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Bronchopneumonia is a common multiple infection disease under 2 years old. Luteolin is a natural flavonoid widely distributed in plants with anti-inflammatory effect. This study aimed to explore the effects of luteolin on lipopolysaccharide (LPS)-induced bronchopneumonia injury in vitro and in vivo. Firstly, the viability and apoptosis of human bronchial epithelial BEAS-2B cells after luteolin treatment were assessed. Then, cells were treated with 10 μM LPS to simulate inflammatory injury. The potential protective effects of luteolin on LPS-induced BEAS-2B cell inflammatory injury were detected. Moreover, after LPS and/or luteolin treatment, the expression of microRNA-132 (miR-132) in BEAS-2B cells was measured. The roles of miR-132 in protective activity of luteolin were investigated. Finally, the LPS-induced bronchopneumonia murine model was established and the anti-inflammatory effects of luteolin in vivo were analyzed. The results showed that LPS decreased BEAS-2B cell viability, increased cell apoptosis and enhanced inflammatory cytokines expression. Luteolin alleviated the LPS-induced viability loss, apoptosis and elevated expression of inflammatory cytokines in a dose-dependent manner. Moreover, luteolin alleviated the LPS-induced miR-132 expression increase in BEAS-2B cells. Overexpression of miR-132 reversed the protective effects of luteolin on LPS-induced inflammatory injury. Mechanistically, luteolin mitigated LPS-induced activation of NF-κB signaling pathway by down-regulation of miR-132. Furthermore, we also found that luteolin alleviated LPS-induced bronchopneumonia model in vivo. In conclusion, this study revealed that luteolin alleviated LPS-induced bronchopneumonia injury in vitro and in vivo through down-regulating miR-132. These findings provide theoretical basis for deeply exploring the treatment of bronchopneumonia in children by using luteolin., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Sepsis is a complex immune disorder that is characterized by systemic hyperinflammation. Alarmins, which are multifunctional endogenous factors, have been implicated in exacerbation of inflammation in many immune disorders including sepsis. Here we show that Galectin-9, a host endogenous β-galactoside binding lectin, functions as an alarmin capable of mediating inflammatory response during sepsis resulting from pulmonary infection with Francisella novicida, a Gram negative bacterial pathogen. Our results show that this galectin is upregulated and is likely released during tissue damage in the lungs of F. novicida infected septic mice. In vitro, purified recombinant galectin-9 exacerbated F. novicida-induced production of the inflammatory mediators by macrophages and neutrophils. Concomitantly, Galectin-9 deficient (Gal-9-/-) mice exhibited improved lung pathology, reduced cell death and reduced leukocyte infiltration, particularly neutrophils, in their lungs. This positively correlated with overall improved survival of F. novicida infected Gal-9-/- mice as compared to their wild-type counterparts. Collectively, these findings suggest that galectin-9 functions as a novel alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.

The aim of the present study was to investigate the relationships between serum amino acid profiles in normal and calves with Mycoplasma bronchopneumonia. Serum free amino acid concentrations in serum obtained from 34 calves with or without Mycoplasma bronchopneumonia were determined by high-performance liquid chromatography. The calves with Mycoplasma were characterized by significantly lower total amino acid and total essential amino acid concentrations and molar ratios of branched-chain amino acid (BCAA) to aromatic amino acid (BCAA/AAA) and BCAA to tyrosine (BTR), and by a significantly higher molar ratio of serine phosphorylation (SPR). The proposed diagnostic cutoffs for BCAA/AAA, BTR and SPR in serum based on ROC analysis for detection of catabolic states associated with Mycoplasma bronchopneumonia were set at <1.75, <2.86 and >0.85, respectively. Our results suggest that determining the profiles of amino acids, especially BTR and SPR, could provide useful diagnostic information in terms of predicting protein catabolism in Mycoplasma bronchopneumonia.

Rationale: The death receptor Fas is critical for bacterial clearance and survival of mice after Pseudomonas aeruginosa infection., Objectives: Fas ligand (FasL)-induced apoptosis is augmented by S-glutathionylation of Fas (Fas-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and Fas in regulating the clearance of P. aeruginosa infection., Methods: Lung samples from patients with bronchopneumonia were analyzed by immunofluorescence. Primary tracheal epithelial cells, mice lacking the gene for Grx1 (Glrx1(-/-)), Glrx1(-/-) mice treated with caspase inhibitor, or transgenic mice overexpressing Grx1 in the airway epithelium were analyzed after infection with P. aeruginosa., Measurements and Main Results: Patient lung samples positive for P. aeruginosa infection demonstrated increased Fas-SSG compared with normal lung samples. Compared with wild-type primary lung epithelial cells, infection of Glrx1(-/-) cells with P. aeruginosa showed enhanced caspase 8 and 3 activities and cell death in association with increases in Fas-SSG. Infection of Glrx1(-/-) mice with P. aeruginosa resulted in enhanced caspase activity and increased Fas-SSG as compared with wild-type littermates. Absence of Glrx1 significantly enhanced bacterial clearance, and decreased mortality postinfection with P. aeruginosa. Inhibition of caspases significantly decreased bacterial clearance postinfection with P. aeruginosa, in association with decreased Fas-SSG. In contrast, transgenic mice that overexpress Grx1 in lung epithelial cells had significantly higher lung bacterial loads, enhanced mortality, decreased caspase activation, and Fas-SSG in the lung after infection with P. aeruginosa, compared with wild-type control animals., Conclusions: These results suggest that S-glutathionylation of Fas within the lung epithelium enhances epithelial apoptosis and promotes clearance of P. aeruginosa and that glutaredoxin-1 impairs bacterial clearance and increases the severity of pneumonia in association with deglutathionylation of Fas.

Interleukin (IL)-33 enhances T helper (Th)2 immunity via its receptor T1/ST2. Infection with the yeast-like pathogen Cryptococcus neoformans is usually controlled by a Th1-mediated immune response. The mechanisms responsible for nonprotective Th2 immunity leading to allergic inflammation in pulmonary cryptococcosis are still not fully understood. Using a murine pulmonary model of C. neoformans infection, we report that T1/ST2 expression correlates with the intensity of Th2 activation, as demonstrated by the expression of CD25 and CD44 and downregulation of CD62L. Antigen-specific T1/ST2(+) Th cells are the primary source of the Th2 cytokines IL-5 and IL-13 as compared with wild-type T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. In addition, T1/ST2(+) Th cells almost exclusively contain bi- and trifunctional Th2 cytokine-producing Th cells compared with T1/ST2(-) Th cells or Th cells from T1/ST2(-/-) mice. Finally, T1/ST2-driven Th2 development resulted in defective pulmonary fungal control. These data demonstrate that T1/ST2 directs Th2 cell activation and polyfunctionality in allergic bronchopulmonary mycosis.

