Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection.

T cells mediating chronic rejection (CR) of human kidney allografts were characterized by comparing them with those mediating acute rejection (AR). Two lines of analysis were performed using biopsy specimens (23 CR and 8 AR). First, the extent of infiltration of CD4+ and CD8+ T cells into allografts was assessed from mRNA expression of CD4 and CD8. The group of CR specimens was not significantly different from the group of AR specimens in terms of the extent of CD4+ and CD8+ T cell infiltration, underlining the importance of the immunological contribution to the progress of CR. Second, Th1/Th2 polarization in infiltrating T cells was investigated by measuring mRNA expression of interferon gamma (IFN-gamma; a Th1 cytokine) and interleukin 4 (IL-4; a Th2 cytokine). IFN-gamma expression was detected in most CR specimens, and was not significantly different between the group of CR specimens and the group of AR specimens. On the other hand, IL-4 expression was detected in only two CR specimens and one AR specimen; from its pathological features, the AR in this last case was concomitant with CR. These results suggest that most cases of CR and of AR are mediated by Th1 mechanisms, although some cases of CR show features of both Th1 and Th2.

Methylprednisolone reduces spinal cord injury in rats without affecting tumor necrosis factor-alpha production.

Methylprednisolone (MPS) is the only therapeutic agent currently available for traumatic spinal cord injury (SCI). However, little is known about its therapeutic mechanisms. We have demonstrated that tumor necrosis factor-alpha (TNF-alpha) plays a critical role in posttraumatic SCI in rats. Since MPS has been shown to inhibit TNF-alpha production in vitro, it is possible that MPS can reduce SCI by inhibiting TNF-alpha production. To examine this possibility, we investigated the effect of MPS on TNF-alpha production in injured segments of rat spinal cord. Leukocytopenia and high-dose intravenous administration of MPS markedly reduced the motor disturbances observed following spinal cord trauma. Both treatments also reduced the intramedullary hemorrhages observed histologically 24 hr posttrauma. Leukocytopenia significantly reduced tissue levels of both TNF-alpha mRNA and TNF-alpha, 1 and 4 hr posttrauma, respectively, and it also inhibited the accumulation of leukocytes in the injured segments 3 hr posttrauma, while MPS had no effects. Lipid peroxidation and vascular permeability at the site of spinal cord lesion were both significantly increased over time after the induction of SCI, peaking 3 hr posttrauma. These events were significantly reduced in animals with leukocytopenia and in those given anti-P-selectin monoclonal antibody compared to sham-operated animals. Administration of MPS significantly inhibited both the increase in lipid peroxidation and the vascular permeability. These findings suggested that MPS reduces the severity of SCI, not by inhibiting the production of TNF-alpha at the site of spinal cord trauma, but by inhibiting activated leukocyte induced lipid peroxidation of the endothelial cell membrane. This suggests that MPS may attenuate spinal cord ischemia by inhibiting the increase in endothelial permeability at the site of spinal cord injury.

Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation.

