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Chronic Infections (chronic + infections)
Selected AbstractsSevere periodontitis is associated with systemic inflammation and a dysmetabolic status: a case,control studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2007Luigi Nibali Abstract Background and Aim: A cluster of metabolic factors defines a syndrome that predisposes to diabetes and cardiovascular disease. Chronic infections such as periodontitis might alter these individual metabolic factors and the systemic inflammatory burden. The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease. Materials and Methods: We examined 302 patients with severe periodontitis and 183 healthy controls, and we collected a blood sample from each subject in order to investigate differences in inflammatory (leukocyte numbers and differential counts) and metabolic markers (lipids and glucose). Results: After correcting for differences in age, gender, smoking and ethnicity, periodontitis subjects exhibited a low-grade systemic inflammation (increased white cell counts, 1.10±1.02 × 109/l, 95%CI 1.05,1.15, p=0.0001), dyslipidemia [lower high-density lipoprotein cholesterol, 1.14±1.03 mmol/l, 95%CI 1.08,1.20, p<0.0001 and higher low-density lipoprotein cholesterol, 1.12±1.03, 95%CI 1.05,1.19, p<0.0001) and increased non-fasting serum glucose levels (1.04±1.01 mmol/l, 95%CI 1.02,1.06, p=0.01) when compared with controls. The associations were confirmed in a subpopulation of Caucasian non-smokers. A trend for a dose dependent effect of the number of periodontal pockets on the tested inflammatory and metabolic markers was observed. Conclusions: These data suggest a possible link between severe generalized periodontitis, systemic inflammation and a dysmetabolic state in otherwise healthy individuals. [source] Sexually transmitted infections: impact on male fertilityANDROLOGIA, Issue 2 2008F. R. Ochsendorf Summary The impact of sexually transmitted diseases (STD) on male fertility is strongly dependent on the local prevalence of the STDs. In Western countries STD-infections are of minor relevance. In other regions, i.e. Africa or South East Asia, the situation appears to be different. Acute urethritis could not be associated with male infertility. Chronic infections (gonorrhoea) can cause urethral strictures and epididymo-orchitis. Chlamydia trachomatis and Neisseria gonorrhoea can be transmitted to the female partner and cause pelvic inflammatory disease with tubal obstruction. Ureaplasma urealyticum may impair spermatozoa (motility, DNA condensation). Trichomonas vaginalis has, if any, only minor influence on male fertility. The relevance of viral infections (HPV, HSV) for male infertility is not resolved. Any STD increases the chances of transmission of the human immunodeficiency virus (HIV). The HIV infection is associated with infectious semen and the risk of virus transmission. Semen quality deteriorates with the progression of immunodeficiency. Special counselling of serodiscordant couples is needed. STDs should be treated early and adequately to prevent late sequelae for both men and women. [source] Mechanisms and consequences of bladder cell invasion by uropathogenic Escherichia coliEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2008B. K. Dhakal ABSTRACT Strains of uropathogenic Escherichia coli (UPEC) are the major cause of urinary tract infections worldwide. Multiple studies over the past decade have called into question the dogmatic view that UPEC strains act as strictly extracellular pathogens. Rather, bacterial expression of filamentous adhesive organelles known as type 1 pili and Afa/Dr fibrils enable UPEC to invade host epithelial cells within the urinary tract. Entry into bladder epithelial cells provides UPEC with a protected niche where the bacteria can persist quiescently for long periods, unperturbed by host defences and protected from many antibiotic treatments. Alternately, internalized UPEC can rapidly multiply, forming large intracellular inclusions that can contain several thousand bacteria. Initial work aimed at defining the host and bacterial factors that modulate the entry, intracellular trafficking, and eventual resurgence of UPEC suggests a high degree of host-pathogen crosstalk. Targeted disruption of these processes may provide a novel means to prevent and treat recurrent, relapsing and chronic infections within the urinary tract. [source] Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2006A. E. R. Kartikasari Abstract Background, Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. Materials and methods, Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. Results, An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. Conclusions, Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis. [source] Effects of clinical isolates of Pseudomonas aeruginosa on Staphylococcus epidermidis biofilm formationFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2010Maria Pihl Abstract Pseudomonas aeruginosa is often found in chronic infections, including cystic fibrosis lung infections and those related to chronic wounds and venous ulcers. At the latter sites, P. aeruginosa can be isolated together with Staphylococcus epidermidis, and we have therefore