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M Maldonado

Publications and source records attributed to M Maldonado.

At least 19 recordsLinked to original sources
PubMed2000

Xanthine oxidase released from reperfused hind limbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock.

We have shown previously that rats subjected to tourniquet shock develop an acute form of remote organ injury of the liver that is both Kupffer cell (KC) and polymorphonuclear (PMN) leukocyte dependent. Circulating plasma xanthine oxidase (XO) has been shown to be responsible for the development of endothelial dysfunction and for remote organ injury of the lung and intestine after ischemia-reperfusion protocols. We now hypothesize that XO is released from rat hind limbs upon reperfusion and that it is responsible for KC and PMN leukocyte activation in this shock model. Our results show that about 30% of rat gastrocnemius muscle xanthine dehydrogenase (XD) is converted to XO during the 5-h tourniquet period and that it is released into the femoral vein within 10 min of reperfusion. Total muscle xanthine oxidoreductase activity (XO + XD) decreases within 30 min of reperfusion and is paralleled by a corresponding increase in femoral vein lactic dehydrogenase. In addition, liver tissue XO increases significantly within 30 min of reperfusion without a corresponding conversion of endogenous XD. Conversion of hepatic XD becomes evident 60 min after reperfusion is initiated, as does XO, and alanine aminotransferase (ALT) release into the hepatic vein, presumably from damaged hepatocytes as a consequence of oxidative stress. Tissue myeloperoxidase activity also increases significantly after the 60-min reperfusion period. That XO mediates KC and PMN activation is supported by the following observations: a) the close relationships between plasma XO and the time courses of tumor necrosis factor-alpha TNFalpha release into the hepatic vein and colloidal carbon clearance by KCs; b) that colloidal carbon clearance, TNFalpha and ALT release, loss of tissue free thiols, lipid peroxidation (TBARS), and liver infiltration by PMN neutrophils can also be induced by the administration of exogenous XO to normal rats; and c) pretreatment of rats with allopurinol inhibits KC activation and liver leukocyte infiltration. These results suggest that XO, released from the ischemic limb on reperfusion, is taken up by the liver were it mediates KC and PMN neutrophil activation and thus contributes to the development of multiple system organ failure after hind limb reperfusion.

Alanine Transaminase↗
PubMed2000

Patient privacy.

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Confidentiality↗
PubMed2000

Bright futures.

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Fellowships and Scholarships↗
PubMed2000

Not for sale.

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Drug Industry↗
PubMed2000

Getting paid.

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Academic Medical Centers↗
PubMed1999

Induction of autoimmunity in a transgenic model of B cell receptor peripheral tolerance: changes in coreceptors and B cell receptor-induced tyrosine-phosphoproteins.

Abrogation of peripheral tolerance in transgenic mice that express a uniform B-cell receptor may create a powerful tool to examine the molecular mechanisms that underlie the autoimmune response in B cells. Here we report that processes that induce a systemic lupus erythematosus-like syndrome in normal mice, namely chronic graft vs host reaction, trigger systemic autoimmunity in a well-established transgenic mice model of B cell receptor peripheral tolerance. The induction of graft vs host reaction in mice that carry both a rearranged B cell Ag receptors specific for hen egg lysozyme and expressing chronically circulating hen egg lysozyme Ag resulted in induction of high and sustained levels of circulating anti-hen egg lysozyme autoantibodies and glomerulonephritis with proteinuria. This was associated with marked changes in expression of cell-surface proteins, such as CD23 and complement receptor 2. B cells from the graft vs host-induced mice could proliferate in vitro in response to self-Ag, and upon stimulation with anti-IgD demonstrated rapid phosphotyrosine phosphorylation of specific proteins, which could not be induced in the anergic double transgenic B cells. Conversely, loss of tolerance was not associated with a higher induction in the level of Syk kinase phosphorylation following stimulation with anti-IgD. Taken collectively, these data establish that 1) processes that induce a systemic lupus erythematosus-like syndrome in normal mice can abrogate peripheral tolerance in transgenic mice expressing self-tolerized B cells, and that 2) loss of tolerance in this model is associated with marked changes in surface expression of B cell coreceptors as well as with selective changes in IgD-induced signaling by discrete tyrosine-phosphoproteins, but not Syk kinase.

