László Pál

Phagocytic index of neutrophil granulocytes and monocytes in healthy and preeclamptic pregnancy

Neutrophil granulocytes and monocytes have been intensively studied, but there is no scientific data on one of their most important functions, namely the phagocyte function in pregnancy and preeclampsia. The aim of this study was to examine this function. Twenty-five healthy pregnant, 25 preeclamptic pregnant, and 20 healthy, non-pregnant women were enrolled into our study. Cells were isolated from peripheral blood samples, marked and evaluated for the phagocytic index with an immunofluorescent microscope after phagocytosing the zymosan molecules. The phagocytic function of monocytes and neutrophil granulocytes decreased significantly in healthy pregnancy compared with non-pregnant women and in preeclampsia, and it decreased significantly compared with healthy pregnancy. Decreased phagocytic function in healthy pregnancy can be a part of the maternal immunosuppression, which is essential for the protection of the hemiallograft fetus. Further reduction of phagocytic function may be one of the immunoregulatory abnormalities found in preeclampsia.

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

Abstract 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.

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 (O2·−) 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 O2·− generation. Aliphatic alcohols consumed as contaminants of illicit spirits may also influence O2·− production thereby contributing to a decrease in microbicidal activity. Objective: The aim of this study was to investigate this possibility. It measured the O2·− 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 O2·− 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 O2·− production in a concentration dependent manner. They suppressed O2·− 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 O2·− production by granulocytes in a concentration-dependent manner. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit O2·− formation in heavy episodic drinkers.

Aliphatic alcohols in spirits inhibit phagocytosis by human monocytes

Abstract 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.

The effect of healthy pregnant plasma and preeclamptic plasma on the phagocytosis index of neutrophil granulocytes and monocytes of nonpregnant women

ABSTRACT Objective: Phagocyte function of neutrophil granulocytes and monocytes is decreased in healthy pregnancy and further decreased in preeclampsia. The cause of the declined function is unknown. Decreased phagocyte function can lead to the higher infection rate in healthy pregnancy and may also be responsible for the increased susceptibility to infections and high trophoblast concentration in preeclampsia. The aim of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes. Methods: Monocytes and neutrophil granulocytes were separated from the peripheral circulation of six nonpregnant patients and incubated in plasma samples from six healthy pregnant, six preeclamptic pregnant, and six nonpregnant patients. The cells were marked and evaluated for the phagocytosis index with immunofluorescent microscope after phagocyting the zymosan molecules. Results: Phagocyte function of neutrophils as well as monocytes from nonpregnant patients were decreased significantly when the cells were incubated in plasma samples from healthy pregnant patients, and further decreased when incubated in plasma samples from preeclamptic pregnant women. Conclusion: The decreased phagocyte function of neutrophil granulocytes and that of monocytes in healthy pregnancy and the further decreased phagocyte function in preeclampsia is caused by factor(s) in the maternal circulation.

Consumption of home-made spirits is one of the main source of exposure to higher alcohols and there may be a link to immunotoxicity

We are grateful to Dr. Lachenmeier and his colleague for their interest in our article. We were surprised by his comments but wonder whether they reflect a difference in terminology in that we included aliphatic alcohols in illegally produced spirits within the category of ‘‘contaminants’’. Dr. Lachenmeier claim that 1-propanol, 1-butanol and isobutanol are considered as ‘‘flavouring agents’’ when spirits contain these substances at certain concentrations. However, those manufacturing spirits seek to avoid their presence at high levels, while methanol, also a component of some spirits, is not a ‘‘flavouring agent’’. We believe that, regardless of the choice of terminology, it is important to know whether the presence of these substances in alcoholic beverages has an impact on human immune system, so justifying our investigation. In our previous work, we found that aliphatic alcohols were more frequently present in home-made spirits than in commercial spirits. We detected methanol in 82% (13% in commercial spirits), 2-butanol in 94% (55% in commercial spirits), 1-propanol 100% (81% in commercial spirits), isobutanol in 100% (81% in commercial spirits), 1-butanol 47% (6% in commercial spirits) and isoamyl alcohol in 100% (71% in commercial spirits) of the home-made spirit samples. Furthermore, the concentration of aliphatic alcohols was significantly higher in home-made spirits than in those of from commercial sources. This is consistent with Dr. Lachenmeier’s own research where he also found higher alcohols more common in unrecorded products (samohon for personal use or for sale) than in commercially manufactured alcohol (vodka). Where we differ is our view about the relative amount of legally and illegally produced spirits being consumed, but this is not something that can be resolved definitively with the data available. If it is felt necessary, the meaning of our ‘‘critical sentence’’ could be easily resolved by modifying it as follows: ‘‘Consumption of contaminated unrecorded alcohols, particularly illicitly produced spirits is one of the most common forms of exposure to AAs affecting large populations worldwide’’. However, we do rather feel that we are getting into semantics. The statement that ‘‘the concentration of higher alcohols in unrecorded alcohols is significantly lower than in commercial alcohol’’ can be disputed for the following reasons. The average level of higher alcohols in unrecorded products shown in their Figure 1 (presented in Lachenmeier D W, Rehm J. What is the main source of human exposure to higher alcohols and is there a link to immunotoxicity? Immunopharmacol Immunotoxicol 2013;35:451–453) is derived from previous studies in which different types of unrecorded alcoholic products were analyzed. These included home-made spirits, illegally imported and untaxed alcohols, smuggled alcoholic beverages, counterfeit or relabeled alcohols, surrogate alcohols, medicinal alcohols, wines and beers from several European countries. However, these studies were not representative and suffer from two important limitations. First, the collection of samples was not systematic and, except in Poland, Russia and Ukraine, only unrecorded products were obtained and examined but their commercially produced, and thus recorded, counterparts were not compared. Second, although to the World Health Organization’s definition of unrecorded alcohol encompasses all of the products tested, this is actually a very heterogeneous group, being produced from different raw materials (grain, a variety of fruits and grapes), by different technologies, including fermentation and brewing (beer), fermentation (wine), fermentation and distillation (spirits). In addition, some smuggled alcohols are industrially produced, subject to quality control and recorded in their countries of origin. *These authors share the first authorship.

