The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma.

BACKGROUND: Under the National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung carcinoma (NSCLC), anaplastic lymphoma kinase (ALK) gene rearrangement is required to be assessed. However, data showing the prevalence of the ALK rearrangement is still deficient and is not yet available in Indonesia. This study used direct smear preparation from transthoracic needle specimens that are minimally invasive. The main objective of the study is to identify the prevalence of the ALK fusion rearrangement gene in cytological specimens. MATERIALS AND METHODS: A total of 35 direct smear preparations diagnosed as lung adenocarcinoma and EGFR mutation negative were involved in this study. The samples were taken between 2017 and 2019. These samples were examined for EML4-ALK fusion rearrangement gene using qRT-PCR. The EML4-ALK rearrangement status was determined by qRT-PCR with high-resolution melting (HRM) analysis. RESULTS: A total of 28 (80%) samples were from males, and 7 samples were from females. Seven (20% 95% CI: 8.4%-36.9%) samples were EML4-ALK rearrangement positive. The average age of the patients was 63.5 years old. The most common sites of metastasis in this study were pleural cavity, bone, liver, and CNS. CONCLUSIONS: qRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.

Evaluation of antioxidant and anti-lipid peroxidation potentials of Nigella sativa and onion extract on nicotine-induced lung damage.

BACKGROUND: The present work aimed to compare the protective effect of Nigella sativa (NS) and onion extract on the nicotine-induced lung damage in rats. The antioxidant and anti-lipid peroxidation potentials of both agents on nicotine-induced lung damage were studied. MATERIALS AND METHODS: Thirty-six Sprague-Dawley albino rats, treated for 18 weeks, were divided into six groups: one negative control group, two positive control groups (oral onion and oral NS), nicotine-treated group, onion extract-treated group (concomitant nicotine and onion extract) and NS-treated group (concomitant nicotine and NS oil). The assessment of lung structure was based on haematoxylin and eosin and transmission electron microscopy. Lung malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase (CAT), lung glutathione (GSH), and epithelial lining fluid GSH (ELF GSH) were used for assessment of the antioxidant and anti-lipid peroxidation potentials of NS and onion extract. RESULTS: The lung of the nicotine-treated group exhibited emphysematous air spaces, collapsed corrugated alveoli with ruptured interalveolar septa in some specimen and thickened septa in the others, massive congestion, extravasation of red blood cells, inflammatory cellular infiltration and fluid exudate. Much improvement was observed in the onion-treated group despite the presence of residual pathological affection. The lung in the NS-treated group showed the nearly normal architecture with slight congestion. Administration of nicotine promoted lipid peroxidation (elevation of MDA) and decreased the level of the antioxidant markers (SOD, CAT, lung GSH and ELF GSH). With the use of onion extract and NS, the level of MDA decreased by 17.85% and 35.71% while the levels of SOD, CAT, GSH, and ELF GSH increased. The increase was more prominent in the NS-treated group. The levels in the NS-treated group reached nearly the level markers of the control group. CONCLUSIONS: Nigella sativa and onion extract attenuate the pathological effect of nicotine in the lung rats through antioxidative and anti-lipid peroxidative mechanisms with higher protection to NS.

Phyllanthin and hypophyllanthin from Phyllanthus amarus ameliorates immune-inflammatory response in ovalbumin-induced asthma: role of IgE, Nrf2, iNOs, TNF-α, and IL's.

