OBJECTIVETo investigate the ultrastructure of ciliated epithelia and inflammatory changes upon repeated exposure to staphylococcal enterotoxin A (SEA) of different concentrations in the maxillary sinus mucosa of rabbits.

METHODSThe rabbits were randomly divided into 2 groups (24 rabbits per group): low-dose SEA group and high-dose SEA group. The low-dose SEA group and high-dose SEA group received daily injections of 0.6 ng of SEA (2 ml) and 60 ng of SEA (2 ml) into the left maxillary sinus of rabbits for 28 days, respectively. Concurrent treatment of the right maxillary sinus with normal saline was used as control. Six rabbits chosen randomly in two groups were examined by computed tomography (CT) scans and then sacrificed to obtain the sinus mucosa from the two-side of maxillary sinuses for histological assessment on days 3, 7, 14 and 28. To characterize the inflammatory changes of the sinus mucosa examined using light microscope, hematoxylin and eosin (HE) and toluidine blue staining was performed. Scanning and transmission electron microscopy were performed to observe ultrastructure of ciliated epithelia in the maxillary sinus mucosa. SPSS 13.0 software was used to analyze the data.

RESULTSOn days 14 and 28, CT images showed opacification of the left maxillary sinus in the high-dose SEA group. The percentage of epithelial disruption was (22.73 ± 5.72) % and (30.79 ± 4.30)% in the high-dose SEA group respectively, and were significantly greater than those in the low-dose SEA group (5.12% ± 1.98% and 5.38% ± 1.64%, q value was 10.079 and 19.132) and control group (4.08% ± 1.29% and 4.81% ± 1.62%, q value was 11.016 and 19.592, respectively, all P < 0.01). The subepithelial thickness in the high-dose SEA group was (113.34 ± 14.81)µm and (120.86 ± 12.35) µm respectively, and were significantly different from those of the low-dose SEA group [(71.08 ± 10.39)µm and (81.63 ± 9.32)µm, q value was 8.090 and 8.782] and control group [(37.45 ± 7.67)µm and (38.79 ± 7.68)µm, q value was 15.759 and 19.541, all P < 0.01]. Viewed under the electron microscope, loss of cilia was observed, a few compound cilia and cytoplasmic protrusion were found, an obvious stretching of the endoplasmic reticulum and an obvious turgescence of the mitochondria was also observed. However, in the low-dose SEA group on days 14 and 28, CT scan of the left maxillary sinus showed transparency; light microscopy observations of the maxillary sinus mucosa showed the number of eosinophils was markedly increased as compared with the high-dose SEA and control groups, the differences were significant (q value was 5.871 and 6.766 on day 14, and q value was 7.572 and 8.970 on day 28, respectively, all P < 0.05). But no significant differences were observed in epithelial disruption between the low-dose SEA and the control groups on days 14 and 28 (q value was 1.512 and 0.859 respectively, all P > 0.05); inordinate array and adhesion of cilia was observed, but cilia loss, compound cilia, cytoplasmic protrusions, mitochondrial swelling and endoplasmic reticulum stretching were not found.

CONCLUSIONSSEA may induce allergic inflammation of the sinus mucosa without damaging the structure of ciliated epithelia at low concentration. Whereas SEA impairs the structure of mitochondria and endoplasmic reticulum in ciliated epithelial cells at high concentration, and results in cilia loss and epithelial disruption, which may be one of the main reasons to induce acute sinusitis.

Animals ; Cilia ; drug effects ; physiology ; ultrastructure ; Cost of Illness ; Enterotoxins ; toxicity ; Eosinophils ; Epithelial Cells ; drug effects ; physiology ; ultrastructure ; Leukocyte Count ; Maxillary Sinus ; drug effects ; metabolism ; ultrastructure ; Mucous Membrane ; drug effects ; physiology ; ultrastructure ; Rabbits ; Sinusitis

OBJECTIVETo evaluate bi-directional modulation effect of Chinese herbal medicine on immunol cells.

METHODTwo different active portions were isolated from Kudzuvine Root(Radix puerariae), one being the ethanol extraction and another the water extraction. Different concentration of these two different portions was studied by using PMA stimulated lymphocyte or eosinophil initiated chemiluminescence system.

RESULTWater extraction of Kudzuvine Root could enhance chemiluminescence concentration dependently whereas enthanol extraction of Kudzuvine Root inhibited the chemiluminescence significantly.

CONCLUSIONThe bi-directional regulation effect of Chinese herbal medicine can be found in the same herb, because of its efficacy of different active compounds.

