Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Histopathology has initially been and is still used to diagnose infectious, degenerative or neoplastic diseases in humans or animals. In addition to qualitative diagnoses semiquantitative scoring of a lesion`s magnitude on an ordinal scale is a commonly demanded task for histopathologists. Multiparametric, semiquantitative scoring systems for mouse models histopathology are a common approach to handle these questions and to include histopathologic information in biomedical research. Inclusion criteria for scoring systems were a first description of a multiparametric, semiquantiative scoring systems which comprehensibly describe an approach to evaluate morphologic lesion. A comprehensive literature search using these criteria identified 153 originally designed semiquantitative scoring systems for the analysis of morphologic changes in mouse models covering almost all organs systems and a wide variety of disease models. Of these, colitis, experimental autoimmune encephalitis, lupus nephritis and collagen induced osteoarthritis colitis were the disease models with the largest number of different scoring systems. Closer analysis of the identified scoring systems revealed a lack of a rationale for the selection of the scoring parameters or a correlation between scoring parameter value and the magnitude of the clinical symptoms in most studies. Although a decision for a particular scoring system is clearly dependent on the respective scientific question this review gives an overview on currently available systems and may therefore allow for a better choice for the respective project.

/pdf/multiparametric-and-semiquantitative-scoring-systems-for-the-3upih0ang8.pdf

Multiparametric and semiquantitative scoring systems for the evaluation of mouse model histopathology - a systematic review

https://www.annalsthoracicsurgery.org/article/S0003-4975(07)00977-0/pdf

Oxidative Stress and Atrial Fibrillation After Cardiac Surgery: A Case-Control Study

Background
Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to neuronal damage and behavioral impairment. Toll-like receptors (TLRs) are signaling receptors in the innate immune system, although emerging evidence indicates their role in brain injury. We have therefore investigated the role played by TLR4 signaling pathway in the development of mechanisms of secondary inflammatory process in traumatic brain injury (TBI) differ in mice that lack a functional TLR4 signaling pathway.

/pdf/absence-of-tlr4-reduces-neurovascular-unit-and-secondary-4wpctqi7s5.pdf

Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice.

Activation of peroxisome proliferator-activated receptor (PPAR)-alpha, a member of the nuclear receptor superfamily, modulates inflammation and tissue injury events associated with spinal cord trauma in mice Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through a mechanism dependent on PPAR-alpha activation The aim of the present study was to evaluate the effect of the PEA on secondary damage induced by experimental spinal cord injury (SCI) in mice SCI was induced by application of vascular clips to the dura mater via a four-level T(5)-T(8) laminectomy This resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, and apoptosis Repeated PEA administration (10 mg/kg ip; 30 min before and 1 and 6 h after SCI) significantly reduced: 1) the degree of spinal cord inflammation and tissue injury, 2) neutrophil infiltration, 3) nitrotyrosine formation, 4) proinflammatory cytokine expression, 5) nuclear transcription factor activation-kappaB activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis Moreover, PEA treatment significantly ameliorated the recovery of motor limb function Together, the results indicate that PEA reduces inflammation and tissue injury associated with SCI and suggest a regulatory role for endogenous PPAR-alpha signaling in the inflammatory response associated with spinal cord trauma

/pdf/effects-of-palmitoylethanolamide-on-signaling-pathways-xjqvfdo78u.pdf

Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury.

Background Trimetazidine is an anti-ischemic agent that is used to treat angina and it has cardioprotective effects without inducing any significant hemodynamic changes. It inhibits the long-chain mitochondrial 3-ketoacyl coenzyme A thiolase enzyme in the myocyte and can improve cardiac mitochondrial metabolism, as well as scavenge free radicals. The aim of this double-blind prospective randomized study was to investigate the effect of preoperative use of trimetazidine on the reduction of oxidative stress during coronary artery bypass grafting (CABG) under cardiopulmonary bypass (CPB). Methods and Results The study group (group T) and the control group (group C) each comprised 12 patients. Pretreatment began 2 weeks before CABG with trimetazidine (60 mg/day po); the control group did not receive any medication. Serial blood samples were collected before and after CPB for measurement of the serum concentrations of these major endogenous antioxidant enzyme systems, which are markers for oxidative degradation of the cellular membranes; postoperative levels were significantly different between the groups (p<0.05). There were no significant difference in hemodynamic values. Conclusion The findings suggest that pretreatment with trimetazidine alleviates malondialdehyde production and preserves endogenous antioxidant capacity during CABG with CPB and cardioplegic arrest. (Circ J 2006; 70: 1169 - 1173)

Trimetazidine reduces oxidative stress in cardiac surgery.