Background: Asthma is a chronic airway immunoinflammatory disorder characterized by airway remodeling. Phyllanthus amarus has been reported to possess antioxidant and anti-inflammatory potential. Aim: To evaluate the possible mechanism of action of isolated phytoconstituents from P. amarus (PA) against ovalbumin (OVA)-induced experimental airway hyperresponsiveness (AHR). Material and method: Phyllanthin and hypophyllanthin were isolated and characterized (HPLC) from the methanolic extract of PA. AHR was induced in Sprague-Dawley rats by OVA-challenged, and animals were treated with PA (50, 100, and 200 mg/kg, p.o.) for 28 days. Results: The HPLC analysis showed the presence of phyllanthin and hypophyllanthin in methanolic extract of PA at RT of 25.243 and 26.832 min, respectively. OVA-induced alterations in hemodynamic parameters, lung functions test, peripheral blood oxygen level, total, and differential cell count in Bronchoalveolar Lavage Fluid was significantly attenuated (p < .05) by PA (100 and 200 mg/kg). It also significantly decreased (p < .05) the levels of total protein and albumin in serum, BALF, and lungs. OVA-induced increase in IgE (total and OVA-specific), and oxido-nitrosative stress (SOD, GSH, MDA, and NO) levels were significantly (p < .05) decreased by PA. RT-PCR analysis revealed that elevated oxido-nitrosative stress (Nrf2 and iNOs), immune-inflammatory makers (HO-1, TNF-α, IL-1ß, and TGF-ß1), Th2 cytokines (IL-4 and IL-6) levels were significantly attenuated (p < .05) by PA. PA also attenuated histological and ultrastructural aberrations induced by OVA. Conclusion: Results of the present investigation demonstrated that the presence of phyllanthin and hypophyllanthin in P. amarus alleviated Th2 response in OVA-induced AHR via modulation of endogenous markers in a murine model of asthma. Thus, phyllanthin and hypophyllanthin may be a new therapeutic approach for the management of asthma.

Curcumin ameliorated ventilator-induced lung injury in rats.

BACKGROUND: Curcumin (CUR) is a Chinese medicine monomer with antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects and mechanisms of CUR treatment on ventilator-induced lung injury (VILI) in rats. METHODS: Total 50 SD rats were divided into five groups: sham, VILI, VILI+CUR-50 (CUR 50?mg/kg pretreated intraperitoneal), VILI+CUR-200 (CUR 200?mg/kg pretreated intraperitoneal) and VILI?+?DXM (5?mg/kg pretreated intraperitoneal). The morphology and ultrastructure were observed by microscope and transmission electron microscope. The wet to dry ratio, protein concentration in bronchoalveolar lavage fluid (BALF), evans blue dye (EBD) content, nuclear factor kappa B (NF-?B) activity, myeloperoxidase (MPO), malondialdehyde (MDA), xanthine oxidase (XO) and total antioxidative capacity (TAOC) levels were measured. RESULTS: Histological studies revealed that inflammatory cells infiltration and alveolar edema were significantly severe in VILI as compared to other groups. CUR-200 and DXM treatment reversed lung injury significantly. The wet to dry ratio, protein concentration in BALF, EBD content, MPO activity, tumor necrosis factor (TNF)-? level and NF-?B activity were significantly increased in VILI group as compared to other groups. CUR-200 and DXM treatment significantly suppressed permeability and inflammation induced by ventilation. Furthermore, the significantly higher MDA content in VILI could be markedly decreased by CUR-200 and DXM treatment while the levels of XO and TAOC were markedly recovered only by CUR (200?mg/kg) treatment after VILI. CONCLUSION: CUR could inhibit the inflammatory response and oxidative stress during VILI, which is partly through NF-?B pathway.

Effect of Qingfei Mixture () on pediatric mycoplasma pneumoniae pneumonia with phlegm heat obstructing Fei (Lung) syndrome.

OBJECTIVE: To explore the effect and mechanism of Qingfei Mixture (), a Chinese medicine, in treating mycoplasma pneumonia (MP) in MP patients and rat model METHODS: A total of 46 MP children with phlegm heat obstructing Fei (Lung) syndrome were randomly assigned to two groups by the method of random number table, with 23 children in each group. The control group was treated with intravenous infusion of azithromycin; the treatment group received intravenous infusion of azithromycin and oral administration of Qingfei Mixture. The treatment course was 7 days. Major symptoms and minor symptoms were observed and scored before and after treatments. A rat model of MP was also established. A total of 120 wistar rats were randomly divided into 5 groups: a normal group, infection group, Qingfei Mixture treatment group, azithromycin treatment group, and Qingfei Mixture + azithromycin treatment group. Each group contained 24 rats, from which every 6 were euthanatized 1, 3, 7 and 14 days after infection. MP DNA in pulmonary tissue homogenates was detected using real-time fluorescence quantitative polymerase chain reaction. Pathology was assessed after hematoxylin (HE) staining and lung tissue pathology scores were determined in pulmonary tissue. Transmission electron microscopic detection and electronic image analysis were performed on lung tissue 3 days after infection. Interleukin (IL)-17 was detected in serum using enzymelinked immunosorbent assay (ELISA) 7 days after infection. RESULTS: In the clinical study, both control and the treatment group showed improved results on removing symptoms of phlegm heat syndrome compared to the control group (P<0.05). In animal experiments, On the 7th day after MP infection, as detected by electron microscopy, the pulmonary capillary basement membranes of the azithromycin + Qingfei Mixture treatment group were much thinner than those of the azithromycin or Qingfei mixture treatment groups (P<0.05). The level of serum IL-17 in the azithromycin + Qingfei Mixture treatment group was lower than that in the azithromycin or Qingfei Mixture groups (P<0.01). CONCLUSION: Both Qingfei Mixture and azithromycin have therapeutic effects on mycoplasma pneumoniae pneumonia, but the combination of both agents had the greatest effect.

