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1.
Curr Med Sci ; 41(5): 894-900, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34652627

ABSTRACT

OBJECTIVE: To observe the influences of branched-chain amino acids (BCAAs) on nutrition metabolism and prognosis of patients with severe abdominal trauma; at the same time, to analyze and evaluate the pharmacoeconomics of it. METHODS: A total of 75 severe abdominal trauma patients were recruited from June 2016 to December 2017 and randomly divided into control group and observation group. After surgery and basic treatment, parenteral nutrition support therapy with iso-nitrogen and iso-calorie of both groups was administered. Meanwhile, an equivalent of 8.5% (18AA-II) and 10% (20AA) compound AA injection was administrated to the control and observation groups, respectively. The nitrogen balance, serum protein level and plasma amino spectrum of the patients were observed before and after treatment. Besides, the hospital stay, survival rate, complications, adverse reactions and hospitalization costs were also compared. RESULTS: After a 7-day course treatment, the nitrogen balance level of the two groups was significantly improved, but no significant difference was found between them. In addition, the serum protein level and plasma amino spectrum of the two groups was generally improved when compared to before treatment. Compared with the control group, the level of albumin and transferrin in the observation group was improved significantly after treatment, while no difference in plasma amino spectrum was found between the two groups. Moreover, the cost analysis showed remarkably reduced hospitalization costs in the observation group. CONCLUSION: To a certain degree, BCAAs could improve the nutritional metabolism and prognosis of patients with severe abdominal trauma, and have good cost-effectiveness.


Subject(s)
Abdominal Injuries/diet therapy , Amino Acids, Branched-Chain/administration & dosage , Length of Stay/economics , Nitrogen/metabolism , Abdominal Injuries/metabolism , Abdominal Injuries/surgery , Adult , Aged , Amino Acids, Branched-Chain/economics , Economics, Pharmaceutical , Female , Humans , Male , Middle Aged , Parenteral Nutrition/economics , Random Allocation , Serum Albumin, Human/metabolism , Survival Analysis , Transferrin/metabolism
2.
Cell Rep ; 37(2): 109827, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34644579

ABSTRACT

Polyploidy frequently arises in response to injury, aging, and disease. Despite its prevalence, major gaps exist in our understanding of how polyploid cells alter tissue function. In the adult Drosophila epithelium, wound healing is dependent on the generation of multinucleated polyploid cells resulting in a permanent change in the epithelial architecture. Here, we study how the wound-induced polyploid cells affect tissue function by altering epithelial mechanics. The mechanosensor nonmuscle myosin II is activated and upregulated in wound-induced polyploid cells and persists after healing completes. Polyploidy enhances relative epithelial tension, which is dependent on the endocycle and not cell fusion post injury. Remarkably, the enhanced epithelial tension mimics the relative tension of the lateral muscle fibers, which are permanently severed by the injury. As a result, we found that the wound-induced polyploid cells remodel the epithelium to maintain fly abdominal movements, which may help compensate for lost tissue tension.


Subject(s)
Abdominal Injuries/pathology , Endoreduplication , Epithelial Cells/pathology , Needlestick Injuries/pathology , Wound Healing , Abdominal Injuries/genetics , Abdominal Injuries/metabolism , Animals , Animals, Genetically Modified , Biomechanical Phenomena , Disease Models, Animal , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Epithelial Cells/metabolism , Mechanotransduction, Cellular , Myosin Type II/metabolism , Needlestick Injuries/genetics , Needlestick Injuries/metabolism , Polyploidy , Stress, Mechanical
3.
Eur J Med Res ; 26(1): 26, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-33722293

ABSTRACT

BACKGROUND: Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma. METHODS: All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals. RESULTS: A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. CONCLUSIONS: This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.


Subject(s)
Abdominal Injuries/surgery , Immunity, Cellular , Leukocytes/immunology , Spleen/injuries , Splenectomy/methods , Wounds, Nonpenetrating/surgery , Abdominal Injuries/immunology , Abdominal Injuries/metabolism , Adult , Female , Humans , Leukocyte Count , Leukocytes/metabolism , Male , Middle Aged , Prospective Studies , Spleen/surgery , Wounds, Nonpenetrating/immunology , Wounds, Nonpenetrating/metabolism , Young Adult
4.
Pancreas ; 48(8): 1015-1025, 2019 09.
Article in English | MEDLINE | ID: mdl-31404030