OBJECTIVE: To examine whether activated protein C (APC) reduces spinal cord injury in rats by inhibiting neutrophil activation after the transient ischemia. SUMMARY BACKGROUND DATA: Ischemic spinal cord injury is an important pathologic mechanism leading to the paraplegia observed after surgery to repair aortic aneurysms. Activated neutrophils play a pivotal role in the development of ischemia/reperfusion-induced tissue injury. Recently, the authors have reported that APC, a physiologic anticoagulant, prevents lipopolysaccharide-induced pulmonary vascular injury by inhibiting neutrophil activation. These observations strongly suggest that APC reduces ischemia/reperfusion-induced spinal cord injury by inhibiting neutrophil activation. METHODS: In rats, spinal cord ischemia was induced by using a balloon catheter placed into the aorta. After the transient ischemia, survival and motor function were evaluated, and histologic examination of the spinal cord was performed by using both hematoxylin-and-eosin staining and 2,3,5, -triphenyltetrazolium chloride (TTC) staining 24 hours after the ischemia. Tissue levels of myeloperoxidase and cytokines, including tumor necrosis factor-alpha (TNF-alpha) and rat interleukin-8, were measured in six experimental groups: sham-operated, control, APC (100 microg/kg, intravenous), dansyl glutamyl-glycyl-arginyl chloromethyl ketone-treated activated factor X (DEGR-F.Xa), a selective inhibitor of thrombin generation (1 mg/kg, intravenous), nitrogen mustard-induced leukocytopenia, and diisopropyl fluorophosphate-treated APC (DIP-APC), active site-blocked APC (100 microg/kg, intravenous). APC, DEGR-F.Xa, and DIP-APC were administered intravenously 30 minutes before aortic occlusion. Control and leukocytopenic rats received saline instead of other drugs. RESULTS: Pretreatment with APC significantly reduced motor disturbances compared with those in control animals. In contrast, neither DEGR-F.Xa nor DIP-APC had any effect. Microinfarctions, evidenced by the absence of TTC staining and histologic change, were markedly reduced in animals given APC. The increases in the tissue levels of TNF-alpha, rat interleukin-8, and myeloperoxidase in the ischemic part of the spinal cord were significantly reduced in animals that received APC. These levels were not reduced in rats given DEGR-F.Xa or DIP-APC. Leukocytopenia produced effects similar to those of APC. CONCLUSIONS: APC reduced the ischemia/reperfusion-induced spinal cord injury by inhibiting neutrophil activation. The therapeutic mechanisms of APC might depend on its inhibitory effect on the production of TNF-alpha, which is a potent activator of neutrophils. Although the anticoagulant effects of APC might not be related to its ability to inhibit TNF-alpha production, its serine protease activity appears to be essential in the therapeutic mechanism. APC appears to have potential as a therapeutic agent for prevention of spinal cord injury in patients undergoing aortic aneurysm repair.

Neuroprotection by recombinant thrombomodulin.

We examined whether recombinant human soluble thrombomodulin (rhs-TM) reduces compression trauma-induced spinal cord injury through protein C activation in rats. Administration of rhs-TM, either before or after the induction of spinal cord injury (SCI), markedly reduced the resulting motor disturbances. However, neither rhs-TM pretreated with an anti-rhs-TM monoclonal antibody (MAb) F2H5, which inhibits thrombin binding to rhs-TM, nor those pretreated with MAb R5G12, which selectively inhibits protein C activation by rhs-TM, prevented the motor disturbances. Intramedullary hemorrhages, observed 24 h after trauma, were significantly reduced in animals given rhs-TM. The increase in the tissue levels of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha mRNA expression, and the accumulation of leukocytes in the damaged segment of the spinal cord were significantly inhibited in animals receiving rhs-TM, but these effects were not observed following administration of rhs-TM pretreated with MAb R5G12 or MAb F2H5. Leukocytopenia and activated protein C all produced effects similar to those of rhs-TM. These findings suggest that rhs-TM prevents compression trauma-induced SCI by inhibiting leukocyte accumulation by reducing the expression of TNF-alpha mRNA and such therapeutic effects of rhs-TM could be dependent on its protein C activation capacity. Findings further suggest that thrombomodulin can be implicated not only in the coagulation system but in regulation of the inflammatory response.

Role of leukocytes in spinal cord injury in rats.

Spinal cord injury (SCI) is a serious condition that produces life-long disabilities. Only limited therapeutic measures are currently available for its treatment. This review describes the role of leukocytes in pathologic mechanisms of trauma-induced SCI in rats, which contributes to new understanding of the pathologic process involved in SCI and could lead to the development of new therapeutic strategies by which leukocyte activation can be regulated. SCI induced by trauma is a consequence of an initial physical insult that is followed by a progressive injury process which involves various pathochemical events that lead to tissue destruction. Therapeutic intervention in SCI should therefore be directed at reducing or alleviating this secondary process. Although the mechanisms are not fully understood, progressive vascular events, especially activated neutrophil-induced endothelial cell damage, have been shown to be implicated. We have found that some therapeutic agents, which inhibit leukocyte activation directly or indirectly, alleviate the motor disturbances observed in a rat model of SCI. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute SCI, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that pharmacological agents that inhibit leukocyte activation used in conjunction with MPS or GM1 may have a synergistic effect in the clinical treatment of traumatic SCI in humans.

