Experimental animal models of pancreatic carcinogenesis and metastasis

Pancreatic cancer is a lethal disease characterized by early metastasis, local invasion, and resistance to conventional therapies. To understand its etiology and eventually make prevention of it possible and effective, appropriate carcinogenesis models will certainly help us understand the effects of environmental and genetic elements on pancreatic carcinogenesis. The development of new treatment strategies to control cancer metastasis is of immediate urgency. Fulfillment of this task relies on our knowledge of the cellular and molecular biology of pancreatic cancer metastasis and the availability of biologically and clinically relevant model systems. Many of the existing pancreatic cancer carcinogenesis and metastasis animal models are described in this review. The advantages and disadvantages of each model and their clinical implications are discussed, and special attention is focused on experimental therapeutic strategies targeting pancreatic cancer metastasis.     

Die Behandlung der Apophysenabrissverletzung des Epicondylus ulnaris im Kindesalter

OBJECTIVE: Surgical reduction and retention of apophyseal avulsion injuries at the medial epicondyle to prevent joint instability, lasting malalignment, or pseudarthrosis. INDICATIONS: Absolute: intraarticular apophyseal dislocation of the medial epicondyle, complete lesion of the ulnar nerve. Relative: dislocation of the apophysis (> 4 mm) in children > 5 years of age; the need for intervention increases in children as the degree of dislocation, age, and athletic activity increase. CONTRAINDICATIONS: Dislocation of the medial epicondyle (< or = 4 mm) in children < 5 years of age, provided the fragment location is not intraarticular. SURGICAL TECHNIQUE: Open reduction of the apophysis through a medial approach. Identification of the ulnar nerve. In young children or with small fragments fixation with Kirschner wire. Screw fixation in older children or for larger fragments. POSTOPERATIVE MANAGEMENT: Long upper-arm plaster cast until wound healing is achieved. Subsequently, upper-arm plaster cast for 3 weeks. Removal of Kirschner wires after 4-6 weeks, screw removal after 8-12 weeks. Physiotherapy only if marked reduction of elbow mobility is found 6 weeks after cast removal. RESULTS: From January 1, 1994 to December 31, 2003, 25 children with an average age of 12 years suffering from medial epicondylar avulsion fractures were operated on using open reduction and Kirschner wire fixation. An average of 3 years after the injury 14 of these children underwent follow-up examination using a procedure that took subjective, clinical and radiologic parameters into account. Two children showed a slight reduction in overall strength of the injured extremity when compared with the contralateral extremity. One child had a flexion deficit of 10 degrees, all other children showed movement limitations of < or = 5 degrees compared to the contralateral extremity. In all the cases available to follow-up, there was a slight increase in valgus alignment of the elbow joint compared with the uninjured side (3 degrees on average). All fractures consolidated within 6 weeks.     

绞股蓝总皂甙对自由基损伤血管内皮的保护作用

本文观察了绞股蓝总皂苷(Gypenosides,GYP)对电解性自由基(OFR)损伤离体兔胸主动脉和脑基底动脉内皮的保护作用:电解性OFR使乙酰胆碱(Ach)诱导的兔主动脉环舒张百分率明显降低,舒张比值(RR)变小,使离体兔脑基底动脉灌流压升高。结果显示绞股蓝能保护血管内皮免受OFR损伤,且呈剂量依赖性,并明显抑制OFR所致灌流压升高。作用似二甲亚砜(DMSO),说明GYP对外源性OFR损伤具保护作用。     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

偏瘫病人下肢功能康复阻碍因素初探

观察了10项因素对偏瘫病人下肢功能康复的影响,其结果表明:①下肢功能水平;②平衡功能障碍;③足下垂内翻;④髋关节屈曲外旋挛缩;⑤深感觉障碍;⑥疼痛等几项因素对偏瘫病人下肢功能康复有显著的影响。     

Effect of gradual rise in plasma calcium concentration on the impairment of atrioventricular nodal conduction due to verapamil

The possible reversal by calcium of the inhibitory action of verapamil on the atrioventricular (AV) node was investigated in anesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitory electrode and the AV node effective refractory period measured by the extrastimulus method. Calcium infusion was effective against the impairment of AV nodal conduction induced by verapamil, provided it remained moderate: the gradual rise in the plasma calcium concentration counteracted the effects of an infusion of verapamil on conduction time and effective refractory period in the AV node, as long as it did not exceed 5 mmol/L. However, beyond this level, calcium appeared less and less capable of reversing the effects of verapamil. Thus, the protective action of calcium had a bell-shaped dose-response curve, with the optimum at 5 mmol/L. This biphasic influence is consistent with the opposite opinions previously given concerning the antagonism between calcium and calcium blockers, depending on whether hypercalcemia brought into play was mild or major. In any case, the prominent role played by calcium in the slow inward current in the AV node accounts for the antagonism, observed in vivo, between calcium and verapamil. The pacemaker activity of the sinoatrial (SA) node was less influenced by both calcium blocker and calcium.