explored the effect of clinical isolates and laboratory strains of P. aeruginosa strains on colonization by S. epidermidis in dual-species biofilms. Biofilm formation was assayed using 16S rRNA FISH and confocal laser scanning microscopy. Among the six P. aeruginosa strains tested, one particular strain, denoted 14:2, exerted a significant inhibitory effect, and even after 6 h, S. epidermidis levels in dual-species biofilms were reduced by >85% compared with those without P. aeruginosa. Interestingly, strain 14:2 was found to be negative for classical virulence determinants including pyocyanin, elastase and alkaline protease. Therefore, we suggest that less virulent phenotypes of P. aeruginosa, which may develop over time in chronic infections, could counteract colonization by S. epidermidis, ensuring persistence and dominance by P. aeruginosa in the host micro-habitat. Further studies are required to explain the inhibitory effect on S. epidermidis, although extracellular polysaccharides produced by P. aeruginosa might play a role in this phenomenon. [source] Anaerobic culture conditions favor biofilm-like phenotypes in Pseudomonas aeruginosa isolates from patients with cystic fibrosisFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Che Y. O'May Abstract Pseudomonas aeruginosa causes chronic infections in the lungs of cystic fibrosis (CF) individuals and remains the leading cause of morbidity and mortality associated with the disease. Biofilm growth and phenotypic diversification are factors thought to contribute to this organism's persistence. Most studies have focused on laboratory isolates such as strain PAO1, and there are relatively few reports characterizing the properties of CF strains, especially under decreased oxygen conditions such as occur in the CF lung. This study compared the phenotypic and functional properties of P. aeruginosa from chronically infected CF adults with those of strain PAO1 and other clinical non-CF isolates under aerobic and anaerobic culture conditions. The CF isolates overall displayed a reduced ability to form biofilms in standard in vitro short-term models. They also grew more slowly in culture, and exhibited decreased adherence to glass and decreased motilities (swimming, swarming and twitching). All of these characteristics were markedly accentuated by anaerobic growth conditions. Moreover, the CF strain phenotypes were not readily reversed by culture manipulations designed to encourage planktonic growth. The CF strains were thus inherently different from strain PAO1 and most of the other non-CF clinical P. aeruginosa isolates tested. In vitro models used to research CF isolate biofilm growth need to take the above properties of these strains into account. [source] Immunisation with non-integral OMPs promotes pulmonary clearance of Pseudomonas aeruginosaFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2-3 2003Linda D. Thomas Abstract Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause fatal acute lung infections in critically ill individuals. Lung damage due to chronic infections in cystic fibrosis sufferers is the major cause of morbidity and mortality in this group. The bacterium produces various immunomodulatory products that enable it to survive in the lung. Innate and increasing resistance to antibiotic therapy shown by this organism heightens the need for development of a vaccine. This study reports the identification of six non-integral protein antigens; Pa 13, azurin, acyl carrier protein (ACP), amidase, aminopeptidase and KatE, purified from a mucoid strain of P. aeruginosa. N-terminal amino acid sequencing was used to identify these proteins and, based on their ascribed functions, determined that their normal cellular location was cytosolic. A rat model of acute pulmonary infection was used to investigate the ability of these protein antigens to enhance pulmonary clearance of a live P. aeruginosa challenge. Mucosal immunisation with four of the six antigens significantly enhanced bacterial clearance from both the lavage fluid and lung tissue. The greatest level of clearance was demonstrated for the antigens; KatE, aminopeptidase and amidase. Enhanced bacterial clearance was maintained when the antigens amidase and aminopeptidase were produced in recombinant form. When delivered parenterally, aminopeptidase demonstrated its continued efficacy as a vaccine candidate. This study has demonstrated that non-integral outer membrane proteins are antigenic and protective and warrant further investigation as potential components of a vaccine. [source] Immunoblot Analysis as an Alternative Method to Diagnose Enterohepatic Helicobacter InfectionsHELICOBACTER, Issue 3 2009Torkel Wadström Abstract Introduction: Enterohepatic Helicobacter species have been associated with chronic infections of the hepatobiliary tract and lower bowel in naturally and experimentally infected mice, Helicobacter -infected animals should thus not be used in studies of diseases associated with chronic inflammation. Helicobacter species induce inflammation and modulate host immune responses, thus emphasizing the need to diagnose these infections in laboratory animals. Materials and Methods: An immunoblot assay was developed to analyze antibodies to enterohepatic