[show abstract][hide abstract] ABSTRACT: Chronic infections have been demonstrated to maintain low-grade systemic inflammation and associate with atherosclerosis. We studied the inflammation- and lipid homeostasis-related effects of Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) infections on the epididymal and inguinal adipose tissue (AT) transcriptomes and fatty acid distribution in apolipoprotein (apo) E-deficient mice. Chow-fed apoE-deficient mice were exposed to 1) chronic intranasal infection with C. pneumoniae (Cpn group), 2) recurrent intravenous infection with A. actinomycetemcomitans (Aa group), 3) a combination of both types of infection (Cpn + Aa group), or 4) infection with the vehicle (control group). Epididymal and inguinal AT gene expression was analyzed using an Illumina Mouse WG-6 v2.0 platform and quantitative PCR (QPCR). Microarray data were analyzed using Gene Ontology enrichment analysis. AT fatty acid analysis was performed using gas--liquid chromatography.
The transcriptomics data revealed significant enrichment in inflammation-associated biological pathways in both AT depots derived from the Aa and Cpn + Aa treated mice compared with the control group. The proportion of saturated fatty acids was higher in the inguinal AT in Aa (p = 0.027) and Cpn + Aa (p = 0.009) groups and in the epididymal AT in Aa group (p = 0.003). The proportion of polyunsaturated fatty acids was significantly lower among all Aa-infected groups in both depots. Chronic Cpn infection displayed only minor effects on transcriptomics and fatty acids of the AT depots.
Systemic infection with A. actinomycetemcomitans activates inflammation-related biological pathways and modulates cellular lipid homeostasis. The adverse changes in adipose tissues during chronic infection may promote atherosclerosis.
[show abstract][hide abstract] ABSTRACT: Pleural effusion (PE), a complication of community-acquired pneumonia (CAP), is usually attributed to a bacterial infection. Nonetheless, viral infections have not been investigated routinely. We searched for bacterial and viral infections among 277 children hospitalized with CAP. Among these children 206 (74%) had radiographic confirmation, of whom 25 (12%) had PE. The aetiology was established in 18 (72%) PE cases: bacterial (n = 5; 28%), viral (n = 9; 50%), and viral-bacterial (n = 4; 22%) infections were found. Infection by rhinovirus (n = 3), enterovirus, Streptococcus pneumoniae (n = 2 each), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, influenza A virus, and respiratory syncytial virus (RSV) (n = 1 each) were detected as probable sole infections. Parainfluenza virus 1/3 + influenza A virus and RSV + influenza A virus (n = 1 each) were identified as mixed viral-viral infections. Probable viral non-bacterial infection was identified in a third of the cases with CAP and PE. It is advisable to investigate viral as well as bacterial infections among children with CAP and PE.
Scandinavian Journal of Infectious Diseases 01/2013; · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Children frequently carry Streptococcus pneumoniae (pneumococcus) in their nasopharynx, even when healthy. Lower carriage rates have been reported in adults and only sparse data are available for the elderly. We sampled healthy elderly subjects for nasopharyngeal carriage to assess the prevalence of pneumococcal carriage using various assays.
A deep nasopharyngeal swab sample was taken from 590 healthy elderly subjects aged ≥ 65 y. The samples were stored in STGG (skim milk-tryptone-glucose-glycerol) medium and cultured directly and after incubation in enrichment broth using routine identification methods. Real-time polymerase chain reaction (PCR) assays specific for pneumolysin and pneumococcal surface antigen A genes was performed on the same samples. Urine was also collected and assayed using the commercial Binax Streptococcus pneumoniae NOW urine antigen test.
The prevalence of pneumococcal carriage in healthy elderly persons was 1.5% for encapsulated pneumococci and 5.3% for all presumptive pneumococci. The use of the enrichment broth did not increase the yield of positives. PCR assays gave higher numbers of positives, but pneumolysin PCR in particular gave probable false-positive results. Only 1 urine antigen test was positive, and this was in a person not carrying pneumococcus.
Nasopharyngeal carriage of pneumococci in the elderly was rare. Identification of presumptive pneumococci in culture requires further confirmation, e.g. by serotyping. The urine antigen test was not affected by concurrent carriage. Low carriage prevalence suggests that encapsulated pneumococci detected in a respiratory tract sample during sickness may be the true cause of disease, since contamination from asymptomatic nasopharyngeal carriage seems unlikely.