ABSTRACT

OBJECTIVE: In a continuation of previous work, Reg3γ protein was further evaluated as a biomarker of pancreatic injury using immunohistochemistry in an additional species. METHODS: Mice and rats were treated with intraperitoneal cerulein injections, creating acute pancreatic injury. Mice received 2, 4, or 6 doses, and rats received 1, 2, or 3 doses of cerulein creating low, medium, and high treatment groups. Control animals were dosed with phosphate-buffered saline at corresponding volumes and intervals. Groups of 6 animals were killed 1, 3, 6, 24, and 48 hours after final treatments. Reg3γ immunohistochemical staining and image analysis were performed on pancreatic tissue obtained 6, 24, or 48 hours after control or cerulein treatment. Staining was quantified using image analysis software to calculate area of positivity as a percentage of total tissue area. RESULTS: Percent positivity of Reg3γ in both species rose by 6 hours, peaked by 24 hours across all 3 cerulein doses, and dropped significantly by 48 hours. In high-dose rats with accompanying gene expression data, Reg3γ gene expression corresponded temporally with quantitative staining data. CONCLUSIONS: Reg3γ staining quantified through image analysis showed a time- and dose-response in cerulein-treated mice and rats.


Subject(s)
Abdominal Injuries/metabolism , Disease Models, Animal , Pancreatic Diseases/metabolism , Pancreatitis-Associated Proteins/biosynthesis , Abdominal Injuries/chemically induced , Abdominal Injuries/genetics , Acute Disease , Animals , Ceruletide , Gene Expression Regulation/drug effects , Immunohistochemistry/methods , Injections, Intraperitoneal , Male , Mice, Inbred C57BL , Pancreatic Diseases/chemically induced , Pancreatic Diseases/genetics , Pancreatitis-Associated Proteins/genetics , Rats, Sprague-Dawley , Time Factors
5.
J Forensic Sci ; 63(3): 842-848, 2018 May.
Article in English | MEDLINE | ID: mdl-28834611

ABSTRACT

Previous research by the authors on an animal model showed that bloodstains can contain additional information about their somatic origin in the form of wound cells. Bloodstains produced by a gunshot wound to the head were distinguished from bloodstains produced by a gunshot wound to the chest by testing the stains for a brain microRNA marker. In this study, the effectiveness of the technique was examined on blood drops shed externally from a stab wound to the liver of rat carcasses. Specifically, investigations were conducted on the liver microRNA marker, rno-mir-122-3p, with the QIAGEN miScript System, and PCR analysis. Between the two stabbing methods used, 67% of the scalpel blades and 57% of the blood drops tested positive for rno-mir-122-3p; however, other samples tested negative giving inconclusive results as to the wound-of-origin. The amount of the liver cells in the bloodstains appeared to be related to the extent of trauma.


Subject(s)
Blood Stains , MicroRNAs/genetics , Wounds, Stab/metabolism , Abdominal Injuries/metabolism , Animals , Forensic Pathology , Genetic Markers , Liver/injuries , Liver/metabolism , MicroRNAs/metabolism , Models, Animal , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Thoracic Injuries/metabolism
6.
J Trauma Acute Care Surg ; 83(6): 1062-1065, 2017 12.
Article in English | MEDLINE | ID: mdl-28806285

ABSTRACT

BACKGROUND: Mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA and N-formylated peptides, are endogenous molecules released from tissue after traumatic injury. mtDAMPs are potent activators of the innate immune system. They have similarities with bacteria, which allow mtDAMPs to interact with the same pattern recognition receptors and mediate the development of systemic inflammatory response syndrome (SIRS). Current recommendations for management of an open abdomen include returning to the operating room every 48 hours for peritoneal cavity lavage until definitive procedure. These patients are often critically ill and develop SIRS. We hypothesized that mitochondrial DAMPs are present in the peritoneal cavity fluid in this setting, and that they accumulate in the interval between washouts. METHODS: We conducted a prospective pilot study of critically ill adult patients undergoing open abdomen management in the surgical and trauma intensive care units. Peritoneal fluid was collected daily from 10 open abdomen patients. Specimens were analyzed via quantitative polymerase chain reaction (qPCR) for mitochondrial DNA (mtDNA), via enzyme immunoassay for DNAse activity and via Western blot analysis for the ND6 subunit of the NADH: ubiquinone oxidoreductase, an N-formylated peptide. RESULTS: We observed a reduction in the expression of ND6 the day after lavage of the peritoneal cavity, that was statistically different from the days with no lavage (% change in ND6 expression, postoperative from washout: -50 ± 11 vs. no washout day, 42 ± 9; p < 0.05). Contrary to expectation, the mtDNA levels remained relatively constant from sample to sample. We then hypothesized that DNAse present in the effluent may be degrading mtDNA. CONCLUSION: These results indicate that the peritoneal cavity irrigation reduces the presence of mitochondrial DAMPs in the open abdomen. It is possible that increased frequency of peritoneal cavity lavage may lead to decreased systemic absorption of mtDAMPs, thereby reducing the risk of SIRS. LEVEL OF EVIDENCE: Prospective study, Case Series, Level V.


