P-hydroxyphenylpyruvate, an intermediate of the Phe/Tyr catabolism, improves mitochondrial oxidative metabolism under stressing conditions and prolongs survival in rats subjected to profound hemorrhagic shock

The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2-4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. © 2014 Cotoia et al

β-Blocker after severe traumatic brain injury is associated with better long-term functional outcome: a matched case control study

PURPOSE: Severe traumatic brain injury (TBI) is the predominant cause of death and disability following trauma. Several studies have observed improved survival in TBI patients exposed to β-blockers, however, the effect on functional outcome is poorly documented.METHODS: Adult patients with severe TBI (head AIS ≥ 3) were identified from a prospectively collected TBI database over a 5-year period. Patients with neurosurgical ICU length of stay &lt;48 h and those dying within 48 h of admission were excluded. Patients exposed to β-blockers ≤ 48 h after admission and who continued with treatment until discharge constituted β-blocked cases and were matched to non β-blocked controls using propensity score matching. The outcome of interest was Glasgow Outcome Scores (GOS), as a measure of functional outcome up to 12 months after injury. GOS ≤ 3 was considered a poor outcome. Bivariate analysis was deployed to determine differences between groups. Odds ratio and 95% CI were used to assess the effect of β-blockers on GOS.RESULTS: 362 patients met the inclusion criteria with 21% receiving β-blockers during admission. After propensity matching, 76 matched pairs were available for analysis. There were no statistical differences in any variables included in the analysis. Mean hospital length of stay was shorter in the β-blocked cases (18.0 vs. 26.8 days, p &lt; 0.01). The risk of poor long-term functional outcome was more than doubled in non-β-blocked controls (OR 2.44, 95% CI 1.01-6.03, p = 0.03).CONCLUSION: Exposure to β-blockers in patients with severe TBI appears to improve functional outcome. Further prospective randomized trials are warranted.</p

Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

Contains fulltext : 51690.pdf (publisher's version ) (Closed access)BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. METHODS: Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. RESULTS: During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTalpha levels. Hepatocyte injury was followed by an inflammatory response. CONCLUSIONS: This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Fluid resuscitation in controlled and uncontrolled hemorrhage [Elektronisk resurs]

Background: For many years, early intravenous fluid resuscitation has been widely accepted as an appropriate treatment of the trauma patient at the scene of the injury, regardless of the type of trauma and hemorrhage. The present Thesis describes the effects of fluid resuscitation on the hemodynamics in the presence of a limited controlled hemorraghe and also particularly in the situation when the bleeding is uncontrolled. Methods: I) Eighteen healthy male volunteers were subjected to a 900-mL withdrawal of blood which was replaced with an i.v. infusion of 900 mL of Ringer's solution (n=12) or albumin 5% (n=6); further on, eight of the volunteers receiving Ringer's solution received another 900 mL. II) Thirty-two anesthetized pigs were prepared in such a way as to induce a standardized intra-abdominal vascular aortic lesion in order to evaluate, the spontaneous changes in hemodynamics during and early on after hemorrhage. III) Thirty-two anesthetized pigs were prepared as in study 11 but randomized to receive at 10 min after starting, either no i.v fluid resuscitation or fluid infusion with Ringer's solution in the ratio of 1:1, 2:1 or 3:1 to the expected blood loss. As in the animal studies IV-VI, the follow-up time was 120 min. IV) Eight anesthetized pigs were prepared as in study III but they received Ringer's solution in the ratio of 3:1 between 10 and 30 min into the study. V) Sixteen anesthetized pigs were prepared as in studies II-IV but were randomized to receive at 10 min after starting, a bolus injection of hypertonic saline/dextran (HSD) amounting to 4 mL/kg and 2.65 mL/kg, respectively. VI) Eight anesthetized pigs were prepared as previously described but also fixed in a missile wound model in order to inflict a standardized high-energy gunshot wound on the thigh in addition to the intraabdominal hemorrhage. Results: I) Withdrawal of 900 mL of blood decreased cardiac output and splanchnic and renal blood flow rates by 16-20%. Autotransfusion of fluid from the extravascular to the intravascular space was indicated by hemodilution. The hemodynamics were better restored with 900 mL of albumin 5% than with 900 mL of Ringees solution. II) The short-term changes in blood flow rates closely follow a simple monoexponential function which makes it possible to express them as half-times (T1/2). Bleeding stops spontaneously after about 3 min. III) During the first 40 min after hemorrhage, compared to baseline, the blood flow rates in the aorta distal to the vascular lesion were 39% (no fluid), 41% (1:1), 56% (2:1), and 56% (3:1), respectively. Rebleeding occurred only when Ringer's solution was infused in the ratio of 2:1 and 3:1. Survival was highest with the 1:1 and 2:1 infusion programs. IV) During the infusion of Ringer's solution between 10 and 30 min after hemorrhage, blood flows, as well as oxygen consumption increased transiently although minor rebleeding episodes during the infusion were observed in three animals. Four animals died in shock. V) The injection of HSD in a bolus injection at 10 min was followed by a prompt increase in all blood flow rates as well as blood pressures. This was closely followed by a rebleeding episode in 13 out of 16 animals and six even had a second episode of rebleeding. Five animals in each treatment group died before the end of the study. VI) The high-energy gunshot wound to the thigh induced instant depressant effects on central hemodynamics which reduced the intra-abdominal bleeding when the aortic vascular lesion was induced. After HSD was injected at 10 min, rebleeding occurred in five animals but the additional blood loss was less than that observed in study V. Conclusions: A controlled hemorrhage of approximately I liter is efficiently compensated for by normal physiological defense mechanisms and rarely needs to be replaced early. In a low-energy trauma with uncontrolled hemorrhage, rebleeding is a serious advent which may occur when fluid resuscitation with Ringer's solution is given in the ratio of 2:1 or 3:1 to the expected blood loss, as well as when HSD is given in a bolus injection. When the trauma is more complicated, hemodynamic mechanisms change, but the risk of rebleeding remains if bleeding is not controlled

[Aggravated uncontrolled hemorrhage induced by intravenous fluid administration]

A model of uncontrolled haemorrhage where a 0.5 mm laceration is made in the porcine abdominal aorta has shown outcome to be impaired by conventional fluid therapy given to restore blood volume. Findings in recent studies where the difference in blood flow rates, proximal vs. distal to the site of vascular lesion, was used as a measure of bleeding suggest the adverse effect of fluid therapy to be strongly associated with re-bleeding after primary haemostasis has occurred. Optimal survival is dependent on a fluid infusion rate ensuring balance between the risk of re-bleeding and the beneficial effects of fluid therapy on oxygen consumption