[show abstract][hide abstract] ABSTRACT: The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.
Journal of clinical microbiology 11/2011; 50(2):264-73. · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Corn mint ( Mentha arvensis ) provides a good source of natural phenols such as flavone glycosides and caffeic acid derivatives, which may have prophylactic properties against inflammations. This study investigated whether corn mint extract would be beneficial against a universal respiratory tract pathogen, Chlamydia pneumoniae , infection. The extract inhibited the growth of C. pneumoniae CWL-029 in vitro in a dose-dependent manner. The inhibition was confirmed against a clinical isolate K7. The phenolic composition of the extract was analyzed by UPLC-ESI/Q-TOF/MS, the main components being linarin and rosmarinic acid. These compounds were active in vitro against C. pneumoniae. Linarin completely inhibited the growth at 100 μM. Inbred C57BL/6J mice were inoculated with C. pneumoniae K7. M. arvensis extract was given intraperitoneally once daily for 3 days prior to inoculation and continued for 10 days postinfection. The extract was able to diminish the inflammatory parameters related to C. pneumoniae infection and significantly (p = 0.019) lowered the number of C. pneumoniae genome equivalents detected by PCR at biologically relevant amounts.
Journal of Agricultural and Food Chemistry 11/2011; 59(24):12836-42. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca(2+)) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca(2+) modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca(2+) modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca(2+) modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 μM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 μM), whereas 10 μM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 μM and 100 μM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 μM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca(2+) modulators potentiate the antichlamydial effects of the phenolic compounds.
The Journal of Antibiotics 09/2011; 64(11):747-52. · 2.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.
Scandinavian Journal of Immunology 06/2011; 74(4):383-9. · 2.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Anxiety frequently accompanies low-grade inflammation-associated conditions like depression, insulin resistance, coronary heart disease and metabolic syndrome. The association between anxiety and low-grade inflammation is, unlike between depression and low-grade inflammation, a very sparsely studied area in general populations. The aim of the present study was to investigate whether anxiety symptoms as well as comorbid anxiety and depressive symptoms are associated with low-grade inflammation at population level.
The general population-based Northern Finland 1966 Birth Cohort was followed until age 31 (n=2688 males and 2837 females), when the highly sensitive CRP concentrations were measured. Anxiety and depressive symptoms were defined by Hopkins Symptom Checklist-25 (HSCL-25).
After adjusting for confounders, logistic regression analyses showed that anxiety symptoms alone increased the probability for elevated hs-CRP levels (>3.0mg/L) in males over two-fold (2.19 CI 95% 1.08-4.46), while comorbid anxiety and depressive symptoms caused a 1.7-fold (1.76 CI 95% 1.13-2.74) increase in the probability for elevated hs-CRP levels (1.0-3.0mg/L).
Our results support the hypothesis that anxiety as well as comorbid anxiety and depression can be associated with an increased risk for low-grade inflammation in males at population level.
European Psychiatry 05/2011; 26(6):363-9. · 3.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pathogens such as Aggregatibacter actinomycetemcomitans (Aa) and Chlamydia pneumoniae (Cpn) associate with an increased risk for cardiovascular diseases by inducing inflammation. We hypothesized that the pathogens affect the vascular wall by disturbing cholesterol homeostasis and endothelial function.
Aa- and Cpn-infections were induced in apoE-deficient mice by intravenous and intranasal applications, respectively. Cholesterol efflux from mouse peritoneal macrophages to apo(lipoprotein)A-I was assessed. The efflux capacity of mouse sera as acceptors of cholesterol from RAW264.7-macrophages was determined. Additionally, endothelial function was studied by following the relaxation capacity of rat mesenteric arteries after incubation in the conditioned culture media of the peritoneal macrophages isolated from the mice.
Infection increased serum phospholipid transfer protein (PLTP) and lipopolysaccharide (LPS) activity, as well as serum amyloid A (SAA) and TNF-α concentrations. Peritoneal macrophages of mice with Aa-infection showed increased cholesterol uptake and reduced cholesterol efflux. Sera of Cpn and Cpn + Aa-infected mice had reduced cholesterol efflux capacity from RAW264.7-macrophages. Conditioned macrophage medium from mice with chronic C. pneumoniae infection induced endothelial dysfunction. Additionally, concentrations of serum adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in Cpn-groups and E-selectin in Cpn + Aa-group, were elevated. The serum markers of endothelial function correlated positively with SAA.