Subject(s)
Abdominal Injuries/genetics , DNA, Mitochondrial/genetics , Mitochondria/metabolism , Mitophagy , Peritoneal Lavage/methods , Abdominal Injuries/metabolism , Abdominal Injuries/therapy , Adult , DNA, Mitochondrial/metabolism , Female , Humans , Male , Pilot Projects , Prospective Studies
7.
Shock ; 47(1): 100-106, 2017 01.
Article in English | MEDLINE | ID: mdl-27559695

ABSTRACT

"Shock bowel" is one of the computed tomographic (CT) signs of hypotension, yet its clinical implications remain poorly understood. We evaluated how shock bowel affects clinical outcomes and the extent of intestinal epithelial damage in trauma patients by measuring the level of intestinal fatty acid binding protein (I-FABP). We reviewed the initial CT scans, taken in the emergency room, of 92 patients with severe blunt torso trauma who were consecutively admitted during a 24-month period. The data collected included CT signs of hypotension, I-FABP, feeding intolerance, and other clinical outcomes. Demographic and clinical outcomes were compared in patients with and without hemodynamic shock and shock bowel. Shock bowel was found in 16 patients (17.4%); of them 7 patients (43.8%) did not have hemodynamic shock. Certain CT signs of hypotension, namely free peritoneal fluid, contrast extravasation, small-caliber aorta, and shock bowel, were significantly more common in patients with hemodynamic shock than in patients without (P < 0.05). Injury severity score and the rate of consciousness disturbance were significantly higher in patients with shock bowel than in patients without (P < 0.05). The rate of feeding intolerance and median plasma I-FABP levels were significantly higher in patients with shock bowel than in patients without (75.0% vs. 22.4%, P < 0.001 and 17.0 ng/mL vs. 3.7 ng/mL, P < 0.001, respectively). There was no difference in mortality. In conclusion, shock bowel is not always due to hemodynamic shock. It does, however, indicate severe intestinal mucosal damages and may predict feeding intolerance.


Subject(s)
Fatty Acid-Binding Proteins/metabolism , Abdominal Injuries/immunology , Abdominal Injuries/metabolism , Adult , Decision Making , Female , Humans , Hypotension/immunology , Hypotension/metabolism , Injury Severity Score , Male , Middle Aged , Wounds, Nonpenetrating/immunology , Wounds, Nonpenetrating/metabolism
9.
Methods Mol Biol ; 1037: 3-25, 2013.
Article in English | MEDLINE | ID: mdl-24029927

ABSTRACT

We describe an in vivo model system designed to evaluate the host response to implanted biomaterials: The partial thickness rat abdominal wall defect model. The model allows for determination of the temporal and spatial distribution of the cellular and vascular response, the remodeling of the implanted material and surrounding host soft tissue, and the function of the remodeled tissue over time.


Subject(s)
Abdominal Injuries/therapy , Biocompatible Materials , Prostheses and Implants , Abdominal Injuries/immunology , Abdominal Injuries/metabolism , Abdominal Injuries/pathology , Animals , Biocompatible Materials/adverse effects , Disease Models, Animal , Guided Tissue Regeneration , Macrophages/immunology , Macrophages/metabolism , Prostheses and Implants/adverse effects , Rats , Wound Closure Techniques
10.
Shock ; 38(6): 664-70, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23042201

ABSTRACT

Despite the high incidence and prognostic relevance of hemorrhagic shock and abdominal and blunt chest trauma in multiply injured patients, there are no animal models combining these injuries. Therefore, we established a new porcine multiple trauma model consisting of blunt chest trauma, penetrating abdominal trauma (two incisions in the right upper liver lobe using a four-edged scalpel and subsequent liver packing), and pressure-controlled hemorrhagic shock with a mean arterial pressure of 30 ± 5 mmHg (a maximum of 45% of the total blood volume). The combined traumatic insult led to severe signs of hemorrhagic shock and impaired pulmonary function. In conclusion, a consistent, reproducible, and clinically relevant porcine model of multisystem injury with controlled (pressure-controlled blood withdrawal) and uncontrolled components of hemorrhage (liver laceration) with the potential for rebleeding was established.