Effects of EPC-K1 on lipid peroxidation in experimental spinal cord injury.

STUDY DESIGN: A study in which levels of lipid peroxidation were measured, the thiobarbituric acid-reactive substances were estimated in an experimental rat model, and the recovery was assessed. OBJECTIVE: To ascertain the occurrence of thiobarbituric acid-reactive substances in the damaged spinal cord, and to investigate the effectiveness of a hydroxyl radical scavenger EPC-K1, a phosphate diester linkage of vitamins E and C, in attenuating the severity of spinal cord injury. SUMMARY OF BACKGROUND DATA: Lipid peroxidation has been reported to play an important role in spinal cord injury. There is no report on the use of EPC-K1 to attenuate the severity of spinal cord injury in either animal or human studies. METHODS: Spinal cord injury was induced by placing a 25-g weight on T12, and the animals were divided into six groups. Group 1 (sham) received only laminectomy. Group 2 (control) received spinal cord injury. Group 3 received EPC-K1 5 minutes before injury. Group 4 received it 5 minutes after injury. Group 5 received it 3 hours after injury. Group 6 received it five times, respectively: at 5 minutes, then 1, 2, 3, and 4 hours after injury. The levels of thiobarbituric acid-reactive substances were measured in the spinal cord, and the recovery was assessed. RESULTS: The thiobarbituric acid-reactive substances content increased after injury, with two peaks, at 1 and 4 hours. Concentration at the 4-hour peak was lower in nitrogen mustard-induced leukocytopenia rats than in the control rats. The EPC-K1 injection reduced thiobarbituric acid-reactive substances content at 1 and 4 hours after injury in Group 3 (respectively, 34.3% and 42.7% vs. control) and only that at 4 hours in Group 6 (24.9% vs. control). Motor function recovery and histologic findings were better in these two groups than in Group 2. CONCLUSION: Repeated injection of EPC-K1 attenuated the severity of spinal cord injury.

The long-term effects of pre-treatment with activated protein C in a rat model of compression-induced spinal cord injury.

OBJECTIVES: Recently, we demonstrated that activated protein C (APC) can lessen the severity of spinal cord injury (SCI) in rats during the acute and subacute phases. The purpose of the present study is to determine the long-term effects of pre-treatment with APC following SCI in rats. METHODS: The motor function of rats was assessed using the inclined-plane test during 8 weeks after SCI, and the grid runway test 7 weeks after the trauma. Somatosensory evoked potentials (SEPs), brainstem-derived motor evoked potentials (B-MEPs) and corticomotor evoked potentials (CMEPs) were used to quantify axonal function 8 weeks after SCI. Morphometric analysis of the spinal cord lesion was carried out to determine lesion size. Twelve male Sprague-Dawley rats were randomly allocated to either APC (25 IU/kg) or saline group and then subjected to 20 g compression injury of the spinal cord for 20 min at T12. The sham group (n=6) received laminectomy alone. RESULTS: APC significantly reduced the motor disturbances and electrophysiological impairments induced by SCI. APC-treated animals also showed a trend towards a reduction in lesion size. However, this change, was not significant. CONCLUSION: Pre-treatment with APC attenuates the harmful effects of SCI not only during the acute and subacute phases but also in the chronic stage.

Regional left ventricular myocardial contraction abnormalities and asynchrony in patients with hypertrophic cardiomyopathy evaluated by magnetic resonance spatial modulation of magnetization myocardial tagging.

