Effect of Baicalin on Transcriptome Changes in Piglet Vascular Endothelial Cells Induced by a Combination of Glaesserella parasuis and Lipopolysaccharide.

Glaesserella parasuis causes porcine Glässer's disease and lipopolysaccharide (LPS) induces acute inflammation and pathological damage. Baicalin has antioxidant, antimicrobial, and anti-inflammatory functions. Long noncoding RNAs (lncRNAs) play key regulatory functions during bacterial infection. However, the role of lncRNAs in the vascular dysfunction induced by a combination of G. parasuis and LPS during systemic inflammation and the effect of baicalin on lncRNA expression induced in porcine aortic vascular endothelial cells (PAVECs) by a combination of G. parasuis and LPS have not been investigated. In this study, we investigated the changes in lncRNA and mRNA expression induced in PAVECs by G. parasuis, LPS, or a combination of G. parasuis and LPS, and the action of baicalin on lncRNA expression induced in PAVECs by the combination of G. parasuis and LPS. Our results showed 133 lncRNAs and 602 genes were differentially expressed when PAVECs were stimulated with the combination of G. parasuis and LPS, whereas 107 lncRNAs and 936 genes were differentially expressed when PAVECs were stimulated with the combination of G. parasuis and LPS after pretreatment with baicalin. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the dominant signaling pathways triggered by the combination of G. parasuis and LPS were the tumor necrosis factor signaling pathway, phosphatidylinositol signaling system, and inositol phosphate metabolism. Protein-protein interaction network analysis showed the differentially expressed target genes of the differentially expressed lncRNAs (DELs) were related to each other. A coexpression analysis indicated the expression levels of the DELs were co-regulated with those of their differentially expressed target genes. This is the first study to systematically compare the changes in lncRNAs and mRNAs in PAVECs stimulated with a combination of G. parasuis and LPS. Our data clarified the mechanisms underlying the vascular inflammation and damage triggered by G. parasuis and LPS, and it may provide novel targets for the treatment of LPS-induced systemic inflammation.

Pulmonary Aggregatibacter actinomycetemcomitans infection masquerades as malignancy in a patient with periodontitis.

A 49-year-old man with a 37.5 pack-year smoking history presented with a suspected neoplasm of the right lung following the discovery of a metabolically active mass on positron emission tomography-CT imaging. The patient, who demonstrated poor oral hygiene, had a history of irregular problem-oriented dental visitation. Having excluded malignancy through histologic investigations, Aggregatibacter actinomycetemcomitans-a well-established periodontal pathogen-was subsequently cultured from his pulmonary aspirate. The patient was therefore managed with systemic antimicrobials and adjunctive dental extractions to eliminate the likely source of infection, whereafter the mass resolved without complication. This case corroborates previous reports of extraoral isolation of A. actinomycetemcomitans, which may mimic cancer clinically and radiographically. While a definitive causative link between untreated periodontitis and systemic infection remains to be elucidated, such cases present a compelling argument in favour of promoting oral health to prevent systemic disease.

Schizophyllum commune ß-glucan: Effect on interleukin-10 expression induced by lipopolysaccharide from periodontopathic bacteria.

ß-glucans are potent immunomodulators, with effects on innate and adaptive immune responses via dectin-1 as the main receptor. In this study, we investigated the biological effect of ß-glucan from Schizophyllum commune, called Schizophyllan (SPG) on Interleukin-10 (IL-10) expression induced by a lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans in murine macrophages (J774.1). SPG and dectin-1 interaction up-regulates LPS-induced IL-10 expression. The regulative effect of SPG on IL-10 expression is dependent on prolongation of nuclear translocation activity of nuclear factor-kappa B (NF-κBα) pathway induced by LPS. We also found that LPS-induced phosphorylation of mitogen- and stress-activated protein kinase 1 (MSK1) and cAMP-responsive-element-binding protein (CREB), followed by up-regulation of IL-10, was stimulated by SPG priming via activation of the spleen tyrosine kinase (Syk). Our data indicate that SPG augments the anti-inflammatory response in murine macrophages which can be useful to create an intervention for periodontal disease treatment.

