Identification of Plasma Lipid Alterations Associated with Melanoma Metastasis.

The aim of this study was to apply a state-of-the-art quantitative lipidomic profiling platform to uncover lipid alterations predictive of melanoma progression. Our study included 151 melanoma patients; of these, 83 were without metastasis and 68 with metastases. Plasma samples were analyzed using a targeted Lipidyzer™ platform, covering 13 lipid classes and over 1100 lipid species. Following quality control filters, 802 lipid species were included in the subsequent analyses. Total plasma lipid contents were significantly reduced in patients with metastasis. Specifically, levels of two out of the thirteen lipid classes (free fatty acids (FFAs) and lactosylceramides (LCERs)) were significantly decreased in patients with metastasis. Three lipids (CE(12:0), FFA(24:1), and TAG47:2-FA16:1) were identified as more effective predictors of melanoma metastasis than the well-known markers LDH and S100B. Furthermore, the predictive value substantially improved upon combining the lipid markers. We observed an increase in the cumulative levels of five lysophosphatidylcholines (LPC(16:0); LPC(18:0); LPC(18:1); LPC(18:2); LPC(20:4)), each individually associated with an elevated risk of lymph node metastasis but not cutaneous or distant metastasis. Additionally, seventeen lipid molecules were linked to patient survival, four of which (CE(12:0), CE(14:0), CE(15:0), SM(14:0)) overlapped with the lipid panel predicting metastasis. This study represents the first comprehensive investigation of the plasma lipidome of melanoma patients to date. Our findings suggest that plasma lipid profiles may serve as important biomarkers for predicting clinical outcomes of melanoma patients, including the presence of metastasis, and may also serve as indicators of patient survival.

Recovery of the Decreased Phagocytic Function of Peripheral Monocytes and Neutrophil Granulocytes following Cytoreductive Surgery in Advanced Stage Epithelial Ovarian Cancer.

(1) Monocytes and neutrophil granulocytes are the phagocytic cells of the innate immune system, playing a crucial role in recognizing and eliminating tumor-transformed cells. Our objective was to assess the impact of advanced-stage epithelial ovarian cancer (EOC) and cytoreductive surgery on the phagocytic function of peripheral monocytes and neutrophil granulocytes. We aimed to compare the pre- and postoperative phagocytic function of these immune cells in EOC patients with healthy control women. Additionally, we aimed to examine the influence of surgery on phagocytic function by comparing pre- and postoperative samples from patients with benign gynecological tumors. (2) We examined peripheral blood samples from 20 patients with FIGO IIIC stage high-grade serous EOC and 16 patients with benign gynecological tumors as surgical controls, collected before and seven days after tumor removal surgery, and from 14 healthy women. After separation, the cells were incubated with Zymosan-A particles, and the phagocytic index (PI) was assessed using immunofluorescence microscopy. One-way ANOVA, the Kruskal-Wallis H-test, and the paired samples t-test were used for the statistical analysis of the data. A significance level of p < 0.05 was applied. (3) Peripheral monocytes and neutrophils from EOC patients exhibited significantly lower preoperative PI values compared to healthy controls (p < 0.001; p < 0.001, respectively). Following cytoreductive surgery, the PI values of immune cells in EOC patients significantly increased by the 7th postoperative day (p < 0.001; p < 0.001), reaching levels comparable to those of healthy controls (p = 0.700 and p = 0.991). In contrast, there was no significant disparity in the PI values of cells obtained from pre- and postoperative blood samples of surgical controls when compared to healthy women (monocytes: p = 0.361 and p = 0.303; neutrophils: p = 0.150 and p = 0.235). (4) EOC and/or its microenvironment may produce factors that reduce the phagocytic function of monocytes and neutrophils, and the production of these factors may be reduced or eliminated after tumor removal.

Evaluating the Phagocytic Index of Peripheral Leukocytes in Endometriosis by Plasma Experiments.

