Effect of a recombinant manganese superoxide dismutase on prevention of contrast-induced acute kidney injury

Background

Contrast media (CM)-induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM mediated to a large extent by the increased production of ROS within the kidney. Aim of this study was to evaluate whether a novel isoform of a recombinant Manganese SOD (rMnSOD) could provide an effective protection against CIN; this molecule shares the same ability of physiological SODs in scavenging reactive oxygen species (ROS) but, due to its peculiar properties, enters inside the cells after its administration.

Methods

We studied the effects rMnSOD on oxidative damage in a rat model of CIN in uninephrectomized rats, that were randomly assigned to 3 experimental Groups: Group CON, control rats treated with the vehicle of CM, Group HCM, rats treated with CM and Group SOD, rats treated with CM and rMnSOD.

Results

In normal rats, pretreatment with rMnSOD, reduced renal superoxide anion production, induced by the activation of NAPDH oxidase, by 84 % (p < 0.001). In rats of Group HCM, ROS production was almost doubled compared to rat of Group CON (p < 0.01) but returned to normal values in rats of Group SOD, where a significant increase of SOD activity was detected (+16 % vs HCM, p < 0.05). Administration of CM determined a striking fall of GFR in rats of Group HCM (?70 %, p < 0.001 vs CON), greatly blunted in Group SOD (?28 % vs CON, p < 0.01); this was associated with a lower presence of both tubular necrosis and intratubular casts in SOD-treated rats (both p < 0.01 vs Group HCM).

Conclusions

Our data indicate that rMnSOD is able to reduce renal oxidative stress, thus preventing the reduction of GFR and the renal histologic damage that follows CM administration.     

Prevention of reperfusion injury of the ischemic spinal cord: use of recombinant superoxide dismutase

We investigated the effect of recombinant superoxide dismutase, an oxygen free radical scavenger, on the prevention of reperfusion injury of the ischemic spinal cord. Somatosensory evoked potentials (SEPs) were obtained in 23 dogs. Spinal cord ischemia was produced by cross-clamping the descending thoracic aorta just distal to the origin of the left subclavian artery through a left thoracotomy. Mean proximal aortic blood pressure was maintained between 90 and 100 mm Hg by partial exsanguination. Serial SEPs were obtained at 60-second intervals until the SEP disappeared. Aortic cross-clamping was continued for 10 additional minutes after the disappearance of the SEP. In Group 1 (N = 8), no medication was given when the aortic cross-clamp was removed. In Group 2 (N = 8), a bolus of 25,000 units of superoxide dismutase was injected into the proximal aorta prior to removal of the aortic cross-clamp, and was followed by 5,000 units per minute for 10 minutes after release of the cross-clamp. In Group 3 (N = 7), 50,000 units of superoxide dismutase was administered as a bolus prior to removal of the aortic cross-clamp, followed by an additional 10,000 units per minute for 10 minutes as in Group 2. The postoperative neurological status was assessed by Tarlov's criteria. There was no significant difference in aortic cross-clamp time among the three groups. Paraplegia developed in 4 animals in Group 1; the remaining 4 dogs had paraparesis. In Group 2, paraparesis developed in 2 of 8 dogs; the other 6 had no neurological injury. All the animals in Group 3 had complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Does prostaglandin E1 and superoxide dismutase prevent ischaemic spinal cord injury after thoracic aortic cross-clamping?

The beneficial use of prostaglandin E1 (PGE1) and superoxide dismutase (SOD) on the tolerance to ischaemia of the spinal cord was evaluated following thoracic aortic cross-clamping in dogs. Aside from spinally evoked somatosensory potential (SEP) by means of a bipolar epidural catheter, postoperative evaluation of motor deficits was used to determine the efficiency of pharmacological protection when compared with controls. The animals were divided into four groups. Group I (n = 12) served as controls. The dogs of Group II (n = 12) were treated with PGE1 (100 ng/kg/min) during clamping and the first hour after declamping. In the third group (n = 12) SOD was given as an intra-arterial bolus (1 mg/kg) prior to declamping which was followed by a continuous perfusion (0.4 mg/kg/min) into the carotid artery for 25 min. In Group IV (n = 12) the dogs were treated with a combination of PGE1 and SOD in the same manner as in Groups 3 and 4. Results after pharmacological protection were significantly better than controls. In Group I all animals but one (92%) were paraplegic, as were five in Group II (42%) and eight in Group III (67%). In contrast no dog in Group IV developed paraplegia. There was a close correlation of SEP and postoperative recovery. The group with combination therapy (PGE1 plus SOD) was characterised by a loss of the evoked potential for a mean of 15 min, the PGE1 group for 45.8 min and the SOD group for 58.5 min. While the control group was characterised by a loss of 72.7 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal insufficiency in acute spinal cord injury