Subject(s)
Abdominal Injuries , Disease Models, Animal , Shock, Hemorrhagic , Swine , Thoracic Injuries , Abdominal Injuries/complications , Abdominal Injuries/metabolism , Abdominal Injuries/pathology , Abdominal Injuries/physiopathology , Animals , Lung/metabolism , Lung/pathology , Lung/physiopathology , Respiratory Function Tests , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/metabolism , Shock, Hemorrhagic/pathology , Shock, Hemorrhagic/physiopathology , Thoracic Injuries/complications , Thoracic Injuries/metabolism , Thoracic Injuries/pathology , Thoracic Injuries/physiopathology
11.
Ann Surg ; 250(6): 995-1001, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19855262

ABSTRACT

OBJECTIVE: We investigated whether Kupffer cell phagocytosis is differentially regulated following hypoxia (by breathing hypoxic gas) and trauma-hemorrhage. We hypothesized that the differences might result from a differential activation of hypoxia-inducible factor (HIF)-1alpha and phosphoinositide 3-kinase (PI3K)/Akt pathway under those conditions. BACKGROUND: HIF-1alpha is a biologic O2 sensor enabling adaptation to hypoxia. Studies have shown that under hypoxic conditions, HIF-1alpha enhances macrophage phagocytosis. Trauma-hemorrhage also produces a hypoxic insult with HIF-1alpha activation; however, macrophage phagocytosis is suppressed under those conditions. Thus, signaling molecules other than HIF-1alpha should be taken into consideration in the regulation of macrophage phagocytosis following cellular hypoxia or trauma-hemorrhage. METHODS: Male C3H/HeN mice were subjected to sham operation, trauma-hemorrhage (laparotomy, 90 minutes hemorrhagic shock, MAP 35 +/- 5 mm Hg followed by resuscitation) or hypoxia (5% O2 for 120 minutes). The trauma-hemorrhage and hypoxia groups received Wortmannin (PI3K inhibitor), YC-1 (HIF-1alpha inhibitor) or vehicle at the time of maximum bleedout in the trauma-hemorrhage group or at a PaO2 of 30 mm Hg during hypoxic air inhalation. Mice were killed 2 hours later and samples/cells collected. RESULTS: While the systemic and Kupffer cell hypoxic states were similar in the trauma-hemorrhage and hypoxia groups, phagocytic capacity was suppressed following trauma-hemorrhage but enhanced in the hypoxia group. Kupffer cells from both groups showed increased HIF-1alpha activation, which was prevented by Wortmannin or YC-1 treatment. The increase in Kupffer cell phagocytosis following hypoxemia was also prevented by Wortmannin or YC-1 treatment. Akt activation was suppressed in the trauma-hemorrhage group, but enhanced in the hypoxia group. Wortmannin and YC-1 treatment prevented the increase in Akt activation. CONCLUSIONS: These findings indicate that the suppression of Kupffer cell phagocytosis following trauma-hemorrhage is independent of cellular hypoxia and activation of HIF-1alpha, but it is possibly related to suppression of the Akt activation.


Subject(s)
Abdominal Injuries/complications , Hemorrhage/complications , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia/metabolism , Kupffer Cells/metabolism , Phagocytosis/physiology , Phosphatidylinositol 3-Kinases/metabolism , Abdominal Injuries/metabolism , Abdominal Injuries/pathology , Animals , Disease Models, Animal , Enzyme Activation , Enzyme-Linked Immunosorbent Assay , Hemorrhage/metabolism , Hemorrhage/pathology , Hypoxia/etiology , Hypoxia/pathology , Kupffer Cells/pathology , Liver/injuries , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C3H
12.
Acta Cir Bras ; 24(2): 156-61, 2009.
Article in English | MEDLINE | ID: mdl-19377786

ABSTRACT

PURPOSE: Multivisceral transplantation (MVTx) has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1+/-0.5 kg) were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively). Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4+/-0.3 vs. 7.6+/-0.4, p<0.05). Three animals died before the 3 hours of reperfusion were completed. Total abdominal exenteration for MVTx in dogs is associated with early major hemodynamics, and metabolic changes. CONCLUSION: The deleterious hemodynamic alterations observed are probably related with the association of severe acidosis, hyperlactemia, hypoglycemia, and reduction of total circulating blood volume. Close hemodynamic and metabolic monitoring should be provided during experimental MVTx in order to promote an increase in successful rates of this complex and challenging procedure.