Background and Objectives: Endometriosis is a benign, chronic disease, that negatively influences the quality of life of affected women and is responsible for a remarkable amount of infertility. The pathophysiology of the disease is still not clarified, but the insufficient immune surveillance plays a significant role in it. The phagocyte function of innate immune cells may play a role in the elimination of ectopic endometrium. The purpose of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes, incubated in heat-inactivated and not-inactivated plasma samples from healthy women and from women with endometriosis before and after the surgical treatment. Materials and Methods: Blood samples were collected from eight preoperative and eight postoperative patients with endometriosis before and after the surgical treatment, and from 16 healthy patients as controls. Neutrophil granulocytes, monocytes and blood plasma samples were isolated. Cells were incubated in different plasma samples, and the phagocytic index was determined with a fluorescence microscope. Results: The phagocytic index of granulocytes and monocytes isolated from patients with endometriosis was significantly decreased compared to healthy women after the cells were incubated in their own plasma. Preoperatively isolated cells from patients with endometriosis demonstrated an improved phagocyte function after incubating them in plasma samples from healthy controls. In contrast, the phagocytic activity of cells from healthy women significantly reduced after being incubated in the plasma of preoperative endometriosis patients. The heat-inactivation of plasma samples did not affect the results. Conclusions: Active endometriosis lesions may produce heat-stable systemic immunomodulatory factors, which reduced the phagocyte function of peripheral monocytes and neutrophil granulocytes. The phagocyte function of these cells can be normalized after the complete surgical removal of endometriosis, which then demonstrates similar values as in healthy women.

Heavy metal contamination in recorded and unrecorded spirits. Should we worry?

Heavy metals can be released into all alcoholic beverages during production and storage. However, there is at least a theoretical risk that they could be present in higher, and potentially toxic, concentrations in those produced in the household and small-scale stills common in Central and Eastern Europe, which lack quality control and whose products are unrecorded by authorities. Yet, so far, few studies comparing concentrations of heavy metals in recorded and unrecorded spirits have been published. In this study we ask whether there is any difference between heavy metal concentrations in recorded and unrecorded spirits and, thus, the related health risk. The levels of heavy metals were determined in recorded (n = 97) and unrecorded (n = 100) spirits using inductively coupled plasma optical emission spectrometric analysis and applied to population-based risk assessments, considering average, regular and chronic heavy drinkers. Concentrations of Cu, Zn, and Sn were significantly higher in unrecorded spirits than those in their recorded counterparts and recorded spirits contained significantly higher levels of Fe, Mn, and Ni than unrecorded spirits. Combined exposure to heavy metals posed a potential health risk in chronic heavy drinkers consuming recorded spirits. However, when compared to the health risk arising from drinking large volumes of ethanol, the risk is negligible. Consequently, there are no grounds to worry about the adverse effects of heavy metals from spirits.

Is there any difference between the health risk from consumption of recorded and unrecorded spirits containing alcohols other than ethanol? A population-based comparative risk assessment.

Alcohol-attributable mortality in certain countries of Central and Eastern Europe (CEE) remains higher than in their western neighbours. The effect of unrecorded alcohol consumption, including home-made fruit spirits have been suggested as an explanation. Besides ethanol, recorded and unrecorded spirits frequently contain other aliphatic alcohols (OAAs). Our aim was to ascertain whether there is any difference in the amounts of OAAs in recorded and unrecorded spirits, and thus the health risk associated with their consumption. The concentrations of ethanol and OAAs in recorded (n = 119) and unrecorded (n = 87) spirits were determined by gas chromatography and used in a Monte Carlo type probabilistic simulation to assess the risk based on average consumption level, consumption by regular drinkers and chronic heavy drinkers. The concentrations of OAAs in unrecorded spirits were significantly higher [median: 9896.1 mg/L, interquartile range (IQR): 7898.3-12 634.6 mg/L] than those in their recorded (median: 975.6 mg/L, IQR: 136.9-4006.7 mg/L) counterparts. Besides ethanol, methanol also posed a health risk at each consumption level. The risk associated with exposure to OAAs was higher only in chronic heavy drinkers consuming unrecorded spirits. These findings reinforce the importance of action to address the risks associated with consumption of recorded and unrecorded spirits.

[Phagocytic function of monocytes and neutrophil granulocytes in ovarian cancer]. / Monocyták és neutrophil granulocyták fagocitafunkciója ovariumcarcinomában.

INTRODUCTION: Recently, tumor-infiltrating immune cells have been studied in various cancers. However, fewer studies address the role of peripheral immune cells in the pathogenesis of cancer. AIM: Our aim was to investigate whether the phagocytic activity of peripheral monocytes and neutrophil granulocytes is affected by the removal of tumor in advanced ovarian cancer. METHOD: We investigated peripheral blood samples from 12 patients with advanced stage of serous epithelial ovarian cancer - which were collected before the optimal tumor reduction surgery and on the 7th postoperative day - and from 8 healthy women. After separation of monocytes and neutrophils, the cells were incubated with opsonized fluorescein isothiocyanate-labeled zymosan A particles as the target of phagocytosis. By using fluorescence microscope we counted the number of particles phagocytized by the cells and calculated the phagocytic index. Statistical analysis of the data was performed using analysis of variances method. RESULTS: Preoperative phagocytic indexes of monocytes and neutrophils from patients were significantly lower than phagocytic indexes of the corresponding cells from healthy women. The phagocytic function of monocytes and granulocytes isolated from postoperative samples of patients significantly increased compared to preoperative values and reached the phagocytic indexes of monocytes and neutrophils from healthy controls. CONCLUSION: Based on our results we assume that the tumor and/or its microenvironment in ovarian cancer may produce factors that can depress the phagocytic function of monocytes and granulocytes. Since the phagocytic indexes increased following the cytoreductive surgery, it can be assumed that after the removal of the tumor, the production of these factors is reduced or eliminated. Orv Hetil. 2018; 159(33): 1353-1359.

Metabolites of Aliphatic Alcohols Detected in Alcoholic Beverages Inhibit Phagocytosis.

AIMS: The aim of our study was to measure granulocyte and monocyte phagocytosis following treatment of cells with some metabolites of aliphatic alcohols alone and in combination with acetaldehyde. METHODS: The cells were separated from human peripheral blood prior to determination of phagocytosis of opsonized zymosan particles by granulocytes and monocytes treated individually with metabolites of aliphatic alcohols including formaldehyde, 1-propanal, acetone, 1-butanal, and 2-butanone and in combination with acetaldehyde. RESULTS: The findings revealed that metabolites of aliphatic alcohols inhibited phagocytosis by granulocytes and monocytes in a concentration-dependent manner and when combined with acetaldehyde, they caused a further decrease in phagocytic activity. CONCLUSION: Due to their additive effects, it is possible that, in combination with acetaldehyde, metabolites of aliphatic alcohols may inhibit phagocytosis at physiologically realistic concentrations in episodic heavy drinkers, thereby contributing to their increased susceptibility to infectious diseases.

Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes.

A large volume of alcoholic beverages containing aliphatic alcohols is consumed worldwide. Previous studies have confirmed the presence of ethanol-induced immunosuppression in heavy drinkers, thereby increasing susceptibility to infectious diseases. However, the aliphatic alcohols contained in alcoholic beverages might also impair immune cell function, thereby contributing to a further decrease in microbicidal activity. Previous research has shown that aliphatic alcohols inhibit phagocytosis by granulocytes but their effect on human monocytes has not been studied. This is important as they play a crucial role in engulfment and killing of pathogenic microorganisms and a decrease in their phagocytic activity could lead to impaired antimicrobial defence in heavy drinkers. The aim of this study was to measure monocyte phagocytosis following their treatment with those aliphatic alcohols detected in alcoholic beverages. Monocytes were separated from human peripheral blood and phagocytosis of opsonized zymosan particles by monocytes treated with ethanol and aliphatic alcohols individually and in combination was determined. It was shown that these alcohols could suppress the phagocytic activity of monocytes in a concentration-dependent manner and when combined with ethanol, they caused a further decrease in phagocytosis. Due to their additive effects, it is possible that they may inhibit phagocytosis in a clinically meaningful way in alcoholics and episodic heavy drinkers thereby contribute to their increased susceptibility to infectious diseases. However, further research is needed to address this question.

Exposure to volatile organic compounds in offices and in residential and educational buildings in the European Union between 2010 and 2023: A systematic review and health risk assessment.

Chronic exposure to indoor volatile organic compounds (VOCs) can result in several adverse effects including cancers. We review reports of levels of VOCs in offices and in residential and educational buildings in the member states of the European Union (EU) published between 2010 and 2023. We use these data to assess the risk to population health by estimating lifetime exposure to indoor VOCs and resulting non-cancer and cancer risks and, from that, the burden of cancer attributable to VOC exposure and associated economic losses. Our systematic review identified 1783 articles, of which 184 were examined in detail, with 58 yielding relevant data. After combining data on VOC concentrations separately for EU countries and building types, non-cancer and cancer risks were assessed in terms of hazard quotient and lifetime excess cancer risk (LECR) using probabilistic Monte Carlo Simulations. The LECR was used to estimate disability adjusted life years (DALYs) from VOC-related cancers and associated costs. We find that the LECR associated with formaldehyde exposure was above the acceptable risk level (ARL) in France and Germany and that of from exposure to benzene was also above the ARL in Spanish females. The sum of DALYs and related costs/1,000,000 population/year from exposure to acetaldehyde, benzene, formaldehyde, tetrachloroethylene, and trichloroethylene were 4.02 and €41,010, respectively, in France, those from exposure to acetaldehyde, benzene, carbon tetrachloride, formaldehyde, and trichloroethylene were 3.91 and €39,590 in Germany, and those from exposure to benzene were 0.1 and €1030 in Spain. Taken as a whole, these findings show that indoor exposure to VOCs remains a public health concern in the EU. Although the EU has set limits for certain VOCs, further measures are needed to restrict the use of these chemicals in consumer products.

Aliphatic alcohol contaminants of illegally produced spirits inhibit phagocytosis by human granulocytes.

CONTEXT: Unregulated production of spirits in many countries leads to products containing appreciable levels of aliphatic alcohols (AAs) and is the main source of human exposure to these substances worldwide. Previous studies have confirmed that alcohol abuse can lead to ethanol-induced immunosuppression and thereby increased susceptibility to infectious diseases. Granulocytes, as professional phagocytic cells, play a crucial role in engulfment and killing of pathogenic microorganisms. Thus, a decrease in their phagocytic activity has been invoked as a factor in the impaired antimicrobial defense observed in alcoholics. However, AAs consumed as contaminants of illicit spirits may also influence phagocytosis, thereby contributing to a further decrease in microbicidal activity but, so far, this has not been studied. OBJECTIVE: Therefore, the aim of this study was to measure granulocyte phagocytosis following treatment of granulocytes with those higher alcohols found in illegal spirits. MATERIALS AND METHODS: Granulocytes were isolated from human peripheral blood. Then phagocytosis of opsonized zymosan particles by granulocytes treated with AAs individually and in combination was determined. RESULTS: These alcohols inhibited phagocytosis in a concentration-dependent manner and at lower concentrations when combined than when tested individually. DISCUSSION AND CONCLUSION: Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit phagocytosis in a clinically meaningful way in episodic heavy drinkers.

Heavy metals in unrecorded Albanian rakia: A pilot study on a potential public health risk.

Unrecorded alcohol has been linked to illness above and beyond that caused by ethanol alone because of the presence of toxic contaminants. While it can be found in all countries, consumption is high in Albania, where it is frequently consumed as a fruit brandy known as rakia. Among the contaminants identified previously in such products, metals including lead have been detected at levels posing a risk to health but there is little information on their presence in rakia. To fill this gap, we measured the level of ethanol and 24 elements among them toxic metals in 30 Albanian rakia samples. We found that 63.3% of rakia samples had ethanol concentration above 40% v/v. We also showed that there was a significant difference between the measured [mean: 46.7% v/v, interquartile range (IQR): 43.4-52.1% v/v] and reported (mean: 18.9% v/v, IQR: 17.0-20.0% v/v) concentrations of ethanol in rakia. Among the metals detected, aluminium, copper, iron, manganese, lead, and zinc were present in rakia samples at concentrations ranging between 0.013 and 0.866 mg/l of pure alcohol (pa), 0.025-31.629 mg/l of pa, 0.004-1.173 mg/l of pa, 0.185-45.244 mg/l of pa, 0.044-1.337 mg/l of pa, and 0.004-10.156 mg/l of pa, respectively. Copper and lead were found to be the greatest concern posing a potential public health risk. Although the estimated daily intake of these heavy metals from unrecorded rakia was below their toxicological threshold, the concentrations of lead and copper exceeded their limit value of 0.2 and 2.0 mg/l of pa specified for spirits in 33% and 90% of samples, respectively. Therefore, the possibility of adverse health effects cannot be excluded completely. Our findings highlight the need for action by policymakers against the risks posed by these products in Albania.

Aliphatic alcohols of illegally produced spirits can act synergistically on superoxide-anion production by human granulocytes.