Helicobacter species in naturally colonized laboratory mouse colonies. We evaluated the serum antibody responses to cell surface proteins of H. bilis, H. hepaticus, and H. ganmani in 188 mouse sera from four different university animal facilities. Lower bowel tissue specimens from 56 of these animals were available and analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and the results compared with matched immunoblot patterns. Results: Specific antibody reactivity to H. bilis was detected in 8 of 186 (4.3%) sera, to H. hepaticus in 45 of 184 (24%) sera, and to H. ganmani in 51 of 188 (27%) of tested sera. These results were compared with PCR-DGGE analyses of tissue samples of corresponding animals, and concordance between the two diagnostic tests was found in 96% for H. bilis, in 91% for H. hepaticus, and in 82% for H. ganmani. The PCR-DGGE also detected DNA of H. typhlonius, H. sp. flexispira, and H. rodentium. Conclusions: Infection with enterohepatic species was common in the laboratory mouse colonies tested, independent of strain and stock. Immunoblot analysis seems to be a promising diagnostic tool to monitor enterohepatic Helicobacter species infections of laboratory rodents. [source] Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia,HEPATOLOGY, Issue 4 2008Maura Dandri Analysis of hepatitis B virus (HBV) kinetics with mathematical models may disclose new aspects of HBV infection and host response mechanisms. To determine the kinetics of virion decay from the blood of patients in different phases of chronic infection, we applied mathematical modeling to real-time polymerase chain reaction assays, which enable quantification of viremia and intrahepatic HBV productivity by measuring both copy number and activity of covalently closed circular DNA (relaxed circular DNA/covalently closed circular DNA) in the liver of 80 untreated chronically active HBV carriers (38 hepatitis B e antigen [HBeAg]-positive and 42 HBeAg-negative individuals). We found that the half-life of circulating virions is very fast (median 46 and 2.5 minutes in HBeAg-positive and HBeAg-negative individuals, respectively) and strongly related to viremia, with clearance rates significantly accelerating as viral loads decrease. To investigate whether immune components can influence the kinetics of virion decay, we analyzed viral dynamics in immunodeficient urokinase-type plasminogen activator chimera mice. Virion half-life in mice (range, 44 minutes to >4 hours) was comparable to estimates determined in high viremic carriers, implying that clearance rates in these patients are mostly determined by common nonspecific mechanisms. Notably, the lack of correlation between virion half-life and viremia in mice indicated that immune components significantly accelerate virion clearance rates in individuals with low titers. Conclusion: Our analyses suggest that both host defense mechanisms and levels of circulating virions affect the kinetics of HBV decay assessed in the serum of chronic carriers. Identification of the factors affecting clearance rates will be important for future antiviral drug developments and it may give insights into the mechanisms involved in clearance of other chronic infections, such as human immunodeficiency virus and hepatitis C virus. (HEPATOLOGY 2008.) [source] HIV-1 proviral resistance mutations: usefulness in clinical practiceHIV MEDICINE, Issue 8 2010B Kabamba-Mukadi Objectives Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. Methods This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. Results Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). Conclusions The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia. [source] Porotic lesions in immature skeletons from Stara Torina, late medieval SerbiaINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 5 2008M. Djuric Abstract Porotic lesions of immature skeletons have been attracting scientific attention for more than a century. These changes have been documented worldwide and are considered to be one of the indicators of health and/or nutritional status of past human populations. These lesions have frequently been referred to as a nutritional stress indicator, a manifestation of iron-deficiency anaemia, and a condition caused by chronic infections. In this study, 327 immature skeletons from the medieval graveyard of Stara Torina (Serbia) were examined for macroscopic signs of four types of porotic lesions: cribra orbitalia, femoral cribra, humeral cribra, and porotic hyperostosis. Femoral cribra was observed in 83.25% of femora, humeral cribra in 58.46% of cases, cribra orbitalia in 46.12% of orbits, while porotic hyperostosis was recorded in only 2.94% of skulls. The majority of skeletons affected by cribra presented symmetrical lesions. Association between all types of cribra was recorded in 33.33% of skeletons. Historical data supported the hypothesis that the investigated population was exposed to frequent infections, especially parasitic ones, which led to the development of porotic bone lesions via several mechanisms: parasite-induced blood loss and diarrhoea (both iron and magnesium malabsorption) or anaemia as a hepcidin-mediated body adaptive response to infection. Copyright © 2008 John Wiley & Sons, Ltd. [source] Association of atherosclerotic risk factors with carotid adventitial thickness assessed by ultrasonographyJOURNAL OF CLINICAL ULTRASOUND, Issue 6 2009Radoslaw Kazmierski MD Abstract Purpose. There is increasing evidence that adventitial inflammation may participate in atherosclerosis development. The aim of this study was to investigate which atherosclerotic risk factors correlated with carotid adventitial thickness (AT) and to compare them with those associated with carotid intima-media thickness (IMT). We also set out to test the hypothesis that there is a significant correlation between IMT and AT in the carotid arteries. Methods. The far carotid artery wall IMT and AT were measured by high-resolution B-mode ultrasound in 128 persons (mean, 65 ± 8 years). A number of conventional and novel, clinically and laboratory-derived risk factors were assessed. Results. Significant correlation (r = 0.35, p < 0.0001) was demonstrated between the IMT and AT. The stepwise forward multiple regression analysis revealed correlations between IMT and leukocyte count, C-reactive protein level, and hypertension, whereas the Chlamydia (C.) pneumoniae IgA antibodies and fibrinogen levels, gender, and smoking correlated merely with AT. The homocysteine/methionine ratio correlated with both IMT and AT. Conclusion. The association between IMT and AT may reflect an interaction between intimal, medial, and adventitial pathology. Different risk factors are associated with the increased AT or IMT. It is possible that inflammation and some chronic infections, such as those induced by C.pneumoniae, could have a marked influence on adventitial cell proliferation. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009 [source] Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/,PD-L1 pathwayAGING CELL, Issue 5 2010Celine S. Lages Summary Programmed cell death-1 (PD-1) is a newly characterized negative regulator of immune responses. The interaction of PD-1 with its ligands (PD-L1 and PD-L2) inhibits T-cell proliferation and cytokine production in young mice. Increased PD-1 expression has been described during chronic infections, inducing chronic activation of the immune system to control it. As aging is associated with chronic immune activation, PD-1 may contribute to age-associated T-cell dysfunction. Our data showed the following results in aged mice: (i) the number of PD-1-expressing T cells and the level of expression of PD-Ls was increased on dendritic cell subsets and T cells; (ii) PD-1+ T cells were exhausted effector memory T cells, as shown by their lower level of CD127, CD25 and CD28, as well as their limited proliferative and cytokine-producing capacity; (iii) the expression of PD-1 was up-regulated after T-cell receptor-mediated activation of CD8+ T cells, but not of CD4+ T cells; (iv) blockade of the PD-1/PD-L1 pathway moderately improved the cytokine production of T cells from old mice but did not restore their proliferation; and (v) blockade of the PD-1/PD-L1 pathway did not restore function of PD-1+ T cells; its effect appeared to be exclusively mediated by increased functionality of the PD-1, T cells. Our data thus suggest that blockade of the PD-1/PD-L1 is not likely to be efficient at restoring exhausted T-cell responses in aged hosts, although improving the responses of PD-1, T cells may prove to be a helpful strategy in enhancing primary responses. [source] Change of hepatitis B virus genotypes in acute and chronic infections in JapanJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Mariko Kobayashi Abstract During 35 years from 1971 to 2005, 153 patients with acute and 4,277 with chronic HBV infection visited the Toranomon Hospital in Tokyo, Japan. They were grouped into seven 5-year periods, and HBV genotypes/subgenotypes were determined. Patients with acute HBV infection were younger (P,=,0.046), predominantly male (P,=,0.004), possessed higher alanine aminotransferase levels (P,<,0.001), positive more frequently for HBeAg (P,<,0.001), and had lower HBV DNA loads (P,=,0.014) than those with chronic infection. Sexual transmission was more frequent in patients with acute than chronic HBV infection (67% vs. 3%, P,<,0.001). The number of patients with acute infection increased throughout 1971,2005. Patients with chronic infection increased since 1971, peaked in 1986,1990 and then decreased. The number of patients increased since 1990,2000 again, however, reflecting recent boost of acute HBV infection. The distribution of HBV genotypes was considerably different between patients with acute and chronic infections (A, B, and C: 28.6%, 10.3%, and 59.5% vs. 3.0%, 12.3%, and 84.5%, respectively, P,<,0.001). Since 1991, genotype A foreign to Japan started to increase sharply in patients with acute infection, and gradually in those with chronic infection. There was a trend for the foreign subgenotype B2/Ba to increase recently (P,<,0.05). Despite immunoprophylaxis of high-risk babies born to carrier mothers with hepatitis B e antigen, implemented nationally since 1986, acute and chronic infections with HBV have been increasing in Japan. Based on genotypes/subgenotypes changing with time, the resurgence of hepatitis B could be attributed to infections, with foreign HBV genotypes/subgenotypes, spreading swiftly by sexual contact. J. Med. Virol. 