The effects of FK 506 on cytokine production are dependent on the mode of cell activation.
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Antibodies↗
Biomedical subjects
S Nagy
Publications and source records attributed to S Nagy.
Histamine release during intestinal ischemia-reperfusion: role of iron ions and hydrogen peroxide.
Reactive oxygen intermediates (ROI) play a major role in the mucosal damage developing during the reperfusion period following intestinal ischemia. We have shown previously that histamine (H) release is related to the ROI generated by xanthine oxidase during intestinal ischemia-reperfusion. The present study sought to determine the possible chain of events leading to H liberation. The artery supplying a segment of the ileum was occluded for 2 hr in 51 anesthetized dogs, and plasma levels of H were determined radioenzymatically in the venous effluent. Catalase was applied to scavenge hydrogen peroxide; dimethylsulfoxide and mannitol were used as hydroxyl radical scavengers; the role of catalytically active iron was assessed by using desferrioxamine. Pretreatment with either catalase or desferrioxamine, but not with dimethyl sulfoxide or mannitol, was effective in reducing the postocclusive H release. The results provide further in vivo evidence that ROI are causative agents in H liberation during reperfusion of the ischemic gut. Hydrogen peroxide can interact with catalytically active iron and generate highly reactive oxidants, which in turn are responsible for H release. The exact nature of these oxidants is still uncertain.
Animals↗
Selected risk factors in adolescent suicide attempts.
This study examined stress, depression, attempted suicide, and knowledge of common signs of potential suicide in Alabama adolescents. A modified version of the National Adolescent Student Health Survey (NASHS) was administered to 3,803 eighth- and tenth-grade public school students during the fall of 1988. The incidence of stress, depression, and attempted suicide was analyzed by gender, ethnicity, locale (urban vs. rural), and participation in sexual intercourse and use of alcohol. Chi-square tests were used to determine if there were significant differences between groups. Findings indicated that females were at greater risk than were males. Both males and females who engaged in sexual intercourse and alcohol consumption were at greater risk than were abstainers. When analyzed by ethnicity, white adolescents who engaged in these behaviors were at significantly greater risk than were those who abstained; differences were not as pronounced for black youth. Comparisons on the knowledge scale indicated that females scored better than males, whites scored better than blacks, and urban students scored better than rural students. The data suggest that many adolescents are having difficulty coping with stress and depression, and that those who are engaging in various types of risk-taking behavior are at greater risk for depression and suicide.
Adolescent↗
A comparison of AIDS and STD knowledge between sexually active alcohol consumers and abstainers.
Effective curricula should influence knowledge levels of all students, including high-risk populations. In this study, a modified version of the National Adolescent Student Health Survey was administered to a group of eighth and 10th grade students (N = 3,803) exposed to a curriculum designed to improve AIDS and STD knowledge levels. The analysis examined the influence of gender, ethnicity, alcohol use, and sexual activity as they related to AIDS and STD knowledge. Findings indicated poor knowledge scores on STD items, with no significant differences on group comparisons. Comparisons of AIDS knowledge scores indicated significant differences based on gender, ethnicity, and behavior. Females scored higher than males, whites scored higher than blacks, and abstainers from sexual activity and alcohol scored higher than their active counterparts. Results suggest current educational efforts are not equally effective. Future educational initiatives should be sensitive to group membership.
Acquired Immunodeficiency Syndrome↗
Modeling of low-frequency pulmonary impedance in dogs.
The mechanical impedance of the lungs (ZL) was measured in open-chest dogs with small-amplitude pseudorandom volume oscillations between 0.125 and 5 Hz, at mean transpulmonary pressures (Ptp) of 0.2, 0.4, and 0.8 kPa. At the lowest frequencies, the pulmonary resistance showed a marked negative frequency dependence and mirrored the changes in the reactance with altered Ptp. The ZL data were evaluated on the basis of two models, each containing the same airway compartment with a resistance and an inertance. The tissue impedance (Zti) in model 1 was represented with two compliances and a resistance (L. E. Mount. J. Physiol. Lond. 127: 157-167, 1955), whereas in model 2 a two-parameter formulation implying rate-independent dissipated work and frequency-dependent elastance (J. Hildebrandt. J. Appl. Physiol. 28: 365-372, 1970) was employed. The estimation of model parameters showed that model 2 was superior to model 1 in both fitting performance and parameter insensitivity to weighting in the fitting criterion. The model 2 coefficients of damping and elastance, characterizing the real and imaginary parts of Zti, respectively, depended on the lung distension and were closely correlated. Although ZL exhibited a slight dependence on the peak-to-peak volume excursion, at a given oscillatory volume no inconsistency with linear tissue viscoelasticity was detected.
Animals↗
The role of histamine release in shock.
More than 80 years after its discovery and nearly 70 years after its first being implicated in the mechanism of shock, the precise role of histamine (H) in the pathophysiology of the condition remains to be determined. The prevailing view over the decades has been that H is a noxious mediator contributing to the fatal outcome of shock. An adequate assessment of its role has long been hampered by the lack of a sufficiently sensitive and specific method for the measurement of H and by deficiencies of design in many studies. We now know that H is released in all types of shock. In low-output, high-resistance states, as in hypovolemic and cardiogenic shock, its effect (contrary to previous notions) appears to be beneficial, probably through the inhibition of excessive vasoconstriction and through a positive inotropic effect. In endotoxin shock the results are conflicting, but seem to indicate that H is not a lethal factor. In human septic shock, patients who died had higher H levels. The role of H release in the various forms of shock, both experimental and human, clearly needs an adequate, critical reevaluation, in carefully designed and executed studies using satisfactory methodology.
Histamine Antagonists↗
A canine model of hyperdynamic sepsis induced by intestinal ischemia.
A hyperdynamic sepsis model was developed in dogs. It is based on a 3-hour clamping of the arteries supplying the middle portion of the jejunum. The ensuing sepsis has a course of several days, during which the animals were studied in the conscious state. 2/3 of the animals developed a sustained 32-108 per cent increase in cardiac output, and survived 7 days or more. In the other 1/3 of the animals, the cardiac output was lower than the control value and all these animals died within 5 days. There were no differences between the two groups in other parameters examined. Sepsis caused a steady, slight decrease in mean arterial pressure, an increase in heart rate, and leukocytosis. The plasma levels of epinephrine and norepinephrine showed a sustained, significant elevation. The level of thromboxane B2 was high only on the first day of sepsis, and that of plasma renin activity on the first 2 days. Necrosis and edema of jejunal villi were demonstrated histologically in the early period. Hemocultures were positive in only 5 of 11 animals examined, suggesting the predominant role of absorbed toxins. This model simulates human sepsis well and is suitable for the study of pathophysiologic mechanisms in hyperdynamic sepsis.
Alkaline Phosphatase↗
Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion.
Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6'-methylene-bis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemia.
Allopurinol↗
Mood state changes of women as a function of regular aerobic exercise.
The present study examined mood states of aerobic exercisers before and after completing a 15-wk. program. The subjects (ages 18 to 36 yr.) were 86 women enrolled in activity classes at a large state school in the southeast. Subjects were initially classified according to previous exercise habits. Analysis indicated both groups of frequent and infrequent exercisers were similar in mood states. Participation in regular exercise did not significantly change or enhance the mood states from pretreatment measures. Pretest measures of mood states provided poor prediction of posttest measures, indicating extreme variability in subjects' scores.
Adolescent↗
Relations between preventive health behavior and hardiness.
To estimate the relationship between hardiness and preventive health behaviors a hardiness scale and a health hazard appraisal were administered to 211 college students. Multiple regression analysis indicated that modest amounts of variance on the hardiness measures were explained by the components of the health-hazard appraisals. Indications are that the concepts of hardiness and preventive health behavior are related and need further clarification.
Adult↗
Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions of rats.
This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hemorrhagic shock in the rat. Allopurinol (Zyloric), an inhibitor of xanthine oxidase (responsible for the formation of superoxide radicals) and MTDQ-DA (Kontrad), a synthetic antioxidant of dihydroquinoline type were used. In the anesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The blood shed was retransfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, the activity of endogenous peroxidase was examined histochemically and a histological grading was made. Both allopurinol and MTDQ-DA significantly protected against hemorrhagic shock-induced gastric lesions and peroxidation. These results suggest that oxygen-derived free radicals play an important role in the formation of gastric lesions produced by ischemia plus 0.1 N HCl.
Allopurinol↗
Chemical characterization of a positive inotropic plasma factor in shock.
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Animals↗
The role of the complement system in the pathogenesis of multiple organ failure in shock.
The results of our experiments suggest that the development of MOF is the result of a concerted autodestructive inflammatory process affecting the endothelium which is probably triggered off by the complement system. The combination of two noxious events (application of a low dose of endotoxin during hemorrhagic shock) leads to an enormous intravasal activation of complement including formation of C5a and the deposition of active split products of C3 (C3a, C3b) in the tissue of lung, liver, small intestine and kidney. Histological examination revealed ARDS-like pulmonary changes with inflammatory microvascular lesions and granulocytic infiltration primarily in the liver and to a lesser degree in the intestines and the kidney. The severity of organic lesion closely correlated with the extent of complement deposited. This corroborates the clinical observation that pulmonary and hepatic lesions are always the first signs of MOF, no matter what kind of noxious influence (trauma or peritonitis) gave rise to its development (Mc Menamy, 1980). Which mechanisms are involved in the processes by which active split products of C3 cause damage to tissue? C3a possesses strong chemotactic forces which can bring about aggregation of granulocytes in the tissue. Deposition of C3b on the contrary may lead to the formation of the cytolytically active membrane-attack-complex with the result of direct cell damage. We did not find any severe organic lesion or deposition of complement in our controls (endotoxin only, hemorrhage only). Our results suggest that MOF is a sequel of a generalized, autodestructive, inflammatory process which results from a hyperintensive and uncontrolled humoral immunoresponse to noxious events.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaphylatoxins↗
Humoral changes in shock induced by cardiac tamponade.
Cardiac tamponade was induced in dogs by the infusion of saline into the pericardial cavity. The mean arterial pressure dropped to approximately one-third and the cardiac output to one-fourth of the control level. This was accompanied by the release of vasoactive humoral mediators. Among the vasoconstrictor mediators measured in the plasma, the greatest rise during early tamponade occurred in vasopressin concentrations. Considerable elevations of epinephrine and nonrepinephrine concentrations and plasma renin activity were also demonstrated, these mediators reaching their maximum levels in late tamponade. This study for the first time demonstrates significant rises in plasma thromboxane B2 and histamine levels in cardiac tamponade. The histamine level elevation was greater in the portal venous blood than in the arterial blood. It is suggested that histamine may play a counterregulatory role in cardiac tamponade by attenuating excessive vasoconstriction caused by the activation of various vasoconstrictor systems.
Animals↗
The measurement of cardia output by the thoracic impedance method.
The aim of our experiments was to study the thoracic electrical impedance method as a method for measuring cardiac output in anesthetized dogs. Four electrodes were placed around the neck and thorax. A 50 kHz, 1 mA electric current was applied to the outer two electrodes and the two inner electrodes were used to measure impedance changes related to the stroke volume during the cardiac cycle at end-expiratory apnea. The cardiac output obtained by the impedance method was compared to the cardiac output measured by isotope dilution and by the electromagnetic flowmeter. Either mean cardiac output or cardiac output determined beat-to-beat from the pulsatile flow was measured with the latter method. Significant correlations were obtained between the impedance and the isotope dilution method (r = 0.8799), and between the impedance and the electromagnetic (mean) flow measurements (r = 0.7330). The comparison of impedance cardiac output to that determined from the pulsatile flow (beat-to-beat) also showed a good correlation (r = 0.7618). The effect of changing the fluid and air contents in the chest on the basal thoracic impedance was also studied.
Animals↗
Low-frequency respiratory mechanical impedance in the rat.
A modified forced oscillatory technique was used to determine the respiratory mechanical impedances in anesthetized, paralyzed rats between 0.25 and 10 Hz. From the total respiratory (Zrs) and pulmonary impedance (ZL), measured with pseudorandom oscillations applied at the airway opening before and after thoracotomy, respectively, the chest wall impedance (ZW) was calculated as ZW = Zrs - ZL. The pulmonary (RL) and chest wall resistances were both markedly frequency dependent: between 0.25 and 2 Hz they contributed equally to the total resistance falling from 81.4 +/- 18.3 (SD) at 0.25 Hz to 27.1 +/- 1.7 kPa.l-1 X s at 2 Hz. The pulmonary compliance (CL) decreased mildly, from 2.78 +/- 0.44 at 0.25 Hz to 2.36 +/- 0.39 ml/kPa at 2 Hz, and then increased at higher frequencies, whereas the chest wall compliance declined monotonously from 4.19 +/- 0.88 at 0.25 Hz to 1.93 +/- 0.14 ml/kPa at 10 Hz. Although the frequency dependence of ZW can be interpreted on the basis of parallel inhomogeneities alone, the sharp fall in RL together with the relatively constant CL suggests that at low frequencies significant losses are imposed by the non-Newtonian resistive properties of the lung tissue.
Animals↗
Respiratory mechanical impedance in the rat.
The forced oscillatory impedance of the total respiratory system (Zrs) was measured in seven anaesthetized, paralysed rats weighing 351 +/- 55 g. Tracheotomy was performed, and the animals were placed in the supine position in a body box. Pseudo-random pressure variations between 0.5 and 10 Hz were applied around the chest. Central airflow was measured with a heated screen pneumotachograph. Total respiratory resistance (Rrs) and elastance (Ers), corrected for the impedance of the tracheal cannula, were markedly frequency-dependent: Rrs fell from 37.3 +/- 19.1 kPa.l-1.s at 0.5 Hz to 17.6 +/- 4.4 at 2 Hz and 10.3 +/- 3.3 at 10 Hz; the corresponding Ers values were 453 +/- 14, 594 +/- 90 and 713 +/- 104 kPa.l-1, respectively. This indicates that in the frequency range encompassing spontaneous breathing rates the classical resistance-intertance-compliance model provides an inadequate description of the respiratory mechanics in the rat.
Airway Resistance↗
Cardiodepressant and cardiostimulant factors in shock.
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Amines↗