Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia

Matrix metalloproteinases (MMPs) are involved in remodelling extracellular matrix. Gelatinase B (MMP-9) is an inducible 92 kDa MMP expressed by neutrophils, microglia, and endothelial cells. Gelatinase A (MMP-2) is a 72 kDa MMP, constitutively expressed in brain. Elevated MMP activity has been linked to various pathologic conditions, and the therapeutic benefit of MMP inhibitors is under study in a few experimental models. Using gelatin zymography, we have compared activities of these MMPs in infarcted and matched non-infarcted cerebral tissue from eight subjects dying at intervals of less than 2 h to several years after a stroke. Gelatinase B activity was markedly elevated in the infarcted tissue at two days post-infarction, and remained elevated in cases dying months after the event. Increases in gelatinase A activity were subtle at 2-5 days; they were marked and significant in cases dying at 4 months and later. The findings indicate distinct temporal profiles of post-ischemic gelatinase activity in human brain, with earlier but equally persistent elevation in gelatinase B when compared to gelatinase A.     

Dermatophilus chelonae sp. nov., isolated from chelonids in Australia

Three isolates of a previously undescribed Dermatophilus sp. obtained from chelonids (two strains obtained from turtles and one strain obtained from a tortoise) were compared with 30 Dermatophilus congolensis isolates obtained from Australian mammals. The microscopic appearance, the colony morphology, and most biochemical test results for the chelonid isolates were characteristic of the genus Dermatophilus. Our isolates differed from the mammalian D. congolensis isolates in a number of cultural characteristics, including faster growth at 27 degrees C than at 37 degrees C, formation of two hemolysis zones around colonies on blood agar at 37 degrees C in the presence of 10% CO2, poor motility, and production of a distinctive odor. The DNA restriction enzyme digestion and protein electrophoresis patterns of our strains were distinct. The electrophoretic mobilities of 11 enzymes differed from the mobilities observed with D. congolensis strains. A monoclonal antibody to a surface antigen of an ovine isolate did not react with zoospores or filaments of the chelonid isolates. Biochemical differences between our isolates and D. congolensis included the ability of the chelonid isolates to reduce nitrate to nitrate and the fact that the chelonid isolates exhibit collagenase activity in vitro. We propose that the chelonid isolates should be placed in a new species, Dermatophilus chelonae. Strain W16, which was isolated from a nose scab on a snapping turtle, is the type strain; a culture of this strain has been deposited in the American Type Culture Collection as strain ATCC 51576.     

Increased nitric oxide deactivation by polymorphonuclear leukocytes in patients with intermittent claudication

PURPOSE: Local activation of polymorphonuclear leukocytes (PMNLs) is considered an important aspect of the pathogenesis of intermittent claudication, although concrete mechanisms of their effects on circulatory homeostasis in peripheral atherosclerotic disease remain unclear. This study evaluated the ability of PMNLs to deactivate nitric oxide (NO), a key regulator of regional circulation, as a possible factor determining PMNL involvement into ischemic disorders in patients who have intermittent claudication before and after vascular reconstruction. METHODS: A total of 57 patients who had peripheral occlusive disease in an aortofemoral segment before surgical treatment (group 1) and 65 patients who had similar occlusive lesions and other clinical and demographic data 6 to 12 months after undergoing inflow vascular reconstruction (group 2) were examined. All patients from group 2 had anatomically patent grafts; their satisfaction and level of function after surgical treatment were assessed by a five-point questionnaire. The sex- and age-matched control group included 35 subjects. NO activity was bioassayed by measuring its ability to increase cyclic guanosine monophosphate (cGMP) accumulation in rat fetal lung-cultured fibroblasts (RFL-6 cells). The ability of PMNLs to deactivate NO was characterized as the percent decrease in NO-induced cGMP accumulation in RFL-6 cells. RESULTS: Stimulated PMNLs caused inhibition of the activity of authentic NO; accumulation of cGMP induced by sodium nitroprusside was not affected. PMNLs from patients with peripheral atherosclerotic disease either before or after vascular reconstruction had a more marked capacity of NO inactivating than the cells from healthy subjects. For both groups of patients, levels of PMNL-induced NO deactivation were higher for patients with diabetes, and especially both diabetes and arterial hypertension. For both groups of patients, there was no correlation between levels of PMNL-induced NO deactivation and resting ankle-brachial indexes (ABIs). In contrast, close correlation was revealed between levels of PMNL-induced NO deactivation and postexercise ABIs and percent decrease in resting ABIs after exercise in patients evaluated either before or after surgical treatment. CONCLUSIONS: The ability of stimulated PMNLs to deactivate NO is elevated in peripheral occlusive disease and may be implicated in the pathogenesis of intermittent claudication. In patients who underwent successful recanalization of magistral arteries, levels of PMNL-induced NO deactivation remained higher than in control subjects. The increase in the ability of PMNL to deactivate NO positively correlated to ABI decreases after exercise in patients with peripheral occlusive disease either before or after surgical treatment.     

Pretreatment with NMDA receptor antagonist MK801 improves neurophysiological outcome after an acute spinal cord injury

Experimental and clinical studies have shown the beneficial effects of triiodothyronine (T3) following myocardial revascularization on cardiopulmonary bypass (CPB). In this study, open-label T3 was administered to 68 high-risk patients undergoing open heart surgery. The New Jersey Risk Assessment was used to calculate the preoperative estimated surgical mortality. A loading dose of T3 was administered: (a) at release of the aortic cross-clamp, (b) whenever the patient became CPB dependent, (c) if the patient exhibited low cardiac output after discontinuing CPB and (d) as pretreatment before initiating CPB. All therapeutic modalities were followed by a continuous T3 infusion. Following T3 therapy, CPB was discontinued in all patients. Based upon discriminant analysis, a total of 26 deaths were expected from the entire group, but only 7 patients died, therefore, the observed mortality was reduced by 72% (p < 0.007). The use of T3 had a major impact on reducing surgical mortality, and may be advocated as a new therapeutic modality in patients with high estimated mortality undergoing open heart surgery.     

Morphogenesis, ATP content and oxytetracycline production by Streptomyces rimosus in solid substrate cultivation

On agar plates, mycelia of Streptomyces rimosus TM-55 had a slender and smooth surface at 24 h, developed a shorter form and rough surface at 116 h, and lysed after 504 h incubation. Oxytetracycline potency reached a maximum at 94 h. During cultivation on solid substrate, mycelia rarely occurred on the surface at 24 h. The organism appeared as short rods at 166 h, and formed spores at 504 h. The ATP content was maximal at 166 h, while energy charge varied between 0.63 and 0.77 during cultivation. The oxytetracycline potency was maximal at 166 h and each gram of substrate produced 11 mg of antibiotic. ATP content and energy charge of mycelia showed a positive correlation with cell activity and oxytetracycline production.     

The effect of selenium supplementation during the early post-mating period on embryonic survival in sheep

The functioning of the guinea-pig isolated portal vein was monitored by measuring spontaneous mechanical activity, responses to electrical stimulation and administered noradrenaline in normoxic conditions. The effect of hypoxia, induced by bubbling the physiological bathing solution with a 95% N(2)/5% CO(2) gas mixture, on the mechanical performance of the vein was then assessed. Spontaneous activity declined in hypoxia, with mean contraction tension reduced by 55 + or - 8.8%. The responses to electrical field stimulation (2-32 Hz, 0.7 msec. 70 V) were lowered by 14 + or - 4.6% but contractions produced by a range of noradrenaline concentrations (0.01-160 mu M) were unaffected by hypoxia. Substitution of glucose in the bathing solution with sucrose, a substrate unavailable to the cells for energy generation, produced a marked enhancement of the effect of hypoxia. Spontaneous activity was reduced by 76 + or - 8.3%, electrically-induced activity by 80 + or - 14.4% and noradrenaline-induced responses by 85 + or - 6.8%. Although in normoxia the activity and responses of the portal vein were unaffected by the presence of alpha-tocopherol, it significantly protected the functioning of the vein in hypoxic conditions. This effect was concentration-dependent within the range 10-160 mu M and was most marked when glucose was replaced by sucrose in the bathing solution.     

Electrocardiographic manifestations following electric injury

Bromomethane (BM) is a fumigant used in agriculture; it readily breaks down to bromide ion. WHO assessed the ADI of BM, at 1 mg/kg, using data on the toxicity of bromide. On the other hand, U.S. EPA used the observation of hyperplasia in the forestomach of rats given BM by gavage and arrived at a value of 0.0014 mg/kg. The validity of EPA's assessment is thus subject to question because of the data involved by (1) direct introduction of this volatile and reactive chemical to the GI by gavage and (2) using lesions in the rat forestomach which is absent in humans.