Global left ventricular (LV) pump function is generally preserved in patients with hypertrophic cardiomyopathy (HCM). However, it is unknown whether regional myocardial contractility is impaired, especially in nonhypertrophied regions. The purpose of this study was to evaluate regional LV myocardial contraction in patients with HCM using magnetic resonance (MR) spatial modulation of magnetization (SPAMM) myocardial tagging. The study group comprised 20 patients with asymmetric septal hypertrophy (HCM group) and 16 age-matched normal patients (control group), and data were collected using transthoracic M-mode and 2-dimensional echocardiography, and MR SPAMM myocardial tagging. The systolic strain ratio, maximum systolic strain velocity, and time from end-diastole to maximum systolic strain (deltaT) in the anterior, ventricular septal, inferior and lateral regions for 2 LV short-axis sections at the levels of the chordae tendineae and papillary muscles were measured at 50-ms intervals by MR myocardial tagging. The end-diastolic anterior and ventricular septal wall thicknesses and LV mass index were significantly different between the HCM and control groups. The systolic strain ratio for all 4 walls, particularly the anterior and ventricular septal regions, was significantly lower in the HCM group. In the HCM group, the maximum systolic strain velocity was significantly lower and deltaT was significantly shorter for all 4 walls, particularly the anterior and ventricular septal regions. The standard deviation for the deltaT, calculated from the deltaT for the 8 regions of the 2 LV short-axis sections, was significantly greater in the HCM group. In conclusion, regional LV myocardial contraction is impaired in both hypertrophied and nonhypertrophied regions, and systolic LV wall asynchrony occurs in patients with HCM.

Spinal cord injury in the rat.

Only limited therapeutic measures are currently available for the treatment of spinal cord injury. This review describes the pathologic mechanisms of trauma-induced spinal cord injury in rats, which will contribute to new understanding of the pathologic process leading to spinal cord injury and to further development of new therapeutic strategies. Spinal cord injury induced by trauma is a consequence of an initial physical insult and a subsequent progressive injury process that involves various pathochemical events leading to tissue destruction; the latter process should therefore be a target of pharmacological treatment. Recently, activated neutrophils have been shown to be implicated in the latter process of the spinal cord injury in rats. Activated neutrophils damage the endothelial cells by releasing inflammatory mediators such as neutrophil elastase and oxygen free radicals. Adhesion of activated neutrophils to the endothelial cell could also play a role in endothelial cell injury. This endothelial cell injury could in turn induce microcirculatory disturbances leading to spinal cord ischemia. We have found that some therapeutic agents that inhibit neutrophil activation alleviate the motor disturbances observed in the rat model of spinal cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that other pharmacological agents that inhibit neutrophil activation used in conjunction with MPS or GM1 ganglioside may have a synergistic effect in the treatment of traumatic spinal cord injury in humans.

Role of neutrophil elastase in compression-induced spinal cord injury in rats.

We have previously demonstrated the importance of activated neutrophils in compression-induced spinal cord injury (SCI) in rats. In the present study, we investigate the action of neutrophil elastase in posttraumatic SCI, using two neutrophil elastase inhibitors (Eglin C and L658,758). SCI was induced by applying a 20-g weight to the spinal cord for 20 min at the level of T12, resulting in hindlimbs motor disturbances, which, when evaluated using a inclined-plane test, were significantly attenuated by Eglin C or L658,758. Histologic examination revealed that intramedullary hemorrhages observed 24 h after trauma were markedly attenuated in these agents. These inhibitors also significantly decreased neutrophil accumulation as shown by myeloperoxidase activity in the damaged spinal cord segment. Induction of leukocytopenia had the same effects as Eglin C or L658,758. These findings implicated neutrophil elastase in SCI. The enzyme may induce vascular damage leading to spinal cord ischemia.

Coronary-pulmonary artery fistulae depicted by multiplanar reconstruction using magnetic resonance imaging.

We compared the imaging capability of magnetic resonance angiography (MRA) with that of conventional coronary angiography in a patient with coronary-pulmonary fistulae. Using the latter procedure, it is difficult to measure abnormal tortuous blood vessels in one section. However, the course of blood vessels could be evaluated quite well by rearranging serial cross-sectional MRA images using multiplanar reconstruction (MPR). This procedure allowed us to determine the anatomic positional relationship of these vessels to the peripheral cardiac great vascular system. MPR may detect sites of influx and outflow of abnormal blood vessels.