Aggregatibacter actinomycetemcomitans pneumonia mimicking lung cancer in a previously healthy 12-year-old child from Saudi Arabia: a case report.

Aggregatibacter actinomycetemcomitans formely known as Actinobacillus actinomycetemcomitans is a known part of the normal oral flora. It can sometimes cause oral or rarely extra-oral infections secondary to hematogenous extension or aspiration. It is a rare cause of invasive pneumonia. It can resemble tuberculosis or lung cancer in its presentation. Making the diagnosis in such case is crucial for better management that usually require tissue biopsy. We report a case of Aggregatibacter actinomycetemcomitans invasive pneumonia in a 12-year-old previously healthy boy from Saudi Arabia. After a prolonged course of antibiotics, clinical and radiological follow up showed complete resolution of the infection.

Mixed Actinomyces israelii and Aggregatibacter actinomycetemcomitans infection causing empyema necessitatis and multiple skin abscesses in an immunocompetent patient.

A 45-year-old- man presented with left chest wall pain, swelling and cough. Over a 2-month period he developed abscesses in the right foot, right anterior thigh, left buttock and left chest. Incision and drainage of the soft tissue abscesses and video-assisted thoracoscopic surgery to drain the loculated empyema contiguous with the chest wall abscess were performed as surgical management. Gram stain showed beaded Gram-positive rods and the culture initially grew Aggregatibacter actinomycetemcomitans and Eikenella corrodens Pathological evaluation of the pleura showed sulfur granules and organisms consistent with Actinomyces spp. on Gomori methenamine silver stain; Actinomyces israelii was recovered in culture with extended incubation. The patient was treated for 3 weeks with ceftriaxone and oral metronidazole, followed by oral amoxicillin. Culture of A. actinomycetemcomitans with other findings consistent with actinomycosis warrants 6-12 months of antibiotic therapy.

Aggregatibacter actinomycetemcomitans pneumonia with chest and abdominal wall involvement.

A 54-year-old man presented with a productive cough, chest pain, fever and weight loss. Initial analysis revealed a palpable chest wall mass and consolidation in the left lower lobe and pleural abnormalities on imaging. At that point no infectious cause or malignancy was identified. Microbiological analysis of a needle biopsy from a newly developed abdominal wall mass revealed growth of Aggregatibacter actinomycetemcomitans The patient was successfully treated with antibiotic therapy for 1 year. Aggregatibacter actinomycetemcomitans is a Gram-negative coccobacillus and is part of the normal oral flora. It is capable of causing infections in humans including periodontitis, soft tissue abscesses and systemic invasive infections, most commonly endocarditis.

Aggregatibacter aphrophilus Sacroiliitis Following Gastroscopy in a Young Sportsman.

We report a case of Aggregatibacter aphrophilus sacroiliitis in a young sportsman, presenting 48 hours after endoscopy and biopsy. Microbiological diagnosis was made only after repeated attempt at joint aspiration. The patient was cured after radiologically guided drainage and a prolonged course of directed antibiotics.

Withaferin A inhibits inflammatory responses induced by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in macrophages.

Periodontitis is a progressive chronic inflammatory disease and a major cause of tooth loss in humans. As a withanolides, withaferin A (WA) is known to exhibit strong anti­inflammatory activity. The present study examined whether WA inhibited inflammatory responses in macrophages in response to two representative periodontal pathogens, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. Murine bone marrow­derived macrophages (BMDMs) were used in this study and cytokine production in culture supernatants was measured by enzyme­linked immunosorbent assays. Western blot analysis was performed to determine the activation of nuclear factor­κB and mitogen­activated protein kinases (MAPKs) and the expression of inducible nitric oxide synthase (iNOS), toll­like receptor (TLR) 2 and TLR4. The production of nitric oxide (NO) was determined by the Griess reaction. WA treatment was shown to decrease interleukin (IL)­6 and tumor necrosis factor (TNF)­α production in BMDMs in response to F. nucleatum and A. actinomycetemcomitans in a dose­dependent manner. The phosphorylation of IκB­α and MAPKs (p38, extracellular signal­regulated kinases and c­Jun N­terminal kinases) induced by F. nucleatum and A. actinomycetemcomitans was also inhibited by WA. F. nucleatum and A. actinomycetemcomitans induced iNOS expression and NO production in BMDMs, which was inhibited by WA in a dose­dependent manner. WA also reduced endogenous and induced expression of TLR2 and TLR4 in these cells. These results suggest that WA may be a potential therapeutic agent or preventive additive for periodontitis control.

