Alveolar Infection Research Articles

Importin-α7 is required for enhanced influenza A virus replication in the alveolar epithelium and severe lung damage in mice.

Influenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism by using various ex vivo imaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-α7 gene-deficient (α7(-/-)) mice with a recombinant H1N1 influenza virus and compared the in vivo viral kinetics with those in wild-type (WT) mice. In WT mice, influenza virus replication in the bronchial and alveolar epithelium already occurred a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction were present in the lungs of infected WT mice, followed by 100% lethality. Conversely, in α7(-/-) mice, virus replication was restricted mostly to the bronchial epithelium with marginal alveolar infection, resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear the virus infection, as well as the host cellular immune responses, did not significantly differ between WT and α7(-/-) mice. However, cytokine and chemokine responses were generally elevated in WT mice, likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-α7, is required for enhanced virus replication in the alveolar epithelium, resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration, and thus, severe pneumonia and enhanced virulence in mice. Importance: Influenza A viruses are respiratory pathogens that may cause pneumonia in humans. Viral infection and replication in the alveoli of the respiratory tract are believed to be crucial for the development of the acute respiratory distress syndrome associated with fatal outcomes in influenza virus-infected patients. Here, we report the requirement of a cellular factor, importin-α7, for efficient virus replication in the alveolar epithelium of mice. Using complementary ex vivo imaging approaches, we show that influenza virus replication is restricted to the bronchial epithelium, followed by enhanced survival in importin-α7-deficient mice. In contrast, the presence of this gene results in enhanced virus replication in the alveoli, elevated cytokine and chemokine responses, mononuclear infiltration, alveolar destruction, and 100% lethality in wild-type mice. Taken together, our results show that importin-α7 is particularly required for virus replication in the alveolar epithelium in association with severe pneumonia and death in mice.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

Glycoprotein B Cleavage Is Important for Murid Herpesvirus 4 To Infect Myeloid Cells

Glycoprotein B (gB) is a conserved herpesvirus virion component implicated in membrane fusion. As with many—but not all—herpesviruses, the gB of murid herpesvirus 4 (MuHV-4) is cleaved into disulfide-linked subunits, apparently by furin. Preventing gB cleavage for some herpesviruses causes minor infection deficits in vitro, but what the cleavage contributes to host colonization has been unclear. To address this, we mutated the furin cleavage site (R-R-K-R) of the MuHV-4 gB. Abolishing gB cleavage did not affect its expression levels, glycosylation, or antigenic conformation. In vitro, mutant viruses entered fibroblasts and epithelial cells normally but had a significant entry deficit in myeloid cells such as macrophages and bone marrow-derived dendritic cells. The deficit in myeloid cells was not due to reduced virion binding or endocytosis, suggesting that gB cleavage promotes infection at a postendocytic entry step, presumably viral membrane fusion. In vivo, viruses lacking gB cleavage showed reduced lytic spread in the lungs. Alveolar epithelial cell infection was normal, but alveolar macrophage infection was significantly reduced. Normal long-term latency in lymphoid tissue was established nonetheless.

Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30

BackgroundThe genetic basis for avian to mammalian host switching in influenza A virus is largely unknown. The human A/HK/156/1997 (H5N1) virus that transmitted from poultry possesses NS1 gene mutations F103L + M106I that are virulence determinants in the mouse model of pneumonia; however their individual roles have not been determined. The emergent A/Shanghai/patient1/2013(H7N9)-like viruses also possess these mutations which may contribute to their virulence and ability to switch species.MethodsNS1 mutant viruses were constructed by reverse genetics and site directed mutagenesis on human and mouse-adapted backbones. Mouse infections assessed virulence, virus yield, tissue infection, and IFN induction. NS1 protein properties were assessed for subcellular distribution, IFN antagonism (mouse and human), CPSF30 and RIG-I domain binding, host transcription (microarray); and the natural prevalence of 103L and 106I mutants was assessed.ResultsEach of the F103L and M106I mutations contributes additively to virulence to reduce the lethal dose by >800 and >3,200 fold respectively by mediating alveolar tissue infection with >100 fold increased infectious yields. The 106I NS1 mutant lost CPSF binding but the 103L mutant maintained binding that correlated with an increased general decrease in host gene expression in human but not mouse cells. Each mutation positively modulated the inhibition of IFN induction in mouse cells and activation of the IFN-β promoter in human cells but not in combination in human cells indicating negative epistasis. Each of the F103L and M106I mutations restored a defect in cytoplasmic localization of H5N1 NS1 in mouse cells. Human H1N1 and H3N2 NS1 proteins bound to the CARD, helicase and RD RIG-I domains, whereas the H5N1 NS1 with the same consensus 103F and 106M mutations did not bind these domains, which was totally or partially restored by the M106I or F103L mutations respectively.ConclusionsThe F103L and M106I mutations in the H5N1 NS1 protein each increased IFN antagonism and mediated interstitial pneumonia in mice that was associated with increased cytoplasmic localization and altered host factor binding. These mutations may contribute to the ability of previous HPAI H5N1 and recent LPAI H7N9 and H6N1 (NS1-103L+106M) viruses to switch hosts and cause disease in humans.

Echinococcus multilocularis infection leads to increased expression of proliferation and anti-apoptosis factors in liver cells in BALB/c mice

To investigate the effects of Echinococcus multilocularis on host liver cell proliferation in vivo using a BALB/c mouse alveolar hydatid infection model. Sixty-five 8-10-week-old female BALB/c mice were randomly divided into an experimental group (n = 40) and a control group (n = 25) and administered an abdominal injection into the left liver lobe of E. multilocularis protoscolices in saline solution or saline solution alone, respectively. At post-injection day 2, 8, 30, 60, and 90, liver samples were collected for analysis of lesions and lesion-adjacent tissue by hematoxylin-eosin staining and differential expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin A, and cyclin B1 by immunohistochemical staining. The significance of intergroup differences was assessed by Student's t-test. The control group showed normal liver histology at all time points. The experimental group developed E. multilocularis lesions that showed increased severity of pathological features, such as inflammatory cell invasion, steatosis and fibrous connective tissue hyperplasia, over time. At post-injection days 2 and 8, enlarged, binuclear and apocyte hepatocytes were observed close to the lesions. At post-injection days 30, 60, and 90, the number of hepatocytes expressing PCNA progressively increased in the experimental group, and the numbers were significantly higher than in the control group (7.01 +/- 1.89 vs. 1.03 +/- 0.52, 8.41 +/- 2.80 vs. 0.93 +/- 0.31, and 13.4 +/- 4.43 vs. 1.07 +/- 0.94; all P < 0.05). The same progressively increasing trend was seen in the number of hepatocytes expressing CyclinD1, but was only significantly different from controls at post-injection days 30 and 60 (6.73 +/- 2.52 vs. 0.48 +/- 0.43 and 8.22 +/- 3.09 vs. 0.55 +/- 0.34; both P < 0.05). In contrast, the number of hepatocytes expressing cyclin A was significantly increased at post-injection day 30 and then showed a decreasing trend at days 60 and 90, although the numbers of expressing cells remained significantly higher than control levels at all time points (7.75 +/- 3.05 vs. 0.69 +/- 0.36, 3.42 +/- 1.80 vs. 1.14 +/- 0.42, and 3.03 +/- 1.50 vs. 0.69 +/- 0.31; all P < 0.05). The number of hepatocytes expressing CyclinB1 in the experimental group was less robust than the other cyclins (with a general temporal trend of increase followed by decrease), but the differential expression was not significantly different from the control levels at any time point. E. multilocularis infection may promote the expression of host factors related to proliferation and anti-apoptosis in liver. This pathogen-mediated modulation of host cell-survival mechanisms may provide a rationale explanation for the clinical observations of hepatomegaly and the unexpected survival of alveolar echinococcosis patients following major hepatic resection.

