The role of gamma globulin, complement component 1q, factor B, properdin, body temperature, C-reactive protein and serum amyloid alpha to the activity and the function of the human complement system and its pathways.

The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum's activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.

Indoor microbial exposure increases complement component C3a and C-reactive protein concentrations in serum.

Indoor exposure to microbial growth, caused by moisture damage, has been an established health risk for several decades. It is likely that a damp indoor environment contains biological pollutants that trigger both the innate and adaptive branches of the immune system. In this study, we investigated the association between moisture damage related microbial exposure and serum C3a, C5a and CRP concentrations in Finnish adults. Serum C3a and CRP concentrations were elevated in individuals exposed to moisture damage and microbial growth in an indoor air environment. The elevated concentrations may be due to environmental factors present in moisture-damaged buildings. Complement activation and the resulting proinflammatory cleavage products may be a driving factor in inflammatory responses following exposure to indoor moisture damage and related microbial growth.

Occupational Risk Factors for Hoarseness Among Police Officers in Finland.

PURPOSE: Police officers have many work-related risks. In Finland, hoarseness and other respiratory symptoms and related risk factors have not been investigated on a national level. In many of the work tasks carried out by the police, an excellent physical and mental condition is essential. METHOD: Our aim was to determine the prevalence of hoarseness and related respiratory symptoms and to investigate eventual occupational risk factors associated with hoarseness. We also compared different work tasks and remediation procedures in three police stations with indoor air problems. MATERIAL: In all, 767 persons completed a nation-wide e-mail survey. The study population is approximately 11% of the total police force in Finland. Half of the study population were men. In three cities, we evaluated the outcome of different type of remediation methods after the moisture damaged buildings were renovated. The prevalence of hoarseness was compared in different work tasks and the risk associated with indoor air, work-related stress, and background factors were estimated. Information on the remediation was obtained from the employer. RESULTS: Altogether, 30.5% of the respondents had hoarseness and 15.5% had work-related stress. Almost 9% were smokers and 43% had pets at home. Of all the respondents, 13% had asthma. Hoarseness was not related to work-related stress. The strongest risk factors for hoarseness were asthma and exposure to mold odor, dusts and cold temperatures after adjusting for age, gender, smoking and pet-owning. When three renovation techniques were compared, the best results were found in the building with a thorough remediation and the removal of mold from the building. CONCLUSIONS: We conclude that the exposure to irritant gases, fumes, and bioaerosols should be minimized whenever possible in order to avoid incident asthma and voice problems.

The prevalence of hoarseness among health care professionals: time trends and effect of remediation in working conditions in 2007-2018.

PURPOSE: The purpose of this study was to investigate time trends in the prevalence of hoarseness among health care professionals in primary health care units (PHC) and in hospitals from 2007 to 2018. Moreover, purpose was to discover potential indoor environmental quality (IEQ) risk factors as well as to determine the effect of the remediation of the indoor air problems on the prevalence of hoarseness. METHODS: The health status was collected from all employees in these units/hospitals (N = 1564/1199) with questionnaires and the follow-ups were carried out as an open cohort. Based on building condition inspections, buildings were classified to be an "exposed" or "reference" buildings by third-party experts. The before and after remediation results were compared to reference buildings. RESULTS: During follow-up, hoarseness has not increased in those PHC units with good IEQ. In the pilot study, the prevalence of hoarseness in non-exposed reference building was 5.9%, and it stayed approximately at the same level throughout the follow-up. Whereas in buildings with an IEQ problem the prevalence of hoarseness varied between 16.2 and 36.1% and it decreased to 11.4% after the remediations. In a large hospital with severe IEQ problems, the prevalence of hoarseness was 39.1%, and in hospital buildings with a milder exposure 23.3%. The most important risk factors for hoarseness were asthma, allergic rhinitis and IEQ problems. CONCLUSION: A good indoor environment and the remediation of damaged buildings seem to promote a better condition of the voice in health care workers.

Groundwater radon exposure and risk of lung cancer: A population-based study in Finland.

Naturally occurring radioactive elements can be found in groundwater and exposure to such elements is associated with an increased risk of lung cancer. In this study, we aimed to observe the association between exposure to these radioactive elements in groundwater and the risk of lung cancer in selected regions in Finland. This is a population-based study from 1955 to 2019 in Finland. The exposed municipalities with their corresponding hospital districts were selected based on radon measurements at groundwater treatment plants. Lung cancer cases were obtained from the Finnish cancer registry. The 5-year incidence rates for lung cancer were calculated and a comparison was made between each of the hospital districts with radon exposure. More than 93,000 cases of lung cancer were reported in the radon-exposed regions over the examined period of 64 years. The highest number of cases was recorded in the Helsinki University hospital district and the least in the Southern Savo hospital district. Similarly, the lung cancer incidence rate was highest in Lapland and lowest in the Southern Savo hospital district. The number of daily smokers in the working-age population appears to have decreased in all the hospital districts from 2013 to 2018. A statistically significant increased risk of lung cancer was observed in the high radon-exposed hospital districts compared to those with lower exposure. Groundwater radon exposure is observed to be associated with an increased risk of lung cancer.