Objective - Paraplegia remains a devastating complication after thoracic and thoracoabdominal aortic surgery for coarctations, dissections or aneurysms. Since the advent of ischaemic preconditioning of the myocardium, attention has been directed to the nervous system. This study was designed to evaluate the acute protective effect of ischaemic preconditioning on the spinal cord. Medhods and results - Thirty-six New Zealand white rabbits were randomly assigned to one of three groups. The preconditioning group had 5 minutes of aortic occlusion, 25 minutes reperfusion and 20 minutes of ischaemia, whereas the controls had only 20 minutes of ischaemia.The sham group was anaesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked potentials were monitored during the experiment. Neurological outcome was clinically evaluated up to 48 hour after ischaemia and motor function was scored.Then the animals were sacrificed. Their spinal cord, abdominal aorta and its branches were removed and processed for histopathological examination. Histhopathological changes of the gray matter in the lumbosacral segments were scored from 0 to 6 according to a semi-quantitative scala. The changes in amplitudes of evoked potentials during ischaemia and recovery periods were similar in preconditioning and control groups. The average motor function score was significantly higher in the preconditioning group than the control group at 24 and 48 hours after the ischaemic event (p < 0.05). Histological observations were consistent with the neurological findings. The histopathological scores in the control group and the preconditioning group were 3.2 (1.4-5.2) and 2.4 (0.8-4.4), respectively (p < 0.05). Conclusions - The results suggest that ischaemic preconditioning reduces the spinal cord injury and improves neurological outcome in transient ischaemia in rabbits. This protective mechanism is rapidly invoked within only 25 minutes interval between the preconditioning stimulus and the ischaemic insult.

Ischaemic preconditioning reduces spinal cord injury in transient ischaemia.

Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery.

Background: Trimetazidine is an anti-ischemic agent with cardioprotective effects. The purpose of this double-blind, controlled, prospective randomized study was to investigate the possible effects of the preoperative use of trimetazidine on the biochemical markers of myocardial injury during open heart surgery and to determine if it has any myocardial protective effects.Methods: Thirty patients undergoing coronary artery bypass grafting surgery, received either trimetazidine (study group, n = 15) or not (control group, n = 15). Pretreatment began 2 weeks before the operation with trimetazidine (60 mg/day orally), and the control group received no medication. We measured the levels of serum creatine kinase (CK), CK isoenzyme MB (CK-MB), myoglobin, and troponin T in venous blood samples obtained before and after the operation to evaluate the effect of this drug against myocardial damage. We also took serial blood samples from the radial artery and the coronary sinus before the institution of cardiopulmonary bypass (CPB) and at 2 and 15 minutes after the removal of the cross-clamp to measure lactate levels and calculate the lactate extraction of the myocardium.Results: Postoperative levels of myoglobin, troponin T, CK, and CK-MB were significantly lower in the trimetazidine group than in the control group (P < .05). There was also a significant difference in the values for the lactate extraction calculation between the groups at minute 2 after the removal of the cross-clamp (P < .05).Conclusion: We conclude that pretreatment with trimetazidine has some beneficial effects in protecting the myocardium and decreasing myocardial injury during the cardioplegic arrest period in open heart surgery without affecting postoperative hemodynamics.

Trimetazidine May Protect the Myocardium during Cardiac Surgery

Background. Cardiac surgery is associated with an inflammatory response that may cause myocardial dysfunction after cardiopulmonary bypass. We examined the efficacy of pentoxifylline to attenuate the cardiopulmonary bypass-induced inflammatory response during heart operations. Methods. In a prospective, randomized study, 30 patients undergoing coronary artery bypass graft surgery received either pentoxifylline (group P, n = 15) (continuous infusion of 1.5 mg/kg per hour during operation) or not (group C [control], n = 15). Blood samples for measurements of tumor necrosis factor (TNF)-?, interleukin (IL)-6, IL-8, and IL-10 were taken from the arterial line in both groups at 5 different time points. Results. TNF-?, IL-6, and IL-8 plasma levels increased in both groups after cardiopulmonary bypass, with a higher increase in the control group ( P Conclusions. Our results indicate that pentoxifylline infusion during cardiac surgery inhibits the proinflammatory cytokine release caused by cardiopulmonary bypass.

Mustafa Cerrahoglu

Papers

Trimetazidine reduces oxidative stress in cardiac surgery.

Ischaemic preconditioning reduces spinal cord injury in transient ischaemia.

Immune and inflammatory role of hydroxyethyl starch 130/0.4 and fluid gelatin in patients undergoing coronary surgery.

Trimetazidine May Protect the Myocardium during Cardiac Surgery

Pentoxifylline affects cytokine reaction in cardiopulmonary bypass.