Chemical composition of Ocimum sanctum by LC-ESI-MS/MS analysis and its protective effects against smoke induced lung and neuronal tissue damage in rats.

Smoke induced oxidative stress is known to cause various cancers and associated health problems including lung cancer. Herbal extracts have been reported as antioxidant supplements which attenuate free radical induced oxidative damage of tissues, among which Ocimum sanctum has been reported as the elixir of life due to its innumerable health benefits. In the present study, we investigated the protective effect of O. sanctum against cracker smoke induced lung and brain tissue damage. The results of the study demonstrate that O. sanctum regulates the hematological and serum biochemical parameters such as RBC, WBC, blood urea nitrogen and creatinine kinase. O. sanctum supplementation inhibited oxidative stress as analyzed by SOD, CAT enzyme levels and i-NOS, HSP-70 protein expression. O. sanctum administration also regulated neurotransmitter levels, such as serotonin, dopamine, and regulated acetylcholine esterase levels which play a vital role in neuronal function. Further O. sanctum treatment also preserved the morphology of lung and brain tissues of smoke stress induced rats as observed by histopathology and transmission electron microscope analysis. The biodistribution of O. sanctum was showed its accumulation in key tissues such as kidney, liver, lungs and heart. The LC-ESI-MS/MS analysis of O. sanctum showed the presence of polyphenols, flavonoids and fatty acids which might be responsible for the observed anti-stress effects.

Efficacy of parthenolide on lung histopathology in a murine model of asthma

BACKGROUND: Parthenolide is the active constituent of the plant 'Tanacetum parthenium' (Feverfew) which has been used for centuries as a folk remedy for inflammatory conditions. Aim of the study: In this study we aimed to investigate the effects of parthenolide in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups; I (control), II (placebo), III (dexamethasone), IV (parthenolide) and V (dexamethasone and parthenolide combination). Lung histology was evaluated after treatment with the study drugs. Levels of interleukin (IL)-4 and IL-5 were determined by ELISA. RESULTS: Histologic parameters except the number of mast and goblet cells improved in the parthenolide group when compared with placebo. All parameters except basal membrane thickness and number of mast cells were improved significantly better in the group receiving dexamethasone when compared with the parthenolide group. Improvement of most of the histologic parameters was similar in Groups III and V. Interleukin-4 levels were significantly reduced in the parthenolide group when compared to the placebo group. CONCLUSION: We demonstrated that parthenolide administration alleviated some of the pathological changes in asthma. But parthenolide alone is not efficient as dexamethasone therapy and the parthenolide and dexamethasone combination also did not add any beneficial effect to the dexamethasone treatment

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Polyacrylate/nanosilica causes pleural and pericardial effusion, and pulmonary fibrosis and granuloma in rats similar to those observed in exposed workers.

Nanomaterials offer great benefit as well as potential damage to humans. Workers exposed to polyacrylate coatings have pleural effusion, pericardial effusion, and pulmonary fibrosis and granuloma, which are thought to be related to the high exposure to nanomaterials in the coatings. The study aimed to determine whether polyacrylate/silica nanoparticles cause similar toxicity in rats, as observed in exposed workers. Ninety male Wistar rats were randomly divided into five groups with 18 rats in each group. The groups included the saline control group, another control group of polyacrylate only, and low-, intermediate-, and high-dose groups of polyacrylate/nanosilica with concentrations of 3.125, 6.25, and 12.5 mg/kg. Seventy-five rats for the 1-week study were terminated for scheduled necropsy at 24 hours, 3 days, and 7 days postintratracheal instillation. The remaining 15 rats (three males/group) had repeated ultrasound and chest computed tomography examinations in a 2-week study to observe the pleural and pericardial effusion and pulmonary toxicity. We found that polyacrylate/nanosilica resulted in pleural and pericardial effusions, where nanosilica was isolated and detected. Effusion occurred on day 3 and day 5 post-administration of nanocomposites in the 6.25 and 12.5 mg/kg groups, it gradually rose to a maximum on days 7-10 and then slowly decreased and disappeared on day 14. With an increase in polyacrylate/nanosilica concentrations, pleural effusion increased, as shown by ultrasonographic qualitative observations. Pulmonary fibrosis and granuloma were also observed in the high-dose polyacrylate/nanosilica group. Our study shows that polyacrylate/nanosilica results in specific toxicity presenting as pleural and pericardial effusion, as well as pulmonary fibrosis and granuloma, which are almost identical to results in reported patients. These results indicate the urgent need and importance of nanosafety and awareness of toxicity of polyacrylate/nanosilica.

Biodistribution and toxicity of spherical aluminum oxide nanoparticles.

With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs.

The effect of electroacupuncture at ST36 on severe thermal injury-induced remote acute lung injury in rats.

OBJECTIVE: Acupuncture at ST36 can produce anti-inflammatory effects, which might be associated with vagus nerve activity. This study explored the effects of electroacupuncture (EA) at ST36 on severe thermal injury-induced remote acute lung injury in rats. INTERVENTIONS: Forty male Sprague-Dawley (SD) rats were randomly divided into five groups: (1) the sham (S) group, (2) the thermal injury (TEM) group subjected to 30% total body surface area (30% TBSA) third-degree scald, (3) the EA at ST36 group subjected to EA stimulation at ST36 (3V, 2ms, and 3Hz) after 30% TBSA scald, (4) the EA at non-acupoint group subjected to EA stimulation at non-acupoint after 30% TBSA scald, and (5) the α-bungarotoxin (α7 nicotinic acetylcholine receptor subunit antagonist) group administered 1.0 µg kg(-1) α-bungarotoxin before EA at ST36. MEASUREMENTS AND MAIN RESULTS: Thermal injury of 30% TBSA induced leukocytosis in the alveolar space, interstitial edema, and the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, and high-mobility group box 1 (HMGB-1); the expression of both HMGB-1 messenger RNA (mRNA) and protein in lung tissue was significantly enhanced. EA at ST36 significantly downregulated the levels of inflammatory cytokines and improved lung tissue injury. However, pretreatment with α-bungarotoxin reversed the effects of electrical stimulation of ST36. CONCLUSIONS: EA at ST36 might have a potential protective effect on severe thermal injury-induced remote acute lung injury via limitation of inflammatory responses in rats.

Hyperbaric oxygen treatment reduced the lung injury of type II decompression sickness.

OBJECTIVE: To detect the ultrastructural changes in rabbits with type II decompression sickness (DCS), and study the therapeutic effects of hyperbaric oxygen (HBO). METHODS: Twenty-seven male New Zealand rabbits were randomly divided equally into the DCS group, HBO treatment group and control group. Experimental models of each group were prepared. Lung apex tissues were harvested to prepare paraffin- and EPON812-embedded tissues. RESULTS: In the DCS group, macroscopic and histological examination revealed severe and rapid damage to lung tissue. Ultrastructural examination revealed exudation of red blood cells in the alveolar space. Type I alveolar epithelial cells exhibited retracted cell processes and swollen mitochondria, and type II cells showed highly swollen mitochondria and decrease in cytoplasmic lamellar bodies. Dilatation and congestion of capillary vessels were accompanied by swelling of endothelial cells and incomplete basement membrane. In the HBO treatment group, the findings were somewhat similar to those in the DCS group, but the extent of damage was lesser. Only a small amount of tiny bubbles could be seen in the blood vessels. Type I alveolar epithelia cells and endothelial cells of the capillaries illustrated slight shortening of cells, swollen cytoplasm and decreased cell processes. Type II alveolar epithelial cells showed slight swelling of the mitochondria, decreased vacuolar degeneration of lamellar bodies, and increase in the number of free ribosomes. CONCLUSIONS: Our microscopic and ultrastructural findings confirm that the lung is an important organ affected by DCS. We also confirmed that HBO can alleviate DCS-induced pulmonary damage.

[The interventional effect of Xuebijing injection on expression of mitochondrial fusion protein 2 and the ultrastructure changes in lung tissues in rats with paraquat poisoning].

OBJECTIVE: To investigate the mechanism of pulmonary fibrosis induced by paraquat (PQ), and the effect of Xuebijing injection in treatment of PQ poisoning. METHODS: Seventy-two male Wistar rats were randomly divided into control group, PQ poisoning group, and Xuebijing intervention group, with 24 rats in each group. Pulmonary fibrosis was induced by single gavage at the dosage of 50 mg/kg of PQ, while 1 mL of distilled water was given by gavage in control group. Xuebijing injection at the dosage of 4 mL/kg were given intraperitoneally at 30 minutes after exposure to PQ in Xuebijing group, and it was repeated every 12 hours; same amount of physiological saline was given intraperitoneally in PQ group and control group. The experiment lasted for 14 days. Six rats in each group were sacrificed on 1, 3, 7, 14 days, respectively, after insult, and 30 minutes after the last intervention. The lung tissues were harvested, the changes in pathology in lung tissue and the degree of pulmonary fibrosis were observed with optical microscope with hematoxylin-eosin (HE) staining and Masson stain. The ultrastructure changes in lung tissues were observed with transmission electron microscopic, and the content of hydroxyproline (HYP) in the lung tissue was determined by alkaline hydrolysis. The expression of mitochondrial fusion protein 2 (Mfn2) was determined by Western Blot. RESULTS: (1) HE staining: in PQ group, inflammation was most marked on the 3rd day. On the 7th day, exudates in the alveoli started to be organized, and hypertrophic fibroblasts were seen to secrete slim collagen fibers, and fibrosis could be seen in alveoli. On the 14th day, intensive hyperplasia of fibroblasts could be observed, and the alveolar structure was destroyed and collapsed, with deposition of collagen deposited with formation of pulmonary fibrosis. At the same time, pathologic changes were milder in Xuebijing group than those in PQ group. (2) Masson staining: the degree of inflammation in alveoli and pulmonary fibrosis were less marked in Xuebijing group than those of PQ group on the 14th day. (3) Under the transmission electron microscopy, it was found that the mitochondria of lung tissue cells was relatively less in number on the 14th day in PQ group, and the majority of them underwent degeneration, swelling and damage. Basement membrane became folded, alveoli were collapsed, and fibrosis was obvious. These changes were less serious in Xuebijing group. (4) Content of HYP: contents of HYP in lung tissues on the 3rd day in PQ group and Xuebijing group were significantly higher than those in control group (743.3±50.2 µg/g, 718.1±34.0 µg/g vs. 665.8±6.6 µg/g, both P<0.05), it then increased gradually, but the contents of HYP in Xuebijing group were significantly lower on the 7th day and 14th day than those in PQ group (790.5±23.8 µg/g vs. 876.7±42.0 µg/g, 812.9±72.3 µg/g vs. 931.3±33.0 µg/g, both P<0.05). (5) Expression of Mfn2: the expression of Mfn2 in control group was relatively lower. The expression of Mfn2 in PQ group was increased gradually under stress, but its rate was low. The expression of Mfn2 (A value) in Xuebijing group was significantly higher than that in PQ group on the 1st day (0.731±0.035 vs. 0.618±0.029, P<0.05), and it was elevated steadily, reaching the peak on the 7th day (0.732±0.037 vs. 0.669±0.034, P<0.05), but it was lower than that of PQ group on the 14th day (0.708±0.034 vs. 0.765±0.041, P<0.05). CONCLUSIONS: Xuebijing reduces lung inflammatory reaction and pulmonary fibrosis as a result of PQ poisoning. The mechanism is that Xuebijing regulates and increases expression of Mfn2 in lung tissue.

Cumulative Retrospective Exposure Assessment (REA) as a predictor of amphibole asbestos lung burden: validation procedures and results for industrial hygiene and pathology estimates.

CONTEXT: A detailed evaluation of the correlation and linearity of industrial hygiene retrospective exposure assessment (REA) for cumulative asbestos exposure with asbestos lung burden analysis (LBA) has not been previously performed, but both methods are utilized for case-control and cohort studies and other applications such as setting occupational exposure limits. OBJECTIVE: (a) To correlate REA with asbestos LBA for a large number of cases from varied industries and exposure scenarios; (b) to evaluate the linearity, precision, and applicability of both industrial hygiene exposure reconstruction and LBA; and (c) to demonstrate validation methods for REA. METHODS: A panel of four experienced industrial hygiene raters independently estimated the cumulative asbestos exposure for 363 cases with limited exposure details in which asbestos LBA had been independently determined. LBA for asbestos bodies was performed by a pathologist by both light microscopy and scanning electron microscopy (SEM) and free asbestos fibers by SEM. Precision, reliability, correlation and linearity were evaluated via intraclass correlation, regression analysis and analysis of covariance. Plaintiff's answers to interrogatories, work history sheets, work summaries or plaintiff's discovery depositions that were obtained in court cases involving asbestos were utilized by the pathologist to provide a summarized brief asbestos exposure and work history for each of the 363 cases. RESULTS: Linear relationships between REA and LBA were found when adjustment was made for asbestos fiber-type exposure differences. Significant correlation between REA and LBA was found with amphibole asbestos lung burden and mixed fiber-types, but not with chrysotile. The intraclass correlation coefficients (ICC) for the precision of the industrial hygiene rater cumulative asbestos exposure estimates and the precision of repeated laboratory analysis were found to be in the excellent range. The ICC estimates were performed independent of specific asbestos fiber-type. CONCLUSIONS: Both REA and pathology assessment are reliable and complementary predictive methods to characterize asbestos exposures. Correlation analysis between the two methods effectively validates both REA methodology and LBA procedures within the determined precision, particularly for cumulative amphibole asbestos exposures since chrysotile fibers, for the most part, are not retained in the lung for an extended period of time.

Pulmonary fibrotic response to inhalation of ZnO nanoparticles and toluene co-exposure through directed flow nose only exposure chamber.

The increasing use of Zinc Oxide nanoparticles (ZnONPs) in paint industry is not supplemented with adequate toxicology data. This report focuses on the fibrogenic toxicity caused due to co-exposure of ZnONPs and toluene in male Wistar rats, exposed for 28 days, through directed flow nose only exposure chamber. The rats were grouped as air control, toluene control (200 ppm), zinc oxide control (10 mg/m(3)), low dose co-exposed (5 mg/m(3) ZnO and 200 ppm of toluene) and high dose co-exposed (10 mg/m(3) of ZnO and 200 ppm of toluene). Our study demonstrates that co-exposure of ZnONPs and toluene (as in paint industry), even at their respective permissible exposure level (5 mg/m(3) for ZnO and 200 ppm for toluene) have the potential to produce a progressive inflammatory and fibrotic response in the alveolar tissues of the lungs. We observed a significant increase in inflammatory markers in BAL fluid and elevated malondialdehyde (MDA) levels with lower levels of intracellular reduced glutathione (GSH) in lungs of rats of co-exposed group. Significant increase in the levels of pro-inflammatory mediators (IL-6, Ikßα, Cox-II, p-NF-κB) in lung tissues also indicated pulmonary damage. To best of our knowledge this is the first study which highlights the toxicity of co-exposed ZnO NPs and toluene.

Electron microscopy of the morphological changes in rat viscera during experimental hyperthermic shock.

Hyperthermic shock is a thermoregulatory disorder that affects living organisms that are acutely or chronically exposed to high temperatures or when performing intense physical activity in a hot environment. In this paper, we will show the changes embodied in hyperthermic shock caused by multiple injuries to vital organs in Wistar rats that were suddenly exposed to high temperatures of up to 410 for about 10-15 minutes, their central temperature rising above 40.60C. This process resulted in multiple injuries of the vital organs, evidenced by electron microscopy. In addition, this suggested that most changes caused by hyperthermic shock are incompatible with life.

Anti-inflammatory and immunoregulatory effects of Yupingfeng powder on chronic bronchitis rats.