A Single Dose of Amoxicillin and Dexamethasone for Prevention of Postoperative Complications in Third Molar Surgery: A Randomized, Double-Blind, Placebo Controlled Clinical Trial

BackgroundThe aim of this study was to assess the efficacy of a single prophylactic dose of amoxicillin and/or dexamethasone in preventing postoperative complications (PC) after a surgical removal of a single mandibular third molar (M3).MethodsThis study is a randomized, placebo controlled clinical trial. Four groups were included: Group 1 (G1) included a prophylactic dose of 2 g of amoxicillin and 8 mg of dexamethasone; Group 2 (G2) included a prophylactic dose of 2 g of amoxicillin and 8 mg of placebo; Group 3 (G3) included a prophylactic dose of 8 mg of dexamethasone and 2 g of placebo and; Group 4 (G4) placebo.ResultsFifty patients were included. It was observed one case of alveolar infection (2%) and two of alveolar osteitis (4%) resulting in three PC (6%). No statistical differences were observed between therapeutic groups for development of PC, trismus, pain and edema. The use of antibiotics showed an absolute risk reduction (ARR) for PC development of 3.52% and the number needed to treat (NNT) was 29.ConclusionProphylactic antibiotics and corticoid in a single dose regimen did not bring any benefit on M3 surgeries.

EComment. Re: Radiological patterns of primary graft dysfunction after lung transplantation

We read with interest the article from Belmaati et al. [1]. Lung-transplantation (LUTX) offers prognostic and quality of life benefits for carefully selected patients. There are many challenges which recipients face early post-transplantation. Amongst the most immediate and potentially devastating of these is the development of primary graft dysfunction (PGD). This post-LUTX complication is a worrying feature and characterised by radiological infiltrates and poor graft function as measured by oxygenation. Observational studies have shown that this problem can be associated with a very poor prognosis in patients with high grades of PGD, which are persistent [2, 3]. This single centre descriptive study seeks to define the early radiological changes associated with PGD and link these to clinical outcomes [1]. The paper describes the radiological changes in patients with varying grades of PGD (0-3) at four different time points (Days 3, 14, 90 and 365). The radiological infiltrates were divided into: ground glass (GG) change, septal thickening (ST), consolidation (Con) or pre-bronchial thickening. These radiological changes are likely to represent a composite end point of a number of insults which a donor lung goes through, including brain stem death, preservation, reperfusion, infection and immunologically mediated injury [4]. The changes were evaluated in a systematic manner by two independent radiologists. The abnormalities are described in relation to the lobe and their distribution (central and peripheral) with each of these four parameters ascribed a score and tracked across the four scans. This systematic approach allows comparisons of regions of the lung across time. Most of the changes resolve over the course of 12 weeks but some patients had persistent changes. ST appeared to be the most predictive finding for PGD. The study raises some very interesting research questions which may help to better define chronic allograft dysfunction post-LUTX in the context of PGD. Whilst the follow up is too short to attempt to link these early radiological changes to the incidence of Bronchiolitis Obliterans Syndrome (chronic allograft dysfunction (CLAD)), it does provide interesting insights into the resolution of changes within the lung allograft exposed to this severe injury. The intervention is not entirely benign and is associated with an increased radiation and contrast burden for the patient. In addition there may be the detection of nodules in the lung, which may require repeated scanning to check for progression of the nodules. However these concerns aside, this study does offer some exciting possibilities. In the future, the potential for correlating these radiological changes with pathological samples is tantalizing. If these abnormalities were identified as either areas of organisation, diffuse alveolar damage or infection, this may provide a better descriptor for patients who are at risk of long term CLAD post-PGD. We can speculate that these early changes may, for example, direct the lung to heal in a particular manner resulting in different spectrums of disease, such as Restrictive Allograft Syndrome (RAS) [5]. If these speculations were borne out, this would allow better prognostication for some patients and potentially different therapeutic options.

