Role of Peritoneal Macrophages in Cytomegalovirus-induced Acceleration of Autoimmune Diabetes in BB-rats

Background: As one of the natural perturbants, infection with cytomegalovirus (CMV) is believed to play a role in the development of Type I diabetes. Using the DP-BB rat model for autoimmune diabetes, we here report about possible mechanisms responsible for R(at)CMV-induced accelerated onset of diabetes

Chlamydia pneumoniae aggravates vein graft intimal hyperplasia in a rat model

<p>Abstract</p> <p>Background</p> <p>Along with angioplasty, autologus vein grafts are commonly used for artery bypass grafting in patients with advanced arterial stenosis and drug-resistant angina pectoris. Although initially a successful procedure, long-term functionality is limited due to proliferation and migration of smooth muscle cells. Like in atherosclerosis, common chronic infections caused by viruses and bacteria may contribute to this process of vein graft failure. Here we investigated the possible role of <it>Chlamydia pneumoniae </it>(<it>Cpn</it>) in the pathogenesis of venous graft failure in an experimental animal model. In 2 groups (n = 10 rats/group), an epigastric vein-to-common femoral artery interposition graft was placed. Immediately thereafter, rats were infected with <it>Cpn </it>(5*10⁸IFU) or injected with control solutions. Rats were sacrificed three weeks after surgery and the grafts were harvested for morphometrical and immunohistochemical analysis.</p> <p>Results</p> <p><it>Cpn </it>administration immediately after vein grafting resulted in a significant increase in medial cross-sectional area, wall thickness and total wall area. There were no significant differences in T-cell or macrophage influx. Likewise, although positive immunostaining for both HSP60 and CRP could be detected, no differences were found between groups. Based on the observation that the number of cells/μm²was also not altered, we conclude that Cpn infection stimulates smooth muscle cell proliferation by hereunto unknown molecular mechanisms, resulting in a significant increase in intimal hyperplasia.</p> <p>Conclusion</p> <p>In conclusion, in a well defined animal model we present here for the first time evidence for a role of <it>Chlamydia pneumoniae </it>in the process of venous graft failure.</p

Cytomegalovirus Infection Modulates Cellular Immunity in an Experimental Model for Autoimmune Diabetes

Background: Viral infections are thought to play a role in the development of autoimmune diseases like type 1 diabetes. In this study we investigated the effect of Rat Cytomegalovirus (RCMV) infection on cellular immunity in a well-defined animal model for diabetes, the Biobreeding (BB) rat

Trends in Antibiotic Prescribing in Adults in Dutch General Practice

Background: Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this study was to determine the antibiotic prescriptions of different antibiotic classes in general practice in relation to age. Methodology: Retrospective study of 22 rural and urban general practices from the Dutch Registration Network Family Practices (RNH). Antibiotic prescribing data were extracted from the RNH database from 2000-2009. Trends over time in antibiotic prescriptions were assessed with multivariate logistic regression including interaction terms with age. Registered ADEs as a result of antibiotic prescriptions were also analyzed. Principal Findings: In total 658,940 patients years were analyzed. In 11.5% (n = 75,796) of the patient years at least one antibiotic was prescribed. Antibiotic prescriptions increased for all age categories during 2000-2009, but the increase in elderly patients (>80 years) was most prominent. In 2000 9% of the patients >80 years was prescribed at least one antibiotic to 22% in 2009 (P<0.001). Elderly patients had more ADEs with antibiotics and co-medication was identified as the only independent determinant for ADEs. Conclusion/Discussion: The rate of antibiotic prescribing for patients who made a visit to the GP is increasing in the Netherlands with the most evident increase in the elderly patients. This may lead to more ADEs, which might lead to higher consumption of health care and more antibiotic resistance

Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilator-associated pneumonia?

INTRODUCTION: Clara cell protein 10 (CC-10) has been associated with inflammatory and infectious pulmonary diseases. This study evaluates CC-10 concentrations in bronchoalveolar lavage (BAL) fluid as a potential marker of ventilator-associated pneumonia (VAP). METHODS: Between January 2003 and December 2007, BAL fluid samples obtained from critically ill patients at the intensive care unit of the Maastricht University Medical Centre clinically suspected of having VAP were included. Patients were divided into two groups: (1) microbiologically confirmed VAP (the VAP group) and (2) microbiologically unconfirmed VAP (the non-VAP group). The concentration of CC-10 was measured by means of a commercially available enzyme-linked immunosorbent assay kit, and retrospective analysis was performed. Areas under the curve of receiver operating characteristic curves were calculated for CC-10 concentrations. RESULTS: A total of 196 patients (122 men, 74 women) were included. A total of 79 (40%) of 196 cases of suspected VAP were microbiologically confirmed. The median CC-10 concentration in the VAP group was 3,019 ng/mL (range, 282 to 65,546 ng/mL) versus 2,504 ng/mL (range, 62 to 30,240 ng/mL) in the non-VAP group (P = 0.03). There was no significant difference in CC-10 concentrations between patients treated with or without corticosteroids (P = 0.26) or antibiotic therapy (P = 0.9). The CC-10 concentration did not differ significantly between patients with Gram-positive versus Gram-negative bacteria that caused the VAP (P = 0.06). However, CC-10 concentrations did differ significantly between the late-onset VAP group and the non-VAP group. CONCLUSIONS: The CC-10 concentration in BAL fluid yielded low diagnostic accuracy in confirming the presence of VAP

Cytomegalovirus Infection Modulates Cellular Immunity in an Experimental Model for Autoimmune Diabetes

Background: Viral infections are thought to play a role in the development of autoimmune diseases like type 1 diabetes. In this study we investigated the effect of Rat Cytomegalovirus (RCMV) infection on cellular immunity in a well-defined animal model for diabetes, the Biobreeding (BB) rat. Methods: Diabetes prone (DP)-and Diabetes resistant (DR)-BB rats were infected with 2 £ 10 6 plaque forming units (pfu) RCMV. Diabetes development was monitored by frequent blood-glucose analysis. Effects of RCMV on CD4 þ , CD8 þ and Vb-TCR þ T-cell subsets were measured in vivo, and in vitro after restimulation with RCMV-infected fibroblasts. Proliferative capacity was determined by 3 H-Thymidine incorporation. Results: RCMV-infection resulted in a significant acceleration of diabetes onset in DP-BB rats ð p ¼ 0:003Þ. Percentages CD4 þ and CD8 þ T-cells were not affected in vivo. In vitro, RCMVrestimulation resulted in a decreased CD4 þ /CD8 þ blastoid T-cell ratio compared to ConA ð p ¼ 0:00028Þ. Furthermore, RCMV-restimulation resulted in a strong RCMV-specific proliferation, which comprises about 50% of the response triggered by ConA. Vb-TCR percentages did not change upon RCMV-infection or RCMV-restimulation. Interpretation: RCMV-restimulation of splenic T-cells in vitro resulted in a strong RCMV-specific proliferation, probably also including autoreactive T-cells. In vivo, this polyclonal response might be involved in the observed accelerated diabetes development in DP-BB rats upon RCMV-infection

The host immune response contributes to Haemophilus influenzae virulence

SummaryBackgroundThere is compelling evidence that infections with non-typeable Haemophilus influenzae (NTHi) are associated with exacerbations in COPD patients. However, NTHi has also been isolated frequently during clinically stable disease. In this study we tested the hypothesis that genetically distinct NTHi isolates obtained from COPD patients differ in virulence which could account for dissimilarities in the final outcome of an infection (stable vs. exacerbation).ResultsNTHi isolates (n = 32) were obtained from stable COPD patients, or during exacerbations. Genetically divergent NTHi isolates were selected and induction of inflammation was assessed as an indicator of virulence using different in vitro models. Despite marked genomic differences among NTHi isolates, in vitro studies could not distinguish between NTHi isolates based on their inflammatory capacities. Alternatively, when using a whole blood assay results demonstrated marked inter-, but not intra-individual differences in cytokine release between healthy volunteers irrespective of the origin of the NTHi isolate used.ConclusionResults suggest that the individual immune reactivity might be an important predictor for the clinical outcome (exacerbation vs. no exacerbation) following NTHi infection

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Background: Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.Results: Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.Conclusions: Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated

Evaluation of the rapid diagnostic test SDFK40 (Pf-pLDH/pan-pLDH) for the diagnosis of malaria in a non-endemic setting

<p>Abstract</p> <p>Background</p> <p>The present study evaluated the SD Bioline Malaria Ag 05FK40 (SDFK40), a three-band RDT detecting <it>Plasmodium falciparum</it>-specific parasite lactate dehydrogenase (Pf-pLDH) and pan <it>Plasmodium</it>-specific pLDH (pan-pLDH), in a reference setting.</p> <p>Methods</p> <p>The SDFK40 was retrospectively and prospectively tested against a panel of stored (n = 341) and fresh (n = 181) whole blood samples obtained in international travelers suspected of malaria, representing the four <it>Plasmodium </it>species as well as <it>Plasmodium </it>negative samples, and compared to microscopy and PCR results. The prospective panel was run together with OptiMAL (Pf-pLDH/pan-pLDH) and SDFK60 (histidine-rich protein-2 (HRP-2)/pan-pLDH).</p> <p>Results</p> <p>Overall sensitivities for <it>P. falciparum </it>tested retrospectively and prospectively were 67.9% and 78.8%, reaching 100% and 94.6% at parasite densities >1,000/μl. Sensitivity at parasite densities ≤ 100/μl was 9.1%. Overall sensitivities for <it>Plasmodium vivax </it>and <it>Plasmodium ovale </it>were 86.7% and 80.0% (retrospectively) and 92.9% and 76.9% (prospectively), reaching 94.7% for both species (retrospective panel) at parasite densities >500/μl. Sensitivity for <it>Plasmodium malariae </it>was 21.4%. Species mismatch occurred in 0.7% of samples (3/411) and was limited to non-<it>falciparum </it>species erroneously identified as <it>P. falciparum</it>. None of the <it>Plasmodium </it>negative samples in the retrospective panel reacted positive. Compared to OptiMAL and SDFK60, SDFK40 showed lower sensitivities for <it>P. falciparum</it>, but better detection of <it>P. ovale</it>. Inter-observer agreement and test reproducibility were excellent, but lot-to-lot variability was observed for pan-pLDH results in case of <it>P. falciparum</it>.</p> <p>Conclusion</p> <p>SDFK40 performance was poor at low (≤ 100/μl) parasite densities, precluding its use as the only diagnostic tool for malaria diagnosis. SDFK40 performed excellent for <it>P. falciparum </it>samples at high (>1,000/μl) parasite densities as well as for detection of <it>P. vivax </it>and <it>P. ovale </it>at parasite densities >500/μl.</p

Detection of amyloid beta aggregates in the brain of BALB/c mice after Chlamydia pneumoniae infection

Neuroinflammation, initiated by cerebral infection, is increasingly postulated as an aetiological factor in neurodegenerative diseases such as Alzheimer’s disease (AD). We investigated whether Chlamydia pneumoniae (Cpn) infection results in extracellular aggregation of amyloid beta (Aβ) in BALB/c mice. At 1 week post intranasal infection (p.i.), Cpn DNA was detected predominantly in the olfactory bulbs by PCR, whereas brains at 1 and 3 months p.i. were Cpn negative. At 1 and 3 months p.i., extracellular Aβ immunoreactivity was detected in the brain of Cpn-infected mice but also in the brain of mock-infected mice and mice that were neither Cpn infected nor mock infected. However, these extracellular Aβ aggregates showed morphological differences compared to extracellular Aβ aggregates detected in the brain of transgenic APP751SL/PS1M146L mice. These data do not unequivocally support the hypothesis that Cpn infection induces the formation of AD-like Aβ plaques in the brain of BALB/c mice, as suggested before. However, future studies are required to resolve these differences and to investigate whether Cpn is indeed an etiological factor in AD pathogenesis