Mpox outbreak in Rio de Janeiro, Brazil: A translational approach.

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

Multicenter Diagnostic Evaluation of a Novel Coronavirus Antigen Lateral Flow Test among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.

The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury.

Acute lung injury (ALI) remains a major cause of mortality. In lipopolysaccharide (LPS)-stimulated macrophages, eugenol reduces cyclooxygenase-2 expression, NF-κB activation, and inflammatory mediators. We examined the anti-inflammatory and anti-oxidative action of eugenol in an in vivo model of LPS-induced lung injury. Lung mechanics and histology were analyzed in mice 24 h after LPS exposure, with and without eugenol treatment at different doses. Additional animals, submited to the same protocol, were treated with eugenol at 150 mg/kg to determine its effect on inflammatory cytokines (ELISA) and oxidative markers. LPS-induced lung functional and histological changes were significantly improved by eugenol, in a dose-dependent way. Furthermore, eugenol (150 mg/kg) was able to inhibit the release of inflammatory cytokines (TNF-α, IL-1ß and IL-6), NADPH oxidase activity, as well as antioxidant enzymes activity (superoxide dismutase, catalase and glutathione peroxidase). Finally, eugenol reduced LPS-induced protein oxidation. In conclusion, eugenol improved in vivo LPS-induced ALI through both anti-inflammatory and anti-oxidative effects, avoiding damage to lung structure.

Polymorphisms in IL-10 and INF-γ genes are associated with early atherosclerosis in coronary but not in carotid arteries: A study of 122 autopsy cases of young adults.

Atherosclerosis is a complex disease, involving both genetic and environmental factors. However, the influence of genetic variations on its early development remains unclear. This study examined the association of 12 different polymorphisms with atherosclerosis severity in anterior descending coronary (DA, n = 103) and carotid arteries (CA, n = 66) of autopsied young adults (< 30 years old). Histological sections (H-E) were classified according to the American Heart Association. Polymorphisms in ACE, TNF-α (- 308G/A and - 238 G/A), IFN-γ (+ 874 A/T), MMP-9 (- 1562 C/T), IL-10 (- 1082 A/G and - 819 C/T), NOS3 (894 G/T), ApoA1 (rs964184), ApoE (E2E3E4 isoforms), and TGF-ß (codons 25 and 10) genes were genotyped by gel electrophoresis or automatic DNA sequencing. Firearm projectile or car accident was the main cause of death, and no information about classical risk factors was available. Histological analysis showed high prevalence of type III atherosclerotic lesions in both DA (69%) and CA (39%) arteries, while severe type IV and V lesions were observed in 14% (DA) and 33% (CA). Allele frequencies and genotype distributions were determined. Among the polymorphisms studied, IFN-γ and IL-10 (- 1082 A/G) were related to atherosclerosis severity in DA artery. No association between genotypes and lesion severity was found in CA. In conclusion, we observed that the high prevalence of early atherosclerosis in young adults is associated with IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes. This association is blood vessel dependent. Our findings suggest that the vascular system presents site specialization, and specific genetic variations may provide future biomarkers for early disease identification.

P2X7 receptor modulates inflammatory and functional pulmonary changes induced by silica.

Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-ß and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1ß secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1ß secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes.

Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning.

We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15µg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.

Eugenol attenuates pulmonary damage induced by diesel exhaust particles.

Environmentally relevant doses of inhaled diesel particles elicit pulmonary inflammation and impair lung mechanics. Eugenol, a methoxyphenol component of clove oil, presents in vitro and in vivo anti-inflammatory and antioxidant properties. Our aim was to examine a possible protective role of eugenol against lung injuries induced by diesel particles. Male BALB/c mice were divided into four groups. Mice received saline (10 µl in; CTRL group) or 15 µg of diesel particles DEP (15 µg in; DIE and DEUG groups). After 1 h, mice received saline (10 µl; CTRL and DIE groups) or eugenol (164 mg/kg; EUG and DEUG group) by gavage. Twenty-four hours after gavage, pulmonary resistive (ΔP1), viscoelastic (ΔP2) and total (ΔPtot) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. We also determined the fraction areas of normal and collapsed alveoli, amounts of polymorpho- (PMN) and mononuclear cells in lung parenchyma, apoptosis, and oxidative stress. Est, ΔP2, ΔPtot, and ΔE were significantly higher in the DIE than in the other groups. DIE also showed significantly more PMN, airspace collapse, and apoptosis than the other groups. However, no beneficial effect on lipid peroxidation was observed in DEUG group. In conclusion, eugenol avoided changes in lung mechanics, pulmonary inflammation, and alveolar collapse elicited by diesel particles. It attenuated the activation signal of caspase-3 by DEP, but apoptosis evaluated by TUNEL was avoided. Finally, it could not avoid oxidative stress as indicated by malondialdehyde.