OBJECTIVE: To investigate the anti-inflammatory and immunoregulatory effects of Yupingfeng (, YPF) Powder and its components in rats. METHODS: A rat chronic bronchitis (CB) model was developed using lipopolysaccharide (LPS) combined with bacillus Calmette Guerin (BCG). YPF, simple recipe Astragalus membranaceus (Fisch.) Bge (AM) and Astragalus membranaceus (Fisch.) Bge plus rhizome of Atractylodes macrocephala Koidz (AM+RA) decoction were administered (intragastric administration, once a day for 21 days) to rats, to prevent and treat CB. Immunoregulatory and anti-inflammatory effects of YPF, AM and AM+RA were tested by serum pharmacology in vitro on splenic lymphocytes of normal rats and alveolar macrophages of CB rats. RESULTS: Inflammation in the pulmonary tissue and the bronchus of CB rats was significantly reduced in the YPF-treatment groups, AM and AM+RA groups demonstrating the efficacy of YPF. Serum samples collected at different times from rats after administration of YPF, AM and AM+RA demonstrated increased proliferation of splenic lymphocytes with area under the effect curve (AUE) of 552.6%, 336.3% and 452.0%, respectively. Treatment of alveolar macrophages with serum samples in YPF, AM or AM+RA group inhibited interleukin-8 (IL-8) in the cell culture media, and the effect was much better in the YPF group compared with AM or AM+RA group, with a higher maximal effect (Emax, P<0.05) and larger AUE (P <0.01 and P<0.05). Moreover, serum from rats treated with AM or AM+RA had similar efficacy, while the efficiency was lower than that treated with YPF. CONCLUSION: YPF demonstrated anti-inflammatory and immunoregulatory effects in a rat model of CB, and timedependent relationships were demonstrated in vitro.

Ultrastructural observation on pulmonary fibrosis in E9 rats treated with compound Carapax trionycis formula.

OBJECTIVE: To investigate ultrastructural changes in pulmonary tissue of a rat model of pulmonary fibrosis following treatment with compound Carapax trionycis (C. trionycis; Biejia in Chinese) formula. METHODS: Sixty male Sprague-Dawley rats were randomly divided into four groups (n=15): compound C. trionycis formula high-, middle-, and low-dose groups as well as model group. Pulmonary fibrosis was induced by bleomycin. Five rats from each group were sacrificed on day 7, 14 and 28 of the drug treatment, respectively. The pulmonary tissue was harvested followed by hematoxylin-eosin staining and subsequent transmission electron microscopy. The Szapiel's method was used to assess the degree of alveolitis and pulmonary fibrosis. RESULTS: Compared with the model group, the compound C. trionycis formula groups had slighter pulmonary alveolitis after the 7-day treatment and also had alleviated alveolar inflammation and pulmonary fibrosis after the 14-day treatment. After the 28-day treatment, the compound C. trionycis formula groups showed deposition of a small amount of fibrous tissue and lesions occupying less than 21% of the whole lung area, while the model group showed focal or diffuse fibrous deposition, narrow alveolar cavity, disordered lung structure, and lesions in larger than 51% of the whole lung area. CONCLUSIONS: The compound C. trionycis formula can inhibit the proliferation of collagen fibers and resist pulmonary fibrosis.

[Morpho-functional characteristics of conducting airways and the respiratory portion of rat lung under the conditions of intratracheal infection from the positions of the neuroendocrine regulation of reparative histogeneses].

With the use of light and electron microscopy and immunohistochemistry, the morpho-functional changes in the lungs, the hypothalamus and the neurohypophysis were studied in 45 outbred albino male rats 1, 3, 7 and 14 days after the intratracheal infusion of Staphylococcus aureus strains either possessing anti-lactoferrin activity (ALfA(+)) or lacking it (ALfA(-)). After the infusion of ALfA(+) bacteria, the bronchial wall and the respiratory portion of the lungs demonstrated the destructive changes of tissues, sclerosis phenomena, disturbances of regeneration processes (polypoid outgrowth, metaplasia), while in the neurohypophysis a delay in the release of neurosecretion into the blood from the terminals of nonapeptidergic neurosecretory cells took place. These phenomena were not observed after the infection with ALfA(-)bacteria. The results obtained indicate the disturbances of the structural-functional homeostasis of pulmonary tissues associated with bacterial ALfa, taking place together with the limitations of the hypothalamic neurosecretion.

Effect of Hedera helix on lung histopathology in chronic asthma.

Hedera helix is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c mice were divided into four groups; I (Placebo), II (Hedera helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet cell numbers and thicknesses of basement membrane were found significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II. Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane in the asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of basement membrane better than Hedera helix.