80:1880,1884, 2008. © 2008 Wiley-Liss, Inc. [source] Periodontology/Oral Medicine: Periodontal infections and cardiovascular disease,how strong is the association?ORAL DISEASES, Issue 6 2000GC Armitage In the past decade there has been renewed interest in the old hypothesis that infections increase the risk of developing cardiovascular disease and stroke. There is now a convincing body of evidence that atherosclerosis has a major inflammatory component and is much more than the simple vascular accumulation of lipids. Infectious agents that have been linked to an increased risk of coronary heart disease (CHD) include Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesviruses. The concept has emerged that each of these agents is an independent risk factor for CHD and that common chronic infections are important. In addition, periodontal infections have also been implicated as one of several factors contributing to the development of CHD. Evidence supporting a causative role of chronic infections in CHD is largely circumstantial. However, the evidence is sufficiently strong to warrant further examination of the possible link between chronic infections and CHD. In this review the lines of evidence for a causative role of C. pneumoniae in the development of CHD are summarized and contrasted with the lines of evidence suggesting a periodontal infection - CHD association. If common or widespread chronic infections are truly important risk factors for CHD, it is unlikely that a single infection will be shown to be causative. It is likely that the entire microbial burden of the patient from several simultaneous chronic infections is more important (eg, H. pylori -caused gastric ulcers +C. pneumoniae -caused bronchitis + periodontitis). Increased cooperation between cardiologists and periodontists will be required to determine if, and what, combinations of common chronic infections are important in the pathogenesis of CHD and stroke. [source] Ethmoid mucocele: A new feature of primary ciliary dyskinesiaPEDIATRIC PULMONOLOGY, Issue 2 2010Marco Berlucchi MD Abstract Primary ciliary dyskinesia (PCD) is a rare congenital autosomal recessive disease that produces impairment of mucosal ciliary movement. Children with this disorder usually manifest recurrent and chronic infections of the upper and lower airways. We describe the history of a 12-month-old boy in whom the correct diagnosis of PCD was achieved after the occurrence of ethmoid mucocele associated with omolateral proptosis. A careful description of this new feature of PCD and its dangerous complications are also presented. Pediatr Pulmonol. 2010; 45:197,201. ©2009 Wiley-Liss, Inc. [source] Chronic lung disease in human immunodeficiency virus (HIV) infected children,PEDIATRIC PULMONOLOGY, Issue 1 2008Heather J. Zar Abstract The development of chronic lung disease is common in HIV-infected children. The spectrum of chronic HIV-associated lung disease includes lymphocytic interstitial pneumonia (LIP), chronic infections, immune reconstitution inflammatory syndrome (IRIS), bronchiectasis, malignancies, and interstitial pneumonitis. Chronic lung disease may result from recurrent or persistent pneumonia due to bacterial, mycobacterial, viral, fungal or mixed infections. In high tuberculosis (TB) prevalence areas, M. tuberculosis is an important cause of chronic respiratory illness. With increasing availability of highly active antiretroviral therapy (HAART) for children in developing countries, a rise in the incidence of IRIS due to mycobacterial or other infections is being reported. Diagnosis of chronic lung disease is based on chronic symptoms and persistent chest X-ray changes but definitive diagnosis can be difficult as clinical and radiological findings may be non-specific. Distinguishing LIP from miliary TB remains a difficult challenge in HIV-infected children living in high TB prevalence areas. Treatment includes therapy for specific infections, pulmonary clearance techniques, corticosteroids for children with LIP who are hypoxic or who have airway compression from tuberculous nodes and HAART. Children who are taking TB therapy and HAART need adjustments in their drug regimes to minimize drug interactions and ensure efficacy. Preventative strategies include immunization, chemoprophylaxis, and micronutrient supplementation. Early use of HAART may prevent the development of chronic lung disease. Pediatr Pulmonol. 