Cell Separation ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Eosinophils ; drug effects ; Ethanol ; Humans ; Luminescent Measurements ; Lymphocytes ; drug effects ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Water

OBJECTIVETo study the effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice.

METHODS48 female Balb/c mice were randomly divided into 6 groups, i.e., the normal control group, the model group, the Dexamethasone group, the low dose icariin group, the middle dose icariin group, and the high dose icariin group, 8 mice in each group. Bronchial asthma in mice were induced by intraperitoneal sensitization and challenged with nebulized ovalbumin (OVA). The mice of each treatment group were administrated with different doses of icariin by peritoneal injection from the first asthma sensitization (the 3rd week after the modeling) to the day before killing once every other day, while mice in the normal control group were administrated with physiological saline. The mice were killed after 6 weeks of treatment. The apoptosis of eosinophils and the Bcl-2 and Bax protein expressions of the lung tissues were detected by TUNEL and immunohistochemical assay respectively.

RESULTSAs compared with the model group, the apoptosis ratio of eosinophils were higher in the rest four treatment groups (P<0.05). The Bcl-2 protein positive areas in the lung tissues and the airway wall were significantly lowered (P<0.05). The Bax protein positive area significantly increased (P<0.05).

CONCLUSIONIn bronchial asthmatic mice, icariin could enhance the apoptosis of eosinophils and lessen their infiltration by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein in lung.

Animals ; Apoptosis ; drug effects ; Asthma ; metabolism ; Eosinophils ; drug effects ; metabolism ; Female ; Flavonoids ; pharmacology ; Mice ; Mice, Inbred BALB C ; bcl-2-Associated X Protein ; genetics ; metabolism

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although mainly metabolized in the liver, abnormal liver function tests were a rare adverse effect during clinical trials and we found no literature about albendazole-induced hepatitis requiring admission. This patient had a previous history of albendazole ingestion in 2002 resulting in increase of liver function tests. And in 2005, the episode repeated. We evaluated the patient for viral hepatitis, alcoholic liver disease, and autoimmune hepatitis, but no other cause of hepatic injury could be found. Liver biopsy showed periportal steatosis and periportal necrosis. The initial abnormal liver function test improved only with supportive care. These findings and the Roussel Uclaf Causality Assessment Method of the Council for International Organizations of Medical Sciences (RUCAM/CIOMS) score of 9 are compatible with drug-induced hepatitis so we report the case of this patient with a review of the literature.
Albendazole/*adverse effects ; Antiprotozoal Agents/*adverse effects ; Eosinophils/metabolism ; Glucose/metabolism ; Hepatitis, Toxic/*diagnosis ; Humans ; Liver/drug effects ; Liver Function Tests ; Male ; Middle Aged ; Necrosis

Administration, Inhalation ; Asthma ; drug therapy ; physiopathology ; Budesonide ; administration & dosage ; Drug Combinations ; Eosinophils ; drug effects ; Ethanolamines ; administration & dosage ; Formoterol Fumarate ; Humans ; Peak Expiratory Flow Rate ; Powders

OBJECTIVETo study the effects of very late antigen(VLA) antagonist BIO-1211 on eosinophil chemotaxis, recruitment and mediator release.

METHODSEosinophil chemotaxis was induced by platelet activating factor(PAF) in vitro and eosinophil recruitment and release were determined in vivo.

RESULTVLA antagonist BIO-1211 inhibited eosinophil chemotaxis induced by PAF. The inhibitory rates at 4x10(-11), 4x10(-10), 4x10(-9) mol x L(-1) were 24.9%, 29.9%, and 31.3%, respectively. Pretreatment by BIO-1211 1, 3 and 10 mg x kg(-1) intraperitoneally inhibited the recruitment of eosinophils in PAF in the rat induced by Sephadex in a dose dependent manner. Inhibitory rates were 60.3%, 68.9%, and 72.9%(P<0.05), respectively. BIO-1211 did not inhibit eosinophil peroxidase(EPO) release from eosinophils.

CONCLUSIONBIO-1211 inhibits eosinophil chemotaxis and recruitment, alleviates local inflammation, and may represent a new type of drug for allergic diseases.

Animals ; Cell Movement ; drug effects ; Chemotaxis, Leukocyte ; drug effects ; Dose-Response Relationship, Drug ; Eosinophil Peroxidase ; Eosinophils ; drug effects ; physiology ; Integrin alpha4beta1 ; antagonists & inhibitors ; physiology ; Male ; Oligopeptides ; pharmacology ; Peroxidases ; secretion ; Platelet Activating Factor ; pharmacology ; Rats ; Rats, Sprague-Dawley

PURPOSE: Since drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is very rare and difficult to diagnose, its exact epidemiology is still unknown. If screening tools based on laboratory results or electronic medical records are available, the occurrence of DRESS syndrome can be monitored in real time. METHODS: To screen cases with DRESS syndrome, all the results of both eosinophil and alanine transaminase (ALT) level from July 2014 to June 2015 were analyzed by 36 searching conditions for the signal detection of 7 definite DRESS cases among 199,924 patients during the study period. Those searching conditions were diverse combinations of different cutoff levels of eosinophil and ALT with or without nursing records presenting skin symptoms. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated for individual searching conditions. RESULTS: As cutoff levels of eosinophil and ALT for screening DRESS increased from 3% to 5% and 40 U/L to 300 U/L, respectively, the sensitivity decreased from 100% to 42.9% and the PPV increased from 0.06% to 13.0%. A combination of eosinophil >10% and ALT >300 U/L which had the highest PPV among 36 search conditions could detect DRESS syndrome by sensitivity 42.9% and PPV 13.0%. When nursing records for skin symptoms were added, PPV was augmented to 21.4%. CONCLUSION: A combination of eosinophil and ALT levels is a useful search condition for the screening of DRESS syndrome. Nursing records can provide an additional increment in PPV.
Alanine Transaminase ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records* ; Eosinophilia* ; Eosinophils ; Epidemiology ; Humans ; Mass Screening ; Methods* ; Nursing Records ; Sensitivity and Specificity ; Skin

PURPOSE: Although there have been reported cases of drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome caused by antituberculosis drugs, there has been no research to examine its prevalence. This study assessed the prevalence and clinical characteristics of DRESS syndrome caused by antituberculosis drugs. METHODS: The electronic medical records of a cohort consisting of adult patients diagnosed with tuberculosis between July 2006 and June 2010 were reviewed and retrospectively inspected. We searched the surveillance system for adverse drug reactions and the electronic medical records to identify patients who reported severe cutaneous adverse reactions to antituberculosis drugs. These patients were then re-assessed using a European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR) scoring system. Clinical characteristics, including the symptoms and latency of DRESS syndrome, the therapeutic dosage and period of steroids, and the final duration of tuberculosis therapy, were examined. RESULTS: Of the 1,253 adult patients with tuberculosis receiving antituberculosis drugs, 15 were identified as potential cases of DRESS syndrome (prevalence of 1.2%). Ethambutol was the most frequently used drug (53.5%), followed by rifampicin (26.7%), pyrazinamide (20.0%), streptomycin (13.3%), and isoniazid (6.7%). The median latency after day 1 of antituberculosis medication was 42 days. The median daily dose of steroids, expressed in prednisone-equivalent units, was 33-mg/day, and the median dosing period was 14 days. The duration of tuberculosis treatment was 76 days longer than the standard treatment period of 180 days. There was a significant difference in the peak eosinophil counts of DRESS syndrome patients according to RegiSCAR scores. Moreover, there was a significant quantitative correlation between the RegiSCAR score and peak eosinophil count. A negative correlation was also found between the RegiSCAR score and latency. CONCLUSIONS: This study confirmed the prevalence of DRESS syndrome in a cohort of adult patients with tuberculosis.
Adult ; Cohort Studies* ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Eosinophilia* ; Eosinophils ; Ethambutol ; Humans ; Isoniazid ; Prevalence* ; Pyrazinamide ; Retrospective Studies* ; Rifampin ; Steroids ; Streptomycin ; Tuberculosis

OBJECTIVEOver the past several decades, there has been a significant increase in allergy and asthma in the world, which correlates with alterations in microflora and widespread use of antibiotics. The authors have developed a mouse model of antibiotics-induced microbiota disruption. In that model, mice were challenged by intranasal exposure to Aspergillus fumigatus allergens to explore the relation of allergic airway response and intestinal microflora disruption.

METHODSSixty female BALB/c mice were divided at random into 6 groups with 10 mice in each. (1) First antibiotic therapy group: the mice were given oral cefoperazone for 7 days, on day 7, mice were inoculated with Candida albicans (10(9)/ml, 50 microl) orally. (2) First control group: the mice were treated as first antibiotic therapy group, but cefoperazone and Candida albicans were replaced by saline. The mice in groups (1) and (2) were sacrificed on day 8, and cecal contents were collected for quantitative analysis of the intestinal bacterial flora. (3) Antibiotic therapy and challenge group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (4) Second antibiotic therapy group: the mice were treated as the first antibiotic therapy group, then challenged (day 9 and 16) by intranasal exposure to saline. (5) Challenge group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to Aspergillus fumigatus allergen. (6) Second control group: the mice were treated as the first control group, then challenged (day 9 and 16) by intranasal exposure to saline. The mice in (3) - (6) group were killed for analysis of allergic airway response on day 19.

RESULTSThe quantity of Enterobacteriaceae, Enterococcus, Bifidobacterium and Lactobacillus in first antibiotic therapy group was significantly lower than that in the first control group, the quantity of Candida albicans increased in the first antibiotic therapy group as compared with the first control group. Mice intestinal microflora were disrupted with weight reduction and increased moisture in feces. After challenging with Aspergillus fumigatus allergens via intranasal inhalation, the total cell count, eosinophils, lymphocytes and neutrophils increased in BALF, especially in bronchoalveolar lavage fluid (BALF) from the mice in antibiotic therapy and challenge groups. IL-4 level in BALF from antibiotic therapy and challenge group (45.35 +/- 2.36) pg/ml was higher than that in the second control group (35.32 +/- 2.53) pg/ml. The expression of GATA-3 mRNA in the mice lung tissue (0.569 +/- 0.023) was higher than that in the second control group (0.410 +/- 0.020), and the ratios of T-bet/GATA-3 (0.578 +/- 0.021) decreased as compared with that in the second control group (0.804 +/- 0.035). IFN-gamma level in BALF from any group was not significantly different. In the absence of antibiotics, mice exposed to Aspergillus fumigatus allergen did not develop an allergic response in the airways.

CONCLUSIONSThe allergic (Th2) immune response can be induced by airway challenge with Aspergillus fumigatus allergen in the mice in which the intestinal microflora disruption resulted from antibiotic therapy, this result suggests that the intestinal microflora disruption resulted from antibiotic therapy is a risk factor for allergy and asthma.

Animals ; Anti-Bacterial Agents ; adverse effects ; Antibiosis ; Aspergillus fumigatus ; chemistry ; growth & development ; Asthma ; drug therapy ; microbiology ; Bronchoalveolar Lavage Fluid ; microbiology ; Cefoperazone ; therapeutic use ; Disease Models, Animal ; Eosinophils ; drug effects ; microbiology ; Female ; Hypersensitivity ; drug therapy ; microbiology ; Hypersensitivity, Immediate ; microbiology ; Intestines ; drug effects ; microbiology ; physiopathology ; Lung ; drug effects ; microbiology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; adverse effects ; immunology ; Respiratory System ; microbiology

Corticosteroids are considered to be one of the most effective medicine for asthma by suppressing airway inflammation. This study was carried out to investigate the effects of prednisolone in the sputum of exacerbated asthmatics. Clinical severity, cell differentials, levels of interleukin (IL)-5, eosinophil cationic protein (ECP), EG2+ eosinophils, and nitric oxide (NO) metabolites were measured. Sputum was examined 2 weeks apart in 13 exacerbated asthmatics before and after prednisolone treatment, and once in 12 stable asthmatics. We used a sandwich ELISA for IL-5, fluoroimmunoassay for ECP, immunohistochemical staining for EG2+ eosinophils, a NO metabolites assay using modified Griess reaction. Exacerbated asthmatics, in comparison with stable asthmatics, had significantly higher proportion of eosinophils, higher level of ECP, higher percentage of EG2+ eosinophils, and NO metabolites. Exacerbated asthmatics after treatment with prednisolone had reduced the proportions of eosinophils, reduced level of IL-5, ECP and percentage of EG2+ eosinophils. FEV1 was correlated with the proportion of eosinophils, ECP, and IL-5 respectively. These findings suggest that prednisolone is considered to be effective medicine for asthma by suppressing eosinophil activation through IL-5.
Administration, Oral ; Adolescence ; Adrenal Cortex/metabolism ; Adult ; Aged ; Anti-Inflammatory Agents, Steroidal/administration & dosage* ; Asthma/metabolism ; Asthma/immunology* ; Asthma/drug therapy* ; Biological Markers ; Blood Proteins/metabolism* ; Eosinophils/metabolism ; Eosinophils/immunology ; Eosinophils/drug effects* ; Female ; Human ; Interleukin-5/metabolism* ; Leukocyte Count ; Male ; Middle Age ; Nitric Oxide/metabolism ; Prednisolone/administration & dosage* ; Sputum/immunology ; Sputum/cytology