Anti-inflammatory effect of erythropoietin pretreatment on cardiomyocytes with hypoxia/reoxygenation injury and the possible mechanism

Objective： To investigate the anti-inflammatory effect of erythropoietin （EPO） pretreatment on cardiomyocytes exposed to hypoxialreoxygenation injury （H/R） and explore the possible mechanism.
Methods： The cultured neonatal rats＇ ventricular cardiomyocytes were divided randomly into 4 groups, control group （C group）, EPO pretreatment group （E group）, EPO and pyrrolidine dithiocarbamate （PDTC） pretreatment group （EP group） and PDTC pretreatment group （P group）. After 24 hours＇ pretreatment, the cardiomyocytes were exposed to H/R. After pretreatment and H/R, the expression of tumor necrosis factor- α （TNF- α ） gene in all the groups was detected by RT-PCR and Western blot. The nuclear factor- κ B （NF- κB） activity was detected by electrophoretic mobility shift assay （EMSA） and the inhibitor- κB α （Ⅰ- κB α） protein level was detected by Western blot.
Results： The decrement of Ⅰ- κB a protein and the increasing NF- KB activity were found in cardiomyocytes pretreated with EPO before H/R compared to other groups （t=3.321, 4.183, P〈0.01）. However, after H/R, NF- κB activity and expression of TNF- α gene were significantly reduced, Ⅰ- κB a protein expression was increased in cardiomyocytes of E group compared to other groups （t=-3.425, 3.687, 3.454, P〈0.01）. All theses changes caused by EPO pretreatment were eliminated by the intervention of PDTC （an antagonist to NF- κB） during pretreatment.
Conclusions： EPO pretreatment can inhibit the activation of NF- κB and upregulation of TNF- α gene in cardiomyocytes exposed to H/R through a negative feedback of NF- κB signaling pathway, and thus produces the anti-inflammatory effect. This might be one of the ways EPO produces the anti-inflammatory effect.     

头低位模拟失重状态对前庭功能的影响

为研究头低位模拟失重对运动病症状、垂直视动眼震（ＶＯＫＮ）及体液重新分配的影响，在头低位－１０°的模拟失重状态下，采用大视野的垂直视动刺激，观察１８名正常人的运动病症状、ＶＯＫＮ、激素（ＡＶＰ、ＶＩＰ、ＣＯＲＴ、ＡＬＤＯ）的反应特点。结果表明，头低位－１０°状态下的大视野垂直视动刺激可以诱发出明显的运动病症状，头低位－１０°的垂直视动刺激比坐位更容易诱发运动病。坐位状态ＶＯＫＮ慢相速度有明显的方向性不对称，敏感组ＶＯＫＮ方向性不对称有显著差异（Ｐ＜０．０５）。头低位－１０°时ＶＯＫＮ的不对称现象不明显，向下方向运动的ＶＯＫＮ慢相速度显著增加。分析指出，头低位－１０°状态下垂直视动刺激比坐位和秋千刺激的贡献率大。尿中ＣＯＲＴ（皮质醇）在秋千和头低位的垂直视动刺激前后有显著性增加。提示：大视野的垂直视动刺激与头低位－１０°两种刺激的结合可能成为预测空间运动病的方法之一．     

Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

Cerebrospinal fluid-filtration reduces TNF alpha in bacterial meningitis-CSF

A 37 year old male was admitted with the diagnosis of bacterial meningitis. Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical condition did not suggest severely raised intracranial pressure, there were no localizing signs and symptoms. CSF was turpid, with 20.100/3/mm³, mainly polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall-filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm³, TNF-alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient could be discharged without sequelae. CSF filtration may be a highly effective method to reduce from the CSF pathogenetically important cytokines, such as TNF-alpha, being responsible for intrathecal/meningeal inflammatory processes and triggered by cell-wall components of bacteria, e.g. pneumococci.     

Enhanced in vivo cytotoxicity of recombinant human tumor necrosis factor with etoposide in human renal cell carcinoma

Summary The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma.Supported by a Merit Review grant, VA Medical Research Service, Durham, NC 27710, USA     

MANAGEMENT OF CHONDROSARCOMA INCLUDING MODULAR CERAMIC AND ALUMINA PROSTHETIC REPLACEMENT

Forty-one cases of chondrosarcoma from varying sites throughout the body, and treated exclusively by one of the authors (R. L. H.) from 1972 to 1990 were reviewed. The symptoms, signs, location of tumours, treatment and progress are presented. Particular attention was paid to modular bone replacement techniques. Excision and reconstruction of the bone or joint were carried out in 17 femora, five tibia and six humeri. Comparison between this method of management and other techniques is discussed. Titanium and alumina prostheses for the hip, femur, tibia, shoulder and humerus have been designed by the senior author. These are both inert and modular, and have been found to be superior to other methods of treatment in both function and cosmesis. They do not possess the same potential donor infection risks and other disadvantages of allograft replacement. Immediate postoperative weight bearing and mobilization are possible with these systems. The Huckstep prostheses allow for bony in growth into their porous coated alumina sleeves, spacers and stems. In addition, the titanium alloy locking component for the femoral stems has an elasticity half that of other metal alloys and this was found to minimize stress shielding.     

Effect of wrist and ulna head position on gliding resistance of the extensor digitorum minimi and extensor digitorum communis III tendons: a cadaver study.

While attrition from sharp bony surfaces is the most common cause of extensor digiti minimi (EDM) tendon rupture, the etiology of other cases of spontaneous EDM tendon rupture is still unknown. Friction within the compartment may play a role, especially with ulna dislocation. The purpose of this study was to compare gliding resistance of the EDM tendon with that of a tendon which rarely ruptures spontaneously, the extensor digitorum communis of the middle finger (EDC III) tendon, under various wrist and ulna head positions. Eight fresh frozen cadavers were used. Gliding resistance between the tendon and its sheath in each compartment was measured in five different wrist positions and three different ulna head positions. Gliding resistance of the EDM tendon (0.13 +/- 0.03 N) was significantly greater than the EDC III tendon (0.09 +/- 0.03 N) (p < 0.05). For the EDM tendon, the gliding resistance in ulnar deviation or pronation was higher than the gliding resistance in neutral, radial deviation, or supination (p < 0.05), and the gliding resistance with ulnar lengthening (over 6 mm) or dorsal ulnar dislocation (over 9 mm) was higher than in neutral ulnar head positioning. For the EDC III tendon, the gliding resistance in ulnar deviation was significantly higher than the gliding resistance in neutral, radial deviation, or supination, or dorsal dislocation with ulnar lengthening (p < 0.05). Wrist ulnar deviation, ulnar dorsal dislocation (over 9 mm), and ulnar lengthening (over 6 mm) increased the gliding resistance of the EDM tendon. In patients at risk for EDM rupture, such as those with rheumatoid arthritis or distal radioulnar joint osteoarthritis, avoiding such positions may be advantageous.     

Intracerebral temperature monitoring in severely head injured patients

Summary In a series of 6 severely head injured patients, intraventricular as well as rectal, bladder and jugular vein temperature is recorded. The relationship between these temperatures in different conditions is evaluated. Intracerebral temperature is 0.5±0.2 °C (mean ± SD) higher than bladder temperature except in conditions such as brain death. It is concluded that rectal temperature is not representative and therefore not a good alternative to the measurement of brain temperature. More data on human intracerebral temperature are mandatory as well as prospective studies correlating intracerebral temperature with final outcome in head injury.     

Contribution of tumor necrosis factor to the lethality of mice with endotoxin shock presensitized by serum from tumor-bearing mice

Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 115, No. 1, pp. 57–59, January, 1993.