Salivary IgA antibody to malondialdehyde-acetaldehyde associates with mild periodontal pocket depth

Objective Oxidized epitopes such as malondialdehyde-acetaldehyde (MAA) play a crucial role in the progression of atherosclerosis through activation of the humoral immune response. The exact mechanism of the association between atherosclerosis and periodontal diseases is not fully understood. The aim of the current study is to evaluate the association of oral humoral immune response to oxidized epitopes with parameters of periodontal disease. Materials and methods The Parogene cohort consist of patients who have undergone coronary angiography due to cardiac symptoms. In this study, 423 patients were randomly selected for an extensive oral examination. Salivary Immunoglobulin A to oxidized epitopes and bacterial antigens was determined by chemiluminescence immunoassay. Results In a binary logistic regression model adjusted with periodontal disease confounders, periodontal pocket depth (PPD) 4-5 mm associated with salivary IgA antibodies to MAA-LDL (p = 0.034), heat shock protein 60 of Aggregatibacter actinomycetemcomitans (p = 0.045), Porphyromonas gingivalis (p = 0.045), A. actinomycetemcomitans (p = 0.005), P. intermedia (p = 0.020), and total IgA (p = 0.003). Conclusions The current study shows the association of salivary IgA to MAA-LDL with PPD 4-5 mm in a cohort of patients with chronic coronary artery disease. Humoral immune cross-reactivation to oxidized epitopes such MAA-LDL could partly explain the link of periodontitis with systemic diseases.Peer reviewe

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD (n = 133), stable CAD (n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL (P = 0.016, P = 0.043), Rgp44 (P = 0.012, P = 0.004), Aa-HSP60 (P = 0.032, P = 0.030), Tannerella forsythia (P = 0.002, P = 0.004), Porphyromonas endodontalis (P = 0.016, P = 0.020), Prevotella intermedia (P = 0.038, P = 0.005), and with total IgA antibody concentration (P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.Peer reviewe

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD (n = 133), stable CAD (n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL (P = 0.016, P = 0.043), Rgp44 (P = 0.012, P = 0.004), Aa-HSP60 (P = 0.032, P = 0.030), Tannerella forsythia (P = 0.002, P = 0.004), Porphyromonas endodontalis (P = 0.016, P = 0.020), Prevotella intermedia (P = 0.038, P = 0.005), and with total IgA antibody concentration (P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.Peer reviewe

Oral humoral immune response to oxidized LDL epitopes and periodontal pathogens in coronary artery disease and periodontitis