Activated protein C reduces the severity of compression-induced spinal cord injury in rats by inhibiting activation of leukocytes.

Activated protein C (APC), an important inhibitor of the coagulation system, has recently been shown to prevent tissue injury by blocking the activation of leukocytes. To determine whether APC can also prevent post-traumatic spinal cord injury (SCI), a condition in which leukocytes play an important role, we tested the effects of APC on SCI induced in rats by compression trauma. Administration of APC, either before or after the induction of SCI, markedly reduced the motor disturbances in these animals. In contrast, neither an inactive derivative of activated factor X (DEGR-Xa), a selective inhibitor of thrombin generation, nor active site-blocked APC (DIP-APC) reduced the motor disturbances. Histological examination revealed that intramedullary hemorrhages, observed 24 hr after trauma, were significantly reduced in the animals administered APC. The increase in the tissue level of tumor necrosis factor-alpha (TNF-alpha) and the accumulation of neutrophils in the damaged segment of the spinal cord were significantly inhibited in the animals that had received APC, but these were not inhibited in those administered DIP-APC or DEGR-Xa. The induction of leukocytopenia had the same effect as APC, in that it significantly reduced motor disturbances, tissue levels of TNF-alpha, and neutrophil accumulation in the animals subjected to compressive SCI. These findings suggest that in SCI, APC reduces motor disturbances primarily by reducing the amount of TNF-alpha at the site of injury, thus inhibiting neutrophil accumulation and the resultant damage to the endothelial cells.

[A case report of complete inversion of the bladder in an old woman].

A 77-year-old Japanese woman was admitted to our hospital complaining of small urinary volume. Physical examination revealed a light red, edematous, pyriform mass, approximately 7 cm in diameter at the vulva. An orifice posterior to the base of the mass was catheterized and 20 ml of urine was obtained. Roentgenograms of contrast material injection to the orifice demonstrated a space of 20 ml. A diagnosis of complete inversion of the bladder was made. Under epidural anesthesia, attempts were made to reduce the mass through the urethra. The manual reduction proved to be difficult, but was successful by manual compression of the bladder wall and squeezing it back through the urethra, which took approximately 60 minutes. Complete transurethral inversion of the bladder is so rare that not much of the pathogenesis is clarified. In our patient, senility, obesity, multiple labor and surgeries are assumed to have resulted in laxity of the pelvic wall which would be one of the major risk factors for this condition.

Role of neutrophils in spinal cord injury in the rat.

Activated neutrophils are thought to be involved in tissue injury through the release of various inflammatory mediators. To understand the role of neutrophils in spinal cord injury, the effects of nitrogen mustard-induced leukocyte depletion and the administration of an anti-P-selectin monoclonal antibody on motor disturbances observed following spinal cord compression were examined in rats. Spinal cord injury was induced by applying a 20-g weight for 20 min at the level of the 12th thoracic vertebra, resulting in motor disturbances of the hindlimbs 24 h postcompression. Motor disturbances, evaluated using Tarlov's index, an inclined-plane test and climbing ability, were markedly attenuated in rats with nitrogen mustard-induced leukocytopenia. Administration of the anti-P-selectin monoclonal antibody, by which adhesion of activated neutrophils to endothelial cells may be inhibited, also attenuated motor disturbances. Histological examination revealed that intramedullary hemorrhages observed 24 h after compression at the 12th thoracic vertebra of the spinal cord were significantly attenuated in leukocytopenic animals and those which received the anti-P-selectin monoclonal antibody. The accumulation of neutrophils at the site of compression, as evaluated by measuring the tissue myeloperoxidase activity, significantly increased with time following the compression, peaking at 3 h postcompression. Spinal cord myeloperoxidase activity did not increase in sham-operated animals. Leukocyte depletion and administration of the anti-P-selectin monoclonal antibody both reduced the accumulation of neutrophils in the damaged spinal cord segment 3 h postcompression. These observations strongly suggest that activated neutrophils play an important role in compression-induced thoracic spinal cord injury and that a P-selectin-mediated interaction between activated neutrophils and endothelial cells may be a critical step in endothelial cell injury leading to spinal cord injury.

[The measurement of the coronary flow by the phase contrast method (cine PC, Fastcard PC)].

We confirmed the accuracy of flow velocity measured by two kinds of phase contrast (PC) sequence. The fast PC sequence(FCARDPC) showed a little different value from the conventional PC, but the linear correlation was found between established values of the instrument and the measured velocity by the fast PC. The flow velocity of the right and left coronary arteries in one cardiac cycle was measured using two PC sequences on the same subject. It was found that the flow velocity in one cardiac cycle was almost the same pattern between the two method, though the absolute values of each other differed slightly. We considered that the comparison in the same sequence would be acceptable even in clinical cases unless the values measured by a different sequence or modality were compared directly. Though our experience on diseases are still preliminary, we suggest that myocardial ischemia and dysfunction will be related with not only the decrease of velocity but also the change of flow pattern of the coronary artery in one cardiac cycle. We believe that this method has a potential becoming one of the routine methods for evaluating cardiac functions.

[Accuracy and clinical utility of quantitative proton magnetic resonance spectroscopy (MRS) on phantom and chronic cerebral ischemia].

We quantified the concentration of metabolites observed by proton MRS using the tissue water signal as an internal standard. A phantom containing known concentrations of NAA (10 mM) and Cr (5 mM) was used for the study of methodological accuracy. Clinical utility was evaluated by the measurement of patients with severe stenosis or obstruction of the unilateral internal carotid artery. The concentration of tissue water was compensated using a proton-density weighted image measured with a water bag attached to the head. The calculated concentrations of NAA and Cr in the phantom were 9.2 mM (SD: 1.2) and 5.6 mM (SD: 0.7), respectively. On the ischemic side of the brain, the concentrations of NAA and Cr were lower than on the opposite side, but the concentration of choline (Cho) was almost the same on the two sides. The NAA/Cr ratio showed no statistically significant differences between the two sides, because the concentration of Cr was shown to be decreased in the ischemic area. We consider that quantitative evaluation of proton MRS might reveal changes in single metabolites clearly, thereby facilitating understanding of the results of proton MRS.

Reduction of spinal cord injury by administration of iloprost, a stable prostacyclin analog.

To investigate whether iloprost, a stable analog of prostacyclin, is useful for the prevention of posttraumatic spinal cord injury, we examined its effects on compression trauma-induced spinal cord injury in rats. Spinal cord injury was induced by applying a 20-g weight for 20 minutes to the spinal cord at the level of T-12, resulting in motor disturbances in the hindlimbs. These motor disturbances, evaluated using Tarlov's index, were markedly attenuated in rats with nitrogen mustard-induced leukocytopenia. Administration of iloprost also attenuated the motor deficits. Histological examination revealed that intramedullary hemorrhages observed 24 hours after trauma were significantly attenuated in leukocytopenic animals and in animals that received iloprost. The accumulation of leukocytes at the site of trauma, evaluated by measuring tissue myeloperoxidase activity, significantly increased with time following the trauma, peaking at 3 hours postinjury. Spinal cord myeloperoxidase activity in sham-operated animals did not increase postoperatively. Leukocyte depletion and administration of iloprost reduced the accumulation of leukocytes in the damaged spinal cord segment 3 hours posttrauma. These findings indicate that iloprost attenuates motor disturbances induced by spinal cord trauma and that its therapeutic efficacy can be partly explained by its inhibition of leukocyte accumulation at the traumatized site.

[Basic and clinical studies of oral barium sulfate preparations for CT].

