Streamline crossing: An essential mechanism for aerosol dispersion in the pulmonary acinus

The dispersion of inhaled microparticles in the pulmonary acinus of the lungs is often attributed to the complex interplay between convective mixing, due to irreversible flows, and intrinsic particle motion (i.e. gravity and diffusion). However, the role of each mechanism, the exact nature of such interplay between them and their relative importance still remain unclear. To gain insight into these dispersive mechanisms, we track liquid-suspended microparticles and extract their effective diffusivities inside an anatomically-inspired microfluidic acinar model. Such results are then compared to experiments and numerical simulations in a straight channel. While alveoli of the proximal acinar generations exhibit convective mixing characteristics that lead to irreversible particle trajectories, this local effect is overshadowed by a more dominant dispersion mechanism across the ductal branching network that arises from small but significant streamline crossing due to intrinsic diffusional motion in the presence of high velocity gradients. We anticipate that for true airborne particles, which exhibit much higher intrinsic motion, streamline crossing would be even more significant.     

Potentially human pathogenic Acanthamoeba isolated from a heated indoor swimming pool in Switzerland

Some free-living amoebae, including some species of the genus Acanthamoeba, can cause infections in humans and animals. These organisms are known to cause granulomatous amebic encephalitis (GAE) in predominantly immune-deficient persons. In the present study, we isolated a potentially human pathogenic Acanthamoeba isolate originating from a public heated indoor swimming pool in Switzerland. The amoebae, thermophilically preselected by culture at 37 °C, subsequently displayed a high thermotolerance, being able to grow at 42 °C, and a marked cytotoxicity, based on a co-culture system using the murine cell line L929. Intranasal infection of Rag2-immunodeficient mice resulted in the death of all animals within 24 days. Histopathology of brains and lungs revealed marked tissue necrosis and hemorrhagic lesions going along with massive proliferation of amoebae. PCR and sequence analysis, based on 18S rDNA, identified the agent as Acanthamoeba lenticulata. In summary, the present study reports on an Acanthamoeba isolate from a heated swimming pool suggestive of being potentially pathogenic to immunocompromised persons.     

Microbiological Identification and Analysis of Swine Lungs Collected from Carcasses in Swine Farms, China

The primary objective of this 3 years study was to determine the prevalence of porcine pathogens of the lungs of swine in swine farms in southern China. A total of 5,420 samples were collected from 200 swine farms. The bacterium that was most commonly isolated was Streptococcus suis, with 10.24 % of the samples being positive, 114 lungs (2.1 %) were positive for pseudorabies virus and 263 (4.85 %) were positive for classical swine fever virus; much lower than positive for PRRSV (15.1 %, p = 0.023) and PCV2 (13.8 %, p = 0.038). lungs that were positive for PRRSV and/or PCV-2 have significantly increased odds of being positive for any of the S. suis (9.79 vs. 0.44 %, p = 0.003).     

十一种无尾两栖类物种皮肤和肺显微结构

无尾两栖类动物的呼吸方式为肺呼吸和皮肤辅助呼吸,为探究两种呼吸器官的显微结构,本文采用解剖学和组织学的方法,对大蹼铃蟾(Bombina maxima)、腺角蟾(Megophrys glandulosa)、中华蟾蜍(Bufo gargarizans)、华西雨蛙(Hyla gongshanensis)、昭觉林蛙(Rana chaochiaoensis)、滇蛙(Dianrana pleuraden)、双团棘胸蛙(Gynandropaa yunnanensis)、贡山树蛙(Rhacophorus gongshanensis)、斑腿泛树蛙(Polypedates megacephalus)、饰纹姬蛙(Microhyla fissipes)、多疣狭口蛙(Kaloula verrucosa)的皮肤和肺的形态及显微结构进行观察。结果显示,背部和腹部皮下可见血管交错成网状,皮肤由表皮层和真皮层构成。除华西雨蛙外,其余10种均有分布于真皮疏松层与致密层间的钙化层;色素细胞位于疏松层上层,体背色素层较发达。肺囊状,中空密布血管,分为大小相当的左右肺叶,两肺叶相通并与心粘连,无气管和支气管。肺由肺囊壁、隔膜、毛细血管、肺泡细胞等结构组成。肺囊壁分为胸膜层、中间层和内层:胸膜层由扁平细胞构成,中间层由结缔组织构成,内层由肺细胞和毛细血管组成,隔膜由毛细血管和结缔组织构成,游离隔膜向中部靠拢可形成半封闭腔室,结合隔膜与肺囊壁形成封闭小腔室。在这11个物种中,肺较发达的个体,其皮肤结构中黏液腺的数量就会相对较少,组织形态学特征表现出与环境适应性关系较大,而受到系统发育关系影响较小。     

Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections

Sublingual route has been widely used to deliver small molecules into the bloodstream and to modulate the immune response at different sites. It has been shown to effectively induce humoral and cellular responses at systemic and mucosal sites, namely the lungs and urogenital tract. Sublingual vaccination can promote protection against infections at the lower and upper respiratory tract; it can also promote tolerance to allergens and ameliorate asthma symptoms. Modulation of lung’s immune response by sublingual immunotherapy (SLIT) is safer than direct administration of formulations by intranasal route because it does not require delivery of potentially harmful molecules directly into the airways. In contrast to intranasal delivery, side effects involving brain toxicity or facial paralysis are not promoted by SLIT. The immune mechanisms underlying SLIT remain elusive and its use for the treatment of acute lung infections has not yet been explored. Thus, development of appropriate animal models of SLIT is needed to further explore its potential advantages. This work shows how to perform sublingual administration of therapeutic agents in mice to evaluate their ability to protect against acute pneumococcal pneumonia. Technical aspects of mouse handling during sublingual inoculation, precise identification of sublingual mucosa, draining lymph nodes and isolation of tissues, bronchoalveolar lavage and lungs are illustrated. Protocols for single cell suspension preparation for FACS analysis are described in detail. Other downstream applications for the analysis of the immune response are discussed. Technical aspects of the preparation of Streptococcus pneumoniae inoculum and intranasal challenge of mice are also explained.SLIT is a simple technique that allows screening of candidate molecules to modulate lungs’ immune response. Parameters affecting the success of SLIT are related to molecular size, susceptibility to degradation and stability of highly concentrated formulations.     

Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis

Eosinophils are an important feature of immune responses to infections with many of the tissue-invasive helminth parasites. The cytokine IL-5 and a high-affinity double GATA-binding site within the GATA-1 promoter are critical for eosinophilopoiesis. In this study, we believe we demonstrate for the first time that defects in eosinophilopoiesis are associated with impaired resistance to Nippostrongylus brasiliensis. Primary and secondary infections were established in wildtype (WT), IL-5(-/-) and DeltadblGATA mice. Resistance to secondary infections was impaired in IL-5(-/-) and DeltadblGATA mice, with significantly more larvae able to reach the lungs 2 days p.i. Pulmonary inflammation was minimal in all strains in the first 2 days of both primary and secondary infections, suggesting that eosinophil-dependent resistance occurred before larvae reached this site. Intestinal worm burdens and/or parasite egg production in primary infections were greater in animals with defective eosinophilopoiesis. While larvae did reach the gut by day 3 of secondary infections of WT and IL-5(-/-) mice, worms were expelled by day 7, even in the complete absence of eosinophils in tissues of the small intestine. This and our previous studies indicate that N. brasiliensis are likely to be exquisitely sensitive to attack by eosinophils soon after entry into the skin. Eosinophils in the gut may make a modest contribution to resistance on first exposure to the parasite, but are not required for expulsion in either primary or secondary infections. In order to mount an effective immune response it may be vital for the host to identify and attack the parasite before it implements immune evasion strategies and migrates to other anatomical sites. These observations may be of particular significance for the development of successful vaccines against hookworms and other nematodes.     

