Preemptive analgesia by zaltoprofen that inhibits bradykinin action and cyclooxygenase in a post-operative pain model

The post-operative pain state results from a barrage of primary afferent inputs exposed to products of tissue damage such as bradykinin and prostaglandins and the central sensitization by the continuing inputs. This provides the rationale for preemptive analgesia, whereby the blockade of primary afferent inputs prior to injury may result in a reduction of post-operative pain. 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl) propionic acid (zaltoprofen) is a unique compound that inhibits cyclooxygenase (COX) and exhibits anti-bradykinin activity. The present study evaluated the preemptive analgesic effect of zaltoprofen in a post-operative pain model produced by plantar incision. When orally, but no intrathecally, administered 30 min prior to incision, zaltoprofen significantly increased the withdrawal threshold 2 h and 1-3 days after incision at 10 mg/kg. While the bradykinin B1 antagonist des-Arg10-HOE-140, the selective COX-1 inhibitor SC-560, and the selective COX-2 inhibitor celecoxib did not affect post-operative pain, the B2 antagonist HOE-140 dose-dependently relieved the post-operative pain at 2-200 microg/kg with a time course similar to that of zaltoprofen. The B2 receptor mRNA was expressed in the hindpaw and the expression did not change before and 24 h after surgery. These results suggest that zaltoprofen produces the preemptive analgesic effect peripherally by blocking the B2 pathway.     

Microsatellite instability in primary and metastatic lung carcinomas

Fifty-seven primary lung carcinomas and 35 metastatic lung carcinomas were analyzed for microsatellite instability at 11 different chromosomal loci. Although no instability was detected in 37 small cell lung carcinomas (SCLC), it was frequently detected in non-small cell lung carcinomas (NSCLC) (16/55, 29%). In NSCLC, the incidence of replication errors (RERs) in metastatic tumors (12/22, 55%) was significantly higher than that in primary tumors (4/33, 12%) (P = 0.0021). Among 10 pairs of primary tumors and corresponding metastases, there were 4 cases which manifested the identical RER phenotypes in both primary and metastatic tumors. In two cases, RER phenotypes were detected in metastatic but not in primary tumors. Never was an RER phenotype found only in a primary tumor but not in the metastases. RERs were detected more frequently in stage III or IV tumors (3/8, 38%) than stage I or II tumors (1/25, 4%) (P = 0.0359). Tumor cells with allelic losses on chromosome arm 3p or 18q tended to have RER phenotypes (P = 0.0432 and P = 0.0187, respectively). The data suggest that microsatellite instability is common in NSCLC but not in SCLC, and that genomic instability appears late in tumor progression and plays an important role in the acquisition of more malignant phenotypes in NSCLC.     

Prevalence of asthma in adults in Menda town rural-mountain area in Japan]

Several reports have suggested that the prevalence of asthma in adults is currently increasing. However, recent prevalence of asthma has not reported in Japan, especially in rural-mountain areas. To investigate the prevalence of asthma in adults in Japan, we conducted clinical epidemiological research on 5066 inhabitants of Menda town, in a rural-mountain area of Japan. The study population comprised 98.7% of adults in the town, including senior high school students whose age were more than 15 years old. The prevalence of asthma among adults was 3.6%. The ratio of prevalence in males to prevalence in females was 1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years old in males, and 15-19, 40-49 and > 70 years old in females.     

Preparation and characterization of poly(methyl-3,3,3-trifluoropropylsiloxane-co-dimethylsiloxane)

Methyl-3,3,3-trifluoropropylsiloxane (F)-dimethylsiloxane (D) random and block copolymers were prepared. The random copolymers were prepared by equilibrium copolymerization starting from a mixture of cyclic F and D siloxanes with potassium silanolate as the catalyst. The F-D block copolymer was prepared by sequential anionic living polymerization of strained cyclic trisiloxanes using butyllithium as initiator, first polymerizing D₃ then adding F₃ after consumption of D₃. The copolymer microstructure was established by means of ²⁹Si NMR, differential scanning calorimetry (DSC), and gel-permeation chromatography (GPC). Characteristic glass transition temperature (T_g) shifts were observed depending on the F:D ratio of the random copolymers. It was demonstrated that the tensile strength of the poly(methyl-3,3,3-trifluoropropylsiloxane)-poly(dimethylsiloxane) (PTFPMS-PDMS) blend system was improved when either of the copolymers was added.     

