Antioxidant effects of phytosterol and its components

Phytosterol contained in vegetable oils is known to exert a hypocholesterolemic function. In the present study, the antioxidant effects of phytosterol and its components, beta-sitosterol, stigmasterol, and campesterol, against lipid peroxidation were examined by making a comparison with 2,2,5,7,8-pentamethyl-6-chromanol (PMC). It was found that these compounds exerted antioxidant effects on the oxidation of methyl linoleate in solution and its effect decreased in the order of: PMC > phytosterol approximately campesterol approximately beta-sitosterol > stigmasterol. Phytosterol also suppressed the oxidation and consumption of alpha-tocopherol in beta-linoleoyl-gamma-palmitoyl phosphatidylcholine (PLPC) liposomal membranes, the effects being more significant than dimyristoyl PC of the same concentration. Stigmasterol accelerated the oxidation of both methyl linoleate in solution and PLPC liposomal membranes in aqueous dispersions, which was ascribed to the oxidation of allylic hydrogens at the 21- and 24-positions. Taken together, the present study shows that phytosterol chemically acts as an antioxidant, a modest radical scavenger, and physically as a stabilizer in the membranes.     

Facilitation of ischemia-induced release of dopamine and neuronal damage by dexamethasone in the rat striatum

Glucocorticoids have been reported to aggravate ischemia-induced neuronal damage in both humans and experimental animals. Because an excess release of neurotransmitters is closely related to the outcome of ischemic neuronal damage, we evaluated the effects of dexamethasone on monoaminergic release and histological outcome. Changes in the extracellular concentrations of monoamines and their metabolites in the striatum produced by occlusion of the middle cerebral artery for 20 min were measured using a microdialysis high-performance liquid chromatography procedure, and the effects of intracerebroventricular administration of dexamethasone (10 microg) were evaluated in halothane-anesthesized rats. The histological outcome was evaluated by light microscopy 7 days after ischemia. Additionally, the effects of lesioning of the substantia nigra were estimated. The extracellular concentrations of neither dopamine nor serotonin were affected by the administration of dexamethasone in the nonischemic state. The occlusion of the middle cerebral artery produced a marked increase in the extracellular concentration of dopamine in the striatum, the peak value being 240 times that before ischemia. The preischemic administration of dexamethasone enhanced the increase in dopamine level during ischemia, and the peak value in the dexamethasone group was 640% of that in the vehicle group. After 7 days, ischemic neuronal damage in the dexamethasone group was severe compared with that in the vehicle group. In rats receiving the substantia nigra lesion, the ischemic release of dopamine was abolished, and the aggravation of ischemic neuronal damage by dexamethasone was completely alleviated. Changes in the release of monoamines may be a contributing factor in the development of the ischemic neuronal damage induced by glucocorticoids.     

Cross-sectional area of a bone-patellar tendon-bone graft for anterior cruciate ligament reconstruction

The cross-sectional area of the 10-mm wide patellar tendon graft was measured in 50 consecutive patients (31 males and 19 females) who underwent isolated anterior cruciate ligament (ACL) reconstruction and the relationship between the graft size and various factors such as physical characteristics was assessed. The effect of cross-sectional area of the implanted graft on postoperative stability of the reconstructed knee also was examined. Mean patient age at surgery was 22.3 years (range: 14-40 years). The cross-sectional area was measured using an instrumented area micrometer intraoperatively, and correlations between the measured value and various factors such as age, gender, height, body weight, and bony geometry were examined. Follow-up was performed 24 months postoperatively. The average cross-sectional graft area was 33.4 mm2. The measured cross-sectional area was larger in male patients and correlated with physical characteristics such as height, body weight, and femoral condyle width. No significant correlation between the size of the graft and postoperative stability was observed.     

Nitroprusside-induced hemodynamic alterations in normotensive and hypertensive pregnant sheep

It has been suggested that sodium nitroprusside, a potent vasodilator, be used in the management of an acute hypertensive crisis during pregnancy. The present study was designed to evaluate the hemodynamic effects of this agent in the same group of chronically instrumented, unanesthetized pregnant sheep during two experimental periods: (a) normotension with intact kidneys, and (b) one-kidney hypertension. The results demonstrate that (1) nitroprusside is a potent vasodilator which lowers mean arterial pressure; (2) nitroprusside-induced tachycardia was greater in the hypertensive animal; (3) uterine blood flow decreased with the development of hypertension; (4) the hypertensive-induced reduction in uterine blood flow was increased by the infusion of nitroprusside.     