Subject(s)
Anesthesia/methods , Hemodynamics/physiology , Organ Transplantation/physiology , Abdominal Injuries/complications , Abdominal Injuries/metabolism , Abdominal Injuries/surgery , Animals , Disease Models, Animal , Dogs , Male , Regional Blood Flow/physiology
13.
Acta cir. bras ; 24(2): 156-161, Mar.-Apr. 2009. ilus, graf, tab
Article in English | LILACS | ID: lil-511331

ABSTRACT

PURPOSE: Multivisceral transplantation (MVTx) has been accepted as standard therapeutic modality for patients with short-bowel syndrome associated with irreversible liver failure. Even nowadays, experimental models of MVTx grounds high incidence of intraoperative or early recipient mortality. Despite the known deleterious effects of hepatosplanchnic exenteration the impact of this procedure on systemic hemodynamics and metabolism remains to be determined. METHODS: Nine dogs (20.1±0.5 kg) were subjected to an en bloc resection of all abdominal organs including, stomach, duodenum, pancreas, liver, spleen, small bowel, and colon. A woven double velour vascular graft was interposed between the suprahepatic and infrahepatic vena cava. Systemic hemodynamic were evaluated through a Swan-Ganz catheter, ultrasonic flowprobes, and arterial lines. Systemic O2-derived variables, glucose, and lactate metabolism were analyzed throughout the experiment. RESULTS: Complete abdominal exenteration was associated with significant reduction in cardiac output, and mean arterial pressure (57% and 14%, respectively). Two hours after reperfusion a significant reduction in arterial pH and glucose were also observed. Oxygen consumption remained unaltered during the first two hours of the experiment, with a significant increase of lactate levels (1.4±0.3 vs. 7.6±0.4, p<0.05). Three animals died before the 3 hours of reperfusion were completed. Total abdominal exenteration for MVTx in dogs is associated with early major hemodynamics, and metabolic changes. CONCLUSION: The deleterious hemodynamic alterations observed are probably related with the association of severe acidosis, hyperlactemia, hypoglycemia, and reduction of total circulating blood volume. Close hemodynamic and metabolic monitoring should be provided during experimental MVTx in order to promote an increase in successful rates of this complex and challenging procedure.


OBJETIVO: O transplante multivisceral (MVTx) é preconizado como tratamento de escolha em pacientes com síndrome do intestine curto associado com falência hepática irreverssível. Modelos experimentais de MVTx apresentam altas taxas de mortalidade intra-operatória e nas primeiras horas apos a reperfusão. Apesar dos deletérios efeitos hemodinâmicos da exenteração abdominal, o impacto deste procedimento na perfusão e no metabolismo sistêmico ainda esta por ser determinado. MÉTODOS: Nove cães (20.1±0.5 kg) foram submetidos a ressecção em bloco de todos os orgãos abdominais incluindo, estômago, duodeno, pancreas, fígado, baço, intestino delgado, e colon. Uma prótese vascular foi interposta entre a veia cava infra e supra-hepática. Efeitos hemodinâmicos foram avaliados por meio de um cateter de Swan-Ganz catheter e Doppler ultrassônico. As variáveis dependentes de oxigênio, e o metabolismo da glicose e lactato foram avaliados durante todo o experimento. RESULTADOS: A evisceração abdominal esteve associada a uma redução significativa do débito cardiaco e da pressão arterial média (57% and 14%, respectivamente). Duas horas após a reconstrução vascular da veia cava inferior observou-se uma redução significativa do pH e da glicose arterial. O consumo de oxigênio se manteve inalterado nas primeiras duas horas do experimento, com um significativo aumento dos níveis séricos de lactato (1.4±0.3 vs. 7.6±0.4, p<0.05). Três animais morreram antes de 180 minutos após a reperfusão. CONCLUSÃO: A evisceração abdominal total esteve associada com graves repercussões hemodinâmicas e metabólicas sistêmicas. Estas graves alterações hemodinâmicas estam associadas, provavelmente, a combinação de vários fatores incluindo: acidose metabólica, hiperlactemia, hipoglicemia e redução do volume de sangue circulante. A cuidadosa monitorização hemodinâmica e metabólica deve ser realizada durante o MVTx experimental com a finalidade de promover um aumento...