2008; 43:1,10. © 2007 Wiley-Liss, Inc. [source] Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistencePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2009Indranil Chatterjee Dr. Abstract Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase-mediated effect on post-stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488,4496). In the present study, the global function of ClpC in physiology, metabolism, and late-stationary phase survival was examined using DNA microarrays and 2-D PAGE followed by MALDI-TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose-phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell-associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late-stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections. [source] IL-10 and the resolution of infections,THE JOURNAL OF PATHOLOGY, Issue 2 2008CM Filippi Abstract Chronic viral infections pose serious health concerns, as secondary complications such as immunodeficiencies and cancers are common. Treating such infections with conventional vaccine approaches has proved to be difficult. Studies in animals and humans suggest that vaccine failure is probably due to exhaustion of antiviral T cell responses, which occurs in a number of chronic infections. Attempts to elucidate the causes of impairment of antiviral immunity have pointed to a role for the immunomodulatory cytokine IL-10 in the ability of viruses to establish persistence. Induction of IL-10 production by the host during chronic infection appears to be one of the viral means to alter the class of the antiviral immune response and induce generalized immune suppression. Recent work by us and others suggests that it is possible to resuscitate antiviral immunity by interfering with the IL-10 signalling pathway. Targeting IL-10 thus constitutes a promising alternative to conventional vaccine strategies which have not proved to be successful in treating chronic infections. In addition, sterile cure may be achieved with minimal side-effects by combining agents that alter the IL-10 signalling pathway with other compounds, such as antiviral drugs or interferon, but also agents neutralizing other crucial elements of T cell exhaustion, such as PD-1. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] An association between chronic infection with Chlamydia pneumoniae and lung cancer.APMIS, Issue 9 2001A prospective 2-year study This study assesses a possible relationship between chronic Chlamydia pneumoniae (Cpn) infection and lung cancer (LC). A total of 210 consecutive patients (136 M, 74 F) were diagnosed with LC during a 2-year period. Blood was obtained from 128 M and 70 F patients for Cpn serology. Repeat blood specimens were taken after 3 months. Throat specimens for Cpn DNA analysis by PCR were taken from 110/136 M and 63/74 F. Seventy-four cytobrush specimens were taken and also analyzed by polymerase chain reaction (PCR). Fifty (29 M, 21 F) bronchial biopsies and 8 (6 M, 2 F) tumors resected at surgery were analyzed for Cpn by immunohistochemistry (IHC). Males had significantly more often squamous-cell carcinoma (SCC) than females. Other types of LC were more equally distributed between males and females. The difference between males and females regarding smoking history was significant, and male LC patients had significantly higher levels of IgG and/or IgA antibodies than female LC patients. Male and female LC patients had significantly higher prevalences of high antibody titers than controls. A high prevalence of unusually high titers of specific Cpn antibodies was found in male LC patients. This could indicate that LC may be induced by chronic Cpn infection, since stable high titers of Cpn antibodies, especially IgA, are a hallmark of chronic infections. [source] Squamous cell carcinoma of the hand masquerading as a cutaneous infectionAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 1 2006Jemima Fisher SUMMARY A 33-year-old male concreter presented with a small abscess on his right index finger following an injury at work. Histological examination of the lesion was consistent with chronic inflammation and Staphylococcus aureus, Streptococcus anginosus and Escherichia coli were isolated on cultures. The lesion was treated as a chronic fungal infection with bacterial superinfection. Seventeen months later, a bone scan showed periarticular involvement, and a diagnostic biopsy identified a well-differentiated squamous cell carcinoma. He underwent amputation of his index and middle fingers. After 4 years of follow up, there has been no evidence of recurrence at the primary site, but he has since developed two further primary squamous cell carcinomas. This case emphasizes the importance of considering malignancy when dealing with chronic infections of the hand. [source] Toward general prophylactic cancer vaccinationBIOESSAYS, Issue 10 2009Uwe Hobohm Abstract It is well established that chronic infections can lead to cancer. Almost unknown is that, in contrast, acute brief viral and bacterial infections may have beneficial effects in cases of established neoplastic disease, while exposure to pathogenic products by infection, vaccination, and inhalation can cause prophylactic effects. In the following I will align evidence from case studies of spontaneous regression and from epidemiological studies with recent immunology to conclude that pathogenic substances belonging to the group of "pathogen-associated molecular patterns" can trigger the innate immune system to establish anti-neoplastic immune responses. A better understanding of the protective role of the innate immune system might leverage considerable prophylactic potential. [source] Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model HIV/AIDSBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010D De Forni BACKGROUND AND PURPOSE Antiviral hyper-activation-limiting therapeutic agents (AV-HALTs) are a novel experimental drug class designed to both decrease viral replication and down-regulate excessive immune system activation for