Does smoking increase the incidence of postoperative complications in simple exodontia?

To investigate whether smoking has adverse effects in simple exodontia. A single-centre, prospective study of postoperative inflammatory complications in simple exodontia was performed. All procedures were conducted under similar and sterile conditions. Postoperative complications (PCs) in exodontia were classified as alveolar osteitis (AO) or alveolar infection (AI) and their incidences then added. A logistic regression model for PCs revealed tooth sectioning [odds ratio (OR) = 4.3, 95% confidence interval (CI) 1.0-18.8; P = 0.050], smoking (OR = 4.5, 95% CI 1.0-18.9; P = 0.03) and amount of smoking (> 20 cigarettes/day: OR = 12.3, 95% CI 1.0-149.8; P = 0.04) to be associated with the occurrence of PCs. Tooth sectioning, smoking and degree of smoking are all associated with the development of PCs such as AO and AI after simple exodontia. Dentists must be alert to these factors when performing simple exodontia in smokers in view of the increased risk for PCs.

Rituximab Associated Pneumonitis in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Rituximab is gaining use in the treatment of antineutrophil cytoplasmic antibody-associated vasculitis. We report the first case of rituximab-induced pneumonitis in a patient with antineutrophil cytoplasmic antibody-associated vasculitis. Our patient with granulomatosis with polyangiitis (Wegener granulomatosis) had a relapse complicated by diffuse alveolar hemorrhage and acute kidney injury. His treatment included rituximab, steroids, cyclophosphamide, and plasmapheresis. Two weeks after his second dose of rituximab, he developed an acute deterioration in respiratory function. Rituximab-induced pneumonitis was diagnosed on a combination of computed tomography imaging, bronchoalveolar lavage, and negative tests for active vasculitis and infection. He was treated with a course of high-dose corticosteroids with improvement in respiratory function, computed tomography imaging of his chest, and inflammatory markers. Acute drug-induced pneumonitis is a rare but serious complication of rituximab. Distinguishing this complication from alveolar hemorrhage or pulmonary infection may be difficult. This diagnosis needs to be considered early in the right clinical context.

Antenatal Phosphodiesterase 4 Inhibition Restores Postnatal Growth and Pulmonary Development in a Model of Chorioamnionitis in Rabbits

Chorioamnionitis is implicated in the pathophysiology of bronchopulmonary disease, and the associated inflammatory response is responsible for adverse effects on alveolar development. The aim of this work was to analyze the effects of a phosphodiesterase 4 (PDE4)-selective inhibitor, rolipram (a modulator of the inflammatory response), in an experimental model of chorioamnionitis on pulmonary development and on the processes of infection and inflammation. Rabbit mothers were assigned to four groups: 1) saline serum inoculation (controls); 2) Escherichia coli intrauterine inoculation (C+); 3) rolipram infusion (R+); and 4) E. coli inoculation + rolipram infusion (C+R+). High rates of morbility and mortality were noticed in mothers and pups (5 of 13 pregnant rabbits in groups with rolipram). Alveolar development, inflammation, and infection were analyzed in pups at day 0 and day 5. At day 0, in the context of chorioamnionitis, rolipram significantly decreased birth weight (p < 0.01) relative to that of controls (p < 0.05). At day 5, weight normalized in group C+R+ but not in group C+ relative to controls (p < 0.001); moreover, alveolar airspace volume was preserved in group C+R+ but not in group C+ (p < 0.05). Interstitial volume decreased in group C+ versus controls (p < 0.05) but was preserved in group C+R+. Specific alveolar area was not significantly modified by rolipram. No significant difference was found concerning bronchoalveolar lavage cellularity, and all blood cultures remained sterile. In this model of impaired alveologenesis, rolipram significantly preserved specific alveolar density. However, PDE4 inhibition induced antenatal fetal demise and growth retardation.