Subject(s)
Animals , Dogs , Male , Anesthesia/methods , Hemodynamics/physiology , Organ Transplantation/physiology , Abdominal Injuries/complications , Abdominal Injuries/metabolism , Abdominal Injuries/surgery , Disease Models, Animal , Regional Blood Flow/physiology
14.
Surgery ; 144(2): 204-16, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18656627

ABSTRACT

BACKGROUND: Hemorrhage induces an imbalance in histone acetyl transferase/histone deacetylase (HAT/HDAC) ratio. Correction of this imbalance with histone deacetylase inhibitors (HDACI) improves survival. We aimed to identify whether this was due to modulation of the post-shock immune response. METHODS: We established a "two-hit" model in which rats (n=11; 5-6/group) and humans (n=10; 5/group) sustained trauma/hemorrhage, followed by exposure of splenic leukocytes to lipopolysaccharide (LPS, 10 ng/mL) for 8 or 24 hours. The leukocytes were treated with: No treatment, SAHA (suberoylanilide hydroxamic acid, HDACI, 400 nM), or Garcinol (HAT inhibitor, 20 microM). RESULTS: Hemorrhage in the animals produced severe shock and a pro-inflammatory state. SAHA reduced TNFa secretion in the hemorrhaged leukocytes after LPS "second-hit" (34.0%, P = .003), whereas it increased transcript levels of TNFa and IL-1b (2.1+/-0.3 and 5.1+/- 2.2 fold respectively, P < .05). Leukocytes from trauma patients displayed 2 distinct responses to SAHA after LPS "second-hit," with markedly increased or decreased cytokine levels. CONCLUSIONS: SAHA normalizes TNFa levels following hemorrhage and LPS "second hit" in the rats, whereas trauma patients respond to SAHA in 2 distinct patterns, with either marked attenuation or exaggeration of inflammatory cytokines. Cytokine levels were independent of gene expression, implicating acetylation of non-nuclear proteins as the dominant regulatory mechanism.


Subject(s)
Abdominal Injuries/metabolism , Histone Acetyltransferases/metabolism , Histone Deacetylases/metabolism , Shock, Hemorrhagic/metabolism , Acetylation , Adult , Animals , Cell Culture Techniques , Female , Hemorrhage/metabolism , Hemorrhage/physiopathology , Histone Deacetylase Inhibitors , Humans , Hydroxamic Acids/pharmacology , Inflammation , Interleukin-1beta/blood , Interleukin-1beta/genetics , Leukocytes/metabolism , Lipopolysaccharides/pharmacology , Male , Rats , Rats, Inbred WKY , Shock, Hemorrhagic/complications , Shock, Hemorrhagic/immunology , Shock, Hemorrhagic/therapy , Spleen/metabolism , Splenectomy , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/metabolism , Transcriptional Activation , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/genetics , Vorinostat
15.
Am J Physiol Cell Physiol ; 294(3): C754-64, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18199702

ABSTRACT

Although splenic dendritic cell (DC) functions are markedly altered following trauma-hemorrhage, the mechanism(s) responsible for the altered DC functions remains unknown. We hypothesized that trauma-hemorrhage inhibits DC function via suppressing toll-like receptor 4 (TLR4) expression and mitogen-activated protein kinases (MAPKs). To examine this, male C3H/HeN (6-8 wk) mice were randomly assigned to sham operation or trauma-hemorrhage. Trauma-hemorrhage was induced by midline laparotomy and approximately 90 min of hypotension [blood pressure (BP) 35 mmHg], followed by fluid resuscitation (4x the shed blood volume in the form of Ringer lactate). Two hours later, mice were euthanized, splenic DCs were isolated, and the changes in their MAPK activation, TLR4-MD-2 expression, and ability to produce cytokines were measured. The results indicate that trauma-hemorrhage downregulated the lipopolysaccharide (LPS)-induced MAPK activation in splenic DCs. In addition to the decrease in MAPK activation, surface expression of TLR4-MD-2 was suppressed following trauma-hemorrhage. Furthermore, LPS-induced cytokine production from splenic DCs was also suppressed following trauma-hemorrhage. These findings thus suggest that the decrease in TLR4-MD-2 and MAPK activation may contribute to the LPS hyporesponsiveness of splenic DCs following trauma-hemorrhage. Hyporesponsiveness of splenic DCs was also found after stimulation with the TLR2 agonist zymosan. Our results may thus explain the profound immunosuppression that is known to occur under those conditions.


