[CORRELATIONAL RELATIONSHIP BETWEEN DURATION OF A "COLD" ISCHEMIA PERIOD, THROMBOCYTOPENIA AND SEVERITY OF A HEPATIC REPERFUSIVE DAMAGE IN PATIENTS AFTER ITS TRANSPLANTATION].

Reperfusive hepatic damage, one of the severe complications after hepatic transplantation, occurs immediately after inclusion of the donor organ into the blood circulation of a recipient. It is considered one of principal causes of early rejection of the transplant. Connection between thrombocytopenia in a patient and duration of period of a donor's "cold" hepatic ischemia was studied. The changes in microcirculation due to the thrombocytes accumulation (sequestration) in a sinusoid vessels constitutes a main target in the ischemic-reperfusive damage of the liver. During the first days after hepatic transplantation the thrombocytes quantity have reduced, the correlation dependence between this process and duration of a "cold" ischemia and functional activity of a liver transplanted was established.

Augmenter of liver regeneration attenuates inflammatory response in the postischemic mouse liver in vivo.

BACKGROUND: Augmenter of Liver Regeneration (ALR), a protein synthesized in the liver is suggested to be protective against oxidative stress-induced cell death. Hepatic ischemia-reperfusion (I/R) injury is triggered by reactive oxygen species. Here, we tested the hypothesis that ALR attenuates hepatic I/R injury in vivo. METHODS: C57BL6 mice were subjected to warm hepatic ischemia for 90 min. Either recombinant ALR (100 µg/kg) or vehicle were administered to mice prior ischemia. During reperfusion, neutrophil and CD4+ T cell migration and sinusoidal perfusion were analyzed using intravital microscopy. Alanine aminotransferase-aspartate aminotransferase (plasma) and caspase-3 (tissue) activities were determined as markers of hepatocellular necrotic and apoptotic injury. RESULTS: Hepatic I/R led to dramatic enhancement of neutrophil and CD4+ T cell recruitment in hepatic microvessels, sinusoidal perfusion failure, and strong elevation of aspartate aminotransferase-alanine aminotransferase and caspase-3 activities. During early reperfusion (60 min), the pretreatment with ALR improved postischemic perfusion failure (P < 0.05) and attenuated liver enzyme activities. Recruitment of CD4+ T cells, but not of neutrophils was attenuated. After 240 min of reperfusion, the protective effect of ALR was stronger, since the liver enzyme activity, perfusion failure, and leukocyte influx were significantly attenuated. As shown by the measurement of caspase-3 activity, postischemic apoptosis was reduced in the ALR-treated group. CONCLUSIONS: Our in vivo data show that ALR has a therapeutic potential against postischemic liver injury. As a mechanism, we suggest a direct protective effect of ALR on apoptotic and necrotic death of hepatocytes and an attenuation of inflammatory cell influx into the postischemic tissue.

Emergence and intensification of dairying in the Caucasus and Eurasian steppes.

Archaeological and archaeogenetic evidence points to the Pontic-Caspian steppe zone between the Caucasus and the Black Sea as the crucible from which the earliest steppe pastoralist societies arose and spread, ultimately influencing populations from Europe to Inner Asia. However, little is known about their economic foundations and the factors that may have contributed to their extensive mobility. Here, we investigate dietary proteins within the dental calculus proteomes of 45 individuals spanning the Neolithic to Greco-Roman periods in the Pontic-Caspian Steppe and neighbouring South Caucasus, Oka-Volga-Don and East Urals regions. We find that sheep dairying accompanies the earliest forms of Eneolithic pastoralism in the North Caucasus. During the fourth millennium BC, Maykop and early Yamnaya populations also focused dairying exclusively on sheep while reserving cattle for traction and other purposes. We observe a breakdown in livestock specialization and an economic diversification of dairy herds coinciding with aridification during the subsequent late Yamnaya and North Caucasus Culture phases, followed by severe climate deterioration during the Catacomb and Lola periods. The need for additional pastures to support these herds may have driven the heightened mobility of the Middle and Late Bronze Age periods. Following a hiatus of more than 500 years, the North Caucasian steppe was repopulated by Early Iron Age societies with a broad mobile dairy economy, including a new focus on horse milking.

Model for end-stage liver disease score in the first 3 weeks after liver transplantation as a predictor for long-term outcome.

BACKGROUND: Early allograft dysfunction after liver transplantation (LTX) is not well defined. The aim of this study was to evaluate the value of early post-transplant model for end-stage liver disease (MELD) scores for predicting long-term outcome after transplantation. METHODS: In this single-center retrospective study, 362 consecutive patients after LTX were included. MELD scores at 7, 14, and 21 postoperative days (PODs) were calculated from primary lab values. Receiver operating characteristic (ROC) analyses were carried out to determine the critical cutoff MELD scores for patient and graft survival. RESULTS: One year after transplantation, the patient and graft survival rates were 85 and 69%, respectively. Although pretransplant MELD scores were similar, they were significantly different at POD7, POD14, and POD21 between patients who died and those who survived the first year after transplantation. As shown by ROC curves, for patient survival, the optimal time point is POD14 with a cutoff MELD of 17. At this time point, patients with a MELD below 17 showed a 1-year survival rate of 94.3% and patients with a MELD of 17 and higher showed a 1-year survival rate of only 75.4%. For graft survival, the optimal time point was day 7 and a cutoff MELD of 29 (92% at MELD<29; 56.4% at MELD≥29). A multivariate analysis of potential risk factors indicated a significant role of serum bilirubin and MELD score determined on POD14 for patient survival. CONCLUSION: In conclusion, early postoperative MELD scores predict outcome after LTX. The postoperative MELD score at POD14 is a good predictor for patient survival and at POD7 for the graft survival after LTX.

Protective Effects of Adenosine Receptor Agonist in a Cirrhotic Liver Resection Model.

OBJECTIVES: To investigate the role of CGS21680, a selective adenosine A2A receptor agonist, on a bile-duct-ligated cirrhotic liver resection model in rats. METHODS: Male Wistar rats were allotted into 3 groups (n = 7 per time-point): the control group, the bile duct ligation + CGS21680 group (BDL + CGS), and the bile duct ligation group (BDL). Biliary cirrhosis had been previously induced by ligature of the common bile duct in the BDL + CGS and BDL groups. After 2 weeks, the animals underwent partial hepatectomy (50%). The BDL + CGS group received a single dose of CGS21680 15 minutes prior to hepatectomy. Blood samples were collected and analyzed. RESULTS: Aspartate transaminase levels were found to be lower in the control vs BDL groups (1, 3, and 24 h) (P < 0.01) and the BDL + CGS (1 and 3 hours) (P < 0.01) and BDL + CGS vs BDL (24 hours) (P < 0.05) groups. Hepatic flow was measured and BDL showed significantly lower values at the 3, 24, and 168 h time-points compared to the control (P < 0.01) and BDL + CGS groups (P < 0.05 at 3 and 168 hours; P < 0.01 at 24 h). O2C velocity was reduced in the BDL compared to the control group (P < 0.001 at 3 hours; P < 0.01 at 24 and 168 hours) and the BDL + CGS group (P < 0.01 at 24 hours). Interleukin-6 levels were abrogated in the BDL + CGS (P < 0.05) and control (P < 0.01) groups versus BDL. Histone-bound low-molecular-weight DNA fragments in the BDL + CGS (P < 0.01) and control (P < 0.05) groups were low compared to the BDL group. CONCLUSIONS: Administration of CGS21680, an adenosine receptor agonist, after the resection of bile-duct-ligated cirrhotic livers led to improved liver function, regeneration, and microcirculation.