In this study we examined the serum activity of lactate dehydrogenase (LDH) and its isoenzyme patterns in 28 calves of a lowland black spotted breed and its crossbreeds at the age of 2-6 months suffering from clinically noticeable manifested respiratory diseases--bronchopneumonia (BRD Group). As a control group we used 35 clinically healthy calves of the same age, breed and nutrition (Healthy Group). The sick calves did not show clinical signs or pathological lesions on other organ systems. The results found in sick calves showed a significantly higher total activity of LDH than in clinically healthy animals (P < 0.01). The mean activity of LDH was 2012 U/I in healthy calves and in calves with respiratory diseases 2529 U/1. The differences in all LDH isoenzyme patterns between both groups of animals were significant (P < 0.001) and in calves with respiratory diseases are characterized by a marked increase of the LDH 1 fraction and a decrease in the proportion of the other four LDH isoenzymes. Our results differ from those observed and presented in respiratory diseases in human medicine or in sheep. The explanation for the obtained results in calves and the determination of their diagnostic significance needs further studies and investigations using more animals with various severity of clinical signs and pathological changes, including analysis and determination of lactate dehydrogenase isoenzyme patterns in healthy and affected cattle lung tissue.

The aim of this study was to evaluate the reliability and effectiveness of direct determination of trace and major element concentrations in bronchoalveolar lavage fluid samples from Holstein calves with Mycoplasma bronchopneumonia (n = 21) and healthy controls (n = 20). The samples were obtained during bronchoscopy using a standard examination method. A total of 18 elements (aluminum, bromine, calcium, chlorine, chromium, copper, iron, potassium, magnesium, manganese, molybdenum, nickel, phosphorous, sulfur, silicon, strontium, titanium, and zinc) were detected by particle-induced X-ray emission. The average bromine, iron, potassium, magnesium, and phosphorous concentrations were higher in calves with bronchopneumonia than in controls (p < 0.05). They were found to have higher amounts of calcium and zinc, and a higher zinc-copper ratio than that in healthy calves (p < 0.001). Based on the receiver operating characteristics curves, we propose a diagnostic cutoff point for zinc-copper ratio for identification of Mycoplasma pneumonia of 8.676. Our results indicate that assessment of the elemental composition of broncholaveolar lavage fluid is a promising diagnostic tool for Mycoplasma bronchopneumonia.

Adjunctive corticosteroid treatment to reduce excessive local inflammatory response in pneumonia is controversial. To study the effects of an early local adjunct dexamethasone treatment on the course of pneumonia and inflammatory/cytokine response, mice were intratracheally inoculated with live Porphyromonas gingivalis and treated with either clindamycin (C), dexamethasone (D), C+D combination, or were not treated (Pg). Six mice from each group were euthanized at 6, 24, 72, and 168 hours after inoculation. Levels of tumor necrosis factor (TNF)-α, soluble TNF-α receptors (sTNFR1 and sTNFR2), interleukin (IL)-1β, and IL-6 in the serum and lung-homogenate supernatant were determined. Lung samples were histopathologically assessed and all findings compared to those found in 24 sham-inoculated mice (phosphate-buffered saline [PBS]). Severe P. gingivalis-induced bronchopneumonia progressed from 24 hours, peaked at 72 hours, and resolved after 168 hours with changes in local and systemic cytokine levels. Clindamycin-treated mice developed only mild bronchopneumonia that resolved fast (72 hours) with an early (6-24 hours) normalization of local and systemic cytokine levels. Similar course of pneumonia and cytokine level changes were observed in mice treated with C+D, but later. Early (6-24 hours) local elevation of sTNFRs was observed in C and C+D groups of mice, whereas nontreated (Pg) mice had increased systemic sTNFRs. Severe bronchopneumonia with delayed resolution was observed in D-group mice, with an early local and systemic decrease in sTNFR1 and persistent elevation of local TNF-α. Clindamycin or a clindamycin-dexamethasone combination treatment significantly improves the course of P. gingivalis-aspiration pneumonia, but more so if clindamycin alone is used. A favorable course of pneumonia seems to be associated with an early elevation of sTNFRs and normalization of TNF-α.

Objective: To study the molecular mechanism of enalapril on rat chronic bronchopneumonia model with proteomics method., Methods: Enalapril treatment applied to the recovery of chronic bronchopneumonia in rats, after enalapril administration, two-dimensional electrophoresis and mass spectrometry were performed to analyze the difference of the peptide finger print map and amino acid sequence of rat lung tissues in acrolein inhalation group and enalapril treatment group., Results: Three differential protein spots from average 545 protein spots were found in lung tissues of two groups. These protein spots were identified as glyceraldehyde-3-phosphate dehydrogenase, T-kininogen 1 precursor and dihydropyrimidinase-like 2 with mass spectrometry. The significant upregulation in the level of dihydropyrimidinase-like 2, downregulation of glyceraldehyde-3-phosphate dehydrogenase, and the lose of T-kininogen 1 precursor in enalapril treatment group were observed., Conclusion: The expression difference in three proteins might contribute to the preventive role of enalapril on acrolein inhalation induced rat chronic bronchopneumonia.

The interaction between air particulates and genetic susceptibility has been implicated in the pathogenesis of asthma. The overall objective of this study was to determine the effects of inhalation exposure to environmentally relevant concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized and challenged Brown Norway rats. Changes in gene expression were compared with lung tissue histopathology, morphometry, and biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the preponderance of gene expression changes, related largely to inflammation. CAPs exposure alone resulted in no significant gene expression changes, but CAPs and ova-exposed rodents exhibited an enhanced effect relative to ova alone with differentially expressed genes primarily related to inflammation and airway remodeling. Gene expression data was consistent with the biochemical and cellular analyses of the BALF, the pulmonary pathology, and morphometric changes when comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the gene expression data were more sensitive than the BALF cell type and number for assessing the effects of CAPs and ova versus the ova challenge alone. In addition, the gene expression results provided some additional insight into the TGF-beta-mediated molecular processes underlying these changes. The broad-based histopathology and functional genomic analyses demonstrate that exposure to CAPs exacerbates rodents with allergic inflammation induced by an allergen and suggests that asthmatics may be at increased risk for air pollution effects.