Aa- and Cpn-infections may generate proatherogenic changes in the vascular wall by affecting the macrophage cholesterol homeostasis and endothelial function.
[show abstract][hide abstract] ABSTRACT: Viruses and bacteria like Chlamydia pneumoniae and Helicobacter pylori have been suggested to have a role in pathogenesis of overweight and obesity.
We studied whether C. pneumoniae-specific IgG antibodies are associated with elevated body mass index (BMI), waist and hip circumference, and/or waist-hip ratio (WHR), and whether the risk is more pronounced in the simultaneous presence of an ongoing inflammation as measured by elevated high-sensitive C-reactive protein (hsCRP) levels.
Our study population was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), a general population sample of 12,058 live-born children. This cross-sectional study consisted of 5044 persons at 31 years of age. Serum C. pneumoniae IgG titers were measured by microimmunofluorescence test, and hsCRP levels by immunoenzymometric assay.
C. pneumoniae IgG positivity (titer ≥ 32), both alone and jointly with elevated hsCRP (≥ 1.64 mg l(-1), an upper quartile), was found to significantly associate with elevated BMI in the whole study population and with elevated hip and waist circumference in women, yet no association with WHR was seen. The analyses were adjusted for sex (when appropriate), smoking, socioeconomic position, glucose, insulin, high- and low-density lipoprotein cholesterols, triglycerides, leukocytes and pulse pressure.
These findings suggest that especially in women, persistent C. pneumoniae infection may be associated with overweight/obesity, independently of more traditional risk factors.
International journal of obesity (2005) 03/2011; 35(12):1470-8. · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: A promoter polymorphism -174 G/C in the inflammatory cytokine interleukin-6 (IL-6) gene has been associated with differences in serum IL-6 levels and a risk for inflammatory conditions, such as cardiovascular diseases. We investigated whether this polymorphism is associated with Chlamydia pneumoniae, a common causative agent of respiratory infection with tendency for persistent infections, in 867 Finnish military recruits. IgG seropositivity in arrival and departure serum samples during 6-12 months of military service was considered as persistence of antibodies and a possible prolonged or chronic infection. The -174C allele was significantly associated with IgG seropositivity (P = 0.0002) and the persistence of IgG antibodies (P = 0.0002) as well as with slightly elevated C-reactive protein (CRP) levels (P = 0.003). In addition, the association was stronger when persistent C. pneumoniae antibodies were present together with elevated CRP than when either of them was positive alone (OR; 95% CI: 3.45; 2.00-5.98 and 1.41; 1.00-1.99, respectively). Our data suggest that IL-6 -174 G/C polymorphism is associated with persistence of C. pneumoniae antibodies and may be linked to the chronic or prolonged infection with systemic low-grade inflammation.
Scandinavian Journal of Immunology 02/2011; 74(1):95-9. · 2.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Xylitol inhibits the growth of Streptococcus pneumoniae. In clinical trials, xylitol decreased the occurrence of acute otitis media in day-care children, but did not decrease nasopharyngeal carriage of pneumococci. We hypothesized that xylitol inhibits biofilm formation of pneumococci, and measured biofilm formation and gene expression levels of the capsule gene cpsB and two other genes: autolysin encoding gene lytA and competence gene comA in different growth media in vitro. Twenty pneumococcal isolates were grown on polystyrene plates for 18 h in test media containing 0.5% xylitol, 0.5% glucose, 0.5% xylitol and 0.5% glucose, 0.5% fructose, 0.5% xylitol and 0.5% fructose or brain heart infusion (BHI) medium supplemented with 10% horse serum. Gene expression levels were measured after 5 h of growth using a relative quantification method with calibrator normalization. Exposure to xylitol lowered OD values, which were used as an indication of biofilm, compared with BHI medium, but when the medium was supplemented with glucose or fructose, biofilm formation was enhanced and the inhibitory effect of xylitol on biofilm formation was not observed. Xylitol also lowered lytA expression levels. Changes in biofilm formation in response to different sugar compounds may partly explain the efficacy of xylitol to prevent acute otitis media in previous clinical trials.
[show abstract][hide abstract] ABSTRACT: Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.
[show abstract][hide abstract] ABSTRACT: The aim was to investigate the prevalence of oropharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and beta-haemolytic streptococci among asthmatic and non-asthmatic young Finnish men and to identify putative risk factors.