Functional genomics and sexual differentiation in amphibians

To succeed on land rather than in water, crabs require a suite of physiological and morphological changes, and ultimately the ability to reproduce without access open water. Some species have modified gills to assist in gas exchange but accessory gas exchange organs, usually lungs, occur in many species. In accomplished air-breathers the lung becomes larger and more vascularised with pulmonary vessels directing oxygenated haemolymph to the heart. The relative abundance of O₂ in air promotes relative hypoventilation and thus an internal hypercapnia to drive CO₂ excretion. Land crabs have a dual circulation via either lungs or gills and shunting between the two may depend on respiratory media or exercise state. During their breeding migration on Christmas Island Gecarcoidea natalis maintained arterial Po₂ by branchial O₂ uptake, while pulmonary O₂ pressure was reduced; partly because exercise doubled relative haemolymph flow through the gills. Related species rely on elevated haemocyanin concentration and affinity for O₂ to assist uptake but this compromises unloading at the tissues and thus the aerobic scope of tissues. Aquatic crabs exchange salt and ammonia with water via the gills but in land crabs this is not possible. Birgus latro has adopted uricotelism but other species excrete ammonia in either the urine or as gas. Land crabs minimise urinary salt loss using a filtration-reabsorption system analogous to the kidney. Urine is redirected across the gills where salt reabsorption occurs in systems under hormonal control, although in G. natalis this is stimulatory and in B. latro inhibitory. While crabs occupy a range of habitats from aquatic to terrestrial, these species do not comprise a physiological continuum but across the crab taxa individual species possess appropriate and specific physiological features to survive in their individual habitat.     

Highly specific expression of luciferase gene in lungs of naïve nude mice directed by prostate-specific antigen promoter

PSA promoter has been demonstrated the utility for tissue-specific toxic gene therapy in prostate cancer models. Characterization of foreign gene overexpression in normal animals elicited by PSA promoter should help evaluate therapy safety. Here we constructed an adenovirus vector (AdPSA-Luc), containing firefly luciferase gene under the control of the 5837 bp long prostate-specific antigen promoter. A charge coupled device video camera was used to non-invasively image expression of firefly luciferase in nude mice on days 3, 7, 11 after injection of 2 x 10(9)PFU of AdPSA-Luc virus via tail vein. The result showed highly specific expression of the luciferase gene in lungs of mice from day 7. The finding indicates the potential limitations of the suicide gene therapy of prostate cancer based on selectivity of PSA promoter. By contrary, it has encouraging implications for further development of vectors via PSA promoter to enable gene therapy for pulmonary diseases.     

Content of bioelements in the lungs and liver in rats with alimentary obesity

The synchrotron radiation X-ray fluorescence technique (SRXRF) was applied to the determination of K, Ca, Mn, Fe, Cu, Zn, Se, Br, Rb, and Sr concentrations in the liver and lungs in Wistar rats. The animals in the experiment included (1) healthy rats, (2) rats with alimentary obesity (AO), and (3) rats with alimentary obesity that were being given zinc sulphate with water for a long time (АО + Zn). Each group was divided into two subgroups. The experiment with the first subgroup was terminated with the animals in the state of physiological hunger and subsequent retrieval of liver and lung tissue, while the animals of the second subgroup were sacrificed two hours after ingestion of lard. The rats in physiological hunger manifested intergroup differences in the content of the bioelements (BEs) neither in the liver nor in the lungs. The rats with AO, as compared with the healthy animals, demonstrated in physiological hunger redistribution of inter-element correlations (IECs), which is an indirect reflection of sustained metabolic disorder. Additional zinc in the rats’ ration did not affect their body weight and the concentration of the BEs (including zinc) in the liver and the lungs. However, the IECs in the tissues of these animals in physiological hunger also changed. This redistribution differed from that in the rats with AO. The IECs soon after ingestion of lard also changed, which also reflects sustained changes in the metabolism in the animals.