Transferring from moisture damaged school building to clean facilities - The avoidance of mold exposure induces a decline in symptoms and improvement in lung function among personnel.

Working in a moisture-damaged building can cause different symptoms and effects on lung functions. Moving to a clean environment, it is believed to reduce symptoms and alleviate potential adverse health effects. This case study monitors the health effects of personnel in one school building before and after all school activities were transferred from a moisture-damaged school building to clean premises. The whole school staff was invited to attend this follow-up study. All participants (N = 45) were interviewed, and pulmonary functions were measured by spirometry and exhaled nitric oxide testing (FENO) before transferring the school activities to a new building and the control measurements were performed twice; three months and six months after the transfer. After transferring to temporary facilities, 82% of participants felt that their symptoms were improved or resolved and the pulmonary functions were improved; 50% of those who had decreased pulmonary functions at the beginning, their pulmonary function values returned to normal after three months. Over the next six months, the perceived symptoms continued to reduce so that 93% of the respondents felt fully asymptomatic with respect to indoor air, and the spirometry results improved further. Transferring workers from the damaged building to healthy environment provided beneficial health effects on pulmonary functions and to perceived symptoms even in a relatively short time period. Based on this study, and from the perspective of promoting and protecting the health and well-being of personnel, transferring school activities from a moisture damaged building to clean facilities brought considerable advantages, despite the possible cost and difficulties of finding replacement facilities.

Prevalence of Hoarseness in Primary Health Care and Hospitals-Associations With Different Work Tasks and Environmental Factors Among Nurses.

OBJECTIVES: The voice is one of the most essential tools necessary for nurses achieve high care satisfaction and safety. Research on hoarseness has mainly focused on professional speakers, like teachers. The aim of this study was to determine the current prevalence of hoarseness among six subgroups of nurses (registered nurses, primary care nurses, pediatric nurses, laboratory nurses, dental nurses, and midwives) and also to identify potential environmental risk factors in their working environment. METHODS: The health data was collected in collaboration with two health care professional trade unions. The findings are based on 15,553 returned health questionnaires which were statistically analyzed. RESULTS: The 1-year prevalence of hoarseness among all participating nurses was 30.2 % in this data, but the variation between different occupational subgroups was significant; ranging from 25 % for laboratory nurses to 38 % for midwives. These findings were in line with perceived environmental problems and the differences between the sub-groups were not explained by the participants suffering from asthma, sinusitis, rhinitis, or common respiratory infections; there were no explanatory differences in the prevalence's of the above-mentioned diseases. CONCLUSIONS: The variation in prevalence of hoarseness between the different occupational subgroups was significant and the prevalence was found to be in line with perceived environmental problems. The most common problems were stuffiness, dry air, and inadequate ventilation. In addition, both a perceived "sewer odor" and "smell of mold or cellar" in one's own working environment were also found to be significant risk factors for hoarseness. Based on this study, the current indoor air problems in Finnish health care facilities can be verified and are a source of risk to nurses' voices.

The Association Between Work-Related Stress, Indoor Air Quality, and Voice Problems Among Teachers is There a Trend?

INTRODUCTION: Hoarseness and other voice problems are common in occupations where the person has to speak, sing or shout in a work environment containing dust, noise, gaseous or particulate irritants. In recent years, stress has often been associated with voice problems. OBJECTIVE: The aim of this study was to examine trends over a period of time of the prevalence of voice problems and reported stress in Finnish school buildings. STUDY DESIGN: School buildings from different parts of the country were studied for ten years using a similar questionnaire (N = 1721). Five schools participated before and after the remediation of an indoor air problem in the school buildings (n = 315). RESULTS: In the pilot study (2007-2008), the reported work-related stress was on a very low level (3%) and the prevalence of hoarseness was 10%. After the economic crisis in 2008, the stress was observed to have increased. During the follow-up (2008-2017), the reported stress had continued to increase and in the latest surveys it was 21% and the prevalence of hoarseness 34%. Indoor air factors correlated significantly with hoarseness even when controlling for age, gender, owning pets and job satisfaction in a logistic regression model. In the school buildings where the remediation of the building was completed, the prevalence of hoarseness decreased but the level of stress increased. In general, the proportion of respondents reporting stress was lower than the proportion of respondents with hoarseness. Additionally, the reported stress also correlated with factors other than health in the education branch, especially economic resources and major changes in the core curriculum. CONCLUSION: Hoarseness and work-related stress have, to a large extent, different risk factors. Over time, the proportion of individuals with stress has been at a lower level than the proportion of respondents with voice problems; hence, we conclude that it is quite unlikely that stress would be a causative risk factor for hoarseness. We recommend that irritant dust and gases should be reduced from the work environment of teachers to enable recovery from hoarseness and other voice problems. Coping with work-related stress should be alleviated with other measures.