Pulmonary inflammation often results in expression of the class II major histocompatibility complex (MHCII) by both professional antigen-presenting cells (APCs; histiocytes and lymphocytes) and non-professional APCs (respiratory epithelium and endothelium). In this study lesions from 17 cases of bovine chronic pneumonia, associated with Mycoplasma bovis infection, were examined immunohistochemically for M. bovis antigen and MHCII expression. Ten cases of chronic necrosuppurative bronchopneumonia (NBP) were shown to be characterized by abundant perinecrotic M. bovis antigen associated with scant MHCII expression by degenerate leucocytes. Seven cases of chronic catarrhal bronchointerstitial pneumonia (CBP) showed prominent MHCII expression by both professional APCs and respiratory epithelium, in the absence of intralesional M. bovis immunolabelling. The results suggest that prominent MHCII expression by both professional and non-professional APCs plays a role in the pathogenesis of M. bovis-induced CBP. Conversely, the role of MHCII expression in necrosuppurative foci typical of M. bovis-associated NBP can be considered negligible.

The aim of this study was to investigate the relationships between the bronchopneumonia and mean concentrations of those trace elements in bronchoalveolar lavage fluid (BALF). Twenty-nine dogs were included this study (17 healthy dogs and 12 dogs with respiratory disease). Each BALF sample had been obtained during bronchoscope examination by use of a standardized method. The concentrations of Al, Br, Ca, Cu, Fe, K, Ni, P, Si, Sr and Zn in BALF were measured by the particle-induced X-ray emission method. We found no relationship between the bronchopneumonia and the levels of elements in the BALF, except Ca, P and Zn. The dogs with respiratory disease were found to have a large amount of Ca and Zn, and a high Ca/P and Zn/Cu ratios in BALF compared to those without respiratory disease.

Background and Purpose: Nerve growth factor (NGF) is a neurotrophin that plays an important role in the development and function of the central and peripheral nervous systems. We investigated the role of NGF receptors in allergic and inflammatory lung diseases., Methods: This study included 90 children who attended the outpatient pediatric clinic or who were admitted to the inpatient pediatric department of El-Minia University Hospital. The children were divided into 3 groups - Group I, asthmatic children who had sustained an acute attack; Group II, children with severe inflammatory lung disease such as bronchopneumonia; and Group III, 20 apparently healthy children who were age- and sex-matched to the diseased groups. Thorough clinical examination, chest X-ray, complete blood count, erythrocyte sedimentation rate, and reverse transcriptase-polymerase chain reaction (RT-PCR) were carried out., Results: RT-PCR revealed only 3 asthmatic cases that showed positive NGF receptors on isolated eosinophils from the peripheral blood. However, all cases with bronchopneumonia had no detectable results. Moreover, there was a statistically significant difference between positive and negative cases for NGF receptors on isolated eosinophils by RT-PCR with regard to age (p<0.001), frequency of recurrence of asthmatic attacks (p<0.005), positive history of other atopic diseases such as allergic dermatitis, and allergic rhinitis (p<0.02). However, there was no statistically significant difference between positive and negative cases with respect to sex, type of feeding, and/or family history., Conclusions: There is a strong association between NGF receptors on isolated eosinophils and the severity of allergic lung diseases and bronchial asthma.

Objectives: To determine the pharmacokinetic parameters of ceftriaxone following an infusion in haemodialysed outpatients and to use these parameters for an optimisation of dosing based on pharmacodynamic indices., Methods: Fifty haemodialysed patients were enrolled in a single-centre, prospective, open-label study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48 hours for bronchopneumonia immediately after the dialysis session. Total plasma concentrations of ceftriaxone were analysed with a population pharmacokinetic approach using nonlinear mixed-effects modelling. Free drug concentrations were derived from published binding parameters in order to estimate the time when they exceed the minimum inhibitory concentration (MIC)., Results: The pharmacokinetics were best described by a two-compartment model. None of the covariates tested (age, bodyweight, height, sex, body mass index, albumin) influenced the pharmacokinetic parameters. The estimated population pharmacokinetic parameters (interindividual variability [percentage of coefficient of variation]) were clearance 0.36 L/h (48%), volume of distribution of the central compartment 4.53 L (47%), intercompartmental clearance 10.8 L/h and volume of distribution of the peripheral compartment 9.54 L (63%). The terminal elimination half-life (t(1/2)beta) from plasma was 27.5 hours. The mean (range) times when the free drug concentration exceeded the MIC (T>MIC) following ceftriaxone 1 g infusion were 60.3 (53.0-67.7) hours and 2.5 (1.0-3.9) hours for the breakpoints 1 and 8 mg/L (based on free drug concentration), respectively. After administration of ceftriaxone 2 g, the T>MIC was 88.5 (78.8-98.3) hours and 17.7 (13.3-22.0) hours for the breakpoints 1 and 8 mg/L, respectively. The simulated free drug concentrations (median, first and third quartile) for 48 and 72 hours following the first dose of ceftriaxone 1g were 1.11, 0.63 and 1.89 mg/L, and 0.63, 0.28 and 1.18 mg/L, respectively. For ceftriaxone 2g infusion, the simulated free concentrations (median, first and third quartile) at 48 and 72 hours were 2.50, 1.40 and 4.52 mg/L, and 1.37, 0.60 and 2.70 mg/L, respectively., Conclusions: On the basis of decreased clearance in haemodialysed patients, it can be argued that the dose of ceftriaxone should be decreased or the delay between doses should be increased. However, taking into account pharmacodynamic considerations, this study showed that following intravenous administration of ceftriaxone 1 g after each dialysis session, some patients were at risk of achieving a concentration below the MIC (1 mg/L), particularly if the second administration occurred 72 hours after the first dosing. Thus, a dose of ceftriaxone 2 g intravenously is recommended immediately following dialysis, particularly in patients with severe infections or when the dosing interval will be higher than 48 hours.

Background: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia., Methods: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography., Results: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 +/- 13 vs. 383 +/- 84 microg/g in noninfected piglets and 10 +/- 3 vs. 129 +/- 108 microg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 +/- 141 microg/g; P < 0.001) and no significant change in infected piglets (111 +/- 104 microg/g)., Conclusion: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia.

Substance P contributes to the physiological homeostasis of pulmonary airways and vasculature. During pneumonia, alterations in substance P production and receptor expression can influence bronchoconstriction and vascular perfusion. The distribution of substance P receptor [neurokinin-1 receptor (NK-1R)] in lungs of normal sheep and sheep with acute (1 day), subacute (15 days), and chronic (45 days) bronchopneumonia caused by Mannheimia haemolytica was determined by immunohistochemistry (IHC). Three rabbit polyclonal antibodies generated to the same cytosolic C-terminal portion of NK-1R (residues 393-407) were tested. NK-1R immunoreactivity was traced in digital images and quantified with IPLAB software. There were no significant differences in NK-1R protein density between normal and infected lambs. Antibody 1 had the broadest distribution and intensity, and stained alveolar septae, smooth muscle cells of airways and vessels, epithelial cells of airways and alveoli, and submucosal glands. When all animals from the study were included, there was a trend towards decreased NK-1R immunoreactivity over time. The work suggests that (a) the density of NK-1R does not change during progression of bacterial (M. haemolytica) bronchopneumonia, (b) NK-1R is widely distributed in ovine lung and decreases with age, and (c) antibodies to the same NK-1R cytosolic region can vary in specificity and affinity.

Objective: Our objective was to construct a population pharmacokinetic model for moxifloxacin disposition in plasma and bronchial secretions in patients with severe bronchopneumonia who were mechanically ventilated., Methods: Seventeen patients receiving 400 mg moxifloxacin intravenously daily were enrolled in this multicenter, prospective, open-label study. Blood and bronchial samples were collected on days 1 and 4. The population pharmacokinetic modeling was performed with NONMEM., Results: Moxifloxacin rapidly appeared in bronchial secretions and reached maximum concentrations within 1 to 2 hours. The concentrations achieved in plasma and bronchial secretions showed parallel profiles versus time on days 1 and 4. The pharmacokinetics was best described by a 2-compartment model with a link to bronchial secretions. The population pharmacokinetic parameters were as follows (given as estimate with percent interindividual variability in parentheses except where otherwise indicated): clearance, 14.3 L/h (25%); central distribution volume, 62.9 L (14%); intercompartmental clearance, 27.2 L/h (36%); peripheral distribution volume; 71 L (32%); fraction of moxifloxacin clearance to bronchial secretions, 0.11 (range, 0.06-0.16); and elimination rate constant for bronchial secretions, 1.7 h(-1) (40%). The plasma terminal half-life was 6.7 hours. The bronchial-to-plasma exposure ratio was 1.0 (range, 0.6-2.0). With a conservative 90% minimum inhibitory concentration (MIC(90)) of 0.25 mg/L, the maximum concentration/MIC(90) ratios were higher than 10 and the area under the curve/MIC(90) ratios were roughly 100 for plasma and bronchial secretions., Conclusions: This study showed the fast diffusion of moxifloxacin into the lungs in ventilated patients with severe respiratory infection. The bronchial secretions reached bactericidal levels for common germs found in respiratory tract infections.

In human alveolar epithelial cell line, we investigated the binding activity of NF-kappaB induced by the bronchoalveolar lavage fluids (BALs) from ventilated patients with acute lung injury (ALI), in correlation with the concentrations of inflammatory cytokines, RNOS, and the severity of the ALI. In BALs obtained in 67 patients (16 bronchopneumonia, 14 infected ARDS, 20 ARDS, and 17 ALI patients without bronchopneumonia and no ARDS), we measured endotoxin, IL-1beta, IL-8, and nitrated proteins (NTP), the activity of myeloperoxidase, and the capacity to activate the NF-kappaB in alveolar A549 cells by electrophoretic mobility shift and supershift assays. The neutrophil counts and mean IL-1beta, IL-8, myeloperoxidase, and NTP values were increased in bronchopneumonia and infected ARDS groups compared to ARDS and ALI without bronchopneumonia and no ARDS groups (P<0.001). The number of neutrophils was correlated to those of IL-1beta, IL-8, myeloperoxidase, NTP, and endotoxin in all groups (P<0.0001). NF-kappaB activity was induced in alveolar like cells by BALs in all groups, was higher in bronchopneumonia and infected ARDS groups (P<0.02), and was correlated to IL-1beta (P=0.0002), IL-8 (P=0.02), NTP (P=0.014), myeloperoxidase (P=0.016), and neutrophil counts (P=0.003). BALs of bronchopneumonia and infected ARDS patients had increased inflammatory mediators (compared to ARDS and ALI without bronchopneumonia and no ARDS patients) that correlated to neutrophil counts and to the NF-kappaB-binding activity. These mediators and NF-kappaB activation may induce an amplification of inflammatory phenomena. By in vitro studies, we confirmed that NO-derived species (10(-6) to 10(-5)M peroxynitrite and 10(-5)M nitrites) and myeloperoxidase (at concentration equivalent to that found in BALs) can participate in the NF-kappaB activation.

Aims: The presence of ground glass hepatocytes in a liver biopsy may be related to different conditions, including fibrinogen storage disease. Three types of fibrinogen storage disease have been described, namely types I, II and III. Type I is an hereditary hypofibrinogenaemia genetically characterized by a mutant variant of the fibrinogen molecule designated as fibrinogen Brescia, consistent with a gamma284 Gly-->Arg mutation. Only rare cases of types II and III fibrinogen storage disease have been described. The purpose of the present paper is to describe two cases of fibrinogen storage disease without associated hypofibrinogenaemia, which appeared during acute infectious diseases., Methods and Results: Both patients were female, aged 77 and 73 years, who developed high transaminases during an infectious disease. In each case blood coagulation tests were within the normal range, and despite clinical and laboratory investigations no possible cause for liver disease could be found. Liver biopsies were performed; in both cases weakly eosinophilic cytoplasmic inclusions were observed. Using immunohistochemistry the inclusions were found to be due to fibrinogen accumulation. At ultrastructural level features corresponding to type II inclusions were observed. Molecular studies, performed in case 2, excluded the mutation typical of type I fibrinogen storage disease. Both patients also presented features of chronic hepatitis. In case 1, giant cell granulomas were additionally present. No close relatives of the patients presented any clinical or laboratory features of liver disease. In both patients altered liver function test values gradually, spontaneously, returned to within normal ranges after infectious disease was resolved., Conclusions: These cases suggest that, on rare occasions, hepatocytes may accumulate fibrinogen during an infectious disease.