Lipopolysaccharide-induced lung injury: role of P2X7 receptor.

RATIONALE: P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages. OBJECTIVES: To determine the role of P2X7R in LPS-induced acute lung injury in mice. METHODS: Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 µg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry. RESULTS: Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-ß, MMP-2, and IL-1ß release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice. CONCLUSION: P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes.

On the crucial ventilatory setting adjustment from two- to one-lung ventilation.

Lung mechanics, histology, oxygenation and type-III procollagen (PCIII) mRNA were studied aiming to evaluate the need to readjust ventilatory pattern when going from two- to one-lung ventilation (OLV). Wistar rats were assigned to three groups: the left lung was not ventilated while the right lung received: (1) tidal volume (V(T))=5 ml/kg and positive end-expiratory pressure (PEEP)=2 cm H(2)O (V5P2), (2) V(T)=10 ml/kg and PEEP=2 cm H(2)O (V10P2), and (3) V(T)=5 ml/kg and PEEP=5 cm H(2)O (V5P5). At 1-h ventilation, V5P2 showed hypoxemia, alveolar collapse and impaired lung function. Higher PEEP minimized these changes and prevented hypoxemia. Although high V(T) prevented hypoxemia and maintained a higher specific compliance than V5P2, a morphologically inhomogeneous parenchyma and higher PCIII expression resulted. In conclusion, the association of low V(T) and an adequate PEEP level could be useful to maintain arterial oxygenation without inducing a possible inflammatory/remodeling response.

LASSBio 596 per os avoids pulmonary and hepatic inflammation induced by microcystin-LR.

Cyanobacterial blooms that generate microcystins (MCYSTs) are increasingly recognized as an important health problem in aquatic ecosystems. We have previously reported the impairment of pulmonary structure and function by microcystin-LR (MCYST-LR) exposure as well as the pulmonary improvement by intraperitoneally injected (i.p.) LASSBio 596. In the present study, we aimed to evaluate the usefulness of LASSBio 596 per os on the treatment of pulmonary and hepatic injuries induced by MCYST-LR. Swiss mice received an intraperitoneal injection of 40 µl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 µg/kg). After 6 h the animals received either saline (TOX and CTRL groups) or LASSBio 596 (50 mg/kg, LASS group) by gavage. Eight hours after the first instillation, lung impedance (static elastance, elastic component of viscoelasticity and resistive, viscoelastic and total pressures) was determined by the end-inflation occlusion method. Left lung and liver were prepared for histology. In lung and hepatic homogenates MCYST-LR, TNF-α, IL-1ß and IL-6 were determined by ELISA. LASSBio 596 per os (LASS mice) kept all lung mechanical parameters, polymorphonuclear (PMN) cells, pro-inflammatory mediators, and alveolar collapse similar to control mice (CTRL), whereas in TOX these findings were higher than CTRL. Likewise, liver structural deterioration (hepatocytes inflammation, necrosis and steatosis) and inflammatory process (high levels of pro-inflammatory mediators) were less evident in the LASS than TOX group. LASS and CTRL did not differ in any parameters studied. In conclusion, orally administered LASSBio 596 prevented lung and hepatic inflammation and completely blocked pulmonary functional and morphological changes induced by MCYST-LR.

Dynamic nonlinearity of lung tissue: frequency dependence and harmonic distortion.

Harmonic distortion (HD) is a simple approach to analyze lung tissue nonlinear phenomena. This study aimed to characterize frequency-dependent behavior of HD at several amplitudes in lung tissue strips from healthy rats and its influence on the parameters of linear analysis. Lung strips (n = 17) were subjected to sinusoidal deformation at three different strain amplitudes (Δε) and fixed operational stress (12 hPa) among various frequencies, between 0.03 and 3 Hz. Input HD was <2% in all cases. The main findings in our study can be summarized as follows: 1) harmonic distortion of stress (HD) showed a positive frequency and amplitude dependence following a power law with frequency; 2) HD correlated significantly with the frequency response of dynamic elastance, seeming to converge to a limited range at an extrapolated point where HD=0; 3) the relationship between tissue damping (G) and HD(ω=1) (the harmonic distortion at ω=1 rad/s) was linear and accounted for a large part of the interindividual variability of G; 4) hysteresivity depended linearly on κ (the power law exponent of HD with ω); and 5) the error of the constant phase model could be corrected by taking into account the frequency dependence of harmonic distortion. We concluded that tissue elasticity and tissue damping are coupled at the level of the stress-bearing element and to the mechanisms underlying dynamic nonlinearity of lung tissue.

Dynamic nonlinearity of lung tissue: effects of strain amplitude and stress level.

Lung tissue presents substantial nonlinear phenomena not accounted for by linear models; however, nonlinear approaches are less available. Our aim was to characterize the behavior of total harmonic distortion, an index of nonlinearity, in lung tissue strips under sinusoidal deformation at a single frequency as a function of strain amplitude and operational stress. To that end, lung parenchymal strips from healthy rats (n = 6) were subjected to sinusoidal deformation (1 Hz) at different strain amplitudes (Δε = 4, 8, 12, 16, and 20%) and operating stresses (σ(op) = 6, 8, 10, 12, 14, and 16 hPa). Additional rats (n = 9) were intratracheally instilled with saline or bleomycin (2.5 U/kg, 3 times 1 wk apart), killed 28 days after the last instillation, and their lung tissue strips were studied at 5 and 10 hPa σ(op) and 5% Δε. In both cases, harmonic distortion (HD%) of input (strain) and output (stress) signals were determined. In healthy strips, HD% increased linearly with Δε, stress amplitude, and minimum stress by cycle variations, but showed no significant change with σ(op) levels. A prediction model could be determined as a function of operational stress and stress amplitude. Harmonic distortion was significantly increased in bleomycin-treated strips compared with controls and showed positive correlation with E behavior in both normal and diseased strips. We concluded that HD% can be useful as a single and simple parameter of lung tissue nonlinearity.

Can LASSBio 596 and dexamethasone treat acute lung and liver inflammation induced by microcystin-LR?

The treatment of microcystin-LR (MCYST-LR)-induced lung inflammation has never been reported. Hence, LASSBio 596, an anti-inflammatory drug candidate, designed as symbiotic agent that modulates TNF-alpha levels and inhibits phosphodiesterase types 4 and 5, or dexamethasone were tested in this condition. Swiss mice were intraperitoneally (i.p.) injected with 60 microl of saline (CTRL) or a sub-lethal dose of MCYST-LR (40 micrg/kg). 6 h later they were treated (i.p.) with saline (TOX), LASSBio 596 (10 mg/kg, L596), or dexamethasone (1 mg/kg, 0.1 mL, DEXA). 8 h after MCYST-LR injection, pulmonary mechanics were determined, and lungs and livers prepared for histopathology, biochemical analysis and quantification of MCYST-LR. TOX showed significantly higher lung impedance than CTRL and L596, which were similar. DEXA could only partially block the mechanical alterations. In both TOX and DEXA alveolar collapse and inflammatory cell influx were higher than in CTRL and L596, being LASSBio 596 more effective than dexamethasone. TOX showed oxidative stress that was not present in CTRL and L596, while DEXA was partially efficient. MCYST-LR was detected in the livers of all mice receiving MCYST-LR and no recovery was apparent. In conclusion, LASSBio 596 was more efficient than dexamethasone in reducing the pulmonary functional impairment induced by MCYST-LR.

In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury.

Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-kappaB (NF-kappaB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 microg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (DeltaP1) and viscoelastic (DeltaP2) pressures, static elastance (E(st)), and viscoelastic component of elastance (DeltaE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-alpha was determined by ELISA. Lung tissue expression of NF-kappaB was determined by EMSA. DeltaP1, DeltaP2, E(st), and DeltaE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-alpha levels and NF-kappaB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.

Lung parenchymal mechanics in health and disease.

The mechanical properties of lung tissue are important determinants of lung physiological functions. The connective tissue is composed mainly of cells and extracellular matrix, where collagen and elastic fibers are the main determinants of lung tissue mechanical properties. These fibers have essentially different elastic properties, form a continuous network along the lungs, and are responsible for passive expiration. In the last decade, many studies analyzed the relationship between tissue composition, microstructure, and macrophysiology, showing that the lung physiological behavior reflects both the mechanical properties of tissue individual components and its complex structural organization. Different lung pathologies such as acute respiratory distress syndrome, fibrosis, inflammation, and emphysema can affect the extracellular matrix. This review focuses on the mechanical properties of lung tissue and how the stress-bearing elements of lung parenchyma can influence its behavior.

Effects of amiodarone on lung tissue mechanics and parenchyma remodeling.

We studied the results of chronic oral administration of amiodarone on in vitro lung tissue mechanics, light and electron microscopy. Fifteen Wistar male rats were divided into three groups. In control (CTRL) group animals received saline (0.5 mL/day). In amiodarone (AMIO) groups, amiodarone was administered by gavage at a dose of 175 mg/kg 5 days per week for 6 (6AMIO) or 12 weeks (12AMIO). Lung tissue strips were analyzed 24h after the last drug administration. Tissue resistance and elastance were higher in 6AMIO and 12AMIO than in CTRL, while hysteresivity was similar in all groups. Total amount of collagen fibers in lung parenchyma increased progressively with the time course of the lesion. However, at 6 weeks there was an increase in the amount of type III collagen fibers, while in 12AMIO mainly type I collagen fibers were found. In our study amiodarone increased lung tissue impedance that was accompanied by matrix remodeling and lesion of type II pneumocytes.

Effects of dexmedetomidine on respiratory mechanics and control of breathing in normal rats.

Dexmedetomidine is a highly selective and specific alpha(2)-adrenergic agonist, with sedative, analgesic, and sympatholytic activities. The aim of the present study was to define the effects of DMED in respiratory mechanics in normal rats. In addition, lung morphometry was studied to determine whether the physiological changes reflected underlying morphological changes defining the sites of action of dexmedetomidine. Arterial blood gases were also determined. Twelve adult Wistar rats were randomly assigned to two groups of six animals each: PENTO and DMED. In PENTO group animals were sedated (diazepam, 5mg, i.p.) and anaesthetised with pentobarbital sodium (20mgkg(-1) i.p.). The rats of the DMED group received dexmedetomidine (250mugkg(-1) i.p. followed by intravenous infusion of 0.5mugkg(-1)h(-1)). In spontaneously breathing rats, minute ventilation, respiratory frequency, and neuromuscular inspiratory drive were lower in dexmedetomidine group, which also presented hypercapnia, whereas tidal volume, inspiratory, expiratory, and total respiratory cycle times were higher in dexmedetomidine group compared to the PENTO group. During mechanical ventilation, respiratory mechanical parameters were similar in both groups. These findings were supported by the absence of histological changes. In conclusion, under the conditions studied, dexmedetomidine did not change respiratory mechanical parameters and lung histology, but induced ventilatory depression.

Respiratory changes in a murine model of spontaneous systemic lupus erythematosus.

The pathophysiology of systemic lupus erythematosus (SLE) has been very well described in many organs. However, the relation between extracellular matrix changes and lung dynamic mechanical behaviour deserves elucidation. To that end, pulmonary mechanics, lung morphometry and the amount of collagen and elastic fibres in the alveolar septa were analysed in mice with SLE [NZB/W (New Zealand Black/White) F1] and non-diseased NZW mice (control). Static (E(st)) and dynamic (E(dyn)) elastances, difference between dynamic and static elastances (DeltaE), airway resistance (R(aw)) and viscoelastic/inhomogeneous pressure (DeltaP(2)) were determined by the end-inflation occlusion method. Lungs were removed and prepared for histology. E(st), E(dyn), DeltaE and DeltaP(2) were higher in SLE than in control group, while R(aw) was similar in both groups. SLE group showed alveolar collapse and increased amount of elastic and collagen fibres. In conclusion, SLE mice showed an increase in elastic and viscoelastic/inhomogeneous pressures that was accompanied by deposition of collagen and elastic fibres in the alveolar septa.

Mouse strain dependence of lung tissue mechanics: role of specific extracellular matrix composition.

This study analyses the differences between C57BL/10 and BALB/c mice in lung tissue micromechanical behaviour and whether specific histological characteristics are related to the mechanical profile. C57BL/10 and BALB/c subpleural lung strips were submitted to multisinusoidal deformation with frequencies ranging between 0.2 and 3.1 Hz. Tissue resistance (R), elastance (E), and hysteresivity (eta) at each frequency were determined before and 30s, 1, 2, and 3 min after acetylcholine (ACh) treatment. BALB/c mice showed higher E and R, at baseline, as well as greater amount of collagen and elastic fibres, and alpha-actin than C57BL/10 mice. However, E, R, and eta augmented with the same magnitude after ACh treatment in both strains. Baseline R was correlated with collagen fibre content and with the volume proportion of alpha-actin, while E was correlated with elastic and collagen fibres, and alpha-actin contents. In conclusion, BALB/c and C57BL/10 mice present distinct tissue mechanical properties that are accompanied by specific extracellular matrix composition and contractile structures.

Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury.

The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 microg it and 125 microg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8. ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling.