Direct Deleterious Effect Research Articles

Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target?

Inflammation is a cornerstone of the post-myocardial infarction healing process. However, an exuberant systemic as well as loco-regional inflammatory response may have a direct deleterious effect on myocytes extending myocardial necrosis and thus altering long-term prognosis. For many years, this overwhelming inflammatory reaction has been proposed as pharmacological target. In animal models, encouraging results have been obtained. However, in human trials, none of the applied medications reached a convincing clinical impact. Nevertheless, this therapeutic strategy remains conceptually valid, especially in the era of reperfusion by percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). In this ischaemic setting, the inflammatory response in the peri-necrotic zone may extend the myocardial scar formation, thus playing an important prognostic role. Not surprisingly, the combination of available and new anti-inflammatory treatments, systemically administrated or locally applied, in association with primary PCI as reperfusion therapy is currently under intensive evaluation. Some promising preliminary results suggest that this treatment modality is likely to become standard care of AMI in the near future.

Constrained evolution of a quantitative character by pleiotropic mutation

The long-term response to directional selection and its selection limit are derived for a quantitative character that is controlled by pleiotropic mutations with direct deleterious effect on fitness. Directional selection is assumed to be weaker than the selection acting directly on mutations via deleterious effects (purging selection), which renders all mutations to eventual elimination. The analysis embedding this restrictive assumption indicates that the evolutionary response of the character starting from an equilibrium state, in which mutation and purging selection balance but no directional selection is operating, decreases monotonically with time at an exponential rate. And the fading rate of responses is mostly determined by the direct deleterious effect. Contrary to the expectation by the standard selection limit theory based on fixation of extant genetic variation, the present model predicts that the selection limit depends on the intensity of directional selection, the limit being proportional to the ratio of the directional selection intensity to the direct deleterious effect. A slightly larger genetic variance is maintained at the selection limit than would be without directional selection.

Invertebrate biodiversity in maize following withdrawal of triazine herbicides

Responses of key invertebrates within Farm Scale Evaluations (FSEs) of maize reflected advantageous effects for weeds under genetically modified herbicide-tolerant (GMHT) management. Triazine herbicides constitute the main weed control in current conventional systems, but will be withdrawn under future EU guidelines. Here, we reappraise FSE data to predict effects of this withdrawal on invertebrate biodiversity under alternative management scenarios. Invertebrate indicators showed remarkably consistent and sensitive responses to weed abundance. Their numbers were consistently reduced by atrazine used prior to seedling emergence, but at reduced levels compared to similar observations for weeds. Large treatment effects were, therefore, maintained for invertebrates when comparing other conventional herbicide treatments with GMHT, despite reduced differences in weed abundance. In particular, benefits of GMHT remained under comparisons with best estimates of future conventional management without triazines. Pitfall trapped Collembola, seed-feeding carabids and a linyphiid spider followed closely trends for weeds and may, therefore, prove useful for modelling wider biodiversity effects of herbicides. Weaker responses to triazines applied later in the season, at times closer to the activity and capture of invertebrates, suggest an absence of substantial direct effects. Contrary responses for some suction-sampled Collembola and the carabid Loricera pilicornis were probably caused by a direct deleterious effect of triazines.

Triamcinolone suppresses human tenocyte cellular activity and collagen synthesis.

Glucocorticoid injection is widely used in tendon disorders. Despite previous studies on the histologic and biomechanical changes in tendons after glucocorticoid injections, the role of glucocorticoid in tendon rupture still is controversial. It was hypothesized that glucocorticoid has a direct deleterious effect on human tenocytes, suppressing its cellular activity and collagen production. Primary cultures of human tenocytes were obtained from explants of healthy patellar tendon harvested during anterior cruciate ligament reconstructions. The effects on cell viability and cell proliferation were measured by [3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and 5-bromo-deoxyuridine incorporations. The effect on collagen synthesis was measured by H-proline incorporation assay. Triamcinolone acetonide at 10 to 10 mol/L decreased human tenocyte viability to 45% to 88% of control in a dose-dependent manner. Cell proliferation was suppressed to 87% +/- 8% at all doses. Treatment with 1 micromol/L triamcinolone acetonide reduced the amount of collagen synthesis as measured by H-proline incorporation from 40 +/- 2 cpm/1000 cells to 27 +/- 4 cpm/1000 cells. The suppressed human tenocyte cellular activity and reduced collagen production may lead to disturbed tendon structure and predispose the tendon to subsequent spontaneous rupture.

Commentary

Commentary

Mycophenolate mofetil: what is the evidence that it decreases chronic rejection?

Purpose of review The question addressed in the title of this paper iscontroversial because of the lack of clear data and conflicts due to the paucity of existing data. Therefore, the purpose of this review is to summarize some of the relevant clinical and experimental findings. Recent findings It has recently been suggested by a retrospective analysis of the United States Renal Data System data that mycophenolate mofetil (MMF) therapy is associated with a significant decrease in the relative risk of chronic allograft failure. Chronic allograft failure, however, may differ from a biopsy-proven chronic allograft nephropathy (CAN). MMF has been shown to inhibit antibody formation in animal models, and alloantibody does correlate with development of chronic allograft injury. Hence, there is compelling rationale to expect MMF therapy to decrease the incidence of chronic rejection of allografts in humans. Nevertheless, current data are only provocative and suggest a need for further direct study of this important question. Summary In summary, it is unclear at this time whether MMF has a direct salutary or deleterious effect on CAN in human renal transplantation.

Limiting mechanisms of force production after repetitive dynamic contractions in human triceps surae.

The influence of repetitive dynamic fatiguing contractions on the neuromuscular characteristics of the human triceps surae was investigated in 10 subjects. The load was 50% of the torque produced during a maximal voluntary contraction, and the exercise ended when the ankle range of motion declined to 50% of control. The maximal torque of the triceps surae and the electromyographic (EMG) activities of the soleus and medial gastrocnemius were studied in response to voluntary and electrically induced contractions before and after the fatiguing task and after 5 min of recovery. Reflex activities were also tested by recording the Hoffmann reflex (H reflex) and tendon reflex (T reflex) in the soleus muscle. The results indicated that whereas the maximal voluntary contraction torque, tested in isometric conditions, was reduced to a greater extent (P < 0.05) at 20 degrees of plantar flexion (-33%) compared with the neutral position (-23%) of the ankle joint, the EMG activity of both muscles was not significantly reduced after fatigue. Muscle activation, tested by the interpolated-twitch method or the ratio of the voluntary EMG to the amplitude of the muscle action potential (M-wave), as well as the neuromuscular transmission and sarcolemmal excitation, tested by the M-wave amplitude, did not change significantly after the fatiguing exercise. Although the H and T reflexes declined slightly (10-13%; P < 0.05) after fatigue, these adjustments did not appear to have a direct deleterious effect on muscle activation. In contrast, alterations in the mechanical twitch time course and postactivation potentiation indicated that intracellular Ca(2+)-controlled excitation-contraction coupling processes most likely played a major role in the force decrease after dynamic fatiguing contractions performed for short duration.

Iron deficiency and cognition

Iron deficiency is the most prevalent nutritional disorder in the world. One of the most worrying consequences of iron deficiency in children is the alteration of behaviour and cognitive performance. In iron-deficient children, striking behavioural changes are observed, such as reduced attention span, reduced emotional responsiveness and low scores on tests of intelligence. Animal studies on nutritional iron deficiency show effects on learning ability that parallel the human studies. Despite the obvious confounding impact of socioeconomic factors, there is a wealth of clinical, biochemical and neuropathological research that shows that iron deficiency can exert a direct deleterious effect on learning and the brain, and that this can occur with normal haemoglobin levels. Nutritional iron replacement therapy readily corrects haematological iron status in iron-deficient children within 2-3 weeks, but behavioural problems persist for several months or years. This resi stance to iron-replacement therapy and its long-term consequences on learning are not quite understood. A recent study in infants showed that the cognitive deficits in iron deficiency was reversed with iron supplementation. This finding provides evidence that in some settings cognitive deficits are not always permanent. Although further research is required to address these issues, several studies support the theory that iron sufficiency throughout the course of brain development is critical to normal brain iron and behavioural outcome.

The role of glial reaction and inflammation in Parkinson's disease.

The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In Parkinson's disease, postmortem examination reveals a loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the propagation and perpetuation of neuronal degeneration. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF-alpha, Il-1beta, IFN-gamma), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase-3 and caspase-8, which are known effectors of apoptosis, has been reported in Parkinson's disease. Yet, caspase inhibitors or invalidation of TNF-alpha receptors does not protect dopaminergic neurons against degeneration in experimental models of the disease, suggesting that manipulation of a single signaling pathway may not be sufficient to protect dopaminergic neurons. In contrast, the antiinflammatory drugs pioglitazone, a PPAR-gamma agonist, and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease.

Histometric evaluation of the effect of nicotine administration on periodontal breakdown: an in vivo study.

The present study investigated the effect of nicotine administration on periodontal breakdown resulting from ligature-induced periodontitis in rats. Twenty adult male Wistar rats were used. After anesthesia, a mandibular first molar was randomly assigned to receive a cotton ligature in the sulcular area while the contralateral tooth was left unligated. The animals were randomly assigned to one of the following treatments. of daily intraperitoneal injections: A - saline solution, B -0.37 mg of nicotine kg, C -0.57 mg of nicotine kg and D -0.73 mg of nicotine/kg. Thirty days later, the animals were sacrificed and the specimens routinely processed for serial decalcified sections. Statistical analysis (ANOVA) revealed greater bone loss (p<0.05) in the ligated teeth of animals which received nicotine (groups B/C D) than in the ligated teeth of animals which received saline solution (group A). In addition, a dose-dependent response was observed among the nicotine groups. A negative effect of nicotine was observed in the unligated teeth of the experimental groups (p<0.05). Therefore, daily administration of nicotine enhanced, in a dose-dependent manner, the effects of local factors in producing periodontal breakdown. Furthermore, the nicotine seemed to have a direct deleterious effect on the periodontal tissues.

Blunted sympathetic response in diabetic patients with decompensated congestive heart failure

Background: The risk for congestive heart failure is strongly increased in diabetes, and the prognosis of diabetic patients with established heart failure is worse compared to nondiabetic patients. Heart failure entails complex alterations in autonomic and neurohormonal responses, which exert a direct deleterious effect on the heart and contribute to progressive circulatory failure. Altered neurohumoral physiology may underlie the poor prognosis of diabetic patients with heart failure. Methods: We studied 88 patients (mean age 61±13 years) admitted for decompensated heart failure. Neurohormonal and cytokine profiles, including plasma renin activity, aldosterone, norepinephrine, endothelin-1, tumor necrosis factor-α, and interleukin-6, were obtained in all patients. In addition, a 24-h Holter recording was performed, and time and frequency domain heart rate variability indices were calculated. Results: Of 88 patients, 48 were classified as having diabetes based on history, diet therapy, or use of oral hypoglycemic agents or insulin. The only difference in the neurohormonal and cytokine profile between the diabetic and nondiabetic groups was a significantly lower norepinephrine level in diabetic patients (668±64 vs. 489±50 pg/ml, P=0.009). Heart rate variability analysis revealed that the low-frequency power in normalized units (an index of sympathetic modulation) was significantly lower in diabetic patients (4.7±1.4 vs. 5.9±0.9, P=0.04). No significant differences occurred in any of the time (the percentage of RR intervals with >50 ms variation and the square root of mean squared differences of successive RR intervals) or frequency domain (high frequency power) indices of parasympathetic modulation between the two groups. Conclusions: Patients with diabetes mellitus exhibit a blunted sympathetic response during heart failure decompensation. Blunted sympathetic activation in the setting of symptomatic heart failure may impair the ability of the myocardium to compensate and contribute to the high incidence of symptomatic heart failure among diabetic patients.

Abortive rabies virus central nervous infection is controlled by T lymphocyte local recruitment and induction of apoptosis.

Nonfatal paralysis, induced by the attenuated Pasteur strain of rabies virus, is characterised by local and irreversible flaccid paralysis of the inoculated limbs. We characterised the spread and localisation of virus in the CNS of infected mice, determined the nature of cell injury and examined the role of the immune response. Data indicate that infection of BALB/c mice induced paralysis in 60% of infected mice, the others recovering without sequelae. In both groups of mice, virus was detected in restricted sub-populations of neurons from the brain and spinal cord, and intensity of the neuropathology correlated with levels of rabies RNA and apoptotic infected neurons. However, apoptosis of neurons and paralysis were not due to a direct deleterious effect of the virus, but induced by a T-dependent immune response, as evidenced by their absence in nude mice. Paralysed and asymptomatic mice developed a similar rabies virus-specific IgG2a antibody response, thus excluding the role of any modification of the humoral immune response. In contrast, three events were critically associated with the development of neurological symptoms: the amount of virus in the CNS, the level of apoptosis in both infected neurons and uninfected surrounding cells and the progressive parenchymal infiltration of CD4+ and CD8+ T cells at the site of infection. These data suggest that during nonfatal rabies infection, the levels of viral replication and primary degeneration of infected neurons by apoptosis could be responsible for the infiltration of T lymphocytes capable of inducing secondary degeneration of neural cells.

Platelet-activating factor plays an important role in reperfusion injury in myocardium

Although platelet-activating factor has been implicated in the pathogenesis of neutrophil-induced reperfusion injury, it has other mechanisms of direct deleterious hemodynamic effect. In this study we evaluated the definitive role of platelet-activating factor in myocardial reperfusion injury. Porcine hearts that underwent 60 minutes of normothermic ischemia with cardioplegia and 60 minutes of reperfusion under cardiopulmonary bypass were divided into three groups according to the methods of 15 minutes of controlled reperfusion: whole blood reperfusion group (n = 6), leukocyte-depleted reperfusion group (n = 6), and platelet-activating factor receptor antagonist (CV-3988) group (n = 6). At 60 minutes of reperfusion, the percentage of recovery of maximum slope of the pressure-volume relationship measured with intraventricular balloon, malondialdehyde value in coronary sinus blood, tissue adenosine triphosphate, and percentage of spontaneous defibrillation were evaluated. The receptor antagonist group showed significantly better recovery of maximum slope of the pressure-volume relationship than did the whole blood reperfusion group. Moreover, the receptor antagonist group showed significantly less release of malondialdehyde in the coronary sinus, higher values of adenosine triphosphate in the myocardium, and a higher percentage of spontaneous defibrillation than did the whole blood reperfusion group. On the other hand, the leukocyte-depleted reperfusion group showed no significant differences of maximum slope of the pressure-volume relationship, malondialdehyde, adenosine triphosphate, or spontaneous defibrillation as compared with the whole blood group. These results suggest that platelet-activating factor receptor antagonist attenuated severe damage in whole blood reperfusion of the myocardium as compared with leukocyte-depleted reperfusion, which also suggests that platelet-activating factor may play a more important role in myocardial reperfusion injury than do neutrophils.

Low-Energy Helium Neon Laser Irradiation Does Not Alter Human Keratinocyte Differentiation

There are reports that low-energy HeNe irradiation can enhance wound healing in vivo. We have previously demonstrated that HeNe irradiation increases the motility of human epidermally derived keratinocytes in vitro. Here we investigate whether HeNe irradiation alters normal keratinocyte differentiation, which is essential for the formation of a normal, functioning epidermis. Subconfluent keratinocyte cultures were irradiated three times within 24 h with either 0, 0.8, 3, or 7.2 J/cm2. After cultures reached post-confluence, parameters of growth and differentiation, such as cell number, cornified envelope (CE) formation, and transglutaminase activity were measured. No significant differences were found between the control (0 J) and irradiated cultures in these assays. We also examined the pattern of newly synthesized keratins in cultures irradiated with 7.2 J/cm2 three times within a 24-h period. Both control and irradiated cultures exhibited similar keratin patterns. These results provide evidence that HeNe irradiations of up to 7.2 J/cm2 have no direct deleterious effect on normal keratinocyte differentiation needed for the formation of a functional epidermis. Hence, it is anticipated that the clinical use of the HeNe laser irradiance that enhances keratinocyte migration in vitro (0.8 J/cm2) to promote wound healing in vivo will not alter the ultimate integrity or differentiated function of the epidermis that migrates to cover the wounded area.

The Desensitization of Normal B-Cells to Glucosein vitroIs Transient and not Related to High Glucose Levels*

To examine the postulated phenomenon of glucotoxicity toward the B-cell, islets isolated from normal adult rats were cultured for 1-6 days in RPMI medium at various glucose concentrations. Insulin release and (pro)insulin biosynthesis by these islets were then measured in short term incubations. The 1-day cultured islets (at 9.7 mM glucose) displayed a deficient glucose-stimulated insulin release which was partially restored in the presence of forskolin (5 microM). By contrast they exhibited a consistent insulin release in response to ketoisocaproate (10 mM), 12-O-tetradecanoylphorbol-13-acetate (2 microM), or the combination of Ba2+ (2 mM) and theophylline (1.4 mM) in the absence of extracellular Ca2+. Desensitization of their B-cells was not specific for glucose, since glyceraldehyde (10 mM) or leucine (10 mM) also failed to stimulate insulin release. Desensitization was not related to glucose concentration (5.6, 9.7, or 16.7 mM) in the medium during the 1-day culture period and was restricted to the secretory function, with no impairment of the biosynthesis process. The desensitization to glucose was transient, and high glucose levels (9.7 and 16.7 mM) in the culture medium favored restoration of the subsequent secretory response to the hexose. Under conditions of recovery of B-cell sensitivity to glucose in vitro (5 days at 9.7 mM glucose), the secretory response to acute glucose was in fact significantly enhanced after an additional exposure (1 day) to very high glucose levels (22 or 55 mM). The present results argue against 1) the possibility that islets suffer from some unspecific decreased viability after a 1-day culture period; and 2) the hypothesis that glucose insensitivity in the 1-day cultured islets is primarily caused by a direct deleterious effect of high glucose concentrations on the B-cells. They, rather, reinforce the view that high glucose levels are actually crucial in the preservation of the insulin secretory response to glucose of islets maintained in tissue culture.

Direct toxic effect of the radiocontrast agent diatrizoate on renal proximal tubule cells.

The pathophysiology of radiocontrast agent-induced acute renal failure is presently unclear. To test for a possible direct deleterious effect of diatrizoate, a commonly used radiocontrast agent, on renal tubule cells, suspensions enriched in rabbit proximal tubule segments were incubated with sodium diatrizoate. After these manipulations, a variety of well-established metabolic parameters to quantitate the extent of cell injury were measured. Diatrizoate sodium (25 mM) produced significant declines in tubule K+, ATP, and total adenine nucleotide (TAN) contents, significant decreases in tubule basal and uncoupled respiratory rates, and a significant increase in tubule Ca2+ content, demonstrating the development of cell injury induced by diatrizoate. These effects were dose related and were progressive with increasing incubation time from 97.5 to 157.5 min. The effects of N-methylglucosamine (meglumine) on renal tubule cell viability was also evaluated. Meglumine is a low molecular weight amino-substituted cationic compound and is commonly added to radiocontrast dye solutions. Meglumine (25 mM) had significant effects to lower tubule K+ content and to decrease both tubule basal and uncoupled respiratory rates. These alterations were slightly additive to diatrizoate in that meglumine diatrizoate produced greater alterations in tubule-metabolic parameters compared to diatrizoate sodium. A period of 22.5 min of hypoxia also caused deleterious changes in each of these quantitative indices of cell viability, and diatrizoate potentiated the degree of hypoxia-induced cell injury. These results demonstrate that the radiocontrast agent, diatrizoate, is directly toxic to renal proximal tubule cells. Meglumine, a cation added to diatrizoate containing radiocontrast solutions, also had a moderate toxic effect on renal epithelial cells and added to the toxicity of diatrizoate. Diatrizoate also aggravated the degree of cell injury induced by a 22.5-min period of hypoxia. These experiments thus provide evidence for a direct toxic effect of diatrizoate on proximal renal tubule cells which was additive to hypoxic cell injury.

Vitreous changes after neodymium-YAG laser photodisruption.