Abstract Atherosclerosis is a chronic inflammatory disease, characterized by retention of low-density lipoproteins (LDL) in the arterial wall, leading to atherosclerotic plaque formation. Subsequently, the retained LDL go through oxidative reactions forming immunogenic Oxidized-LDL (Ox-LDL). The humoral immune response to model oxidized epitopes, such as Malondialdehyde-acetaldehyde adducts (MAA-LDL), and copper-oxidized LDL play a key role in atherogenesis. Accumulating evidence has shown the link of atherosclerosis with oral health. Periodontitis is an inflammatory disease where the tooth-surrounding tissue is compromised. Periodontitis contributes to systemic inflammation and if left untreated, leads to tooth loss. The association of atherosclerosis with periodontitis has been extensively studied and several mechanisms have been suggested. Molecular mimicry of malondialdehyde epitopes with key periodontal pathogen virulence factor Porphyromonas gingivalis A hemagglutinin domain (Rgp44) epitope has been reported. On the other hand, an atherosclerotic mouse model immunized with Rgp44 showed increased levels of IgM to MAA-LDL. The above-mentioned findings raise the question whether atherosclerosis and periodontitis are associated through the cross-activation of mucosal humoral immune response by molecular mimicry. The aim of the current thesis work was to characterize salivary antibodies to oxidized epitopes and examine their cross-reactivity with antibodies to periodontal pathogens. Finally, the aim was to explore whether salivary immunoglobulins are associated with coronary artery disease (CAD) or periodontal diseases. In the first study, the salivary immunoglobulins to oxidized epitopes were characterized. In study I and II, the cross-reactivities of salivary IgA to MAA epitopes with periodontal pathogens virulence factors Rgp44 and Aggregatibacter actinomycetemcomitans Heat Shock Protein 60 (Aa-HSP60) were shown. In the second study, an independent association of salivary IgA to MAA-LDL with CAD and acute coronary artery syndrome (ACS) was also reported. Finally, in the third study, salivary IgA to MAA-LDL was shown to associate independently with periodontal pocket depth (PPD) 4- 5 mm, which is a major symptom of periodontitis. The findings of this thesis highlight the potential role of humoral mucosal immune response to oxidized epitopes in atherosclerosis and periodontal disease.Tiivistelmä Ateroskleroosiin eli valtimonkovettumatautiin liittyy krooninen matala-asteinen tulehdustila, jossa LDL (low-density lipoprotein) kolesteroli kertyy verisuonien seinämiin muodostaen ateroskleroottista plakkia. Myöhemmässä vaiheessa LDL-lipidiperoksidaatio tuottaa reaktiivisia aldehydejä, kuten malondialdehydi-asetaldehydi (MAA) -epitooppia. Hapettuneiden epitooppien synnyttämällä humoraalisella immuniteetilla on merkittävä rooli ateroskleroosin kehityksessä. Infektiot edesauttavat valtimokovettumataudin kehittymistä. Tutkimukset ovat osoittaneet, että hampaita ympäröivän kudoksen tulehdustila eli parodontiitti on valtimokovettumataudin merkittävä riskitekijä. Ateroskleroosin ja parodontiitin yhteyttä on tutkittu laajasti, mutta tarkkaa mekanismia ei vielä tunneta. On raportoitu, että MAA-epitoopilla on rakenteellista samankaltaisuutta parodontaalisen patogeenin virulenssitekijän Porphyromonas gingivalis hemagglutiniini-domeenin (Rgp44) molekyylien kanssa. Toisaalta Rgp44:llä immunisoiduilla ateroskleroottisilla hiirillä on korkeampi MAA-LDL-IgM taso kuin kontrollihiirillä. Edellä mainitut havainnot herättivät kysymyksen siitä, millainen rooli suun humoraalisella immuunivasteella on ateroskleroosin ja parodontiitin välisessä assosiaatiossa. Tämän väitöstyön tarkoituksena oli karakterisoida hapettuneita epitooppeja tunnistavia syljen vasta-aineita sekä niiden spesifisyyttä ja ristireagointia parodontaalisten patogeenien kanssa. Myös syljen hapettuneiden epitooppien vasta-aineiden assosiaatiota sepelvaltimotautiin (CAD) tai parodontaalisiin sairauksiin tutkittiin. Ensimmäisessä työssä karakterisoitiin syljen vasta-aineita, jotka tunnistavat hapettuneita epitooppeja. Tutkimustyön I ja II osassa osoitettiin, että syljen IgA MAA vasta-aineet ristireagoivat Rgp44:n ja Aggregatibacter actinomycetemcomitans heat shock protein 60:n (Aa-HSP60) kanssa. Toisessa tutkimustyössä havaittiin myös, että syljen MAA-LDL IgA-vasta-aineiden pitoisuus liittyy itsenäisenä riskitekijänä sepelvaltimotautiin. Lopuksi kolmannessa osatyössä osoitettiin, että syljen MAA-LDL IgA-vasta-aineet assosioituvat itsenäisesti 4–5 mm:n ientaskusyvyyteen (PPD). Tämän väitöskirjan tutkimustulokset osoittavat suun humoraalisen immuniteetin mahdollisen roolin ateroskleroosin ja parodontaalisairauksien välisessä yhteydessä

Potential role of nuclear magnetic resonance spectroscopy to identify salivary metabolite alterations in patients with head and neck cancer