Are there specific benefits of amoxicillin plus metronidazole in Aggregatibacter actinomycetemcomitans-associated periodontitis? Double-masked, randomized clinical trial of efficacy and safety.

BACKGROUND: It has been suggested that prescription of amoxicillin plus metronidazole in the context of periodontal therapy should be limited to patients with specific microbiologic profiles, especially those testing positive for Aggregatibacter actinomycetemcomitans. The main purpose of this analysis is to determine if patients positive for A. actinomycetemcomitans with moderate to advanced periodontitis benefit specifically from amoxicillin plus metronidazole given as an adjunct to full-mouth scaling and root planing. METHODS: This is a double-masked, placebo-controlled, randomized longitudinal study including 41 participants who were positive for A. actinomycetemcomitans and 41 participants who were negative for A. actinomycetemcomitans. All 82 patients received full-mouth periodontal debridement performed within 48 hours. Patients then received either systemic antibiotics (375 mg amoxicillin and 500 mg metronidazole, three times daily) or placebo for 7 days. The primary outcome variable was persistence of sites with a probing depth (PD) >4 mm and bleeding on probing (BOP) at the 3-month reevaluation. Using multilevel logistic regression, the effect of the antibiotics was analyzed according to the following factors (interaction effect): A. actinomycetemcomitans-positive or -negative at baseline, sex, age, smoking, tooth being a molar, and interdental location. RESULTS: At reevaluation, participants in the test group had significantly fewer sites with a persisting PD >4 mm and BOP than control patients (P <0.01). Being A. actinomycetemcomitans-positive or -negative did not change the effect of the antibiotics. Patients benefited from the antibiotics irrespective of sex, age, or smoking status. Molars benefited significantly more from the antibiotics than non-molars (P for interaction effect = 0.03). CONCLUSIONS: Patients who were positive for A. actinomycetemcomitans had no specific benefit from amoxicillin plus metronidazole. Sites on molars benefited significantly more from the antibiotics than non-molar sites.

Actinobacillus endocarditis associated with hypertrophic cardiomyopathy.

Infective endocarditis can be associated with complex clinical presentations, sometimes with a difficult multi-disciplinary management. Actinobacillus actinomycetemcomitans belongs to the Haemophilus species, Actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella species group, responsible for 5% to 10% of infective endocarditis in native heart valves. These organisms have slow fastidious growth pattern, often associated with negative cultures, and cause systemic embolism with abscess formation. The authors present the case of a 59-year-old man, admitted due to fever of unknown origin, with a personal history of obstructive hypertrophic cardiomyopathy and recent dental manipulation. The diagnosis of mitral valve's endocarditis was established after a transoesophageal ecocardiography, with a late isolation of A actinomycetemcomitans in blood culture. Despite the institution of antibiotic therapy, the patient suffered from multiple episodes of septic embolism: skin, mucosae, cerebral abscesses, spondylodiscitis and uveitis. He was submitted to heart surgery with miectomy and replacement of the native mitral valve by a mechanical prosthesis, while on antibiotics.

PDT in non-surgical treatment of periodontitis in HIV patients: a split-mouth, randomized clinical trial.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the clinical and microbiological effect of photodynamic therapy (PDT) in the non-surgical treatment of periodontitis in HIV patients. METHODS: Twelve HIV patients from the CEAPE/UNIP, Brazil, with periodontitis were included in this 6-month, split-mouth, double-blind, controlled clinical trial. Patients were placed in the following groups: Group SRP-scaling and root planning with an ultrasonic device (SRP); and Group SRP + PDT-SRP associated with a course of PDT with a diode laser with a wavelength of 660 nm and 0.03 W power associated with methylene blue 0.01% lasting 133 seconds. All clinical measurements (periodontal probing depth (PPD), gingival recession (GR), clinical attachment level (CAL), full-mouth plaque index (FMPI), bleeding score (FMBS)), and microbiological parameters (detection of Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), and Aggregatibacter actinomycetemcomitans (Aa)) were assessed at baseline and at 45 days, and 3 and 6 months after therapy. The ANOVA/Tukey was used for statistical analysis (α = 5%). RESULTS: There were no differences in any of the investigated parameters observed at baseline in the two groups (P > 0.05). Moreover, participants in the SRP + PDT group presented a higher PPD reduction and CAL gain than those in the SRP group at 45 days and 3 and 6 months. At 6 months, sites receiving SRP + PDT showed a significant PPD reduction of 1.4 ± 0.5 mm, while those in the SRP group showed a 0.3 ± 0.8 mm reduction (P < 0.05). The CAL gain at the sixth month was 1.3 ± 0.5 mm and 0.2 ± 0.7 mm for participants in the SRP + PDT and SRP groups, respectively (P < 0.05). Microbiologically, both therapies presented a reduction in the detection of Pg, Tf, and Aa, and there was no difference between them (P > 0.05). CONCLUSION: We concluded that PDT therapy used adjunctively to SRP could promote additional benefits in the treatment of HIV-associated periodontitis.

Pyogenic cervical spondylitis caused by Pasteurella haemolytica attributed to excessive contact with dogs.

The bacterium Pasteurella haemolytica is resident in the oral cavities of dogs and cats and is often a cause of zoonotic infection. However, it is rare for it to be the pathogenic bacteria behind pyogenic spondylitis, and few studies have been conducted on it. This article reports a case of pyogenic cervical spondylitis thought to be caused by excessive contact with pet dogs.A 52-year-old man reported neck pain and pain in the right upper limb. He was admitted after plain radiographs and magnetic resonance imaging suggested pyogenic spondylitis. Pasteurella haemolytica was detected by needle aspiration biopsy of the intervertebral disk. Because the patient owned 2 dogs and frequently kissed them on the mouth, the cause of infection was thought to be excessive contact with pet dogs. Symptoms were alleviated with bed rest and administration of antibiotics with a higher sensitivity to this bacterium.

Recurrent infective endocarditis due to Aggregatibacter actinomycetemcomitans: reinfection or relapse?

Aggregatibacter actinomycetemcomitans is commonly part of the normal microflora of the human upper respiratory tract. It has been implicated in periodontal disease and various infections, particularly endocarditis. We report here what we believe to be the first case of recurrent infective endocarditis due to A. actinomycetemcomitans in a 44-year-old woman occurring 5 years after the initial episode. Genomic analysis proved that the strains were closely related. Despite efficient antibiotic treatment, surgery was necessary for recovery.

Detection of tetracycline-resistant and susceptible pasteurellaceae in the nasopharynx of loose group-housed calves.

The aim of the present study was to determine which Pasteurella and Mannheimia species are present in the upper respiratory tract of healthy calves with no history of antimicrobial treatment prior to sampling. The presence of subpopulations of tetracycline-resistant Pasteurellaceae was also investigated. Nasal swabs from 61 loose group-housed, clinically healthy calves, 1 to 4 months old, from 16 dairy herds were inoculated aerobically on a selective medium (Columbia agar with 5% ovine blood and 16 mg/L bacitracin) with or without 4 mg/L oxytetracycline (OTC). A total of 43 strains belonging to the family Pasteurellaceae were isolated from 38 calves (62.3%) out of 13 herds (81.3%). The predominant organisms were Pasteurella multocida subsp. multocida (57.4%), Mannheimia varigena (4.9%) and M. haemolytica (3.2%). Growth of Pasteurellaceae on the OTC-containing medium was seen only with samples from two herds (6 animals; 9.8%), and on only one farm this proved to be an OTC-resistant subpopulation. Minimum inhibitory concentration (MIC) determinations by means of agar dilution confirmed a low prevalence of OTC-resistant Pasteurellaceae, with overall MIC(50) and MIC(90) values of 0.25 and 32 mg/L, respectively. These data do not support the hypothesis that the relative high frequency of tetracycline-resistant P. multocida isolates from fatal cases of bovine respiratory disease is related to the presence of minor tetracycline-resistance subpopulations within this species.