Hydroxyethyl Starch Improves the Prognosis of Rats with Traumatic Shock via Activation of the ERK Signaling Pathway in Lymphocytes.

OBJECTIVE: Severe traumatic shock is one of the leading causes of death in young adults. A large number of studies have shown that effective volumetry resuscitation on the basis of controlled injury can not only increase the success rate of early resuscitation but also reduce systemic inflammatory response and improve the cure rate of severe traumatic shock. The study explored the effects of hydroxyethyl starch (HES) on the survival rate, lymphocyte function and proliferation of rats with traumatic shock, and the potential mechanisms. METHODS: Traumatic shock was constructed in rats as experimental model, and liquid resuscitation was performed using HES and lactated Ringer's (LR). 24-h mortality was recorded, and lymphocytes were isolated. The expressions of signaling pathway factors was detected by qPCR and Western blot. ELISA was performed to determine the expression of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant. RESULTS: HES for fluid resuscitation augmented the survival of traumatic shock rats, upregulated the expressions of MEK and ERK1/2, and downregulated the expressions of IL-6 and TNF-α. However, inhibition of ERK signaling pathway reversed the effect of HES on the immune improvement and the 24-h survival rate of the traumatic shock rats (P < 0.05). CONCLUSION: HES could exert the anti-inflammatory effects on lymphocytes by mediating the phosphorylation of proteins of the ERK signaling pathway. HSE demonstrated a high efficacy in effectively treating traumatic shock, thus could be used in clinical practice.

Traumatic shock and electroshock: the difficult relationship between anatomic pathology and psychiatry in the early 20th century.

In the conviction that a look at the past can contribute to a better understanding of the present in the field of science too, we discuss here two aspects of the relationship between early 20th century anatomic pathology and psychiatry that have received very little attention, in Italy at least. There was much debate between these two disciplines throughout the 19th century, which began to lose momentum in the early years of the 20th, with the arrival on the scene of schizophrenia (a disease histologically sine materia) in all its epidemiological relevance.The First World War also contributed to the separation between psychiatry and pathology, which unfolded in the fruitless attempts to identify a histopathological justification for the psychological trauma known as shell shock. This condition was defined at the time as a "strange disorder" with very spectacular symptoms (memory loss, trembling, hallucinations, blindness with no apparent organic cause, dysesthesias, myoclonus, bizarre postures, hemiplegia, and more), that may have found neuropathological grounds only some hundred years later.Among the doctors with a passed involvement in the conflict, Ugo Cerletti, the inventor of electroshock treatment, focused on the problem of schizophrenia without abandoning his efforts to identify its organic factors: if inducing a controlled electric shock, just like an experimentally-induced epileptic seizure, seems to allay the psychotic symptoms and heal the patient, then what happens inside the brain? In seeking histological proof of the clinical effects of electroconvulsive therapy ("the destruction of the pathological synapses"), and attempting to isolate molecules (that he called acroagonins) he believed to be synthesized by neurons exposed to strong electric stimulation, Cerletti extended a hand towards anatomic pathology, and took the first steps towards a neurochemical perspective. However his dedication to finding a microscopic explanation for schizophrenia - in the name of a "somatist" approach that, some years earlier, the psychiatrist Enrico Morselli had labelled "histomania" - was unable to prevent psychiatry from moving further and further away from anatomic pathology.

Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock.

BACKGROUND: Endothelial cell damage and glycocalyx shedding after trauma can increase the risk of inflammation, coagulopathy, vascular permeability, and death. Bedside sublingual video-microscopy may detect worse flow and perfusion associated with this endotheliopathy. We compared markers of endotheliopathy with physical flow dynamics after traumatic hemorrhagic shock. METHODS: Sublingual incident dark field video-microscopy was performed at three time points after injury (<10 hours, 10-30 hours, and 30-50 hours). Values for microcirculatory flow index (MFI), Point Of carE Microcirculation assessment (POEM) score, proportion of perfused vessels (PPV), microcirculatory heterogeneity index (MHI), perfused vessel density (PVD), and total vessel density (TVD) were obtained. ELISAs were performed to measure concentrations of thrombomodulin and syndecan-1 as biomarkers of endothelial cell damage and glycocalyx shedding respectively. Flow parameters were dichotomized to above and below average, and biomarkers compared between groups; below average MFI, POEM, PPV, PVD, and TVD, and above average MHI were considered poor microcirculatory flow dynamics. RESULTS: A total of 155 sublingual video-microscopy clips corresponding to 39 time points from 17 trauma patients were analyzed. Median age was 35 (IQR 25-52); 16/17 were men. Within 10 hours of injury, syndecan-1 concentrations were significantly higher compared to 17 age- and sex-matched healthy controls (30 [IQR 20-44] ng/mL) for worse TVD (78 [IQR 63-417] ng/mL), PVD (156 [IQR 63-590] ng/mL), PPV (249 [IQR 64-578] ng/mL), MFI (249 [IQR 64-578] ng/mL), MHI (45 [IQR] 38-68) ng/mL), and POEM scores (108 [IQR 44-462] ng/mL) (all p < 0.01). Thrombomodulin was also raised within 10 hours of injury when compared to healthy controls (2.9 [IQR 2.2-3.4] ng/mL) for worse PPV (4.1 [IQR 3.4-6.2] ng/mL) and MFI (4.1 [IQR 3.4-6.2] ng/mL) (both p < 0.05). CONCLUSIONS: Endothelial cell damage and glycocalyx shedding are associated with worse flow, density, and heterogeneity within microvessels after traumatic hemorrhagic shock. The clinical utility of these biomarkers and flow parameters at the bedside are yet to be elucidated. LEVEL OF EVIDENCE: Prognostic study, level III.

Efficacy of Uncross-Matched Type O Packed Red Blood Cell Transfusion to Traumatic Shock Patients: a Propensity Score Match Study.

A new blood bank system was established in our trauma bay, which allowed immediate utilization of uncross-matched type O packed red blood cells (UORBCs). We investigated the efficacy of UORBC compared to that of the ABO type-specific packed red blood cells (ABO RBCs) from before the bank was installed. From March 2016 to February 2017, data from trauma patients who received UORBCs in the trauma bay were compared with those of trauma patients who received ABO RBCs from January 2013 to December 2015. Propensity matching was used to overcome retrospective bias. The primary outcome was 24-hour mortality, while the secondary outcomes were in-hospital mortality and intensive care unit (ICU) length of stay (LOS). Data from 252 patients were reviewed and UORBCs were administered to 64 patients. The time to transfusion from emergency room admission was shorter in the UORBC group (11 [7-16] minutes vs. 44 [29-72] minutes, P < 0.001). After propensity matching, 47 patients were included in each group. The 24-hour mortality (4 [8.5%] vs. 9 [13.8%], P = 0.135), in-hospital mortality (14 [29.8%] vs. 18 [38.3%], P = 0.384), and ICU LOS (9 [4-19] days vs. 5 [0-19] days, P = 0.155) did not differ significantly between groups. The utilization of UORBCs resulted in a faster transfusion but did not significantly improve the clinical outcomes in traumatic shock patients in this study. However, the tendency for lower mortality in the UORBC group suggested the need for a large study.

[THE PRINCIPLES OF ORGANIZATION AND TREATMENT FOR SORTING OF WOUNDED PERSONS WITH A COMBAT SURGICAL TRAUMA OF EXTREMITIES ON THE IV LEVEL OF THE MEDICAL CARE PROVISION].

Experience of medical sorting of 434 injured persons with a gun-shot woundings of extremities in 2014-2015 yrs is adduced. The principles of organization and treatment for medical sorting of wounded persons were elaborated. Prognostic intrahospital, diagnostic and evacuation--transport sorting was introduced in wounded persons in the IV level hospital, concerning severity of traumatic shock and prognosis of their survival.

[PROGNOSIS OF INFECTIVE COMPLICATIONS OF THE GUN-SHOT WOUNDS OF SOFT TISSUES].

The method of prognostication of infectious complications in a gun-shot wound was elaborated, using the methods of logistic regression analysis.

[Protective effect of necrostatin-1 on the liver of rats with trauma induced hemorrhagic shock].

OBJECTIVE: To investigate the effects of necrostatin-1( Nec-1) on the liver of rats with trauma induced hemorrhagic shock. METHODS: Trauma induced hemorrhagic shock model was produced by adopting the left femur, tibia fracture and soft tissue injury, bleeding and reperfusion in male Sprague-Dawley (SD) rats. A total of 22 rats were divided into model group and Nec-1 group with 11 rats in each group by randomized digital number method and the 72-hour mortality was observed. In addition, 72 rats were randomly divided into sham group, model group, Nec-1 group with 24 rats in each group. Rats in sham group were only received anesthesia, separating a nd ligating blood vessels, without trauma induced hemorrhagic and reperfusion, and the rats in Nec-1 group were received 1 mg/kg Nec-1 through femoral vein 5 minutes before reperfusion, and the rats in Nec-1 group were received the same amount of solvent. The serum and liver tissues of each group were collected at 2, 4, 8 hours after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by automatic biochemistry analyzer. The pathology changes in liver were observed by hematoxylin-eosin (HE) staining. The mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin -1ß (IL-1ß) in the liver were determined by reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of receptor interaction of protease 1/3( RIP1/RIP3) were also assessed by Western blot analysis. RESULTS: Compared to the model group, Nec-1 significantly reduced the 72 hour mortality [18.18% (2/11) vs. 63.64% (7/11), P = 0.040]. Two hours after trauma induced hemorrhagic shock and reperfusion, the expressions of ALT and AST in model group were significantly increased compared with those in sham group. [ ALT (U/L): 110.21 ± 22.32 vs. 80.98 ± 19.94, AST (U/L): 364.29 ± 64.83 vs. 279.76 ± 70.64, both P<0.05], and reached the peak at 8 hours [ALT (U/L): 387.41± 47.11 vs. 82.76 ±22.44, AST ( U/L): 973.35 ±77.51 vs.261.49 ± 52.03, both P <0.01]. Levels of serum ALT and AST in NEc-1 group were significantly decreased compared with model group [ALT (U/L) 4 hours: 144.64 ± 33.79 vs. 213.96 ± 36.21, 8 hours: 159.48 ± 43.57 vs. 387.41>11; AST (U/L): 4 hours: 398.78 ± 59.48 vs. 630.61 ± 59.93, 8 hours: 427.38 ± 80.75 vs. 973.35 ± 77.51, all P < 0.01] Under light microscopy, it was noted that the hepatic sinus expansion, liver cells degeneration, necrosis, as well as infiltration of abundant inflammatory cells were observed. But the pathology changes in hepatic tissues were significantly mitigated in Nec-1 group. Along with the time extension, the mRNA expressions of TNF-α and IL-ß and the protein expressions of RIP1 and RIP3 were markedly up-regulated. Compared with model group, difference in the mRNA expressions of TNF-α and IL-ß in hepatic tissues in Nec-1 group were statistically significant, and the most obvious difference was at 8 hours [TNF-α mRNA: 1.457 ± 0.081 vs. 2.317 ± 0.062, IL-ß mRNA: 0.690 ± 0.087 vs. 1.812 ± 0.112, both P<0.01]. But there was no statistically significant difference in RIP1 and RIP3 between Nec-1 group and model group [RIP1 protein 8 hours: 0.561 ± 0.033 vs. 0.587 ± 0.036, RIP3 protein 8 hours: 0.976 ± 0.040 vs. 1.044 ± 0.115, both P > 0.05]. CONCLUSION: Nec-1 may be remarkable protect effect on the liver of rats with trauma induced hemorrhage shock and reperfusion, and the intrinsic mechanisms need further investigation.

Traumatic injuries to the craniovertebral junction: a review of rare events.

The craniovertebral junction is a specific region of the spine with unique anatomical and biomechanical properties that yields a wide variety of injury patterns. Junctional traumatic fractures and/or dislocations are widely reported in clinical practice, but we could identify only a subgroup of upper cervical spine traumatic injuries with very few cases reported in the literature, and for this reason may be considered rare. In some of these cases, the absence of spinal biomechanical instability, in association with moderate clinical symptoms (neck stiffness and pain) and the difficulty in fracture identification through standard cervical radiographs, leads to a high percentage of missed injuries. In other cases, traumatic events have been commonly described only in autopsy series due to the high degree of spinal biomechanical instability. Herein, we have summarized all the relevant literature concerning this issue and also included our cases, with the aim of emphasizing prompt diagnosis and correct management. We provide a guide for correctly identifying "rare" craniovertebral junction traumatic injuries.

[Expression of VCAM-1 and caspase-3 in myocardium of persons who died from viral myocarditis].

OBJECTIVE: To observe the expression and distribution of vascular cell adhesion molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral myocarditis and to explore its pathogenesis and death mechanism. METHODS: Twenty cases died from viral myocarditis were selected as the experimental group. Ten cases died from traumatic shock and massive hemorrhage shock after traffic accidents were selected as the control group. The sections of myocardium were stained by immunohistochemistry for VCAM-1 and caspase-3, and observed under microscope. The positive expressions of VCAM-1 and caspase-3 of the two groups were compared with each other by image analysis and statistical analysis. RESULTS: (1) The vascular endothelial cells expressed VCAM-1 with dark-brown colors in the experimental group, and weak expression was observed in the control group. The average optical density in the experimental group was higher than that in the control group (P < 0.05). (2) The caspase-3 positive cells were mostly inflammatory cells around the myocardial vessels with brown-red granules in the experimental group. The positive cell number in the experimental group was higher than that in the control group (P < 0.05). CONCLUSION: VCAM-1 may play an important role in the inflammatory cells exudation caused by viral myocarditis, and may provide the reference for diagnosis of viral myocarditis in forensic pathology. However, the myocardial apoptosis mediated by caspase-3 doesn't affect the lethal mechanism in the late stage of viral myocarditis.

Organ failure in the obese adipocytes prime polymorphonuclear cell inflammation under stress conditions.

BACKGROUND: Obesity is associated with a higher risk of remote organ failure after shock and trauma. The mechanism(s) is poorly understood. Polymorphonuclear cell (PMN) inflammatory responses are important in the pathogenesis of organ injury following shock. Morbid obesity is a low-grade inflammatory state associated with proinflammatory mediator production from adipose tissue. We hypothesized that adipose tissue may modulate PMN inflammatory potential and is dependent on the magnitude of the injury-related stress response. This was studied in an in vitro model. METHODS: Adipose-derived stem cells (ADSCs) conditioned to behave as mature adipocytes were incubated with physiologic and stress concentrations of adrenaline for 12 hours, and cell culture supernatants were obtained. PMNs from normal human volunteers were cocultured with the ADSC supernatants (priming) followed by addition of 1-µM fMLP (activation). PMNs alone served as control. PMN activation was indexed by superoxide anion (O2) production, elastase release (%) and CD11b expression (mean fluorescent intensity). RESULTS: Physiologic and stress levels of adrenaline resulted in significantly increased PMN activation in the presence or absence of adipocytes. However, the largest increase was noted in PMNs exposed to ADSC culture supernatants that had been cocultured with stress levels of adrenaline for 12 hours, twofold increase in CD11b expression and fourfold increase in superoxide anion and percent elastase release. CONCLUSION: Adipocyte-derived mediators prime PMNs in vitro. There was a graded PMN response to adrenaline concentration with or without adipocytes in these experiments. The most profound increase in PMN inflammatory potential was noted with the adipocyte supernatant + stress adrenaline group. The clinical impact of obesity on remote organ injury is likely dependent on patient body mass index and the injury-related sympathetic responses. These data suggest a potential role for ß blockade in this patient population.

Shock, diaschisis and von Monakow.

The concept of shock apparently emerged in the middle of the 18th century (Whyett) as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall). The concept was extended (Brown-Séquard) and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance"). The term "diaschisis" (von Monakow), proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

Shock, diaschisis and von Monakow / Choque, diasquise e von Monakow

The concept of shock apparently emerged in the middle of the 18th century (Whyett) as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall). The concept was extended (Brown-Séquard) and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance"). The term "diaschisis" (von Monakow), proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

O conceito de choque aparentemente surgiu em meados do século 18 (Whyett), como ocorrência observada experimentalmente após seção transversa da medula, e foi identificado como fenômeno de "choque" um século mais tarde (Hall). O conceito foi estendido (Brown-Séquard) e sugeriu-se que lesões cerebrais produziam ruptura funcional em regiões distantes à da lesão ("action à distance"). O termo "diásquise" (von Monakow), proposto como nova modalidade de choque, teve seu conceito ampliado, fundamentado em observações em pacientes. Visava distinguir sintomas de lesões cerebrais focais de efeitos transitórios que produziam, atribuíveis à depressão de partes distantes do cérebro conectadas à área lesada. Atualmente, diásquise é relacionada principalmente a lesões cerebrovasculares e classificada de acordo com as fibras de conexão envolvidas, como proposto por von Monakow. Depressão do metabolismo e fluxo sanguíneo em regiões anatomicamente separadas, mas relacionadas por conexões à lesão, permitem observar diásquise por meio de neuroimagem.

Early trauma-hemorrhage-induced splenic and thymic apoptosis is gut-mediated and toll-like receptor 4-dependent.

Immune depression after trauma-hemorrhage has been implicated as an important factor in the pathogenesis of sepsis and septic-organ failure. Although recent studies have implicated immune-cell apoptosis as an important factor in the evolution of this posttrauma immune-suppressed state, neither the initial triggers that induce this response nor the cellular pathways through which these triggering pathways act have been fully defined. Thus, the current study tests the hypothesis that acute splenic and thymic immune-cell apoptosis developing after trauma-hemorrhagic shock (T/HS) is due to gut-derived factors carried in intestinal lymph and that this T/HS lymph-induced immune depressed state is mediated through Toll-like receptor 4 (TLR4). The first set of experiments documented that T/HS caused both thymic and splenic immune-cell apoptosis as measured by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase-3 immunohistochemistry and that this increase in apoptosis was totally abrogated by mesenteric lymph duct ligation. In subsequent experiments, mesenteric lymph collected from animals subjected to T/HS or trauma-sham shock were injected into TLR4-deficient (TLR4mut) mice or their wild-type (WT) littermates. Trauma-hemorrhagic shock, but not trauma-sham shock, lymph caused splenic apoptosis in the WT mice. However, the TLR4mut mice were resistant to T/HS lymph-induced splenic apoptosis. Furthermore, the WT, but not the TLR4mut mice developed splenic apoptosis after actual T/HS. In conclusion, gut-derived factors appear to initiate a sequence of events that leads to an acute increase in splenic and thymic immune-cell apoptosis, and this process is TLR4-dependent.

Modulation of the unfolded protein response during hepatocyte and cardiomyocyte apoptosis in trauma/hemorrhagic shock.

Trauma with hemorrhagic shock (T/HS), has been shown to result in liver injury marked by hepatocyte apoptosis and heart failure marked by cardiomyocyte apoptosis, both of which we have shown to be prevented by IL-6 administration at resuscitation, and Stat3 largely mediated this. As specific mediators have not been delineated, we investigated the unfolded protein response (UPR), which, with marked activation, can lead to apoptosis. Prior studies of hepatic and cardiac injury examined limited repertoires of UPR elements, making it difficult to assess the role of the UPR in T/HS. This study describes the first global examination of the UPR transcriptome in the liver and heart following T/HS, demonstrating organ-specific UPR transcriptome changes. The non-canonical UPR chaperone, Hsp70, was most dysregulated following T/HS and may contribute to hepatocyte protection via an IL-6-mediated pathway, identifying a potential new therapeutic strategy to prevent hepatocyte death and organ dysfunction in T/HS.

Expression of VCAM-1 and caspase-3 in myocardium of persons who died from viral myocarditis / 法医学杂志

OBJECTIVE@#To observe the expression and distribution of vascular cell adhesion molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral myocarditis and to explore its pathogenesis and death mechanism.@*METHODS@#Twenty cases died from viral myocarditis were selected as the experimental group. Ten cases died from traumatic shock and massive hemorrhage shock after traffic accidents were selected as the control group. The sections of myocardium were stained by immunohistochemistry for VCAM-1 and caspase-3, and observed under microscope. The positive expressions of VCAM-1 and caspase-3 of the two groups were compared with each other by image analysis and statistical analysis.@*RESULTS@#(1) The vascular endothelial cells expressed VCAM-1 with dark-brown colors in the experimental group, and weak expression was observed in the control group. The average optical density in the experimental group was higher than that in the control group (P < 0.05). (2) The caspase-3 positive cells were mostly inflammatory cells around the myocardial vessels with brown-red granules in the experimental group. The positive cell number in the experimental group was higher than that in the control group (P < 0.05).@*CONCLUSION@#VCAM-1 may play an important role in the inflammatory cells exudation caused by viral myocarditis, and may provide the reference for diagnosis of viral myocarditis in forensic pathology. However, the myocardial apoptosis mediated by caspase-3 doesn't affect the lethal mechanism in the late stage of viral myocarditis.

[On the problem of traumatic shock associated with a combined injury (based on the materials of one forensic medical expertise)].

The author presents the results of the critical analysis of the materials of forensic medical expertise of a case of the serious harm to health that has led to involunry manslaughter. According to the expert opinion, the death resulted from the traumatic shock associated with the combined head and the chest injury. Such conclusion levels out the difference between the two accused persons and their "contribution" to the extent and severity of the inflicted damage to the victim's body; thereby, it equalizes the degree of their guilt and criminal responsibility. The present study showed that such interpretation of tanatogenesis associated with the combined injury is erroneous. The death of the injured person resulted from cerebral coma that developed following a severe craniocerebral injury as a constituent component of the combined trauma. It is emphasized that the thorough investigation of tanatogenesis based on the reliable elucidation of the immediate cause of death makes it possible to avoid poorly substantiated expert conclusions and their potential dire legal consequences.

Molecular pathology of pulmonary edema after injury in forensic autopsy cases.

The lung is vulnerable to trauma; pulmonary edema starts quickly as part of the systemic responses involved in shock. The present study investigated the molecular pathology of posttraumatic alveolar damage and responses involving pulmonary edema in forensic autopsy cases of injury (n = 66) compared with acute cardiac death cases (n = 13). Intrapulmonary mRNA and immunohistochemical expressions of matrix metalloproteinases (MMPs; MMP-2 and MMP-9), intercellular adhesion molecule-1, claudin-5, and aquaporins (AQPs, AQP-1 and AQP-5) were examined. Subacute injury deaths showed an increase in lung weight similar to that in acute cardiac death, but relative mRNA quantification using the Taqman real-time PCR assay demonstrated different findings among the causes of death; higher expressions were detected for all markers, except for AQP-5 in sharp instrument injury, for MMP-2 in blunt brain injury, and for MMP-9 in non-brain blunt injury, but these expression levels were lower in acute cardiac death. In immunostaining, only MMPs showed differences among the causes of death: MMP-2 expression was evident in most subacute deaths due to blunt brain injury and sharp instrument injury, whereas MMP-9 was intensely positive in those of non-brain blunt injury and sharp instrument injury. These findings suggest significant differences in the mechanism of pulmonary edema among fatal injuries and acute cardiac death, especially between blunt and sharp instrument injury. Systematic analysis of gene expressions using real-time PCR in combination with immunohistochemistry may be useful in evaluating pulmonary damage and responses after injury in death investigations, especially in connection with posttraumatic shock.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

MOTIVATION: Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. RESULTS: In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship.

[The effect of the membrane attack complex C5b-9 on liver cells during traumatic hemorrhagic shock in rat].

OBJECTIVE: To observe whether the membrane attack complex C5b-9 would accumulate in the rats' liver after receiving the assault of traumatic hemorrhagic shock, and whether the membrane attack complex deals an impact on liver apoptosis. METHODS: Fifty male healthy Wistar rats were randomly divided into five groups: normal group, 1, 3, 6, 24 hour model groups. The model of traumatic hemorrhagic shock was reproduced by withdrawal of blood from carotid artery after a bone fracture till the blood pressure lowered to 40 mm Hg (1 mm Hg=0.133 kPa). Plasma membrane attack complex C5b-9 concentration was assayed using enzyme linked immunoadsorbent assay. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood was determined by Rate method. Immunohistochemistry was used to detect C5b-9 deposition in the liver. Apoptosis of liver cells was then detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. The pathological changes in paraffin sections stained with hematoxylin eosin (HE) were observed under light microscope. RESULTS: A small amount of C5b 9 in plasma was found in normal group, and the values (ng/L) of 1, 3, 6 hour models were significantly higher than those of the normal group (272.91 ± 9.56, 192.01 ± 9.04, 156.78 ± 8.37 vs. 25.98 ± 5.87, all <0.05 ). ALT (U/L) in 3 hour model group and AST (U/L) in 1 hour model group were increased significantly (92.90 ± 8.83, 264.83 ± 31.4), peaked at 24 hours (184.30 ± 12.98, 647.36 ± 60.02), and there was significant difference compared with normal group (38.75 ± 5.40, 66.69 ± 19.95, all P <0.05). In the normal group and the 1 hour and 6 hour model groups, no C5b 9 was found in liver, but in the 3 hour model group a large number of liver parenchymal cells in the portal area were found to contain C5b 9 22.60 ± 1.06), however the number decreased significantly in the 24 hour model (2.20 ± 0.60, P<0.05). In normal group there was no apoptotic cell, and in 1, 6, 24 hour model groups there were scattered apoptotic cells (1.20 ± 0.25, 5.60 ± 0.37, 1.60 ± 0.26). In the 3 hour model group apoptosis of hepatic cells around the central vein was increased to the peak (20.60 ± 0.47), and there was significant difference compared with other groups (all P <0.05) . In the model groups the liver cells became edematous, and the integrity of the membrane was lost, and some cells were even lysed.The pathological damage is most serious in 24 hour model group. CONCLUSION: The membrane attack complex C5b-9 insulted the rats' liver after a traumatic hemorrhagic shock, and apoptosis of hepatic cells and the content of C5b-9 peaked in 3 hour model , though they do not occur in the same site. A low level of C5b-9 in blood 3 hours after shock predict a poor prognosis.