Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta.

In rats, it has been reported that rofecoxib, a cyclooxygenase-2 (COX-2) inhibitor, reacts with the aldehyde group of allysine in elastin to give a condensation covalent adduct, thereby preventing the formation of cross-linkages in the elastin and causing degradation of the elastic fibers in aortas in vivo. Acid, organic solvent, and proteolytic enzyme treatments of human aortic homogenate after incubation with [(14)C]rofecoxib demonstrated that most of the radioactivity is covalently bound to elastin. The in vitro covalent binding was inhibited in the presence of beta-aminopropionitrile, D-penicillamine, and hydralazine, which suggested that the aldehyde group of allysine in human elastin was relevant to the covalent binding. The in vitro covalent binding of [(14)C]rofecoxib was significantly decreased by the addition of only nonradiolabeled rofecoxib but not the other COX-2 inhibitors, celecoxib, valdecoxib, etoricoxib, and CS-706 [2-(4-ethoxyphenyl)-4-methyl 1-(4-sulfamoylphenyl)-1H-pyrrole], a novel selective COX-2 inhibitor. All the above COX-2 inhibitors except for rofecoxib had no reactivity with the aldehyde group of benzaldehyde used as a model compound of allysine aldehyde under a physiological pH condition. On the other hand, no retention of the radioactivity of [(14)C]rofecoxib was observed in human aortic endothelial cells in vitro, suggesting that rofecoxib is not retained in aortic endothelial cells in vivo. These results suggest that rofecoxib, but not other COX-2 inhibitors, is capable of covalently binding to the aldehyde group of allysine in human elastin. This might be one of the main causes of cardiovascular events by rofecoxib in clinical situations.     

Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

The bronchodilating effect of pirenzepine]

The purpose of this study was to clarify the bronchodilating effect of pirenzepine (PZ) and to verify its mechanism. Ten asthmatic patients (6 men, 4 women: aged 20 to 65, 5 atopic 5 non-atopic) and ten non-asthmatic volunteers (8 men, 2 women: aged 25 to 60) were studied. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0) and peak expiratory flow rate (PEFR) were measured after intravenous administration of 20 mg PZ. PZ increased FVC, FEV1.0 and PEFR significantly by 15%, 29% and 37% respectively in asthmatic patients (p less than 0.01). We also studied the effects of PZ on the contractile responses of tracheal smooth muscle to intra-arterially administered acetylcholine (ACh) and the electrical stimulation of the vagus nerves (VNS) using isometric technique in situ in 5 mongrel dogs. PZ significantly inhibited the contractile responses elicited with ACh at doses larger than 1000 micrograms/kg (p less than 0.01). PZ also significantly inhibited the contractile responses elicited by VNS at doses larger than 100 micrograms/kg (p less than 0.01). These data demonstrate that intravenously administered PZ dilates the airway in asthmatic patients and also suggest that the bronchodilating effect of PZ related to inhibition of the M1 and M3 muscarinic receptors.     

Hematopoietic recovery in a patient with acute lymphoblastic leukemia after an autologous marrow graft purged by combined hyperthermia and interferon in vitro.

We describe a patient with acute lymphoblastic leukemia (ALL) in whom hemopoiesis recovered after an autologous marrow graft purged by in vitro hyperthermia. A 17-year-old woman was diagnosed as having ALL in April 1985. After clinical remission was induced, marrow cells were harvested. The marrow cells were treated with hyperthermia at 42.0 degrees C for 1 h in the presence of alpha-interferon to eliminate residual leukemic cells, and then cryopreserved. In January 1990, during her fourth remission she was treated with busulfan and cyclophosphamide, and then received the thawed autologous marrow. Her hematopoietic recovery was prompt with normal trilineage regeneration without any life-threatening complications. She is in good health without evidence of a leukemic relapse at 6 months after autologous bone marrow transplantation. This case suggests that human multilineage progenitor cells retain self-renewal capacity in vivo even after treatment with heat and alpha-interferon in vitro followed by the freezing and thawing procedures.     

Techniques of nasotracheal intubation with the fiberoptic bronchoscope

When nasotracheal intubation with a fiberoptic bronchoscope is performed, the tube may be blocked in the nasal cavity or larynx, resulting in several complications including epistaxis and hoarseness. We review the causes and complications of tube blockage and discuss optimal techniques for minimizing it.     

Glomerular deposition of complex-forming glycoprotein heterogenous in charge (protein HC) in IgA nephropathy.

IgA immune complexes and polymeric IgA are presumed to play important roles in the development and progression of IgA nephropathy. Complex-forming glycoprotein heterogenous in charge (protein HC), being inhibitors of neutrophilic chemotaxis, has been reported as binding to IgA. As a working hypothesis it was assumed that complexes of protein HC and IgA are present in glomeruli from IgA nephropathy patient in stable state. In this study, we examined the glomerular deposition of protein HC in 40 patients with IgA nephropathy and in 10 patients with non-IgA nephropathy. We used highly specific antibody against protein HC, that does not cross-react with alpha-1-microglobulin. An immunofluorescent study revealed that 10 out of the 40 patients (25%) showed an intensity of 1+, 16 (40%) showed weak positive (+/-), and the other 14 (35%) were negative. There was no deposition of protein HC in non-IgA nephropathy patients. Histopathological analysis demonstrated a significant correlation between the intensity of glomerular-deposited protein HC and pathological activity (p less than 0.005); the latter was defined as having either crescents in more than 15% of the remaining glomeruli (excluding global sclerotic glomeruli), or segmental necrosis or sclerosis in more than 30% of the remaining glomeruli. A significant correlation was observed between pathological activity and the intensity of deposited IgG, IgA and IgM (p = 0.01), and lambda chain (p less than 0.005). Considering anti-inflammatory activity of protein HC, these results suggest that protein HC cannot protect sufficiently acute inflammation or tissue damages due to co-deposited IgG and IgM and/or other factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suprasellar pituitary adenoma arising from the pars tuberalis: case report

A rare case of suprasellar pituitary adenoma arising from the pars tuberalis in a 53-year-old woman is presented. The tumor was located exclusively above the diaphragma sellae, and no invasion into the sella turcica was noted.