the treatment of chronic infections, including human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. VS411, a first-in-class AV-HALT, is a single-dosage form combining didanosine (ddI, 400 mg), an antiviral (AV), and hydroxyurea (HU, 600 mg), a cytostatic agent, designed to provide a slow release of ddI to reduce its maximal plasma concentration (Cmax) to potentially reduce toxicity while maintaining total daily exposure (AUC) and the AV activity. EXPERIMENTAL APPROACH This was a pilot phase I, open-label, randomized, single-dose, four-way crossover trial to investigate the fasted and non-fasted residual variance of AUC, Cmax and the oral bioavailability of ddI and HU, co-formulated as VS411, and administered as two different fixed-dose combination formulations compared to commercially available ddI (Videx EC) and HU (Hydrea) when given simultaneously. KEY RESULTS Formulation VS411-2 had a favourable safety profile, displayed a clear trend for lower ddI Cmax (P= 0.0603) compared to Videx EC, and the 90% confidence intervals around the least square means ratio of Cmax did not include 100%. ddI AUC, was not significantly decreased compared to Videx EC. HU pharmacokinetic parameters were essentially identical to Hydrea, although there was a decrease in HU exposure under fed versus fasted conditions. CONCLUSIONS AND IMPLICATIONS A phase IIa trial utilizing VS411-2 formulation has been fielded to identify the optimal doses of HU plus ddI as an AV-HALT for the treatment of HIV disease. [source] Mutualism versus pathogenesis: the give-and-take in plant,bacteria interactionsCELLULAR MICROBIOLOGY, Issue 3 2009María J. Soto Summary Pathogenic bacteria and mutualistic rhizobia are able to invade and establish chronic infections within their host plants. The success of these plant,bacteria interactions requires evasion of the plant innate immunity by either avoiding recognition or by suppressing host defences. The primary plant innate immunity is triggered upon recognition of common microbe-associated molecular patterns. Different studies reveal striking similarities between the molecular bases underlying the perception of rhizobial nodulation factors and microbe-associated molecular patterns from plant pathogens. However, in contrast to general elicitors, nodulation factors can control plant defences when recognized by their cognate legumes. Nevertheless, in response to rhizobial infection, legumes show transient or local defence-like responses suggesting that Rhizobium is perceived as an intruder although the plant immunity is controlled. Whether these responses are involved in limiting the number of infections or whether they are required for the progression of the interaction is not yet clear. Further similarities in both plant,pathogen and Rhizobium,legume associations are factors such as surface polysaccharides, quorum sensing signals and secreted proteins, which play important roles in modulating plant defence responses and determining the outcome of the interactions. [source] Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic areaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2006C. C. Obihara Summary Background Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. Objective To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. Methods In this cross-sectional study, 841 children aged 6,14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. Results Children with positive TST (10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24,0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). Conclusions These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB. [source] Growth of Brucella abortus in macrophages from resistant and susceptible mouse strainsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2000J. Sathiyaseelan C57Bl/10 mice have a superior ability to control chronic infections with virulent strains of the intracellular bacteria Brucella abortus compared with BALB/c mice. While a number of differences in the cytokines produced by lymphocytes following infection of these two strains of mice have been shown, macrophages have not been evaluated for their role in conveying relative resistance. The importance of macrophages in control of brucella infections is demonstrated by the observations that intracellular survival of various strains of B. abortus directly correlates with their virulence in vivo, and the ability of macrophages to control brucellae in vitro has been shown to correlate with a brucella-resistant phenotype in ruminants. While both BALB/c and C57Bl are Nramp -susceptible mouse strains, additional differences in macrophage function outside of the Nramp1 gene effects could influence susceptibility to brucellosis. The studies conducted here comparing the ability of macrophages from C57Bl/10 and BALB/c mice indicate that the macrophages from resistant mice did not control intracellular growth of B. abortus strain 2308 more efficiently than those from the susceptible mice, either in the absence of, or following, interferon-gamma activation or iron supplementation. A number of different conditions for culturing macrophages were evaluated to rule out the influence of antibiotics on the conclusions drawn from the results. [source] | ||||||||||||||||