Additional file 1. In the Supplemental Material Section an Excel file with detailed information a... more Additional file 1. In the Supplemental Material Section an Excel file with detailed information about the cases included in the study is presented.
Periodontitis affects the recovery phase after invasive intervention in patients with coronary ar... more Periodontitis affects the recovery phase after invasive intervention in patients with coronary artery disease : correlation with hepatocyte growth factor activity
Background When post-neurosurgery patients develop fever, there are no convenient methods to imme... more Background When post-neurosurgery patients develop fever, there are no convenient methods to immediately indicate the site of infection. The choice of empirical antibiotic therapy is evidently different in nosocomial meningitis compared to ventilator-associated pneumonia or urinary tract infection. Conventional bacterial cultures have a risk of being false negative due to antibiotic prophylaxis, and direct microscopic analysis of cerebrospinal fluid from such patients has limited diagnostic value. Due to the substantial mortality associated with nosocomial meningitis, broad spectrum antibiotics in high dosage are therefore commonly administered. Neutrophils as innate immunity system, trap and kill bacteria by neutrophil extracellular traps (NETs). NETs is composed of extracellular DNA and is released in cerebrospinal fluid during bacterial meningitis. Using a combination of sulphated-glycosaminoglycan and aniline dyes a platform was developed that reacted to extracellular host DNA a...
Background and Objective: Several studies have shown an association between periodontitis and car... more Background and Objective: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro. Material and Methods: Plasma lipoproteins were isolated from whole blood treated with wild-type and gingipain-mutant (lacking either the Rgp-or Kgp gingipains) P. gingivalis by density/gradient-ultracentrifugation and were studied using 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid-reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation. Results: Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high-density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation. Conclusion: Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.
Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both... more Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention.The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary:In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD.Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group.In study III, higher HGF serum concentrations (p<0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity.In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p<0.001, gingival crevicular fluid p<0.0001, and in serum p<0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p<0.0001) and GCF samples (p<0.0001 for HSPG and p<0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p<0.05), which might reflect that patients had active bursts of periodontitis.In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts.
Antibiotic treatment of multiple resistant bacteria in biofilms might result in therapy failure a... more Antibiotic treatment of multiple resistant bacteria in biofilms might result in therapy failure and organ injuries. A case of infected decubital ulcer and severe periodontitis with growth of multiple resistant grampositive and-negative bacteria is presented. The patient was successfully treated after revisions with antibiotic directed against gram-positive bacteria.
Additional file 3: Figure S2. Agaros gel electrophoresis of samples. The gel was dyed with 1:5000... more Additional file 3: Figure S2. Agaros gel electrophoresis of samples. The gel was dyed with 1:5000 CYBR green dye for both single and double-strand DNA. The second lane on left is the renentate from the pus from tooth abscess that was centrifuged 60,000 rpm in 60 min in ultra-filtration 30 kDa filters (index test highly positive), the fourth lane on left is 0.5 ml air-dried sputum sample reconstituted in 100 µl MQ (index test positive). The sixth lane on left is the renentate from the sputum sample that was centrifuged 60,000 rpm in 60 min in ultra-filtration 30 kDa filters (index test highly positive). The first lane on the right is the filtrate from same sputum sample (index test negative). The experiment was repeated six times.
concentration but low biological activity of hepatocyte growth factor in patients with chronic re... more concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure
An antithrombin III product containing biologically active hepatocyte growth factor may be benefi... more An antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in depp ulcer infections
22 Porphyromonas gingivalis is an etiological agent strongly associated with periodontal disease ... more 22 Porphyromonas gingivalis is an etiological agent strongly associated with periodontal disease and 23 correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating 24 bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions 25 between neutrophils and platelets, causing reactive oxygen species (ROS) production and 26 aggregation. Lipoxin A4 (LXA4) is an endogenous anti-inflammatory and pro-resolving mediator 27 that is protective of inflammatory disorders. The aim of this study was to investigate the effect of 28 LXA4 on the P. gingivalis-induced activation of neutrophils and platelets, and the possible 29 involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and 30 ROS production was examined by lumi-aggregometry and fluorescence microscopy. Integrin 31 activity was studied by flow cytometry, detecting surface expression of CD11b/CD18 as well as 32 exposure of high affinity integrin epitope,...
Point of Care: The Journal of Near-Patient Testing & Technology, 2020
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of... more An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is 0910-0582 (expires 08/31/2019).
Objective: Cough and fever are the initial symptoms of lower respiratory infection. Severe cases ... more Objective: Cough and fever are the initial symptoms of lower respiratory infection. Severe cases might be fatal. Therefore, particularly in the non-equipped centers, the lack of diagnostic methods to identify the severe cases has resulted in overconsumption of antibiotics. On the basis of the knowledge about non-specific immune response at the site of injury, we developed a colorimetric dip-test that shows abrupt, sensitive and quite specific color change upon contact with sputum in the cases of lower respiratory infection. We further explored the mechanism of the test. Results: We detected deoxyribonucleic acid (DNA) and hepatocyte growth factor in the sputum of patients that suffered from respiratory infection (n = 18). The results differed significantly (P < 0.0001) from age-matched patients (n = 18) with other respiratory disorders and highly correlated with the index-test results (Spearman Rank test = 0.84). DNA with a concentration more than 0.03 mg/ml induced a visible and stable color change on index-test within 1 min. The test recognized all of the cases with respiratory infection and the specificity was 72%. With a high negative predictive value. The index test detects, inter alia, cell-free DNA in sputum and might safely rule-out respiratory infection in 2/3 of cases that present symptoms of acute respiratory infection.
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
A large body of data accumulated over the past several years suggests that the periodontal pathog... more A large body of data accumulated over the past several years suggests that the periodontal pathogen Porphyromonas gingivalis is associated with cardiovascular disease. Circulating bacteria may cont ...
Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated with periodontit... more Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated with periodontitis. This study aims to develop antibodies to P. gingivalis in vitro for realtime detection of bacteria in clinical samples. Lymphocytes were isolated from whole blood of patient treated for periodontitis and were stimulated with P. gingivalis ATCC 33277. B-cell maturation to long-living antibody secreting-plasma cells was studied using flow cytometry and immunofluorescence staining. The antibodies developed in vitro were immobilized onto a CM-5 sensor chip of a biosensor to detect the presence of P. gingivalis in the gingival crevicular fluid of patients with periodontitis compared to periodontally healthy controls (n = 30). Surface plasmon resonance (SPR) analysis was performed to evaluate specific interactions of bacteria in samples with the immobilized antibodies. The results of SPR analysis were compared to the detection of P. gingivalis in the samples using DNA-DNA checkerboard hybridization technique. A clear and distinct change in lymphocyte morphology upon stimulation with P. gingivalis was observed. Anti-P. gingivalis antibodies secreted by CD38+ plasma cells showed the presence of all the four IgG subclasses. The results of DNA-DNA checkerboard analysis were in agreement with that of SPR analysis for the detection of P. gingivalis in patient samples. Furthermore, incubation with anti-P. gingivalis attenuated the bacterial response in SPR. The in vitro method for antibody production developed during this study could be used for an efficient real-time detection of periodontitis, and the attenuating effects of in vitro antibodies suggest their role in passive immunization to prevent periodontitis and their associated risk factors.
Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and inc... more Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNFalpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.
Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercia... more Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), highsensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r = À0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.
Additional file 1. In the Supplemental Material Section an Excel file with detailed information a... more Additional file 1. In the Supplemental Material Section an Excel file with detailed information about the cases included in the study is presented.
Periodontitis affects the recovery phase after invasive intervention in patients with coronary ar... more Periodontitis affects the recovery phase after invasive intervention in patients with coronary artery disease : correlation with hepatocyte growth factor activity
Background When post-neurosurgery patients develop fever, there are no convenient methods to imme... more Background When post-neurosurgery patients develop fever, there are no convenient methods to immediately indicate the site of infection. The choice of empirical antibiotic therapy is evidently different in nosocomial meningitis compared to ventilator-associated pneumonia or urinary tract infection. Conventional bacterial cultures have a risk of being false negative due to antibiotic prophylaxis, and direct microscopic analysis of cerebrospinal fluid from such patients has limited diagnostic value. Due to the substantial mortality associated with nosocomial meningitis, broad spectrum antibiotics in high dosage are therefore commonly administered. Neutrophils as innate immunity system, trap and kill bacteria by neutrophil extracellular traps (NETs). NETs is composed of extracellular DNA and is released in cerebrospinal fluid during bacterial meningitis. Using a combination of sulphated-glycosaminoglycan and aniline dyes a platform was developed that reacted to extracellular host DNA a...
Background and Objective: Several studies have shown an association between periodontitis and car... more Background and Objective: Several studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low-density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro. Material and Methods: Plasma lipoproteins were isolated from whole blood treated with wild-type and gingipain-mutant (lacking either the Rgp-or Kgp gingipains) P. gingivalis by density/gradient-ultracentrifugation and were studied using 2-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid-reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation. Results: Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high-density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation. Conclusion: Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.
Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both... more Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention.The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary:In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD.Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group.In study III, higher HGF serum concentrations (p<0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity.In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p<0.001, gingival crevicular fluid p<0.0001, and in serum p<0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p<0.0001) and GCF samples (p<0.0001 for HSPG and p<0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p<0.05), which might reflect that patients had active bursts of periodontitis.In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts.
Antibiotic treatment of multiple resistant bacteria in biofilms might result in therapy failure a... more Antibiotic treatment of multiple resistant bacteria in biofilms might result in therapy failure and organ injuries. A case of infected decubital ulcer and severe periodontitis with growth of multiple resistant grampositive and-negative bacteria is presented. The patient was successfully treated after revisions with antibiotic directed against gram-positive bacteria.