BACKGROUND/OBJECTIVE: A 21-year-old man with a C6 American Spinal Injury Association A spinal cord injury (SCI) developed symptomatic hypotension resistant to vasopressors and volume replacement 2 weeks after injury and was diagnosed with adrenal insufficiency by cosyntropin test. Adrenal insufficiency has been documented in chronic SCI; this case shows documented adrenal insufficiency in acute SCI. DESIGN: Case report. RESULTS: Secondary adrenal insufficiency complicated the medical and rehabilitative course of this patient with SCI. During 2 infectious episodes, this patient's dosage of hydrocortisone had to be doubled to control symptomatic hypotension, lethargy, diffuse weakness, and anorexia. CONCLUSIONS: The nonspecific symptomatology of adrenal insufficiency can be easily overlooked in patients with SCI. Low basal cortisol levels may be an important clue to this disorder. Low-dose adrenocorticotropic hormone stimulation may be more sensitive than high doses for detecting subclinical adrenal insufficiency. A high index of clinical suspicion is needed for the correct diagnosis of acute and chronic adrenal insufficiency.     

Spinal cord evoked injury potentials in patients with acute spinal cord injury

Six patients were examined in the acute stage of spinal cord injury, between 11 h and 12 days posttrauma. Quadripolar epidural electrodes were positioned either percutaneously using a Tuohy needle or directly into the epidural space during surgical intervention. These electrodes were combined with a common reference to obtain monopolar recordings of spinal cord evoked potentials resulting from either median nerve stimulation at the wrist or tibial nerve stimulation at the popliteal fossa. Spinal cord evoked injury potentials (SCEIPs), stationary potentials with positive polarity on the distal aspect of the lesion and negative polarity on the proximal aspect, were recorded in all cases. The average amplitude (n = 3) of the SCEIP resulting from tibial nerve stimulation as measured across the lesion was 13.5 microV with an average duration of 12.7 msec. For median nerve stimulation, the average amplitude (n = 3) of the SCEIP was 16.3 microV with an average duration of 6.7 msec. There was a change in polarity in all cases over a distance of less than 6 mm, the distance between the electrode contacts on the epidural electrode. In one case, recordings were performed initially at 11 h and repeated at 21 days posttrauma. In the latter recording, the SCEIP was still present but was five times smaller in amplitude. Coincidentally, the patient also showed clinical signs of improvement in sensory and motor spinal cord function. This study demonstrates the feasibility of recording the SCEIP in patients with acute spinal cord injury, describes the features of these SCEIPs, discusses their origins, and explores the utility of recording the SCEIP as an aid in determining the severity of the injury as well as a means of monitoring changes in spinal cord function.     

急性脊髓损伤的实验研究进展

急性脊髓损伤（ASCI）是一种严重的损伤。多见于16～30岁的年青人群,对患者和社会均可造成身心和经济上的沉重负担,据统计,仅在美国每年发生ASCI的新病例约1万名左右,耗资达100亿美元[1]。本文介绍近年来国外对ASCI的实验研究方面的主要进展。动物实验模型研究ASCI的形态学特征及后果取决于脊髓压迫重量,脊髓移位程度,暴力加速度和动态能量吸收等因素。目前,有许多动物实验模型被用于模拟ASCI。1911年Allen[2]首次报告了一种器械用于犬的打击模型。该模型经过反复多次的改良,现仍被广泛采用。还有不少模型可模拟脊     

Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury

Small bowel toxicity represents a major dose-limiting side effect of radiation treatment for many malignancies. We examined the effects of overexpressing human manganese superoxide dismutase (MnSOD) in the small intestine in mice to prevent radiation enteritis. Mice were treated with the human MnSOD gene delivered enterally using a nontoxic, replication-defective herpes simplex virus (HSV)-1-based vector. HSV vectors containing the human MnSOD transgene and green fluorescent protein (GFP) transgene, or GFP transgene alone, were constructed and injected intraluminally into a 2cm length of small intestine of C3H/HeNsd mice. Total body irradiation of 15 Gy was delivered to mice inoculated 24 hours earlier with either HSV-MnSOD (10³ to 10⁸ plaque-forming units), control HSV-GFP, or no vector. At 24 or 72 hours after irradiation, mice were killed and villi areas were measured from appropriate segments of the small intestine. Control irradiated mice showed a decreased villi area of 82% by day 3 after irradiation, whereas treatment of mice with HSV-MnSOD 10⁸ plaque-forming units led to only a 16% decrease in villi area (P< 0.001) before radiation. Similar findings were seen on day 3 and were associated with a significant (P< 0.001) preservation of enteric protein content in HSV-MnSOD-treated mice. A dose-dependent effect of MnSOD in preventing radiation-induced small bowel injury was evident. These data demonstrate that overexpression of human MnSOD via a replication-defective herpes viral vector is an efficacious method of protecting the small intestine from ionizing radiation damage. Presented in part at the Annual Meeting of the American Society of Hematology 2001 and at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Current status of spinal cord cooling in the treatment of acute spinal cord injury

In order to determine any beneficial effects of parenteral steroid administration and local cord cooling following complete cord injury, ten patients in the present series were treated by a combination of these modalities within 8 1/2 hours after injury. There was a better than expected rate of recovery of motor function and sensation and the mortality rate was reduced compared with more traditional forms of therapy. A literature review showed that local cord cooling had been applied to 52 patients with complete cord injuries in various centers. The rate of neurologic improvement was 48%, the ambulation rate was 17% and the 1-year mortality rate was reduced to 17%. These figures appear considerably better than the comparable expected rate for traditional treatment of such injuries. The results are encouraging enough to suggest further trials of treatment using localized cord cooling where such treatment can be instituted within 4 hours following injury.     

