Increased resistance to plasmic degradation of fibrin with highly crosslinked alpha-polymer chains formed at high factor XIII concentrations

We have previously demonstrated that increasing factor XIII concentrations above that present in plasma (1 U/mL) results in the formation of very high molecular weight alpha fate polyacrylamide and agarose gel electrophoresis (SDS-PAGE). In this report, we have examined the effect of such crosslinking on plasmic susceptibility of fibrin prepared from purified fibrinogen and from plasma in the presence of factor XIII concentrations between 0 and 10 U/mL. The crosslinking achieved with purified fibrinogen at 1 U/mL factor XIII increased resistance to plasmic degradation by 32% as measured in a radiolabeled clot lysis system. However, further increases in plasmic resistance occurred at factor XIII concentrations of 2 and 10 U/mL, the latter decreasing the lysis rate to 45% of that which occurred in the absence of factor XIII. To achieve the same rate of clot lysis with fibrin formed using 10 U/mL rather than 1 U/mL of factor XIII, an increase in plasmin concentration of up to 4.2-fold was required. Similar results were obtained using clots prepared from plasma in the presence of factor XIII concentrations greater than 1 U/mL. Since the alpha 2-plasmin inhibitor content was the same for fibrin at 1 or 10 U/mL factor XIII, the increasing plasmic resistance could not be attributed to increased binding of the inhibitor. We conclude that fibrin prepared in the presence of factor XIII at concentrations exceeding that in plasma shows increased resistance to plasmic degradation, which is likely explained by the formation of very high molecular weight alpha polymer chains.     

Ethnoveterinary Application of Morinda Citrifolia Fruit Puree on a Commercial Heifer Rearing Facility with Endemic Salmonellosis

We have previously reported that Morinda citrifolia (noni) puree modulates neonatal calves developmental maturation of the innate and adaptive immune system. In this study, the effect of noni puree on respiratory and gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic salmonellosis was examined. Two clinical trials were conducted whereby each trial evaluated one processing technique of noni puree. Trials 1 and 2 tested noni versions A and B, respectively. Puree analysis and trial methods were identical to each other, with the calf as the experimental unit. Calves were designated to 1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every 12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning age, weight gain from admission to weaning, and weaned by 6 weeks, were used as clinical endpoints for statistical analysis. In trial 1, calves supplemented with 15 mL noni puree of version A every 12 hr had a higher probability of being weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical treatments by 42 days of age when compared to controls (P = 0.02). There was a trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when compared to controls (P = 0.06 and 0.08, respectively). There were no differences in weight gain or mortality for any treatment group in either trial.     

Near-triploid and near-tetraploid acute lymphoblastic leukemia of childhood

Cytogenetic and DNA flow cytometric analyses of leukemic cells from 1,971 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified stem lines with modal chromosome numbers greater than 65 in 26 patients (1.3%). Near-triploidy (66 to 73 chromosomes) was found in six cases and near-tetraploidy (82 to 94 chromosomes) in 20. A striking morphologic finding was the presence of clumped chromatin with grooved nuclei or Rieder cell formation in 20 cases. Other than a slight excess of the pre-B immunophenotype, the near-triploid cases did not appear to differ substantially from the general ALL population in clinical features. In contrast, near-tetraploid cases were more often associated with a T-cell immunophenotype (47% v 14%, P less than .001) and L2 morphology (30% v 22%, P less than .01), and were older at diagnosis (median age, 8.6 v 4.8 years, P = .01) than cases with other ploidies. Moreover, an unusually high proportion of near-tetraploid cases tested (6 of 15) expressed one or more of the myeloid-associated antigens CD13, CD15, and CD33. Despite the use of contemporary intensive chemotherapy and short follow-up for most patients, 6 of the 20 near- tetraploid cases have relapsed or died. This study suggests that the near-tetraploid subtype differs from other cases of hyperdiploid greater than 50 ALL, which have been associated with a favorable prognosis.     

Are beta-adrenoreceptors involved in the intestinal absorption and tissue distribution of iron in the rat?

⁵⁹Fe was incorporated in vivo into intestinal sacs prepared in iron deficient rats and ⁵⁹Fe counts were detected in blood, spleen, liver, femur and intestine. The i.v. injection of isoproterenol (i.v. 2 μg/rat) or N′,O′-dibutyryladenosine 3′,5′-cyclic monophosphate (10 μM/100 g b.w.) enhanced significantly the iron counts in blood, spleen, liver and femur but not in intestine. (−)-Propranolol (2 mg · kg⁻¹ b.w.i.v.) antagonized the stimulatory effect of isoproterenol. It is suggested that isoproterenol increases iron absorption via the stimulation of β-adrenoreceptors of the intestinal mucosa.     

Oxygen-derived free radicals and postischemic myocardial reperfusion: therapeutic implications

Oxygen-derived free radicals have been implicated in the pathogenesis of various disease states, including myocardial ischemia and reperfusion. In this article, we review 1) the evidence linking free radical production and myocardial injury during myocardial ischemia and reperfusion and 2) results of studies of the effects of the pharmacological therapies available potentially to prevent free radical-mediated injury. Free radicals can be produced during ischemia and reperfusion by several different biochemical pathways. Of these, the xanthine oxidase reaction and the output of free radicals by neutrophils that have accumulated in damaged tissue have been studied extensively. When produced, free radicals can potentially damage myocytes or endothelial cells through peroxidation of membrane lipids or damage to proteins or nucleic acids. Using electron spin resonance spectroscopy, several studies have shown a 'burst' of oxygen free radicals immediately after reperfusion. Moreover, exogenous generation of intravascular free radicals has been shown to produce marked vascular and myocyte damage, as well as contractile dysfunction. 'Anti-free radical' interventions, such as xanthine oxidase inhibitors and free radical scavengers have been reported to prevent contractile dysfunction and reperfusion-induced arrhythmias after an episode of reversible ischemic injury. However, after more severe episodes of ischemia, such interventions have had conflicting effects on myocardial infarct size. 'Anti-free radical' interventions could be of potential use in situations where reversible ischemic injury occurs. In situations where reperfusion is achieved after irreversible ischemic injury has occurred, the potential beneficial effect of these treatments on infarct size is more doubtful.