Additional file 3: Figure S2. Agaros gel electrophoresis of samples. The gel was dyed with 1:5000... more Additional file 3: Figure S2. Agaros gel electrophoresis of samples. The gel was dyed with 1:5000 CYBR green dye for both single and double-strand DNA. The second lane on left is the renentate from the pus from tooth abscess that was centrifuged 60,000 rpm in 60 min in ultra-filtration 30 kDa filters (index test highly positive), the fourth lane on left is 0.5 ml air-dried sputum sample reconstituted in 100 µl MQ (index test positive). The sixth lane on left is the renentate from the sputum sample that was centrifuged 60,000 rpm in 60 min in ultra-filtration 30 kDa filters (index test highly positive). The first lane on the right is the filtrate from same sputum sample (index test negative). The experiment was repeated six times.
concentration but low biological activity of hepatocyte growth factor in patients with chronic re... more concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure
An antithrombin III product containing biologically active hepatocyte growth factor may be benefi... more An antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in depp ulcer infections
22 Porphyromonas gingivalis is an etiological agent strongly associated with periodontal disease ... more 22 Porphyromonas gingivalis is an etiological agent strongly associated with periodontal disease and 23 correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating 24 bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions 25 between neutrophils and platelets, causing reactive oxygen species (ROS) production and 26 aggregation. Lipoxin A4 (LXA4) is an endogenous anti-inflammatory and pro-resolving mediator 27 that is protective of inflammatory disorders. The aim of this study was to investigate the effect of 28 LXA4 on the P. gingivalis-induced activation of neutrophils and platelets, and the possible 29 involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and 30 ROS production was examined by lumi-aggregometry and fluorescence microscopy. Integrin 31 activity was studied by flow cytometry, detecting surface expression of CD11b/CD18 as well as 32 exposure of high affinity integrin epitope,...
Point of Care: The Journal of Near-Patient Testing & Technology, 2020
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of... more An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is 0910-0582 (expires 08/31/2019).
Objective: Cough and fever are the initial symptoms of lower respiratory infection. Severe cases ... more Objective: Cough and fever are the initial symptoms of lower respiratory infection. Severe cases might be fatal. Therefore, particularly in the non-equipped centers, the lack of diagnostic methods to identify the severe cases has resulted in overconsumption of antibiotics. On the basis of the knowledge about non-specific immune response at the site of injury, we developed a colorimetric dip-test that shows abrupt, sensitive and quite specific color change upon contact with sputum in the cases of lower respiratory infection. We further explored the mechanism of the test. Results: We detected deoxyribonucleic acid (DNA) and hepatocyte growth factor in the sputum of patients that suffered from respiratory infection (n = 18). The results differed significantly (P < 0.0001) from age-matched patients (n = 18) with other respiratory disorders and highly correlated with the index-test results (Spearman Rank test = 0.84). DNA with a concentration more than 0.03 mg/ml induced a visible and stable color change on index-test within 1 min. The test recognized all of the cases with respiratory infection and the specificity was 72%. With a high negative predictive value. The index test detects, inter alia, cell-free DNA in sputum and might safely rule-out respiratory infection in 2/3 of cases that present symptoms of acute respiratory infection.
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
A large body of data accumulated over the past several years suggests that the periodontal pathog... more A large body of data accumulated over the past several years suggests that the periodontal pathogen Porphyromonas gingivalis is associated with cardiovascular disease. Circulating bacteria may cont ...
Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated with periodontit... more Porphyromonas gingivalis (P. gingivalis) is a major etiological agent associated with periodontitis. This study aims to develop antibodies to P. gingivalis in vitro for realtime detection of bacteria in clinical samples. Lymphocytes were isolated from whole blood of patient treated for periodontitis and were stimulated with P. gingivalis ATCC 33277. B-cell maturation to long-living antibody secreting-plasma cells was studied using flow cytometry and immunofluorescence staining. The antibodies developed in vitro were immobilized onto a CM-5 sensor chip of a biosensor to detect the presence of P. gingivalis in the gingival crevicular fluid of patients with periodontitis compared to periodontally healthy controls (n = 30). Surface plasmon resonance (SPR) analysis was performed to evaluate specific interactions of bacteria in samples with the immobilized antibodies. The results of SPR analysis were compared to the detection of P. gingivalis in the samples using DNA-DNA checkerboard hybridization technique. A clear and distinct change in lymphocyte morphology upon stimulation with P. gingivalis was observed. Anti-P. gingivalis antibodies secreted by CD38+ plasma cells showed the presence of all the four IgG subclasses. The results of DNA-DNA checkerboard analysis were in agreement with that of SPR analysis for the detection of P. gingivalis in patient samples. Furthermore, incubation with anti-P. gingivalis attenuated the bacterial response in SPR. The in vitro method for antibody production developed during this study could be used for an efficient real-time detection of periodontitis, and the attenuating effects of in vitro antibodies suggest their role in passive immunization to prevent periodontitis and their associated risk factors.
Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and inc... more Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNFalpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.
Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercia... more Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), highsensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r = À0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.
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