Animals↗
PubMed1999

The multicomponent automated dissolution system: an alternative in the development and pharmaceutical analysis of generic polydrugs.

The necessity of assuring the quality of polydrugs, especially those with low aqueous solubility and in vivo absorption, has led to the development and evaluation of new techniques that can reduce the time and cost of analysis. This study examines the efficiency and accuracy of an automated dissolution system, fitted with an integrated multicomponent detector, for analysis of generic polydrugs using multiple linear regression (MLR). Trimethoprim and sulphamethoxazole were chosen as model drugs for this study and comparison was made with a conventional analysis based on HPLC. Both analytical systems under study gave reproducible and accurate results. Analysis of variance showed that there was no significant statistical difference between the methods of analysis, nor any statistical difference between the measured amounts of drug in the three different formulations. We have demonstrated that low cost instrumentation coupled with MLR data processing provides entirely satisfactory drug analysis to standard at least as good as that achieved using HPLC and provides an opportunity to reduce the time and analysis cost of other generic formulations.

Automation↗
PubMed1999

Percutaneous mitral valvotomy in patients eighteen years old and younger. Immediate and late results.

OBJECTIVE - To analyze immediate and late results of percutaneous mitral valvotomy (PMV) in patients < or = 18 year. METHODS - Between August '87 and July '97, 48 procedures were performed on 40 patients. The mean age was 15.6 years; 68.7% were females four of whom were pregnant. RESULTS - Success was obtained in 91.7% of the procedures. Immediate complications were severe mitral regurgitation (6.3%) and cardiac tamponade (2.0%). Late follow-up was obtained in 88.8% of the patients (mean value=43.2+/-33.9 months). NYHA functional class (FC) I or II was observed in 96.2% of the patients and restenosis developed in five patients, at a mean follow-up of 29.7+/-11.9 months. Three patients presented with severe mitral insufficiency and underwent surgery. Two patients died. CONCLUSION - PMV represents a valid therapeutic option in young patients. In these patients, maybe because of subclinical rheumatic activity, restenosis may have a higher incidence and occur at an earlier stage than in others persons.

Adolescent↗
PubMed1999

Medicare's new army.

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Centers for Medicare and Medicaid Services, U.S.↗
PubMed1999

Escape from a PPMC.

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Contract Services↗
PubMed1999

Closing the loophole.

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Employee Retirement Income Security Act↗
PubMed1999

The big payback.

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Blue Cross Blue Shield Insurance Plans↗
PubMed1999

Role of Küpffer cells and PMN leukocytes in hepatic and systemic oxidative stress in rats subjected to tourniquet shock.

Küpffer cells (KCs) have been implicated in leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs and polymorphonuclear (PMN) leukocytes on the oxidative stress elicited in the liver as a consequence of hind limb reperfusion in rats subjected to tourniquet shock, a shock model that differs from other models in that hepatic injury is a consequence of remote organ damage. Colloidal carbon clearance from blood and its incorporation into KCs demonstrate that these cells are activated after the 2 h hind limb reperfusion period and that they are responsible for the observed oxidative stress and for PMN leukocyte recruitment and activation. Liver oxidative stress in this model is evidenced by increased liver tissue GSSG/GSH ratio, thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, and a significant loss in total tissue superoxide dismutase (SOD) activity. Mean arterial blood pressure (MAP), as well as plasma levels of alanine aminotransferase (ALT), an index of hepatic tissue injury, total SOD activity, plasma levels of alpha-tocopherol and beta-carotene, and total plasma nitrite are also affected as a consequence of KC activation after the 2 h hind limb reperfusion period. Inhibition of KC activity by gadolinium chloride (GdCl3) reverted most of the above alterations to values that do no differ from those found in control animals. These results support the hypothesis that hepatic and systemic oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock is both KC and PMN leukocyte dependent.

Alanine Transaminase↗