Subject(s)
Abdominal Injuries/complications , Cytokines/metabolism , Dendritic Cells/metabolism , Hemorrhage/metabolism , Inflammation Mediators/metabolism , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/metabolism , Spleen/metabolism , Abdomen/surgery , Abdominal Injuries/enzymology , Abdominal Injuries/immunology , Abdominal Injuries/metabolism , Animals , Cells, Cultured , Dendritic Cells/drug effects , Dendritic Cells/enzymology , Dendritic Cells/immunology , Disease Models, Animal , Down-Regulation , Enzyme Activation , Hemorrhage/etiology , JNK Mitogen-Activated Protein Kinases/metabolism , Lipopolysaccharides/pharmacology , Lymphocyte Antigen 96/metabolism , MAP Kinase Signaling System/drug effects , Male , Mice , Mice, Inbred C3H , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Spleen/drug effects , Spleen/enzymology , Spleen/immunology , Time Factors , Toll-Like Receptor 2/agonists , Toll-Like Receptor 4/metabolism , Zymosan/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism
16.
Ann Surg ; 245(2): 297-304, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17245185

ABSTRACT

OBJECTIVE: To determine the mechanism by which flutamide administration following trauma-hemorrhage (T-H) decreases cytokine production and hepatic injury under those conditions. SUMMARY BACKGROUND DATA: Although studies have demonstrated that flutamide administration following T-H improves hepatic and immune functions, the mechanism by which flutamide produces the salutary effects remains unknown. METHODS: Male Sprague-Dawley rats underwent a 5-cm laparotomy and hemorrhagic shock (40 mm Hg for approximately 90 minutes), followed by resuscitation with 4 times the shed blood volume in the form of Ringer's lactate. Flutamide (25 mg/kg body weight, sc) was administered at the middle of resuscitation and animals were killed 2 hours thereafter. To block estrogen receptor (ER), ER antagonist ICI 182,780 was administrated with flutamide. RESULTS: Hepatic injury, myeloperoxidase activity, nuclear factor-kappaB (NF-kappaB) DNA binding activity and protein expression of intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-3) markedly increased following T-H. Hepatic mRNA and plasma IL-6 levels were also elevated following T-H. The alterations in these parameters induced by T-H were significantly attenuated by flutamide administration. The decreased plasma estradiol levels following T-H were restored to sham levels in the flutamide-treated T-H animals. Coadministration of ICI 182,780 prevented those salutary effects of flutamide administration on pro-inflammatory responses and hepatic injury following T-H. CONCLUSION: These findings suggest that the reduction in the production of pro-inflammatory mediators and hepatic injury produced by flutamide administration following T-H is likely due to the down-regulation in hepatic NF-kappaB DNA binding activity. Moreover, the salutary effects of flutamide administration appear to be mediated at least in part via ER-related pathway.


Subject(s)
Abdominal Injuries/complications , Androgen Antagonists/therapeutic use , Flutamide/therapeutic use , Interleukin-6/biosynthesis , Liver Diseases/drug therapy , Receptors, Estrogen/metabolism , Shock, Hemorrhagic/complications , Abdominal Injuries/metabolism , Animals , Chemokine CXCL1 , Chemokines, CXC/biosynthesis , Disease Models, Animal , Electrophoresis , Enzyme-Linked Immunosorbent Assay , Intercellular Adhesion Molecule-1/biosynthesis , Intercellular Adhesion Molecule-1/genetics , Interleukin-6/blood , Interleukin-6/genetics , Laparotomy/adverse effects , Liver/metabolism , Liver Diseases/etiology , Liver Diseases/metabolism , Male , NF-kappa B/genetics , NF-kappa B/metabolism , Oligonucleotide Array Sequence Analysis , Peroxidase/metabolism , Prognosis , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Shock, Hemorrhagic/metabolism
17.
Mol Cell Biochem ; 291(1-2): 161-6, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16733803

ABSTRACT

Reactive oxygen species have been implicated in the etiology of multiple organ dyspepsia syndrome and infection's complications in patients with trauma. But the oxidative stress and antioxidants levels in abdominal trauma have not yet been studied. Therefore, this study was planned to measure lipid peroxidation for oxidative stress and reduced glutathione, catalase and superoxide dismutase (SOD) for antioxidant levels in plasma & heamolysate of 30 patients with abdominal trauma and 30 controls. From this study we can summarize that there was an increase in oxidative stress and decrease in antioxidant levels (causing oxidative stress) on day zero in patients with abdominal trauma. This oxidative stress on day zero was not related to the development of complications. There was no significant difference in oxidative stress between patients with solitary and multiple abdominal organ injury and also between patients with hollow viscus injury and solid organ injury on day zero. From this study, we conclude that in patients with abdominal trauma there was increase in oxidative stress and decrease in antioxidant levels on day zero.