A total of 224 asthmatics and 668 non-asthmatic men (mean age 19.6 years) from two intakes of conscripts to the Kainuu Brigade, Finland in July 2004 and January 2005 were enrolled upon entering military service.
Oropharyngeal specimens were examined for bacteria by routine culture methods. All the participants filled in questionnaires concerning risk factors for asthma and respiratory infections. Results: S. pneumoniae (48 cases, 5.4%), Group A streptococci (16, 1.8%), H. influenzae (45, 5.0%), M. catarrhalis (24, 2.7%) and N. meningitidis (20, 2.2%) were isolated from the 892 participants. Ten putative risk factors for oropharyngeal colonization (asthma, atopy, allergic rhinitis, smoking, current use of asthma medication, history of adeno/tonsillectomy, level of highly sensitive C-reactive protein, peak expiratory flow, results of a 12-min running test and body mass index) were evaluated. The only significant risk factor for S. pneumoniae carriage was asthma (OR, 2.04; 95% CI 1.12 to 3.72).
Pneumococcal carriage is more common in asthmatic than in non-asthmatic young men.
The Clinical Respiratory Journal 10/2010; 4(4):222-9. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: The principal virulence factor of Streptococcus pneumoniae is capsular polysaccharide, and encapsulated pneumococci are more common causes of disease than unencapsulated strains. This study analysed the presence of capsular genes in 59 pneumococcal isolates using two PCR methods targeted at the cpsA and cpsB genes of the capsular biosynthesis locus. The PCR method targeted at the cpsB gene, reported to be essential for encapsulation, was developed in this study. Of 59 pneumococcal isolates, 49 (83 %) were obtained from the sputum samples of elderly patients (≥65 years) with community-acquired pneumonia (CAP) and 10 (17 %) were from those with other acute lower respiratory tract infections (ARIs). Forty (82 %) of the CAP isolates and two (20 %) of the ARI isolates were encapsulated, as assessed by conventional immunochemical methods. Forty-one (98 %) of the 42 encapsulated strains had the cpsB gene present, and in 38 strains the cpsA gene was also detected. One of the unencapsulated isolates gave a positive result for the cpsB gene, and neither of the capsular locus genes were present in all the other unencapsulated strains. The distribution of encapsulated and unencapsulated isolates differed significantly between the two patient groups regardless of whether the presence of capsule was determined immunochemically (P<0.001) or by cpsB PCR (P=0.002). The cpsB PCR developed here was found to be a rapid and reliable method to detect the pneumococcal capsule locus and may have potential in sputum diagnostics when investigating the pneumococcal aetiology of CAP.
Journal of Medical Microbiology 10/2010; 59(Pt 10):1140-5. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interleukin-1 (IL-6) is an important mediator of inflammatory response in the respiratory tract during an infection, and the action of IL-6 is mediated by an IL-6 receptor. Several polymorphisms in the IL-6 and IL-6R genes have been associated with different inflammatory disease states. We studied the association between 2 IL-6 (IL6A and IL6B) and 5 IL-6R gene polymorphisms (IL6R1 to IL6R5) and respiratory infections in 511 Finnish military recruits whose respiratory infectious episodes were followed during 6 months of service. A promoter polymorphism of the IL-6R gene, IL6R1 (-183G/A), and two intron 1 polymorphisms, IL6R2 (A/G) and IL6R3 (T/A), were associated with infections. The strongest associations were found for the IL6R1 and IL6R2 polymorphisms, which were in the same linkage disequilibrium block. Conscripts with the A/A (IL6R1), G/G (IL6R2), and A/A (IL6R3) genotypes had an increased risk for respiratory infections during service as follows: odds ratio (OR) 1.72, 95% confidence interval (CI) 1.35-2.19; OR 1.66, 95% CI 1.23-2.26; and OR 1.23, 95% CI 0.98-1.55, respectively. IL-6 gene polymorphism IL6A (-174C/G) was associated with infections only in combination with an IL-6R polymorphism. Our data suggest that polymorphisms in the 5' area of the IL-6R gene may be associated with increased susceptibility to respiratory infections.