Elicitation of Anti-1918 Influenza Virus Immunity Early in Life Prevents Morbidity and Lower Levels of Lung Infection by 2009 Pandemic H1N1 Influenza Virus in Aged Mice

The Spanish influenza virus pandemic of 1918 was responsible for 40 million to 50 million deaths and is antigenically similar to the swine lineage 2009 pandemic influenza virus. Emergence of the 2009 pandemic from swine into humans has raised the possibility that low levels of cross-protective immunity to past shared epitopes could confer protection. In this study, influenza viruslike particles (VLPs) were engineered to express the hemagglutinin (HA) and genes from the 1918 influenza virus to evaluate the duration of cross-protection to the H1N1 pandemic strain by vaccinating young mice (8 to 12 weeks) and then allowing the animals to age to 20 months. This immunity was long lasting, with homologous receptor-blocking antibodies detected throughout the lifespan of vaccinated mice. Furthermore, the 1918 VLPs fully protected aged mice from 2009 pandemic H1N1 virus challenge 16 months after vaccination. Histopathological assessment showed that aged vaccinated mice had significant protection from alveolar infection but less protection of the bronchial tissue than adult vaccinated mice. Additionally, passive transfer of immune serum from aged vaccinated mice resulted in protection from death but not morbidity. This is the first report describing the lifelong duration of cross-reactive immune responses elicited by a 1918 VLP vaccine in a murine model. Importantly, these lifelong immune responses did not result in decreased total viral replication but did prevent infection of the lower respiratory tract. These findings show that immunity acquired early in life can restrict the anatomical location of influenza viral replication, rather than preventing infection, in the aged.

The mucosal and systemic immune status for diabetic and non-diabetic Dentialvcolar infected patients

From a group of 60 patients with dentoalveolar infections among which 10 were diabetic and 10 non-diabetic were elected as test group as well as 10 normal subjects as control group. Six Staphylococcus aureus and Streptococcus anginousus were diagnosed in the first and second group of the patients the immune status of the patients and control subject were tested by pathogen specific antibody titre, neotrophil NBT reduction phagocytosis and leukocyte inhibition LIF. Diabetic patients with dentoalveolar infection shows decreased specific antibody titers, subnormal neutrophil NBT phagocytic % as well as non significant LIF % in comparison non diabetic reveal high specific antibody titers against , high neutrophil NBT% and significant LIF% respectively thus diabetic indicate humoral and cellular immune suppression along the den to alveolar infection.

The mucosal and systemic immune status for diabetic and non-diabetic Dentialvcolar infected patients

From a group of 60 patients with dentoalveolar infections among which 10 were diabetic and 10 non-diabetic were elected as test group as well as 10 normal subjects as control group. Six Staphylococcus aureus and Streptococcus anginousus were diagnosed in the first and second group of the patients the immune status of the patients and control subject were tested by pathogen specific antibody titre, neotrophil NBT reduction phagocytosis and leukocyte inhibition LIF. Diabetic patients with dentoalveolar infection shows decreased specific antibody titers, subnormal neutrophil NBT phagocytic % as well as non significant LIF % in comparison non diabetic reveal high specific antibody titers against , high neutrophil NBT% and significant LIF% respectively thus diabetic indicate humoral and cellular immune suppression along the den to alveolar infection.

Treatment of a Case of Mesangioproliferative Glomerulonephritis Secondary to Echinococcus alveolaris with Albendazole

Parasitic infections lead to significant morbidity and mortality, especially in tropical regions. The renal damage caused by these infections occurs via various mechanisms. Two forms of parasitic echinococcus infection widely responsible for infection in humans are Echinococcus granulosus and Echinococcus multilocularis. E. multilocularis causes Alveolar echinococcus infection in humans. Alveolar echinococcus has high mortality, and the possible limits of surgery are generally exceeded by the time of diagnosis. The literature contains no case reports of comorbidity of alveolar echinococcus and glomerulonephritis. Here we discuss the treatment of a patient with comorbid mesangioproliferative glomerulonephritis and alveolar echinococcus, behaving like a tumor, using albendazole since there was no possibility of surgery. This is the first ever such case report.

Effect of submucosal and intramuscular dexamethasone on postoperative sequelae after third molar surgery: comparative study

We compared the effects of dexamethasone sodium phosphate given submucosally and intramuscularly on postoperative complications after removal of impacted lower third molars in a preliminary randomised prospective clinical trial. Thirty patients, each of whom required removal of a single impacted mandibular third molar under local anaesthesia, were randomly allocated to one of 3 groups of 10 each. The 2 experimental groups were given dexamethasone 4 mg submucosally or intramuscularly, and the control group had no steroid. Facial swelling and maximal interincisal distance were measured by an independent examiner at baseline (preoperatively), and at 1, 3, and 7 days postoperatively. Pain was measured by counting the number of rescue analgesic tablets taken, and from the patients’ response to a visual analogue scale (VAS). The mean age of the 16 men and 14 women was 27 years (range 20–48). Both dexamethasone groups showed significant reductions in swelling ( p < 0.001) and in pain ( p < 0.05) compared with the control group at all intervals. Submucosal dexamethasone resulted in significantly less trismus than controls on day 1 postoperatively ( p = 0.04), but there were no significant differences among the groups at the other times. The effects of the two routes of dexamethasone were comparable for all variables. There were no cases of alveolar osteitis or wound infection. Dexamethasone 4 mg given submucosally is an effective way of minimising swelling, trismus, and pain after removal of impacted lower third molars, and is comparable with the intramuscular route. It offers a simple, safe, painless, non-invasive, and cost-effective treatment in moderate and severe cases.

The 2009 H1N1 Pandemic Adds to Our Knowledge of Influenza Pathogenesis

This commentary discusses the pathology and pathogenesis of the 2009 H1N1 influenza A pandemic.

Incidence of Dry Socket, Alveolar Infection, and Postoperative Pain Following the Extraction of Erupted Teeth

The aim of this study was to determine the incidence of dry socket, alveolar infection, and postoperative pain following the routine extraction of erupted teeth. Using a questionnaire, this prospective cross-sectional study evaluated 357 consecutive surgeries in which 473 erupted teeth were extracted by dental students under rigorous control of microbiologic contaminants during a 22-month period. The subject sample consisted of 210 (58.8%) male patients ranging in age from 11 to 79 years (mean 41 +/- 16.3). The most prevalent self-reported ethnicity was Caucasian (78.2%). The questionnaire consisted of 60 questions directed to the patient and to the dental student who performed the surgical procedure. The questionnaires were completed before and within seven days after the surgery to obtain outcomes data. Forty-five questionnaires were excluded due to lack of information, inconsistencies, or lack of contact with the patient; however, none had indications of alveolar infection or dry socket. The data were analyzed using descriptive statistics, chi-square tests (x(2)), and an odds ratio (OR) as appropriate at the critical level of significance, set at p<0.05 (x(2)) or p<0.01 (x(2), with the Monte Carlo simulation). The observed incidence was 0.6% (two cases each) for both alveolar infection and dry socket. Higher pain levels and pain persisting longer than two days were observed with more traumatic surgeries, or associated with postoperative complications. Smoking was found to be statistically associated with the development of postoperative complications. The incidence of alveolar infection, dry socket, and severe pain were very low for the routine extraction of erupted teeth. Severe pain that persists for more than two days can represent a sign of a postoperative complication such as dry socket. Dental extraction is part of the dentists' daily work and intercurrences like dry socket, infection, and pain can occur. This manuscript reports the incidence of these occurrences and search for its predisposing factors.