The analysis of the salivary metabolomic profile may offer an early phase approach to assess the changes associated with a wide range of diseases including head and neck cancer. The aim of the present study was to investigate the potential of nuclear magn16567956800The authors acknowledge the contribution of NMR Metabolomics Laboratory at the University of Eastern Finland (Kuopio, Finland). Funding The present study was supported by the Finnish Funding Agency for Technology and Innovation (Tekes) project ‘Novel spe

nim-Gen-unabhängige Metronidazolresistenz von Bacteroides fragilis in Surgical Site Infections

Background: Bacteroides fragilis is the most common anaerobic pathogen isolated from surgical site infections (SSIs). Metronidazole resistance is increasing and the mechanisms of resistance are not clear in some isolates. The aim of the present study was to investigate the metronidazole susceptibility prevalence, and detect nim genes in B. fragilis isolates from SSIs. Methods: This study included 100 surgery patients with signs and symptoms indicative of SSIs. Syringe aspiration of the infected site was used to collect specimens. All specimens were cultured on BBA (Brucella blood agar), KVLB (kanamycin-vancomycin laked blood), and BBE (Bacteroides bile esculin) agar. The MIC (minimum inhibitory concentration) of metronidazole was determined by the agar dilution method according to the Clinical and Laboratory Standard Institute (CLSI). Then the PCR method was used to determine the presence of the nim gene.Results: In the present study, 26 B. fragilis were isolated from 100 SSIs specimens. Eight isolates were metronidazole resistant; the metronidazole MIC was 32 µg/mL for 7 isolates and 64 µg/mL for one isolate. All isolates were nim gene negative. Conclusion: The emergence of metronidazole-resistant B. fragilis limits the application of this drug for treatment and prophylaxis of SSIs. Thus, rapid identification of metronidazole-resistant B. fragilis is essential to restrict inappropriate, superfluous administration. In spite of various metronidazole resistance mechanisms other than that depending on the nim gene, detection of nim by PCR is unsuitable for identifying resistant isolates. Therefore, phenotypic methods are better to screen for and identify metronidazole-resistant B. fragilis .Hintergrund: Bacteroides fragilis ist der häufigste bei Surgical Site Infections (SSI) isolierte Anaerobier. Da die Resistenz gegen Metronidazol im Anstieg begriffen ist und die Resistenzmechanismen bei einigen Isolaten unklar sind, sollten die Prävalenz Metronidazol-sensibler Erreger und das Vorkommen von nim -Genen bei B. fragilis -Isolaten von SSIs untersucht werden.Methode: Es wurden 100 Patienten mit diagnostizierter SSI untersucht. Die mikrobiologischen Proben wurden mittels Nadelaspiration aus dem Infektionsherd gewonnen. Die Kultivierung erfolgte auf Brucella-Blutagar, Kanamycin-Vancomycin-Laked Blutagar und Bacteroides-Galle-Esculin-Agar. Die minimale Hemmkonzentration (MHK) von Metronidazol wurde im Agarverdünnungstest gemäß Clinical and Laboratory Standard Institute (CLSI) bestimmt. Der Nachweis des nim -Gens erfolgte mittels PCR.Ergebnisse: In 26 Fällen wurde B. fragilis isoliert. Acht Isolate waren gegen Metronidazol resistent (MHK 32 µg/mL bei 7, 64 µg/mL bei einem Isolat). In keinem Isolat war das nim -Gen nachweisbar.Schlussfolgerung: Das Vorkommen Metronidazol-resistenter B. fragilis -Stämme kann den Erfolg der perioperativen Antibiotikaprophylaxe und ebenso der Therapie infrage stellen. Daher ist die rasche Identifikation Metronidazol-resistenter B. fragilis -Stämme wichtig, um eine ungeeignete Verabreichung zu verhindern. In Anbetracht verschiedener nim -Gen-unabhängiger Resistenzmechanismen ist der Nachweis des nim -Gens mittels PCR zur Identifikation resistenter Isolate ungeeignet. Stattdessen eignen sich phänotypische Methoden zum Screening Metronidazol-resistenter B. fragilis -Stämme