Subject(s)
Abdominal Injuries/metabolism , Oxidative Stress , Abdominal Injuries/enzymology , Adult , Antioxidants/metabolism , Case-Control Studies , Catalase/metabolism , Female , Glutathione/metabolism , Hemoglobins/metabolism , Humans , Kidney Function Tests , Lipid Peroxidation , Liver Function Tests , Male , Middle Aged , Superoxide Dismutase/metabolism
18.
Biomed Khim ; 51(3): 329-34, 2005.
Article in Russian | MEDLINE | ID: mdl-16104396

ABSTRACT

Platelet nitric oxide production has been investigated in patients with thoracic and abdominal wounds, thermal trauma, varicose disease, methanol and leponex poisoning. There is correlation between absolute platelets nitric oxide production and fibrinogen plasma level in these patients. The maximal absolute platelets nitric oxide production has been revealed at surgical diseases, and minimal has been observed at methanol poisoning. Irrespectively to etiology and danger of disease, reliable correlation between absolute platelets nitric oxide production and fibrinogen plasma level of these patients is established. Consequently platelets nitric oxide production may be important for haemostatic processes.


Subject(s)
Blood Platelets/metabolism , Fibrinogen/metabolism , Nitric Oxide/biosynthesis , Abdominal Injuries/metabolism , Burns/metabolism , Clozapine/poisoning , Emergencies , Humans , Methanol/poisoning , Thoracic Injuries/metabolism , Varicose Veins/metabolism , Wounds, Penetrating/metabolism
19.
Patol Fiziol Eksp Ter ; (4): 24-5, 2004.
Article in Russian | MEDLINE | ID: mdl-15568500

ABSTRACT

An experimental study on 62 guinea pigs was made to examine a magnetic-laser effect on the levels of histamin, serotonin, catecholamine, heparin and pathomorphology of wound healing after operations in the abdominal cavity. Magnetolaser therapy promotes fast normalization of the above levels, suppression of inflammatory-necrotic processes and stimulation of reparative and regenerative processes.


Subject(s)
Abdominal Injuries/radiotherapy , Biogenic Amines/metabolism , Heparin/metabolism , Infrared Rays/therapeutic use , Low-Level Light Therapy , Wound Healing/radiation effects , Abdominal Injuries/metabolism , Animals , Disease Models, Animal , Guinea Pigs , Intestine, Large/injuries , Intestine, Large/radiation effects
20.
J Trauma ; 56(5): 1068-74; discussion 1074-5, 2004 May.
Article in English | MEDLINE | ID: mdl-15179248

ABSTRACT

BACKGROUND: The initial assessment of the child with blunt injury should lead ideally to a low rate of missed intraabdominal injury (IAI) while avoiding unnecessary imaging among children without IAI. The purpose of this study was to determine the utility of clinical and laboratory data for predicting the risk for IAI. METHODS: Among 351 children evaluated for possible blunt abdominal trauma, 23 variables potentially associated with IAI were determined retrospectively. Logistic regression and recursive partitioning were used to identify variables and develop predictive models. RESULTS: Logistic regression identified four positive predictors (abdominal tenderness, abrasion, ecchymoses, and alanine aminotransferase) and two negative predictors (injury caused by a motor vehicle crash and hematocrit) for IAI. The recursive partitioning model predicted the absence of IAI with a sensitivity of 100% (95% CI confidence interval, 86-100%) and a specificity of 87% (95% CI confidence interval, 81-91%) using abdominal examination and aspartate aminotransferase as discriminating variables. CONCLUSIONS: Physical examination combined with selected laboratory studies can be used to predict the risk of IAI accurately among children who sustain blunt trauma. Application of these findings may be useful in reducing costs and improving the accuracy of diagnosing IAI among children.


Subject(s)
Abdominal Injuries/diagnosis , Clinical Laboratory Techniques/standards , Physical Examination , Wounds, Nonpenetrating/diagnosis , Abdominal Injuries/complications , Abdominal Injuries/metabolism , Accidents, Traffic/statistics & numerical data , Age Factors , Alanine Transaminase/blood , Algorithms , Child , Child, Preschool , Decision Trees , Discriminant Analysis , Ecchymosis/etiology , Female , Hematocrit , Humans , Lacerations/etiology , Logistic Models , Male , Missouri , Physical Examination/methods , Physical Examination/standards , Predictive Value of Tests , Retrospective Studies , Statistics, Nonparametric , Trauma Centers , Urinalysis/standards , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/metabolism
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