In bronchoalveolar lavage (BAL) fluid from ventilated patients, cytotoxic oxidant activity is correlated with neutrophil activation. The aim of the present study was to investigate the hypothesis that BAL fluid induces activation of the transcription nuclear factor-kappaB (NF-kappaB) in human alveolar cells, in correlation with inflammatory mediators. We measured endotoxin, inflammatory cytokines [interleukin-1beta (IL-1beta), IL-8], nitrated proteins and the activity of myeloperoxidase (MPO) in BAL fluid from ventilated patients developing bronchopneumonia ( n =19 samples) or with acute respiratory distress syndrome (ARDS) ( n =14), and from ARDS/infection-free patients ( n =11). We also exposed alveolar cells to the BAL fluid or to human MPO, H(2)O(2) or HOCl, and tested nuclear extracts for the activation of NF-kappaB. IL-1beta, IL-8, nitrated protein, MPO and endotoxin levels were significantly higher in BAL fluid from patients with bronchopneumonia than in that from the ARDS and ARDS/infection-free groups. A correlation was observed between IL-8 and MPO values ( r =0.82). The level of NF-kappaB activity induced by the BAL fluid was correlated with levels of IL-1beta ( P <0.001), IL-8 ( P <0.005) and MPO ( P <0.002), and with the neutrophil count ( P <0.002), and was higher for BAL fluid from the bronchopneumonia group. NF-kappaB activation by MPO was also demonstrated. The activation of NF-kappaB by BAL fluid, especially that from bronchopneumonia patients, suggests that a similar phenomenon may occur in vivo, leading to potential amplification of the inflammatory reaction.

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units. g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.

In a previous study, moxifloxacin was shown to ameliorate immunosuppression and enhance cytokine production in several tissues, including the lungs of cyclophosphamide-injected mice. We examined here the effects of moxifloxacin on Candida albicans lung infection in cyclophosphamide-injected mice. Mice were injected on day 0 with 250 mg of cyclophosphamide/kg, and on days 1 to 4 they were given moxifloxacin at 22.5 mg/kg/day compared to controls given ceftazidime at 75 mg/kg/day or saline. On day 6, C. albicans (10 7 CFU/mouse) was inoculated intratracheally, and animals were observed for the development of bronchopneumonia, weight loss, mortality, the presence of C. albicans, and lung cytokine production. Histopathology on day 10 postinoculation revealed bronchopneumonia in 50, 67, and 0% of saline-, ceftazidime-, and moxifloxacin-treated mice, respectively (P < 0.05). The mortality rates were 28, 17, and 5%, respectively (P < 0.05), and weight loss occurred at 20, 32, and 0%, respectively (P < 0.05). By day 15, C. albicans was eliminated from all moxifloxacin-treated mice but was still isolated from lung homogenates of 50 to 60% of the saline- and ceftazidime-treated groups. Among the cytokines tested on days 0 to 15, we found an increased production of tumor necrosis factor alpha, KC (functional interleukin-8), and gamma interferon in the lungs of ceftazidime- and saline-treated controls compared to the moxifloxacin pretreatment that abolished their secretion. In conclusion, moxifloxacin protected cyclophosphamide-injected mice from C. albicans-induced lung infection and significantly reduced pneumonia, weight loss, and mortality despite the lack of direct antifungal activity. This is most likely due to an immunomodulating activity conferred by moxifloxacin, as shown in this model and in our previous studies. Its potential protective role should be studied in patients undergoing chemotherapy and immune suppression.

Background: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration., Methods: An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections., Results: Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more., Conclusions: In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.

With the aid of gaschromatographic techniques a fatty-acid composition was studied of lipids of the expired air condensate and sweat of patients in uncomplicated/complicated course of acute myocardial infarction versus morphological changes in the blood-air barrier. The complicated course of the condition vs uncomplicated one has been found out to be accompanied by a significant increase in the lipid content of the polyunsaturated fatty acids--linoleic and arachidonic acids--in the studied biological objects, which fact can be used in diagnosis and prognostication of development of complications in the acute period of myocardial infarction.

Objective: To compare concentrations of 3-methyleneindolenine (3MEIN) in lung tissues obtained from feedlot cattle that died as a result of acute interstitial pneumonia (AIP) and cattle that died as a result of other causes and to compare blood concentrations of 3MEIN in healthy feedlot cattle and feedlot cattle with AIP., Study Population: Blood samples and lung tissues collected from 186 cattle housed in 14 feedlots in the western United States., Procedure: Samples of lung tissues were collected during routine postmortem examination and submitted for histologic, microbiologic, and toxicologic examination. Blood samples were collected from cattle with clinical manifestations of AIP and healthy penmates. Histologic diagnoses were categorized as AIP, bronchopneumonia (BP), control samples, and other disorders. Concentrations of 3MEIN were determined in lung tissues and blood samples, using an ELISA., Results: Concentrations of 3MEIN in lung tissues were significantly greater in AIP and BP samples, compared with control samples. Absorbance per microgram of protein did not differ between BP and AIP samples. Blood concentrations of 3MEIN were significantly greater in cattle with AIP, compared with healthy cattle or cattle with BP. Odds of an animal with AIP being a heifer was 3.1 times greater than the odds of that animal being a steer., Conclusions and Clinical Relevance: Increased pulmonary production of 3MEIN may be an important etiologic factor in feedlot-associated AIP.

The study was designed to identify markers of oxidative injury, related to the nitric oxide derived cascade, in bronchoalveolar lavage (BAL) fluid from intensive care patients suspected of ventilator-associated pneumonia (VAP) and/or acute respiratory distress syndrome (ARDS). Thirty-eight patients developing VAP and/or ARDS (VAP/ARDS group) were compared to 20 ventilated patients without VAP/ARDS (control group). Myeloperoxidase (MPO) and elastase, taken as markers of neutrophil activation were measured by enzymatic techniques, and nitrated proteins (NTPs) by an immunological method. The cytotoxicity of the BAL fluid was tested using cultured human epithelial alveolar cells by the release of pre-incorporated 51Cr. Mean NTP concentration and, MPO and elastase activities were different between the VAP/ARDS and control groups (p<0.05 for NTPs; p<0.005 for MPO; p<0.005 for elastase). NTP concentration correlated with MPO and elastase activity and neutrophil number (r=0.93, 0.91 and 0.87, respectively), but not to protein concentration and arterial oxygen tension/inspiratory oxygen fraction. The cytotoxicity of BAL correlated with NTP concentration (r=0.92) and MPO activity (r=0.89). It was concluded that the concentrations of nitrated proteins in bronchoalveolar lavage fluid correlated with the oxidant activity of neutrophils and that, bronchoalveolar lavage fluid cytotoxicity was correlated with the nitrated protein concentration and may be mediated by oxidants.

The mechanism responsible for the increased air-space permeability in cigarette smokers is unknown. The aim of this study was to assess the acute and chronic effects of cigarette smoking on epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. Fourteen cigarette smokers underwent 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) lung scans after abstaining from smoking for 12 h (chronic smoking) and 1 h after smoking two cigarettes (acute smoking). Each smoker also underwent bronchoscopy and bronchoalveolar lavage (BAL) after either chronic (n = 8) or acute smoking (n = 7). Seven nonsmokers also underwent bronchoscopy and BAL. The time to 50% clearance of 99mTc-DTPA (t50) after chronic smoking was 16.7 +/- 1. 3 min (mean +/- SE), and was further reduced after acute smoking to 14.8 +/- 1.0 min (p < 0.01). Neutrophil numbers were increased in bronchoalveolar lavage fluid (BALF) in the acute smoking group as compared with the nonsmokers (p < 0.05). Superoxide release from mixed BAL leukocytes was increased after chronic (p < 0.01) and acute (p < 0.001) smoking, as were thiobarbituric acid-reactive species (TBARS), providing evidence of lipid peroxidation in plasma (chronic, p < 0.05; acute, p < 0.05). Trolox equivalent antioxidant capacity (TEAC) was reduced in plasma (p < 0.001) and increased in BALF (p < 0.05) in both smoking groups. The study therefore showed an acute increase in epithelial permeability and an increase in the number of neutrophils in the air spaces of cigarette smokers concomitant with evidence of increased oxidant stress.

Polymorphonuclear leukocytes (PMN) are the predominant inflammatory cells recruited in acute lung injury. This study compares the concentration of interleukin-8 (IL-8) to those of GRO alpha, both of which are CXC chemokines, in bronchoalveolar lavage fluid (BALF) in three acute pathologic states: bacterial pneumonia (BPN); adult respiratory distress syndrome (ARDS); and Pneumocystis carinii pneumonia (PCP). Levels of both IL-8 and GRO alpha were below 5 pg/ml in 16 nonsmoking volunteers who served as controls. Despite more than twice as many neutrophils in the BALF of the BPN group (n = 12) than in the group with ARDS (n = 13), both groups had similar levels of IL-8, of 569 +/- 120 pg/ml and 507 +/- 96 pg/ml, respectively. The GRO alpha concentrations in the BPN and ARDS patients were respectively 3.3 and 3.4 times those of IL-8, reaching 1,870 +/- 314 pg/ml for the BPN and 1,699 +/- 377 for the ARDS patients. In the PCP group (n = 48, 45 human immunodeficiency virus [HIV]-positive, 3 HIV-negative), GRO alpha levels (897 +/- 172 pg/ml) were sevenfold higher than IL-8 levels (123 +/- 40 pg/ml). In all pathologic states there was a good correlation between GRO alpha and IL-8 (r = 0.53, p = 0.0001). GRO alpha or IL-8 both correlate with the absolute neutrophil number/ml when all groups were studied together (r = 0.52, p = 0.0001). Only in the PCP and ARDS groups did IL-8 correlate with the PMN number.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To analyze the measured resting energy expenditure, the clinical evolution and the nutritional therapy of two pregnant women complicated by post-traumatic coma and sepsis., Design: Clinical study., Setting: The ICU of Neurosurgery in Regional Hospital in Italy., Patients: Two subjects with head trauma due to a motor vehicle accident., Method: The resting energy expenditure was measured (M-REE) by indirect calorimetry by oxygen consumption (VO2) and carbon dioxide production (VCO2). Values were controlled in patients with a hemodynamic stability every 4 hours. Predicted REE (P-REE) was calculated according to the Harris-Benedict formula. A total parenteral nutrition (1.2-1.3 x M-REE) composed of dextrose (70-80% of total caloric amount) and fat (20-30%) was infused in both the subjects. As an average 12-15 g of nitrogen were infused daily., Results: VO2 and VCO2 increased during the study (case 1: from 225 +/- 33 to 325 +/- 35 ml/min; p < 0.02; LR: p < 0.0001; VCO2: from 170 +/- 24 to 289 +/- 23 ml/min; p < 0.0001. Case 2: VO2: from 239 +/- 22 to 315 +/- 35 ml/min; p < 0.05; LR: p < 0.01. VCO2 from 177 +/- 31 to 247 +/- 22 ml/min; p < 0.05; LR: p < 0.001). M-REE/kg increased with statistical significance during the study (case 1: from 23.6 +/- 4.1 to 34.1 +/- 4.3, p < 0.05, LR: p < 0.005; case 2: from 23.7 +/- 5.8 to 33.4 +/- 7.7, p < 0.05, LR: p < 0.05). A physiological variation in oxidative capacity on nutritional substrates was reported throughout the study., Conclusion: Sepsis and miscarriages following trauma seem to be the cause in an increase of the energy expenditure rather than pregnancy itself. However our observations must be viewed with caution because they are based on a small number of patients.

Out of a number of 2113 of COLD ambulatory cases followed-up over 20 years, 170 cases of death were registered. The causes were: heart in 54%, cancer in 42% among which 37% lung cancer, exceeding 8 times the mean figures on the whole country. These diseases: COLD, atherosclerosis inducing heart disease and lung cancer have common risk factors which unbalance respiratory homeostasis. By obstructing the airways they lead to cellular O2 deficit. In this way the cell is compelled to shift to anaerobic glycolysis in order to supply the bioenergy necessary for life, resulting in malignancy mutagenesis. On a control group of 166 cases of lung cancer a ventilatory impairment was noted in the history: obstructive syndrome in 63.8%, restrictive syndrome in 28.3%, which means chronic respiratory insufficiency.

Type II (inducible) nitric oxide synthase (NOS) may play an important role in pulmonary pathophysiology, yet it remains controversial whether human tissues are capable of expressing this protein. Therefore, a polyclonal antibody (8196) was raised against type II NOS from induced RAW 264.7 macrophages and used to investigate the expression of this enzyme in human lung tissue. Anti-type II NOS antibody did not cross-react with either neuronal (type I) or endothelial (type III) constitutive NOS, whereas a 130-kDa protein was detected in cytosol from induced macrophages or liver removed from lipopolysaccharide (25 mg/kg)-treated rats. Cells or tissues that lacked NOS activity did not express immunoreactive proteins. Similarly, in grossly normal human lung tissue, no immunoreactivity was detected with the anti-type II NOS antibody. In contrast, strong immunoreactivity was detected in alveolar macrophages present in lung tissue from a patient with bronchiectasis and acute bronchopneumonia. These data demonstrate that human alveolar macrophages are able to express type II NOS and support a role for this enzyme in pulmonary inflammatory pathophysiology.

The aim of the study was to evaluate the penetration of ciprofloxacin into bronchial secretions from mechanically ventilated patients with nosocomial bronchopneumonia. For this purpose, in each patient studied, simultaneous serial blood and bronchial secretion samples were obtained over a 12-h period on days 2 and 4. Eight patients were included in the study. Ciprofloxacin was given at a dose of 200 mg over 30 min by using an automatic pump. Ciprofloxacin was measured by high-performance liquid chromatography. Peak levels of drug in serum were 2.95 +/- 1 mg/liter on day 2 and 2.43 +/- 0.7 mg/liter on day 4. Peak and trough levels in bronchial secretions were 0.95 +/- 0.51 and 0.21 +/- 0.12 mg/liter, respectively, on day 2 and 0.76 +/- 0.17 and 0.18 +/- 0.14 mg/liter, respectively, on day 4. The ratios of peak concentrations in bronchial secretions/serum were 0.32 +/- 0.11 and 0.33 +/- 0.06 on days 2 and 4, respectively. The ratios of the area under the concentration-time curve from 0 to 12 h (AUC0-12) for bronchial secretions/those for serum were 0.66 +/- 0.40 and 0.55 +/- 0.30 on days 2 and 4, respectively. A significant positive correlation was found on day 4 between the AUC0-12 for serum and the AUC0-12 for bronchial secretions. No significant correlations were found between peak values in serum and bronchial secretions.

The excretion of gamma-glutamyltranspeptidase (GGTP) in 240 hour urine was studied in 21 patients treated with gentamicin for bronchopneumonia. The treatment was conducted for a period of 8-10 days using gentamicin in a dose of 2-5 mg/kg body weight daily. The studies of GGTP urine excretion were carried out on the first and the last day of the treatment, and on the 10th day after completion of treatment. A statistically significant increase of GGTP excretion was found during the treatment with gentamicin, as well as return of enzymuria to the initial values on the 10th day after competition of treatment. Only in three patients an increase was found of serum creatinine concentration > or = 0.5 mg% (44 mcmol/l).

During the last few years, several observations point out that oxygen-free radicals may play a pivotal role in the development of myocardial ischaemic/reperfusion injury, chronic obstructive pulmonary disease (COPD) and aging. With particular reference to acute myocardial ischaemic syndrome, these compounds may account for reperfusion-mediated ventricular arrhythmias, myocardial stunning and cell death. Such molecules may also be involved in lung damage during the course of COPD. In this regard, polymorphonuclear cell (PMN) recruitment at myocardial and/or lung level play an important role in oxygen-free radical overproduction. Several factors may, in fact, trigger PMN adhesion, respiratory burst and/or lysosomal enzyme release, this leading to a deleterious effect for the host. As far as elderly is concerned, evidence has been provided for a strict relationship between oxygen-free radical generation and metabolic rate. Nevertheless, the occurrence of PMN impaired functions and malnutrition in aged subjects gives rise to an enhanced synthesis of these compounds. All together, these findings outline the toxicity of oxygen-derived radicals and suggest the usefulness of a therapeutical approach to antagonize their effects.

The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90-140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P less than 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central fluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue-depletion models using multiple regression improved the prediction of a concentration in a given tissue.

Sixty-two patients with bronchopneumonia or bronchitis were treated with cefaclor. In 42 patients (= 68%), the therapy was clinically successful. Of the patients who did not respond to therapy, cefaclor-resistant bacteria were found in the sputum culture of seven. Of the remaining 13 patients, ten suffered a secondary infection with cefaclor-resistant bacteria, and in three patients the pathogen found before therapy persisted, although sensitive to cefaclor on testing. In seven patients therapy was clinically successful although cefaclor-resistant pathogens were present before the start of therapy. In the entire group of patients investigated no increase of SGOT, SGPT, alkaline phosphatase, bilirubin, urea or creatinine was observed. In two patients alkaline phosphatase and SGOT increased slightly; in three patients SGPT increased slightly. On the other hand, in several patients initially elevated SGOT, SGPT and alkaline phosphatase activity decreased during therapy. Clinical side-effects were seen in two patients. In one patient with known penicillin allergy a pruritic exanthema developed; in the other patient, who had dermatitis herpetiformis, exacerbation of skin efflorescences occurred.

The paper is concerned with metabolic reconstitution in a pathologically changed lung tissue in rabbits with acute and chronic bronchopulmonary inflammation. Acute bronchopulmonary inflammation is associated with a drastic increase of the adrenaline, noradrenaline, acetylcholine, histamine and serotonin content in the abnormal lung tissue. The concentration of these substances in the blood outflowing from the lungs is also increased. The intensity of changes in the content of the biologically active substances correlated with the pattern of the developing pathological process. In lingering and chronic bronchopulmonary inflammation, the changes in the content of the biologically active substances were of undulatory character which was consequent on repeated exacerbations.

Immunohistochemical localization of S-100b protein and S-100ao protein in human lymphoreticular system was studied by using monospecific antibody directed against either the alpha subunit or beta subunit of S-100 protein. S-100b protein immunoreactivity was detected in Langerhans cells, interdigitating reticulum cells, and histiocytosis X cells, but not in ordinary macrophages and blood monocytes. In contrast, S-100ao protein immunoreactivity was detected in blood monocytes, macrophages of lymph node, alveolar macrophages of lung, and small numbers of Kupffer cells of liver. S-100ao immunoreactivity was also detected in epithelioid cells, Langhans giant cells, and foreign body giant cells. The present findings suggest that the presence of S-100ao protein in the cytoplasm is one of the characteristic features of cells in the human mononuclear phagocyte system. The detection of S-100b, but not S-100ao, immunoreactivity in Langerhans cells and interdigitating reticulum cells also suggests that they are independent of the monocyte-macrophage system. S-100ao protein may be a novel cytoplasmic marker for cells of the human monocyte-macrophage system.

The phospholipid composition of 35 human lungs with pathological lesions was analysed by means of thin-layer chromatography and densitometric scanning. The pathological conditions studied were: bronchopneumonia, myocardial infarction, chronic heart failure, chronic obstructive airway disease and tuberculosis. The phospholipid composition was compared with that of a control group consisting of sudden death cases (due to unnatural causes), i.e. relatively normal lungs. The phospholipid composition of the lungs in a specific pathological group showed the same pattern. However, significant differences were observed between corresponding phospholipid fractions from lungs in the various pathological groups. Compared with the lipid fractions from relatively normal lungs, these differences were even more marked. From the results it would appear that the abnormal composition of the phospholipid fractions might possibly be a cause of lung pathology. The increase and/or decrease in individual fractions and abnormal ratios between fractions might indicate abnormalities in the biosynthesis and catabolism of the lung phospholipids. Further is necessary to elucidate the association of phospholipids with lung pathology. Phospholipid analysis of lung lavages and lung biopsies could be helpful in the diagnosis of lung diseases. Phospholipids in aerosol form could perhaps be used in treating certain lung disorders.

Josamycin is a new macrolide antibiotic with low toxicity and effective therapeutic activity in many bacterial diseases, particularly bronchopulmonary infections. In the present study the pharmacokinetics of josamycin were investigated in a group of 10 patients suffering from acute exacerbation of chronic bronchitis, with purulent or mucopurulent expectoration. Patients were given one oral administration of 1 g of josamycin every 12 hours for seven days. Serum, urinary parameters and the profile of bronchial mucus diffusion were assessed after the first and the last administration.

A detailed pharmacokinetic study of cefuroxime has been carried out. Levels of cefuroxime were determined in the blood, sputum, saliva, and urine of 23 patients receiving parenteral cefuroxime eight hourly for chest infections. Profiles were obtained after the first dose and on the final (fifth) day of treatment. Antibiotic levels in the sputum reached 0.8 mg/l within one hour of the first injection, and were maintained close to this value for six hours. There was a build-up by the fifth day, mean cefuroxime concentrations at this time reaching 1.8 mg/l. This concentration was maintained for a prolonged period. Salivary concentrations were detectable but low (maximum mean value was 0.6 mg/l). Concentrations of antibiotic were significantly higher in the serum than those observed after the same doses in volunteers. In the patients there was no build-up in serum levels between the first and fifth days. The data obtained explain the clinical efficacy of cefuroxime in the treatment of lower respiratory infections, and suggest that a 12-hour schedule may be feasible.

Cefotiam (CTM) was given to 25 mature and premature infants, ranging in age from 0 to 24 days, who have various nearly-healed bacterial infections. CTM was administered at the dose of 10 mg/kg by intravenous injections or by 1-hour intravenous drip infusions, or at the dose of 20 mg/kg by intravenous injections. Only a small number of subjects being examined, they were divided by their aged day into 3 groups; 0-3 days old, 4-7 days old and 8-24 days old. We compared the time courses of changes in serum and urine levels of CTM in these groups. The clinical study was done with 8 male and 4 female infants ranging in age from 3 days to 4 months. One had septicemia, 4 had bronchopneumonia, 3 had urinary tract infection, 1 had colitis, 2 had abscess, and 1 had maxillary sinusitis. Changes in serum and urinary levels of CTM Changes in serum levels after 10 mg/kg intravenous injection. Peak serum CTM levels of all 3 groups were achieved at 30 minutes after administration; the levels were between 11.7 and 23.6 micrograms/ml; and differences were not significant. Serum levels then gradually decreased in all the groups to 0.5-7.0 micrograms/ml at 6 hours after administration. Half-lives of serum CTM levels tended to be shorter in older infants; means were 2.7, 2.2 and 1.3 hours for the 0-3 day-old, the 4-7 day-old and the 8-24 day-old respectively. Changes in serum levels of CTM after 10 mg/kg 1-hour intravenous drip infusion. The 0-3 day-old and the 4-7 day-old had peak serum CTM levels, ranging from 16.3 to 35.8 micrograms/ml, at the end of drip infusion. Half-lives of serum CTM levels tended to be shorter in older infants, with 3.2 hours for the 0-3 day-old and 2.0 hours for the 4-7 day-old groups. Changes in serum levels after 20 mg/kg intravenous injection. The 0-3 day-old and the 4-7 day-old had peak serum levels, ranging from 30.6 to 42.1 micrograms/ml, at 30 minutes after administration, then serum levels of CTM in either group showed a gradual decrease to 2.5-11.4 micrograms/ml at 6 hours after injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Studied was the chemical composition of musculus longissimus dorsi and the liver of 16 emergency-slaughtered calves, affected with bronchopneumonia, along with 10 normal calves used as controls. Special attention was paid to the content of water, fats, ashes, total and extractive and protein nitrogen, and the amount of essential amino acids (tryptophane) and nonessential (hydroxyproline) proteins. It was demonstrated that the sampled muscle tissue of the diseased calves had higher content of water (1.81 per cent) and lower content of fats (1.68 per cent) and caloric value (16.11 Kcal) as against the values of the same indices for the analogous muscle of normal calves (P less than 0.001). No essential differences (P greater than 0.05) were found in the average values of the crude protein, the essential and nonessential proteins and their ratio in the tissues sampled from the forcedly slaughtered calves as compared to the controls.

The mechanism of pathogenesis underlying the development of corneal lesions in measles was investigated in 125 children suffering from measles and 66 age- and sex-matched healthy controls. Forty age-matched children with bronchopneumonia were investigated on similar lines to delineate the role played by vitamin A and measles individually in the development of corneal lesions. The results indicate that the pathogenesis of corneal lesions in measles is indeed multifactorial. Vitamin A deficiency alone or measles keratitis per se may not explain the mechanism completely. The immunosuppression induced by the local proliferation of the measles virus in the eye might trigger the invasion of pathogenic microbes which damage the cornea. The structural integrity of the cornea is already compromised by vitamin A deficiency and lesions of measles keratitis.

Composite histoenzymochemical characteristics of the nervous apparatus of bronchi in vagotomy, desympathetization, histamine shock, and development of pneumonia experimentally and clinically were obtained. The development of bronchospasm under the above effects and in pneumonia was found to be accompanied by decreases in the activity of acetylcholinesterase, the content of noradrenaline, a high content of nucleoproteins, polysaccharides, a high activity of oxidoreductases in different structures of the nervous apparatus of the bronchi. Bronchodilatation was accompanied by a decrease of all the above-mentioned indicators of the status of the nervous apparatus as well as destructive changes in its elements. The condition of production and utilization of the cholinergic and adrenergic mediators is discussed on the basis of the data obtained.