We investigated physicochemical changes in the vitreous body after photodisruption with a Q-switched neodymium-YAG laser. In vivo proton nuclear magnetic resonance imaging techniques were employed to assess alterations in the vitreous of irradiated rabbit eyes. Measurements of proton relaxation times (T1 and T2), viscosity, and chromatographic spectra were made in vitro on irradiated bovine and rabbit vitreous, and circular dichroism measurements were used to study changes in an irradiated sodium hyaluronate solution. Statistically significant changes in T1, were observed immediately after irradiation, but the small magnitude and reversibility of those changes, combined with the fact that the other measurements detected no changes, suggest that neodymium-YAG laser photodisruption does not have a direct deleterious effect on the structural integrity of the normal vitreous body.

Is the renin-angiotensin system really unnecessary in patients with severe chronic heart failure: The price we pay for interfering with evolution

Inhibition of the angiotensin-converting enzyme has become an established approach in the management of patients with severe chronic heart failure (1,2). Both captopril and enalapril produce shortand long-term hemodynamic and clinical improvement in these patients (3), and both drugs have been shown to be more effective than placebo in randomized double-blind clinical trials (4-9). The most recently published trial documenting the efficacy of enalapril in ambulatory patients with heart failure by Creager et al. (9) appears in this issue of the Journal. Other studies (I) suggest that the benefits of long-term treatment with captopril are greater than can be achieved with other vasodilator drugs, particularly hydralazine and prazosin. Furthermore, converting enzyme inhibition may reduce the frequency of ventricular tachyarrhythmias in patients with severe left ventricular dysfunction, perhaps by reducing circulating levels of catecholamines or preserving total body stores of potassium (6). By these favorable hemodynamic and antiarrhythmic actions, long-term therapy with captopril and enalapril may prolong survival in selected patients (10,11). This accumulated evidence creates a compelling case for a direct deleterious effect of the renin-angiotensin system in severe

The challenge for reconceptualization.

ITH CHARACTERISTIC scholarly perception a d breadth of perspective, Robin Room has provided a provocative paper on priorities in social science research on alcohol. By applying the historical framework of the_last third of a century to his analysis, and by viewing social science research on alcohol in the broader perspective of the social science and the alcohol problems fields generally, Room has helped pinpoint the parochial pitfalls that have prevented a more effective impact of alcohol research on social science perceptions and of social science research on alcohol problems and policies. As Room has pointed out, alcohol social science research in the last four decades has been heavily weighted with efforts to identify social causes of alcohol problems rather than the effects of such problems on society. Room believes that this may be due in part to the reluctance of the scientists entering the field in the 1940s to be identified with the temperance movement and its stress on the dire consequences of drinking. It should be remembered that the national prohibition experiment was still a recent experience in the 1940s and that people interested in alcohol problems were assumed to be either wet ...... or dry. It can also be noted that several prevailing biological scientific assumptions in the 1940s were diametrically opposite to claims of the temperance movement. For example, temperance messages emphasized that alcohol could have a direct deleterious effect on body organs; that it could damage the brain, stomach, liver, heart and fetus. Most scientists tended to reject the concept of direct damage and assumed that alcohol-related isease was due to nutritional deficiency, unhygienic living, or other concomitants of heavy drinking. In light of recent modifications of scientific thinking about the relationship between alcohol and organic disease and fetal damage, it is interesting to conjecture whether the need of scientists to dissociate from the temperance ideology and from

Accelerated Removal of Platelets during Perfusion of Isolated Lungs with Perfluoro Erythrocyte Substitute

SummaryAn emulsion of a fluorochemi-cal (FC-80), which has been shown to function as a substitute for the erythrocyte in the transport of O2 and CO2, has been found to cause lung damage when infused intravenously in intact animals. Addition of this emulsion to the fluid perfusing rat and guinea pig isolated lung preparations caused no significant changes in the pressures required for ventilation and perfusion of the lungs at constant flow rates, or in the weight of the lungs. Addition of this emulsion after prior addition of human blood platelets, caused a large increase in the rate of removal of platelets from the perfusion fluid. These results indicate that the fluorochemical emulsion does not have a direct deleterious effect on the lungs but that an interaction between fluorochemical particles, blood platelets, and the lung occurs, which might lead to lung damage.