Indoor-related microbe damage induces complement system activation in building users.

In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli-lux bioluminescence system and comparison was made at a group level between the experimental and reference group. The complement activity was higher in users of microbe-damaged buildings compared with the reference group and the significant (P < 0.001) increase in activity was found in the classical reaction pathway. This study strengthens our notion that exposure to indoor-related microbe damage increases the risk for systemic subclinical inflammation and creates a health risk for building users.

Investigating the short- and long-term effects of antibacterial agents using a real-time assay based on bioluminescent E. coli-lux.

We have previously established that the E. coli-lux assessment is a convenient tool for rapid measurements of the kinetical features of short-term toxicity caused by various factors. In this study, kinetic measurements of seven specifically acting model antibacterials (i.e., polymyxin B, chloramphenicol, nalidixic acid, kanamycin, deoxynivalenol, erythromycin and tetracycline) and two metals (AgNO3 and CdCl2) against E. coli-lux through a bioluminescence- and optical density-based real-time assay that combined short- and long-term toxicity assessments were performed. Bacteria were exposed to antibacterials and the effects were reported as the half-maximum effective concentration (EC50) after 30 min and 10 h. Regarding the 10-hour endpoints, all reference compounds, except deoxynivalenol, showed dose-response inhibition in the studied concentration range. The analysis of chloramphenicol, kanamycin, erythromycin, tetracycline and nalidixic acid clearly revealed the limitations of short-term inhibition tests. No significant differences were observed between the results obtained from luminescence inhibition and growth inhibition assays. The kinetical data from measurements provide differentiation between bacteriostatic and bactericidal mechanisms of various types of antibacterial agents. The combined assessment of short- and long-term effects reduces the risk of the underestimation of toxicity due to an inaccurate endpoint selection. The cost-efficient and fully automated E. coli-lux assessment technique may offer possibilities for high-throughput screening procedures.

Indoor exposure to Streptomyces albus and Aspergillus versicolor elevates the levels of spore-specific IgG, IgG1 and IgG3 serum antibodies in building users - A new ELISA-based assay for exposure assessment.

Moisture-indicative microbes in buildings are associated with a variety of symptoms, ranging from mild irritation to severe clinical illnesses. These symptoms are caused principally by dried, dormant and dead microbe material like spores, mycelium and microbe metabolites, leading to the activation of the immune system and formation of the antigen-specific immunoglobulins. This activation presumably takes place through the respiratory track and is a normal immune reaction against pathogenic invaders. During continuous exposure, a prolonged state of inflammation will follow, and this forms a considerable health risk for a building's occupant. A new ELISA system utilizing spores from two species Streptomyces albus and Aspergillus versicolor as an antigen was developed to reveal the related immunological processes. In 159 persons, microbial exposure was observed to increase the levels of spore-specific IgG, IgG1 and IgG3 serum antibody levels of individuals residing in microbe-dense buildings compared with the control reference buildings. No differences were detected in the levels of S. albus- and A. versicolor-specific serum IgA or IgM levels.

A real-time-based in vitro assessment of the oxidative antimicrobial mechanisms of the myeloperoxidase-hydrogen peroxide-halide system.

Mammals have evolved a special cellular mechanism for killing invading microbes, which is called the phagocytosis. Neutrophils are the first phagocytosing cells that migrate into the site of infection. In these cells, hypochlorite (HOCl) and other hypohalites, generated in the myeloperoxidase (MPO)-hydrogen peroxide (H2O2)-halide system is primarily responsible for oxidative killing. Here, we present a method for assessing these oxidative mechanisms in an in vitro cell-free system in a kinetical real-time-based manner by utilizing a bioluminescent bacterial probe called Escherichia coli-lux. The E. coli-lux method provides a practical tool for assessing the effects of various elementary factors in the MPO-H2O2-halide system. Due to the reported versatile intracellular pH and halide concentration during the formation of the phagolysosome and respiratory burst, the antimicrobial activity of the MPO-H2O2-halide system undergoes extensive alterations. Here, we show that at a physiological pH or lower, the antimicrobial activity of MPO is high, and the system effectively enhances the H2O2-dependent oxidative killing of E. coli by chlorination. The HOCl formed in this reaction is a prominent microbe killer. During the respiratory burst, there is a shift to a more alkaline environment. At pH 7.8, the chlorinating activity of MPO was shown to be absent, and the activity of the HOCl decreased. At this higher pH, the activity of H2O2 is enhanced and high enough to kill E. coli without the participation of MPO, and the lowered chloride concentration seemed still to enhance the H2O2-dependent killing capacity.