STARTING POINT OF BUCKWHEAT BREEDING IN BANGLADESH

Buckwheat is not commonly cultivated in Bangladesh because it is an ancient minor crop. Common buckwheat is familiar as a rabi season crop and is rarely cultivated in some areas of northern part in Bangladesh. Henceforth, organized research improvement has not been established yet on buckwheat and so research information about buckwheat breeding is very limited. Again no developed variety available in Bangladesh. The varieties which are being cultivated in farmer’s level are actually local cultivar. Bangladesh Agricultural Research Institute (BARI) started working on buckwheat with five genotype, since 2018 and collected from PGRC, BARI. Characterization, different yield trial in different regions of Bangladesh have been conducted for selection of promising genotype

Bakterielle Ätiologie und Antibiotikaempfindlichkeit von Erregern von Infektionen des diabetischen Fußes

Aim: The aim of this study was to investigate anaerobic and aerobic bacteria profile and determination of antibiotic susceptibility pattern in aerobic bacteria.Method: Specimens were cultured using optimal aerobic and anaerobic microbiological techniques. Identification of bacterial isolates was performed by standard microbiological methods and antibiotic susceptibility testing was performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI).Result: 92 bacterial strains were isolated from 60 samples of diabetic foot ulcers. Predominant aerobic bacteria isolated from these infections were S. aureus (28%) followed by Enterobacteriaceae family (24%) including Escherichia coli (15%), Citrobacter spp. (4%), Enterobacter spp. (4%), and coagulase-negative Staphylococcus spp. (17%), Enterococcus spp. (15%), Pseudomonas aeruginosa (7%) and Acinetobacter spp. (4%). No Clostridium spp. were isolated and 4% Bacteroides fragilis obtained from anaerobic culture. All Gram-positive isolates were susceptible to linezolid while all Enterobacteriaceae showed sensitivity to imipenem.Conclusion: Most of DFIs specimens were poly microbial infection and predominant bacteria were S. aureus and B. fragilis . These wounds may require use of combined antimicrobial therapy for initial management.Zielsetzung: Es sollte die bakterielle Ätiologie (anaerobe und aerobe Flora) und Antibiotikaempfindlichkeit von Erregern beim diabetischen Fußsyndrom analysiert werden.Methode: Die Kultivierung erfolgte unter optimalen aeroben und anaeroben Bedingungen. Die Identifizierung der bakteriellen Isolate wurde mit mikrobiologischen Standardmethoden vorgenommen. Die Testung der Antibiotikaempfindlichkeit erfolgte gemäß den Richtlinien des Clinical und Laboratory Standards Instituts (CLSI).Ergebnisse: Von 60 Proben diabetischer Fußulcera wurden 92 Bakterienstämme isoliert. Dominierende Aerobier waren S. aureus (28%), gefolgt von Vertretern der Enterobacteriaceae (24%) einschließlich Escherichia coli (15%), Citrobacter spp. (4%), Enterobacter spp. (43%) und Coagulase-negativen Staphylococcus spp. (17%), Enterococcus spp. (15%), Pseudomonas aeroginosa (7%) und Acinetobacter spp. (4%). In den anaeroben Kulturen war in 4% der Ulcera Bacteroides fragilis nachweisbar, jedoch in keinem Fall Clostridium spp. Alle Gram-positiven Isolate waren gegen Linezolid empfindlich; alle Vertreter der Enterobacteriaceae waren gegenüber Imipenem empfindlich.Schlussfolgerung: Die meisten Infektionen bei den diabetischen Fußulcera waren durch eine Mischflora mit Dominanz von S. aureus und B. fragilis gekennzeichnet. Die Ulcera können daher in der Initialtherapie sinnvollerweise eine kombinierte antimikrobielle Therapie erfordern

Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein

Abstract Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL) and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and toPg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS), and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis