Airway responsiveness and airway remodeling after chronic exposure to procaterol and fenoterol in guinea pigs in vivo

BACKGROUND: Chronic exposure to fenoterol (FEN), a beta(2)-adrenergic receptor (beta(2)-AR) agonist, was shown to induce both airway hyperresponsiveness and airway remodeling in experimental animals. OBJECTIVE: We wanted to know the effects of chronic exposure to procaterol (PRO), a beta(2)-AR agonist, on airway function and structure, because this agent is widely used as a bronchodilator in Japan. For comparison, the effects of FEN were also examined. METHODS: Aerosolized PRO (0.1 or 1 mg/ml), FEN (1 mg/ml) or vehicle (0.9% NaCl) was given to guinea pigs 3 times a day for 6 weeks. Sublaryngeal deposition of these agents was calculated using radioisotopes. At 72 h after the last inhalation of PRO, FEN or vehicle, the dose-response relationship between lung resistance (R(L)) and intravenously administered acetylcholine (ACh) was measured. After measuring R(L), histological changes in noncartilaginous airway dimensions were evaluated. RESULTS: The amount of sublaryngeal deposition of 0.1 mg/ml PRO in the present study was speculated to be 100 times larger than that of therapeutic dose. ACh concentrations causing 2-fold, 10-fold and maximal increases in R(L) were not different in 4 groups tested. In the smaller membranous airways (<0.4 mm in diameter), but not the larger ones, thickening of adventitial areas was significantly greater in animals treated with beta(2)-AR agonists than in control animals (23 and 25, and 96% higher in animals treated with 0.1 and 1 mg/ml PRO or 1 mg/ml FEN, respectively). The degree of the increase was significantly less in PRO-treated animals than in FEN-treated animals (p < 0.01). CONCLUSION: Our results did not provide any evidence that regular inhalation of PRO at the therapeutic dose might induce bronchial hyperresponsiveness. In addition, huge amounts of PRO only caused a mild thickening of the adventitial areas, suggesting that PRO may be a weak inducer of airway remodeling compared with FEN.     

A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep]

In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).     

Quantitative analysis for soluble elastin in circulation and cell culture fluids using monoclonal antibody-based sandwich immunoassay

We have newly established 3 distinct murine monoclonal antibodies (MoAbs) against human soluble elastin by using chemically denatured immunogen isolated from human aorta; they are designated as HASG-2, HASG-30, and HASG-61-1. All of these MoAbs were highly reactive with soluble forms of native elastin in normal human serum. HASG-2 and HASG-61-1 MoAbs can recognize soluble bovine elastin as well as human antigen, but HASG-30 cannot. The sandwich enzyme-linked immunosorbent assay (ELISA) for human soluble elastin was developed with HASG-61-1 labeled with peroxidase and HASG-30 immobilized on the microplates. The circulating levels of soluble elastin in human healthy subjects (mean +/- SD; 42.9 +/- 19.9ng/mL; n = 85) could be measured with full accuracy and reproducibility, and gradually increased with aging. The positive correlation between the levels and ages was statistically significant (r = 0.581, p < 0.0001). In addition, we could also determine the concentration of tropoelastin secreted from cultured human dermal fibroblasts accurately by this ELISA. This simple assay can be utilized for the routine clinical laboratory screening of patients with arteriosclerotic vascular diseases or to accurately determine the concentrations of tropoelastin secreted from cultured human cells.     

Immunohistochemical study of copper-zinc and manganese superoxide dismutases in the lungs of human fetuses and newborn infants: Developmental profile and alterations in hyaline membrane disease and bronchopulmonary dysplasia

To determine the late gestational development of copper-zinc (CnZn) and manganese (Mn) superoxide dismutases (SOD) in human lung, immunohistochemical localization was performed for each SOD. The lung samples were taken from five aborted fetuses, four fetuses in which intrauterine death occurred, one full-term neonate, two premature infants with hyaline membrane disease and one premature infant with bronchopulmonary dysplasia (BPD). Morphometry was performed, and the percent area of positive staining was computed. The bronchial epithelium was intensely stained from the early stages of gestation (i.e. 17 weeks), while the staining intensity for both CuZnSOD and MnSOD in the peripheral airways increased gradually during lung development. The mean percent area of the staining for CuZnSOD and MnSOD from 16 to 38 weeks was increased 30-fold and 8-fold, respectively, and further increases were observed postnatally. CuZnSOD staining was markedly decreased in lungs with respiratory disorders. However, proliferating type II pneumocytes were intensely stained for MnSOD in the BPD lungs, making the staining area 3-fold larger than that in the control lungs. These results clearly depict age-related increases in staining for both CuZnSOD and MnSOD and an alteration in SOD distribution associated with neonatal respiratory disorders.     

An immunohistochemical study of bone morphogenetic protein in pleomorphic adenoma of the salivary gland

Bone morphogenetic protein (BMP) is a potent induction factor for new bone formation including heterotopic chondro-ossification in soft tissues. The immunohistochemical reaction for BMP was studied in 23 cases of pleomorphic adenoma of salivary gland by using a monoclonal antibody produced by hybridoma technique. Positive BMP immunoreactivity was seen in 87% of tumours. Immunohistochemical expression of BMP was observed in modified myoepithelial cells (88% cases), luminal tumour cells of tubulo-ductal structures (78% cases) and chondroid cells in hyaline tissue (22% cases). The authors concluded that the simultaneous presence of glycosaminoglycans as matrix substance and S-100 protein for calcium signalling are associated with BMP-mediated cellular activity of modified myoepithelial cells in the formation of chondroid structures in pleomorphic adenomas of the salivary glands.     

Phylogenetic association of Pneumocystis carinii with the 'Rhizopoda/Myxomycota/Zygomycota group' indicated by comparison of 5S ribosomal RNA sequences

The cytoplasmic 5S ribosomal RNA (5S rRNA) sequence from Pneumocystis carinii was determined. A sequence comparison matrix of 382 eukaryote 5S rRNA sequences and an evolutionary tree were constructed to establish the phylogenetic position of Pneumocystis. The data suggest that Pneumocystis is associated with the Rhizopoda/Myxomycota/Zygomycota group (= 'Protista fungi') but not with common fungi, such as Ascomycota or Basidiomycota, nor with other protozoa.     

Comparison of standard and hand-assisted laparoscopic radical nephrectomy for renal cell carcinoma.

A laparoscopic radical nephrectomy (LRN) for renal cancer can be performed using two methods, hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS). This institute initially used HALS to perform all radical nephrectomy, but gradually shifted to SLS. This study compared the two methods of radical nephrectomy: HALS vs. SLS, which were performed at a single institute. From March 1999 to November 2006, a total 129 patients with pathologically confirmed renal cell carcinoma underwent LRN, including 73 patients with the HALS and 56 patients with SLS. The median operative time was 264 minutes, and median estimated blood loss was 200 ml in the HALS group, respectively. The median operative time and median estimated blood loss in the SLS were 215 minutes and 100 ml, respectively. There was no significant difference in either the operative time or estimated blood loss between HALS and SLS. The median time to both postoperative oral intake and ambulation in the SLS were 1 day. Neither of these events after SLS was significantly shorter than that after HALS. The 4-year disease-free and overall survival rates in the HALS patients were 97.5% and 98.2%, respectively. Both the 4-year disease-free and overall survival rates in the SLS patients were 100%. Since no significant differences were observed between the two operative methods (SLS and HALS) regarding the operative data, postoperative course and oncological outcome, the surgical method for LRN can be selected according to characteristics of each surgical method.     

Effects of L-DOPA and L-5-HTP on the visual evoked response

Small doses (10 and 20 mg/kg) of L-DOPA inhibited the amplitude of the visual evoked response (VER), while large doses (40 and 80 mg/kg) enhanced it. Though low doses (12.5 and 25 mg/kg) of L-5-HTP caused a slight increase in amplitude of the VER, the simultaneous administration of 12.5 mg/kg of L-5-HTP and 10 mg/kg of L-DOPA produced a marked enhancement. The peak latency was prolonged after the injection of any doses of L-DOPA, L-5-HTP, or both.