Human immunology 10/2010; 72(1):63-8. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to examine the association between bacterial colonization/infection and respiratory outcomes in children younger than 3 years old who were hospitalized for their first wheezing episode. This was an observational study. The primary outcome was hospitalization time and the secondary outcomes included relapses within 2 months and time to recurrent wheezing (i.e. three physician confirmed wheezing episodes) within 12 months. Bacterial antibody assays for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydia pneumoniae were studied as well as nasopharyngeal bacterial culture for the three former and urine pneumococcal antigen. Nasopharyngeal bacterial culture was positive in 31/52 (60%) children, serologic evidence of bacterial infection was found in 17/96 (18%) children, urine pneumococcal antigen was positive in 24/101 (24%), and any bacterial detection method was positive in 53/106 (50%) children. The children with positive nasopharyngeal bacterial culture had longer duration of hospitalization (hazard ratio 2.4) and more often relapsed within two months than those with negative culture (odds ratio 7.3). In this study, half of the first time wheezing children had bacterial colonization or symptomatic or asymptomatic bacterial infection. The bacterial colonization (i.e. positive nasopharyngeal bacterial culture) was associated with longer duration of hospitalization and higher risk of recurrent wheezing.
European Journal of Clinical Microbiology 10/2010; 30(2):233-41. · 3.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Information about the risk of invasive pneumococcal infection (IPI) among adults with asthma is limited and inconsistent. To evaluate this association, a population-based case-control study was conducted.
Cases of IPI (Streptococcus pneumoniae isolated from blood or cerebrospinal fluid) were identified through national, population-based laboratory surveillance during 1995-2002. To maximise exclusion of chronic obstructive pulmonary disease, the analysis was limited to patients aged 18-49 years and 10 selected age-, sex- and health district-matched controls for each case from the Population Information System. Information on underlying medical conditions was obtained through linking surveillance data to other national health registries. Asthma requiring > or =1 hospitalisation in the past 12 months was defined as high risk asthma (HRA); low risk asthma (LRA) was defined as entitlement to prescription drug benefits and no hospitalisation for asthma in the past 12 months.
1282 patients with IPI and 12 785 control subjects were identified. Overall, 7.1% of cases and 2.5% of controls had asthma (6.0% and 2.4% had LRA whereas 1.1% and 0.1% had HRA, respectively. After adjustment for other independent risk factors in a conditional logistic regression model, IPI was associated with both LRA (matched OR (mOR) 2.8; 95% CI 2.1 to 3.6) and HRA (mOR, 12.3; 95% CI 5.4 to 28.0). The adjusted population-attributable risk was 0.039 (95% CI 0.023 to 0.055) for LRA and 0.01 (95% CI 0.0035 to 0.017) for HRA.
Working age adults with asthma are at increased risk of IPI. In this population, approximately 5% of disease burden could be attributed to asthma. These findings support adding medicated asthma in adults to the list of indications for pneumococcal vaccination.
[show abstract][hide abstract] ABSTRACT: Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.
Scandinavian Journal of Immunology 08/2010; 72(2):150-7. · 2.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Rapamycin, an immunosuppressive and antiproliferative drug, is used to prevent neointima formation to reduce the risk of in-stent restenosis with rapamycin eluting-stents. Chronic infection of Chlamydia pneumoniae has been associated with cardiovascular diseases, and could play an important role in the mechanism of restenosis. We examined the effect of rapamycin on the growth of C. pneumoniae in cell cultures.
HL cell monolayers were inoculated with C. pneumoniae CWL029 or C. trachomatis L2. Different concentrations of rapamycin were present in the culture medium continuously or for 8-hour periods. After incubation the infected cells were repassaged to fresh HL cell monolayers and incubated in the medium without rapamycin. The newborn inclusions from both passages were checked by fluorescent microscope or electron microscope.
The presence of 23 microg/ml rapamycin restricted over 90% of the growth of C. pneumoniae. Continuous presence of 11 microg/ml rapamycin inhibited the growth of C. pneumoniae up to 80% and caused smaller inclusions, fewer chlamydial particles and fewer matured EBs. 11 microg/ml rapamycin presented in first passage caused the reduction of C. pneumoniae to 57% at first passage and 24% at second passage.
Sufficient rapamycin can inhibit the growth of C. pneumoniae effectively, but it should be applied at the early stage of the chlamydial infections. Rapamycin eluting-stents can induce a high enough local concentration of rapamycin. This provides a possibility for us to suppose that the beneficial effect of rapamycin in preventing in-stent restenosis might partly be explained by its inhibitory effects on the growth of C. pneumoniae.
Cardiovascular Drugs and Therapy 06/2010; 24(3):189-95. · 2.67 Impact Factor