The Response of Phagocytes to Indoor Air Toxicity.

This perspective presents a viewpoint on potential methods assessing toxicity of indoor air. Until recently, the major techniques to document moldy environment have been microbial isolation using conventional culture techniques for fungi and bacteria as well as in some instances polymerase chain reaction to detect microbial genetic components. However, it has become increasingly evident that bacterial and fungal toxins, their metabolic products, and volatile organic substances emitted from corrupted constructions are the major health risks. Here, we illustrate how phagocytes, especially neutrophils can be used as a toxicological probe. Neutrophils can be used either in vitro as probe cells, directly exposed to the toxic agent studied, or they can act as in vivo indicators of the whole biological system exposed to the agent. There are two convenient methods assessing the responses, one is to measure chemiluminescence emission from activated phagocytes and the other is to measure quantitatively by flow cytometry the expression of complement and immunoglobulin receptors on the phagocyte surface.

Repeated dose 28-day oral toxicity study of moniliformin in rats.

Moniliformin is a Fusarium mycotoxin mainly produced by several species infecting grains in different climatic conditions. According to our previous studies, it is acutely toxic to rats, with an LD50 cut-off value of 25mg/kg b.w. To further assess the possible health risks of low dose exposure to moniliformin, a subacute oral toxicity study was conducted in Sprague-Dawley rats, adapting OECD guideline 407. Five dose groups and two satellite groups, each consisting of five male rats, were daily exposed to moniliformin by gavage. Two rats in the highest dose group, showed decreased activity followed by acute heart failure and death. The rats of the lower doses (<9mg/kg b.w.) showed no signs of toxicity. The daily intake of moniliformin strongly reduced the phagocytic activity of neutrophils in all dose groups. The decrease continued in the satellite group during the follow-up period, indicating a severe impact on the immune system and a LOAEL value of 3mg/kg b.w. for moniliformin. Moniliformin was rapidly excreted into urine, ranging between 20.2 and 31.5% daily and showed no signs of accumulation. The concentration of moniliformin in faeces was less than 2%, which suggests efficient absorption from the gastrointestinal tract.

Escherichia coli K-12 (pEGFPluxABCDEamp): a tool for analysis of bacterial killing by antibacterial agents and human complement activities on a real-time basis.

Photorhabdus luminescens luxCDABE genes were integrated into E. coli K-12 using a high copy number plasmid containing modified luxABCDE genes under the control of the powerful Lac promoter. This strain emitted 10 times higher bioluminescence (BL) than P. luminescens. BL production under different growth conditions was studied. In both bacterial strains, the increase in BL signal correlated with the increase in optical density (OD) in a rich growth medium. However, at the logarithmic growth phase, the BL signal was roughly constant. By contrast, in minimal growth media, there was no substantial growth and the BL/cell was approximately five times higher than in the rich medium. The dynamic measurement range of BL was 10(2) -10(7) colony-forming units (CFU) in E. coli and 10(3) -10(7) CFU in P. luminescens. Because the decrease in the BL signal correlated with the decrease in CFU and OD, i.e. the number of bacterial cells killed, it proved to be very suitable for assessing the antibacterial effects of different antimicrobial agents. Unlike with plate counting, the kinetics of killing can be monitored on a real-time basis using BL measurements. Complement activities in different samples can be estimated using only one serum dilution. The transformed E. coli strain appeared to be superior to P. luminescens in these applications because E. coli was complement sensitive, the detection limit of E. coli was one order lower and the BL-producing system of P. luminescens appeared to be quite unstable.

Bacteriolytic activity of the alternative pathway of complement differs kinetically from the classical pathway.

The interaction between bacterial cells and activated complement components as a kinetic biological event is described. The bacteriolytic activity of complement in human and fish serum was assayed by measuring the decrease of bioluminescence of Escherichia coli transformed with lux genes. From the kinetic curves, the bacteriolytic CB(50)- and AB(50)-units were derived at any desired time point. It was observed that these values were irregular but decreased as a function of incubation time, and reached equal values during prolonged incubation, suggesting that the difference between the classical and alternative pathway activity is kinetic. From the kinetic curves, entirely new parameters could be derived: rate of the activation phase, rate of killing by the lytic phase and rate of killing by the entire pathway in undiluted serum. The rates of human and fish classical pathway were about five and two times higher than those of the alternative pathway respectively.