CONTEXT: Aliphatic alcohols present in illegally produced spirits in a large number of low and middle income countries have been implicated in the etiology of chronic liver disease and cirrhosis. Previous studies have confirmed that chronic alcoholism can lead to increased susceptibility to infectious diseases. Reduced superoxide-anion (O(2)·(-)) production by granulocytes could provide a mechanism by which antimicrobial defense is impaired in alcoholics. In vitro experiments have also demonstrated that ethanol can inhibit granulocyte O(2)·(-) generation. Aliphatic alcohols consumed as contaminants of illicit spirits may also influence O(2)·(-) production thereby contributing to a decrease in microbicidal activity. OBJECTIVE: The aim of this study was to investigate this possibility. It measured the O(2)·(-) production by human granulocytes following treatment of the cells with aliphatic alcohol contaminants found in illicit spirits. MATERIALS AND METHODS: Granulocytes were isolated from human buffy coats with centrifugal elutriation and then treated with individual aliphatic alcohols and their mixture. The O(2)·(-) production was stimulated with phorbol-12-13-dibutyrate and N-formyl-methionyl-leucyl-phenylalanine (FMLP) and measured by superoxide dismutase inhibitable reduction of ferricytochrome c. RESULTS: Aliphatic alcohols of illegally produced spirits inhibited the FMLP-induced O(2)·(-) production in a concentration dependent manner. They suppressed O(2)·(-) generation at 2.5-40 times lower concentrations when combined than when tested individually. DISCUSSION AND CONCLUSION: Aliphatic alcohols found in illegally produced spirits can inhibit FMLP-induced O(2)·(-) production by granulocytes in a concentration-dependent manner. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit O(2)·(-) formation in heavy episodic drinkers.

Methanol in unrecorded fruit spirits. Does it pose a health risk to consumers in the European Union? A probabilistic toxicological approach.

Methanol is present at high concentrations in unrecorded fruit spirits, placing consumers of these beverages at risk of exposure at high levels. When assessing any health risk it is necessary to consider blood methanol levels (BMLs), reference dose (RfD), and maximum tolerable blood methanol level (MTBML). The aim of our study was to estimate daily methanol intake and related BMLs attributable to drinking unrecorded fruit spirits in the European population using a probabilistic Monte Carlo simulation. Data on the concentration of methanol in unrecorded fruit spirits in European Union member states were collected and the health risk posed by consumption of unrecorded fruit spirits was estimated. We found that drinking unrecorded fruit spirits containing methanol at a concentration higher than 8598.1 mg/litre of pure alcohol (p.a.) or 6382.1 mg/litre of p.a. and also at least 10 g ethanol can result in a methanol intake above the RfD by men and women, respectively. We confirmed that consumption of unrecorded fruit spirits containing methanol does not result in BMLs higher than the MTBML. Further studies are required to assess whether there is any health risk from chronic exposure to methanol above the RfD from unrecorded fruit spirits.

Health and economic gain attributable to the introduction of the World Health Organization's drinking water standard on arsenic level in Hungary: A nationwide retrospective study on cancer occurrence and ischemic heart disease mortality.

The World Health Organization (WHO) estimates that 140 million individuals are at risk from consumption of drinking water containing arsenic at concentrations above the WHO guideline value of 10 µg/l. Arsenic mitigation is considered to be the most effective way to prevent arsenic related diseases. After joining the European Union, Hungary implemented a Drinking Water Quality Improvement Programme (DWQIP) to reduce levels of arsenic in drinking water below the WHO guideline value. But what impact did this have on health? We estimated the change in lifetime excess skin, lung, and bladder cancer risks and mortality from ischaemic heart disease (IHD) associated with chronic arsenic intake among those exposed before (2004-2007) and after (2014-2017) the implementation of DWQIP. A population-based risk assessment approach was used to assess lifetime excess cancer risk applying two scenarios for lung and bladder cancers. The economic benefits of the DWQIP were estimated by the combination of cost of illness and value per statistical life methods. Compared to the period before the DWQIP, its implementation was associated with a significant reduction in arsenic in drinking water [median: 3.0 µg/l interquartile range (IQR): 1.5-12.0 µg/l to median: 2.15 µg/l IQR: 1.0-5.79 µg/l]. The two scenarios were estimated to be associated with 225.2 and 35.9 fewer cancer cases each year. The number of annually prevented IHD deaths was estimated to be 88.9. It was estimated that the benefits of the DWQIP will outweigh its costs. We conclude that reducing arsenic levels in drinking water to 10.0 µg/l resulted in significant health and economic benefits. Our study goes beyond the existing research, offering both new insights into the impact of arsenic mitigation and providing a methodological template for similar studies in the many parts of the world that have yet to reduce arsenic exposure.

Obesity-Related Changes in Human Plasma Lipidome Determined by the Lipidyzer Platform.

