Inactivation of purified human alpha 2-antiplasmin and purified human C1 inhibitor by synthetic fibrinolytic agents

3-Hydroxypropyl flufenamide (Flu-HPA) is one of a series of flufenamic acid derivatives that enhances blood clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The profibrinolytic activity of Flu-HPA in clot lysis assays was found to be dependent on plasminogen. The influence of Flu-HPA on the ability of purified alpha 2-antiplasmin to inhibit purified plasmin was studied. Plasmin activity was determined using 125I-fibrin plates or the spectrophotometric tripeptide substrate, Val-Leu-Lys-paranitroanilide. At Flu-HPA concentrations greater than 1 mM, the inhibitory activity of alpha 2-antiplasmin was abolished in a time-dependent and concentration- dependent manner. The influence of Flu-HPA on the ability of purified Cl inhibitor to inhibit purified plasma kallikrein and beta-Factor XIIa was also studied. Cl inhibitor activity was abolished by Flu-HPA at concentrations greater than 2 mM. Notably, Flu-HPA up to 60 mM did not affect the amidolytic activities of plasmin, kallikrein, or beta-Factor XIIa. Flu-HPA did not release enzyme activity from preformed complexes of either alpha 2-antiplasmin and plasmin of Cl inhibitor and kallikrein. A water-soluble derivative of flufenamic acid, N-flufenamyl- glutamic acid, also inactivated alpha 2-antiplasm and Cl inhibitor. This inactivation was shown to be reversible. These results indicate that synthetic fibrinolytic compounds such as flufenamic acid derivatives may promote fibrinolysis by directly inactivating alpha 2- antiplasmin and Cl inhibitor.     

Mini-plasminogen: a mechanism for leukocyte modulation of plasminogen activation by urokinase

Urokinase activation of blood fibrinolysis involves polymorphonuclear leukocytes. To determine if a leukocyte proteinase can modulate plasminogen activation, plasminogen was digested with leukocyte elastase. A major product was a small, approximately 34,000 dalton fragment (mini-plasminogen), without lysine-binding function, but with fibrin-binding activity. After urokinase activation, the resulting mini- plasmin had amidolytic activity for a tripeptide plasmin substrate and fibrinolytic activity. By 125I-fibrin assay, activities of mini-plasmin and plasmin (12 nmole/liter) were 38 and 20 ng fibrin lysed/min, respectively. Lysis times of fibrin clots containing urokinase, and mini-plasminogen or plasminogen (800 nmole/liter), were 282 and 290 sec, respectively. Mini-plasmin and plasmin were inhibited similarly by epsilon-aminocaproic acid and normal plasma, but differed in responses to gel filtration fractions of plasma containing alpha 2-antiplasmin and alpha 2-macroglobulin, the primary and secondary plasmin inhibitors. With purified inhibitors, mini-plasmin required higher concentrations of, or longer preincubation with, alpha 2-antiplasmin, and lower concentrations of, or shorter preincubation with, alpha 2- macroglobulin, to produce inhibition equivalent to that observed with plasmin. Leukocyte elastase digests plasminogen to generate a mini- plasminogen which, when activated by urokinase, has a novel pattern of response to the major plasmin inhibitors in plasma.     

Membrane fluidity changes accompanying phagocytosis in normal and in chronic granulomatous disease polymorphonuclear leukocytes

We have studied membrane fluidity changes in polymorphonuclear leukocytes (PMN) during phagocytosis. Membrane fluidity was assessed by electron spin resonance (ESR) using a nitroxide-substituted stearic acid analog (5DS) as a spin probe. PMN from normal subjects and from 3 CGD patients (2 males, 1 female) were incubated in Kreb's Ringers phosphate with or without opsonized zymosan. ESR spectra were obtained and the order parameter (S), which is inversely related to membrane fluidity, was calculated. Without zymosan addition, S for normal (0.638) and for CGD (0.635) were not significantly different (p less than 0.35). The S values indicate that under resting conditions the molecular environment of the CGD membrane is similar to that of normal PMN membranes. However, with addition of opsonized zymosan, the normal, but not the CGD, PMN showed a significant increase (CGD, S = 0.638; normal, S = 0.647; p less than 0.001). This change in S for the normals is consistent with a more restricted movement of 5DS. Treatment of normal PMN with a mixture of scavengers specific for H2O2 (catalase, 1600 U/ml), O2-.(superoxide dismutase, 100 micrograms/ml), and for HO., (sodium benzoate, 1mM) during zymosan stimulation gave S values similar to those of resting cells. Catalase alone also lowered S value, suggesting that H2O2 was instrumental in causing the initial S value increase. This idea was supported by studies in which CGD cells were incubated with zymosan in the presence of glucose oxidase, an enzyme that catalyzes glucose oxidation resulting in the direct reduction of molecular oxygen to H2O2. Our results indicate that reduced O2 by- products, particularly H2O2, can cause altered biophysical properties of PMN membrane during phagocytosis.     

Percutaneous cholecystography in children

Percutaneous cholecystography was performed on 13 children who had biliary system abnormalities: two had biliary hypoplasia, five had sclerosing cholangitis, three had cirrhosis, two had distal choledochal obstruction, and one had an obstructed portoenterostomy. In 12 patients transcholecystic cholangiography showed, without significant complications, the intra-and extrahepatic bile ducts. In one patient with primary sclerosing cholangitis, the intrahepatic bile ducts were not opacified satisfactorily; dilatation of the gallbladder required surgical drainage. The transcholecystic technique is indicated when the intrahepatic bile ducts are either mildly dilated or not dilated.     

Rotator cuff lesions of the shoulder: evaluation by direct sagittal CT arthrography

Direct sagittal computed tomographic scanning (DSCT) of the shoulder was performed in 42 symptomatic patients, six healthy volunteers, and two cadaver shoulders. Axial CT scanning and double-contrast arthrography with plain radiographs were performed in 41 patients for comparison. DSCT enabled correct identification of 27 of 29 lesions in 24 patients. Seventeen patients had normal shoulders. Axial CT scanning and DSCT together enabled correct identification of all lesions and were markedly superior to plain-film arthrography. DSCT enabled diagnosis of all cases of complete rotator cuff tear plus three cases of incomplete tear and three of rotator cuff atrophy not identified by the other techniques. Axial CT scanning was better than DSCT for diagnosis of Bankart lesions.     

The Quality of Life of Family Caregivers of Eating Disorder Patients

Having a relative with an eating disorder (ED) affects the life of family caregivers and may thus affect their quality of life. To study this aspect, 40 caregivers of ED patients filled out a health-related quality of life questionnaire (Short Form-36) and a questionnaire on the impact of the ED on various areas of life domains, and on the relationship with the ED patient and the need for professional support. Quality of life of caregivers was worse than in a normal reference group. Specifically, mental health, vitality and emotional role functioning were reported to be most impaired. ED appeared to affect families’ lives substantially. In response to the ED, caregivers felt anxious, powerless, sad, or desperate. The relationship of the caregiver with the ED patient had also changed. Caregivers were more worried, lost their trust, and reported more conflicts. Seventy five percent welcomed professional support. Caregivers need practical advice, information on ED, and emotional support. Quality of life of caregivers should be addressed in the treatment of ED.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

肛门镜压迫下内痔注射法治疗Ⅱ、Ⅲ期内痔的临床疗效

为探讨新型肛门镜压迫下内痔注射法治疗Ⅱ、Ⅲ期内痔的临床疗效,本研究采用多中心随机对照方法,选取200例Ⅱ、Ⅲ期内痔患者分为试验组及对照组,各i00例,试验组采用新型肛门镜压迫下内痔注射法治疗,对照组采用传统消痔灵注射法治疗,观察两组疗效及不良反应。结果显示,试验组治愈84例,好转12例,无效4例,治愈率为84．0％;对照组治愈30例,好转58例,无效12例,治愈率为30．0％。试验组治愈率明显高于对照组,P〈0．01。两组术后第3天出血治愈率差异无统计学意义,P〉0．05;但试验组术后痔核脱出、肛门坠胀治愈率明显高于对照组,P〈0．01。结果表明,肛门镜压迫下内痔注射法治疗Ⅱ、Ⅲ期内痔疗效确切,与传统消痔灵注射法比较,在治疗内痔脱出方面具有更高的临床实用价值。？