; In the early stage of SFTSV-infection, serum ALT/AST/LDH/CK markedly elevated and WBC and PLT in peripheral blood decreased significantly. The level of ALT/AST/LDH/CK, WBC and PLT in 19 cured patients was gradually backed to normal with the reducing of viral load. The elevated level of serum AST/LDH/CK and SFTSV load positively correlated, PLT and SFTSV load negatively

correlated. At the same stage of infection process, ALT/AST/LDH/CK in incurable patients were significantly higher than in cured Cisplatin cell line patients; Compared with healthy population, the number of CD4+ cells was lower in the onset of the first 5 to 9 days; CD8+ cells was higher and NK cells was lower this website in 9 to 15 days. Lymphocyte subsets of most patients were normal with the viral load undetectable; The number of T cells of incurable patients significantly decreased, while NK cells increased. A variety of detection indicators could not recover with extension of disease course. Conclusion Liver may

be one of the target organs of SFTSV-infection injuries. Severity of tissue damage is closely related to serum SFTSV load. High viral load, decreasing of T cells, increasing of NK cells may be the important factors of poor prognosis. Disclosures: The following people have nothing to disclose: Jun Li, Yaping Han, Longfeng Jiang, Zuhu Huang Background: Conventional resuscitation (CR) from hemorrhagic shock (HS) that restores

central hemodynamic function nonetheless Celastrol results in gut and liver hypoperfusion and hypoxia, organ and cellular edema, and liver injury. This can lead to multi-system organ failure and death. Minocycline stabilizes mitochondrial membrane function inhibiting mitochondrial transition pore opening and cytochrome C release-mediated apoptosis. We hypothesized that minocycline might improve post-resuscitation (post-RES) hepatic function and, thus, prevent hepatic injury following hemorrhagic shock. Methods: Anesthetized male Sprague-Dawley rats were randomized to groups (n=7/group): 1) Sham (no HS); 2) Sham + Minocycline at time of RES (Sham + Min(0″)); 3) Sham + Min at 120″ min post-RES (Min(120″)); 4) HS + CR; 5) HS + CR + Min(0″); and 6) HS + CR + Min(120″). At 4 hours post-RES, we measured: 1) effective hepatic blood flow (EHBF) by galactose clearance; 2) hepatic injury (serum ALT); 3) CMP & CBC; 4) tissue edema (lung, liver, or ileum wet-dry weight ratios); and 5) lung, liver, and ileum histopathology. Results: Histopathology showed lung and liver injury in HS + CR at 4 hours post-RES. Serum ALT levels were increased in HS+CR but not in HS + CR + Min(0″) or HS + CR + Min(120″). During HS, all HS + CR groups had decreased EHBF that was restored by i.v. blood and saline RES.