Endocytosis of human thyroglobulin (TG) in adenomatous goiter studied by an immuno-electron microscopic procedure

Five cases of adenomatous goiter have been studied by an electron microscope using an immuno-reaction for thyroglobulin (TG) and focusing on the mechanism of endocytosis. Positive stain for TG was demonstrated in follicular lumina, large reabsorbed colloid droplets and small subapical vesicles. Endocytotic vesicles ranging from 320 nm to 1600 nm in diameter were observed in the cytoplasm as pits in the apical plasma membrane. Some of them showed direct connection with the positive stain for TG in the follicular lumen and the others were completely ingested in the cytoplasm. With statistic analysis, a majority of the vesicles showing the positive stain for TG in the cytoplasm distributed in the range of 200 nm to 1200 nm in diameter with the peak in 300 nm to 399 nm and was situated within an extent of the diameter measured from the endocytotic vesicles. Engulfment of colloid by pseudopods and fusion of the reabsorbed colloid droplets were encountered as extremely rare findings and appeared to play no major role for formation of large colloid droplets in adenomatous goiter.     

Endogenous peroxidase activity in primary culture of human thyroid cells. Localization and measurement

Intracellular localization of and an assay method for endogenous peroxidase (PO) activity were studied using primary culture of thyroid cells obtained from patients with hyperthyroidism. PO activity was visualized by cytochemical reaction and was located mainly in perinuclear cisternae and rough endoplasmic reticulum. With increased culture time, the number of cells showing positive PO activity and amount of the enzyme reaction product in individual cells showed a parallel decrease. For measurement of PO activity, cultured thyroid cells were frozen and thawed and then incubated with citric acid buffer solution containing o-phenylenediamine (opd) and hydrogen peroxide. After incubation, the optical density (OD) of the solution colorized by endogenous peroxidase was measured at 405 nm using a microplate reader. About 1 X 10(4) cells were sufficient for assay of PO activity. Using the above method to assay PO activity and sandwich enzyme immunoassay for thyroglobulin (TG), chronological changes in the PO activity and TG concentration in the culture medium were examined. Although the cells showed no decrease in number, PO activity and TG concentration decreased chronologically. When the ratio of PO activity to TG concentration was calculated, in 3 cases the ratio was almost constant, and in the remaining two, it decreased chronologically. The present biochemical method thus seems useful for determining peroxidase activity of cultured thyroid en masse.     

Immunohistochemical,ultrastructural and biochemical studies of an amylase-producing breast carcinoma

Summary We describe a breast cancer with ectopic production of amylase, found in the patient's serum, urine and in the tumour. Clinically, serum amylase levels reflected both the progression of the disease and regression induced by various therapies. Using agarose gel electrophoresis and a wheat protein inhibitor assay, the predominant serum amylase appeared to be identical to pancreatic-type isoenzyme. However, the action mode analysis using a new fluorogenic substrate revealed that the serum contained non-salivary, non-pancreatic amylase. The tumour had microscopic features of invasive ductal carcinoma with some argyrophilic differentiation. The component cells stained positively for amylase, and ultrastructurally numerous secretory granules were seen.     

Muddy lung

A 31-year-old man, a racing car driver, was submerged in muddy water as the result of an accident. He died from respiratory failure after a 17-day clinical course. Foreign body granulomatosis and massive fibrosis of the lung were revealed at autopsy. The crystalline foreign bodies mainly were composed of silicon and ranged in size from 20 micron to 500 micron in diameter (average, 90 micron). Their distribution in the lungs corresponded to the areas of lung carnification. In this study, the authors demonstrate that near drowning in muddy water causes pulmonary silicate granulomatosis associated with carnificating fibrosis of the lung and term the pulmonary changes "muddy lung."