Biomechanical analysis of supra-acetabular insufficiency fracture using finite element analysis

Background

Supra-acetabular insufficiency fractures (SAIFs) occur in the upper acetabulum and are rare compared with insufficiency sacral, femoral head, or ischial fractures. However, SAIFs are known to occur in low grade trauma, and the underlying mechanism is still remained unclear.

Acetabular reinforcement ring with additional hook improves stability in three-dimensional finite element analyses of dysplastic hip arthroplasty

Background

The stability of acetabulum reconstructions using reinforcement rings and hooks is important for successful replacement surgery. The objective of this study was to biomechanically determine the effects of the hook on stress and the related micromotions of the acetabular reinforcement ring during the immediate postoperative period.

Methods

Acetabular reinforcement ring models were developed using a nonlinear, three-dimensional, finite element method. Using a pre-prepared template, we constructed without-hook and bone graft models of varying volumes and material properties.

Results

The stress on the inferior margin of the acetabulum was higher in the with-hook model than in the without-hook model, especially with increased bone graft volumes, and the stiffness of the bone graft material was decreased. Relative micromotions in the without-hook model were higher than in the with-hook models. The highest relative micromotion was observed in the model with increased bone graft volume and lower stiffness of bone graft material.

Conclusions

In biomechanical analyses, the hook effectively dispersed stress and improved the initial fixation strength of the acetabular reinforcement ring.

     

Inhibitory effect of the 4-aminotetrahydroquinoline derivatives, selective chemoattractant receptor-homologous molecule expressed on T helper 2 cell antagonists, on eosinophil migration induced by prostaglandin D2

Prostaglandin (PG) D2, a major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is known to induce activation and chemotaxis in eosinophils, basophils, and T helper 2 (Th2) lymphocytes via a newly identified PGD2 receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). CRTH2 is hypothesized to play an important role in the outcome of allergic responses. However, the absence of selective CRTH2 antagonists has prevented the elucidation of the role of CRTH2 in pathogenesis of allergic diseases. We now report compounds discovered as selective CRTH2 antagonists, (2R*,4S*)-N-(1-benzoyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-phenylisobutyramide (K117) and (2R*,4S*)-N-(1-benzoyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-N-phenylcyclopropanecarboxamide (K604). K117 and K604 have inhibitory effects on human CRTH2 with Ki values of 5.5 and 11 nM, respectively. The effect of these compounds is CRTH2-specific with no cross-reactivity against 15 other receptors and four arachidonic acid-metabolizing enzymes. K117 and K604 has no effect on the basal Ca2+ level and inhibited the Ca2+ response induced by PGD2 in 293EBNA cells expressing human CRTH2. Also, K117 and K604 inhibit PGD2-induced human eosinophil chemotaxis with IC50 values of 7.8 and 42.2 nM, respectively, but they do not inhibit the CC-chemokine receptor 3 agonist eotaxin-induced chemotaxis. These results indicate that K117 and K604 are highly potent and selective antagonists for human CRTH2. These compounds have possibilities to become useful tools to explore CRTH2 functions in allergic diseases.     

Application of an automated cardiopulmonary resuscitation device for kidney transplantation from uncontrolled donation after cardiac death donors in the emergency department

Morozumi J, Matsuno N, Sakurai E, Nakamura Y, Arai T, Ohta S. Application of an automated cardiopulmonary resuscitation device for kidney transplantation from uncontrolled donation after cardiac death donors in the emergency department.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01140.x.
© 2009 John Wiley & Sons A/S. Abstract: Vital‐organ transplantation has become acceptable as the treatment of choice for end‐stage organ failure. If the patient, facing the end of life, wishes to donate organs after cardiac arrest (CA), donation after cardiac death (DCD) is increasingly important for the realization of the patient’s desires after CA. In Japan, kidney transplantation from uncontrolled DCD donors, who are identified in modified Maastricht categories II or V, is one of the critical factors in expanding the donor pool. However, according to the forensic code for post‐mortems and the requirement of legal consent for transplantation, the time required to meet all procedural requirements has sometimes prohibited organ procurement from uncontrolled DCD donors. We have therefore attempted to use an automated cardiopulmonary resuscitation (CPR) device and maintain arterial pressure for uncontrolled DCD donors during all interim procedures after sudden CA. Comparing kidneys procured from standard DCD donors (n = 10) and uncontrolled DCD donors (n = 4), significant differences were seen in warm ischemic time (WIT), defined as the time from CA to initiation of cooling in situ. However, our early experience showed good tolerance and viability of uncontrolled DCD kidneys. Immediate availability of an automated CPR device might provide a bridge to kidney procurement from uncontrolled DCD donors.