Venous thromboembolism in acute spinal cord injury patients

Background:

The western literature on deep vein thrombosis (DVT) and pulmonary embolism (PE) following spinal cord injury (SCI) report an alarmingly high incidence, necessitating thromboprophylaxis. The literature on incidence from the Asian subcontinent is scanty and from India is almost nonexistent.

Materials and Methods:

Seventy hospitalized acute SCI patients presenting within five days of the injury were included in the present analysis. Forty-two cases were subjected to color Doppler studies and 28 cases had to be subjected to venography due to lack of facility at some point of time. The clinical course of the patients was closely observed during the period of hospitalization. All except 14 were managed nonoperatively. Thromboprophylaxis was not given to any patient at any stage; however, treatment was instituted in those showing the features of DVT on investigations.

Results:

Twelve patients died during the period of hospitalization. Deep vein thrombosis could be detected in seven patients only, three in the proximal and four in the distal segment of the lower limb and of these three died. Based on the clinical course and positive investigation report in favor of DVT, we presumed that the cause of death in these three patients was pulmonary embolism. In the other nine, in the absence of an autopsy report, the cause of deaths was considered as pulmonary infection, asphyxia, diaphragmatic paralysis, hematemesis, cervicomedullary paralysis etc. Clinical features to diagnose DVT were of little help.

Conclusions:

There is a much lower incidence (10%) of DVT and PE following spinal cord injury (SCI) in India than what is reported from the western countries. Higher age group and quadriplegia were the only factors which could be correlated. Deep vein thrombosis extending proximal to the knee was significant. In the absence of autopsy and other screening tests like D-dimer test or 125I fibrogen uptake study, the true incidence of venous thromboembolism remains uncertain. Noninvasive screening of all patients for the detection of deep vein thrombosis in SCI patients is strongly recommended.     

自血光量子疗法对家兔脊髓损伤后超氧化物歧化酶的影响

目的：探讨自血光量子疗法治疗脊髓损伤的作用机制。方法４２只家兔随机分成对照组、损伤组和治疗组,用化学比色法分别测定各组血液和脊髓组织中超氧化物歧化酶（ＳＯＤ）活力。结果伤后不同时点血液和脊髓组织中ＳＯＤ活力与对照组比较均明显下降（Ｐ〈０．０１）;治疗组在采用自血光量子疗法治疗后,与相应时点损伤组比较均明显升高（Ｐ〈０．０１）。结论自血光量子疗法可以提高血液和脊髓组织中ＳＯＤ活性。     

Anaesthetic considerations for acute spinal cord injury

The recently published research data on the possible pathophysiology of acute spinal cord injury provide the basis of a number of exciting possibilities for its treatment. The present article reviews these lines of investigation. It focusses on methylprednisolone, which is the only effective proven therapy to limit secondary spinal cord injury known to date. In addition, the initial evaluation of patients with possible spinal cord trauma and airway management in patients with cervical spine injury are also discussed. Finally, the anaesthetic regimen in patients with these injuries is reviewed, showing that no anaesthetic agent or technique is superior to other anaesthetic methods.     

急性颈髓损伤后的低钠血症

[目的]探讨急性颈髓损伤后低钠血症的病因、发病机制、诊断和治疗。[方法]回顾性分析2004年-2006年收治的急性颈髓损伤后低钠血症患者15例的临床资料。[结果]全组患者入院24—72h内血钠低于130mmol／L，其中5例低于120mmol／L。14例尿钠40—68mmol／L，1例尿钠为148mmol／L；尿渗透压420～980mmol／L，12例患者经适当的补盐和限制水摄入量治疗，低钠症状2～3周内改善；2例发热患者因发热不能严格限制水摄入，其中1例2个月后恢复，另1例失访；1例患者补盐限水后病情加重，调整治疗方案后恢复。[结论]颈髓损伤越重，损伤后低钠血症发生率越高；颈髓损伤后低钠血症多由抗利尿激素分泌异常综合征引起；血钠浓度，血、尿渗透压等是诊断依据；适当补充钠盐和液体量是有效的治疗方法。     

Detection of sacral sparing in acute spinal cord injury

Sacral dermatomal-evoked responses (DEP) and posterior tibial nerve (PTN) somatosensory-evoked potentials (SSEP) were recorded 28 hours after gunshot injury to the 12th thoracic vertebra of a 17-year-old male. Repeatable responses were obtained from stimulation of the fourth sacral dermatome despite absence of repeatable PTN responses. This suggestion of "sacral sparing" was accompanied by clinical improvement of neural function during the hospital course and 10 months after discharge. This case suggests DEP can make valuable contributions in the diagnosis of sacral sparing in acute spinal cord injury. Considerations regarding the unusual ipsilateral scalp recording location for sacral DEP are discussed.