In CT examination of the abdomen and pelvis, oral iodinated contrast agents and oral barium sulfate preparations are now being used to improve diagnostic accuracy, and studies have been carried out on their clinical usefulness. Although helical CT has come into wide spread use recently, most studies have used the ordinary type of CT. There have been no reports on studies using barium sulfate preparations with helical CT. We, therefore, prepared several barium sulfate preparations with different concentrations and particle diameters, and conducted a basic study to determine the optimal conditions for helical CT. In addition, we conducted a similar study using the ordinary imaging method for comparison with helical CT. Based on the results of these studies, we conducted a clinical study with several volunteers to find the most suitable barium sulfate preparation. Our basic study compared Baritop CT and Gastrografin, and a concentration of 1.5%-2.0% was found suitable. In our examination of particle size using animal intestines, fine particles were found to be most appropriate. Although little difference was observed between the helical procedure and the ordinary imaging procedure, the possible development of artifacts specific to the helical procedure was suggested. In the clinical study, the 2.0% preparation tended to show better contrast and a better filling rate for the upper abdominal organs than the 1.5% preparation. However, little difference in artifacts was found between them. The artifacts tended to be intensified when barium migrated toward the distal portion of the small intestine. Judging from these results, a 2.0% fine particle preparation appeared to be suitable for examination of the upper abdominal organs. For organs in the pelvic region, preparations with a lower concentration were considered suitable.

[Transverse relaxation time of metabolites by proton MRS: one of the parameters concerned with quantification].

We examined the transverse relaxation time of metabolites observed by proton MRS at 6 different points of TE(18, 30, 60, 90, 135, and 270ms). The double exponential curve was better fitted to the 6 points than the single exponential curve for calculating the T2 values of the three major metabolites. We considered that these metabolites would have a long T2 component and short T2 component, and the correct T2 value is difficult to obtain under the limitations of measurement time available in clinical applications.

Gabexate mesilate, a synthetic protease inhibitor, prevents compression-induced spinal cord injury by inhibiting activation of leukocytes in rats.

OBJECTIVE: Gabexate mesilate is a synthetic protease inhibitor capable of inhibiting both coagulation and cytokine production by monocytes. To investigate whether gabexate mesilate is useful for the prevention of posttraumatic spinal cord injury, we examined its effect on compression trauma-induced spinal cord injury in rats. DESIGN: Prospective, randomized, blinded, controlled study. SETTING: Research laboratory at a university medical center. SUBJECTS: Male Wistar rats weighing 300 to 350 g. INTERVENTIONS: Spinal cord injury was induced by applying a 20-g weight extradurally to the spinal cord at the level of the 12th thoracic vertebra for 20 mins. Spinal cord injury was evaluated by assessing the motor function of the rats 24 hrs posttrauma. The accumulation of leukocytes and histologic changes in the injured spinal cord tissue also were examined. Rats received gabexate mesilate (10 or 20 mg/kg i.p.) 30 mins before or after the compressive trauma. The effects of heparin or an inactive derivative of activated factor X (a selective inhibitor of thrombin generation) on compressive trauma-induced spinal cord injury also were examined. Leukocytopenia was induced by the administration of nitrogen mustard. MEASUREMENTS AND MAIN RESULTS: The motor disturbances observed following traumatic spinal cord compression, evaluated by Tarlov's score, and the accumulation of leukocytes in the injured tissue, evaluated by measuring tissue myeloperoxidase activity, were markedly reduced by leukocyte depletion induced by nitrogen mustard and by pre- or posttreatment of animals with gabexate mesilate. Neither heparin nor the inactive derivative of activated factor X prevented the motor disturbances and the accumulation of leukocytes. Histologic examination demonstrated that intramedullary hemorrhages observed 24 hrs after trauma at the 12th thoracic vertebra were significantly attenuated by nitrogen mustard-induced leukocytopenia and the administration of gabexate mesilate. CONCLUSIONS: The compression trauma-induced spinal cord injury demonstrated by this model was mainly mediated by leukocytes. Gabexate mesilate prevented spinal cord injury not by inhibiting coagulation, but by inhibiting the activation of leukocytes.