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.

Special Health Care Utilization Pattern with Elevated Costs and High Risk of Premature Death Among Adults Living in Segregated Roma Settlements

Roma is the largest ethnic minority of Europe with poor health status, which is poorly explored due to legal constrains of ethnicity assessment. We aimed to elaborate health-indicators for adults living in segregated Roma settlements (SRS) representing the most vulnerable Roma subpopulation. SRSs were mapped in a study area populated by 54682 adults. Records of all adults living in the study area were processed in the National Institute of Health Insurance Fund Management. Aggregated, age-sex standardized SRS-specific and non-SRS-specific indicators on healthcare utilization and premature death along with the ratio of them (RR) were computed with 95% confidence intervals. The rate of GP appointments was significantly higher among SRS inhabitants (RR=1.152, 95%CI: 1.136–1.167). The proportion of subjects hospitalized (RR=1.286, 1.177–1.405), and the reimbursement for inpatient care (RR=1.060, 1.057–1.064) were elevated for SRS. Premature mortality was significantly higher in SRSs (RR=1.711, 1.085-2.696). Our study demonstrated that it is possible to compute the SRS-specific version of the routine healthcare indicators without violating the protection of personal data by converting a sensitive ethical issue to a non-sensitive small area geographical analysis; there is an SRS-specific healthcare utilization pattern, which is associated with elevated costs and increased risk of premature death.

Association between the General Practitioner Workforce Crisis and Premature Mortality in Hungary: Cross-Sectional Evaluation of Health Insurance Data from 2006 to 2014

The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) positions, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18–64 years old adults was calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP positions was evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta = −0175; p < 0.001), followed by urban residence (beta = −0.149; p < 0.001), and bigger list size (beta1601–2000 = −0.054; p < 0.001; beta2001−X = −0.096; p < 0.001). The geographical localization also significantly influenced the risk. Although GMPs with a GP aged older than 65 years (beta = 0; p = 0.995) did not affect the risk, GP vacancy was associated with higher risk (beta = 0.010; p = 0.033), although the corresponding number of attributable cases was 23.54 over 9 years. The vacant GP position is associated with a significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.

Healthcare Utilization and All-Cause Premature Mortality in Hungarian Segregated Roma Settlements: Evaluation of Specific Indicators in a Cross-Sectional Study

Roma is the largest ethnic minority of Europe with deprived health status, which is poorly explored due to legal constrains of ethnicity assessment. We aimed to elaborate health indicators for adults living in segregated Roma settlements (SRS), representing the most vulnerable Roma subpopulation. SRSs were mapped in a study area populated by 54,682 adults. Records of all adults living in the study area were processed in the National Institute of Health Insurance Fund Management. Aggregated, age-sex standardized SRS-specific and non-SRS-specific indicators on healthcare utilization and all-cause premature death along with the ratio of them (RR) were computed with 95% confidence intervals. The rate of GP appointments was significantly higher among SRS inhabitants (RR = 1.152, 95% CI: 1.136–1.167). The proportion of subjects hospitalized (RR = 1.286, 95% CI: 1.177–1.405) and the reimbursement for inpatient care (RR = 1.060, 95% CI: 1.057–1.064) were elevated for SRS. All-cause premature mortality was significantly higher in SRSs (RR = 1.711, 1.085–2.696). Our study demonstrated that it is possible to compute the SRS-specific version of routine healthcare indicators without violating the protection of personal data by converting a sensitive ethical issue into a non-sensitive small-area geographical analysis; there is an SRS-specific healthcare utilization pattern, which is associated with elevated costs and increased risk of all-cause premature death.