Obesity is an increasing public health concern both in the developed and developing countries. Previous studies have demonstrated that considerable alterations in lipid metabolism and consequently marked changes in lipid profile are associated with the onset and progression of obesity-related complications. To characterize the full spectrum of obesity-induced changes in lipid metabolism, direct infusion tandem mass spectrometry analysis is the most promising approach. To better understand which of the many lipid species are the most strongly associated with obesity, the aim of our work was to measure and profile plasma lipids in normal (n = 57), overweight (n = 31), and obese (n = 48) individuals randomly selected from samples of Hungarian general and Roma populations by using the targeted quantitative lipidomics platform, the Lipidyzer. Principal component and stepwise regression analyses were used to identify the most significant clusters and species of lipids by increasing body mass index (BMI). From the 18 clusters identified four key lipid species (PE P-16:0/20:3, TG 20:4_33:1, TG 22:6_36:4, TG 18:3_33:0) showed a strong significant positive and three others (Hex-Cer 18:1;O2/22:0, LPC 18:2, PC 18:1_18:1) significant negative association with BMI. Compared to individual lipid species alone, the lipid species ratio (LSR) we introduced showed an extremely strong, at least 9 orders of magnitude stronger, association with BMI. The LSR can be used as a sensitive and predictive indicator to monitor obesity-related alterations in human plasma and control the effectiveness of treatment of obesity associated non-communicable diseases.

Phagocyte function of peripheral neutrophil granulocytes and monocytes in endometriosis before and after surgery.

INTRODUCTION: Endometriosis is a chronic systemic disease, which influence negatively the quality of life of affected women and responsible for infertility and chronic pelvic pain. Pathophysiology of the disease is still enigmatic, but insufficient immune surveillance may play a role in it. Peripheral natural immune cell function is rarely examined. The aim of the study was to examine phagocyte function of peripheral neutrophil granulocytes and monocytes, whether this phagocytic activity is affected by the presence or removal of endometriotic lesions in women with endometriosis. MATERIAL AND METHODS: Twenty-six preoperative, 13 postoperative samples from women with endometriosis, 23 samples from healthy women, 14 pre- and postoperative samples from the surgical control group were enrolled. Cells were isolated from peripheral blood samples, marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosane molecules. RESULTS: Phagocyte function of monocytes and neutrophil granulocytes decreased significantly women with endometriosis before surgery compared to healthy controls. However, 7 days after surgery the postoperative values showed significant improvement compared to the preoperative results of women with endometriosis. This increment reached the values of the healthy women. In the surgical control group no difference was detected between the pre- and postoperative outcomes. DISCUSSION: Decreased phagocyte function of the examined cells, which can be the result of the circulating immunosuppressive factors, may play a role in the deficient clearance of ectopic endometrial tissue. Based on the postoperative results, these immunosuppressive factors may be reduced or eliminated 7 days after surgery in women with endometriosis.

Effect of normal and preeclamptic plasma on superoxide-anion production of neutrophils from healthy non-pregnant women.

This study has examined whether production of superoxide-anion by granulocytes differs between non-pregnant, healthy pregnant and preeclamptic pregnant women. First, we assessed superoxide-anion production in 13 non-pregnant women, 11 healthy pregnant women and 14 preeclamptic pregnant women. Then, we examined the effect of plasma samples of healthy pregnant and preeclamptic pregnant women on superoxide production by neutrophils separated from healthy pregnant women. Superoxide generation was measured by ferricytochrome-c reduction. Phorbol-12,13-dibutyrate- and n-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide-anion production was significantly decreased in healthy pregnant women's granulocytes compared with non-pregnant women. There was no significant difference between granulocyte superoxide-anion production in preeclamptic pregnant and non-pregnant women. When neutrophils from non-pregnant women were incubated in plasma from healthy pregnant women, the granulocyte phorbol-12,13-dibutyrate-stimulated superoxide-anion production was significantly inhibited. With the same stimulator, there were no significant differences between superoxide-anion production of neutrophils incubated in autologous, non-pregnant and preeclamptic pregnant plasma. If n-formyl-methionyl-leucyl-phenylalanine was used for stimulation, there were no significant differences in the superoxide-anion production of granulocytes in either group. Granulocyte superoxide-anion production decreases during pregnancy; this decrease does not occur in preeclampsia, and may cause endothelial damage. It is conceivable that there are unidentified factors in maternal circulation which inhibit superoxide-anion production by granulocytes in healthy pregnant women.