Morphine Induces Defects in Early Response of Alveolar Macrophages to Streptococcus pneumoniae by Modulating TLR9-NF-κB Signaling

Resident alveolar macrophages and respiratory epithelium constitutes the first line of defense against invading lung pneumococci. Results from our study showed that increased mortality and bacterial outgrowth and dissemination seen in morphine-treated mice were further exaggerated following depletion of alveolar macrophages with liposomal clodronate. Using an in vitro alveolar macrophages and lung epithelial cells infection model, we show significant release of MIP-2 from alveolar macrophages, but not from lung epithelial cells, following 4 h of exposure of cells to pneumococci infection. Morphine treatment reduced MIP-2 release in pneumococci stimulated alveolar macrophages. Furthermore, morphine treatment inhibited Streptococcus pneumoniae-induced NF-kappaB-dependent gene transcription in alveolar macrophages following 2 h of in vitro infection. S. pneumoniae infection resulted in a significant induction of NF-kappaB activity only in TLR9 stably transfected HEK 293 cells, but not in TLR2 and TLR4 transfected HEK 293 cells, and morphine treatment inhibited S. pneumoniae-induced NF-kappaB activity in these cells. Moreover, morphine treatment also decreased bacterial uptake and killing in alveolar macrophages. Taken together, these results suggest that morphine treatment impairs TLR9-NF-kappaB signaling and diminishes bacterial clearance following S. pneumoniae infection in resident macrophages during the early stages of infection, leading to a compromised innate immune response.

Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome

BackgroundKerbs von Lungren 6 antigen (KL-6) is expressed on the surface of alveolar type II cells, and elevated plasma and epithelial lining fluid levels of KL-6 have previously been shown to correlate with the severity of disease and survival in acute respiratory distress syndrome (ARDS). The relationship between alveolar inflammation and KL-6 measurements has not been ascertained. We hypothesized that the elevation of KL-6 in ARDS is dependent upon the severity of neutrophilic inflammation. Furthermore we were interested in the relationship between significant alveolar infection and KL-6 levels.MethodsPlasma arterial samples were collected from ARDS patients on day 1 and when possible on day 4 along with bronchoalveolar lavage fluid (BALF) samples on the same day. Bacterial growth in the BALF was determined by quantitative cultures and was defined as significant at counts >1 × 104 colony-forming units.ResultsPlasma KL-6 levels in ARDS patients were elevated compared with at-risk control individuals (P = 0.014) and with normal control individuals (P = 0.02). The plasma KL-6 level correlated with the Murray Lung Injury Score (r = 0.68, P = 0.001) and with BALF KL-6 (r = 0.3260, P = 0.04). The BALF KL-6 level was detectable in all ARDS cases and was lower on both day 0 and day 4 in those who survived. BALF KL-6 also correlated with the BALF myeloperoxidase activity (r = 0.363, P = 0.027), with the BALF cell count per millilitre (r = 0.318, P = 0.038), with BALF epithelial-cell-derived neutrophil attractant 78; (r = 0.37, P = 0.016) and with BALF vascular endothelial growth factor (r = 0.35, P = 0.024). The BALF KL-6 level of ARDS patients with significant pathogenic bacterial growth was similar compared with those without significant infection.ConclusionKL-6 may represent a useful marker of alveolar type II cell dysfunction in ARDS since the levels reflect the severity of lung injury and neutrophilic inflammation. KL-6 release across the alveolar epithelial barrier is associated with a poor prognosis. The pathophysiological roles of KL-6 in the development of ARDS warrant further study.

Diffuse alveolar hemorrhage (DAH) and infection associated alveolar hemorrhage (IAH) following hematopoietic stem-cell transplantation: Related and high risk clinical syndromes with poor response to high-dose corticosteroids

Diffuse alveolar hemorrhage (DAH) and infection associated alveolar hemorrhage (IAH) following hematopoietic stem-cell transplantation: Related and high risk clinical syndromes with poor response to high-dose corticosteroids