Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Formation of pyridinium species of haloperidol in human liver and brain

Recent interest in the neurotoxicity of haloperidol is based on its oxidation in rodents to the pyridinium derivative, HPP⁺, a structural analog of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP⁺). Recently, we reported that HPP⁺ and a newly identified reduced pyridinium, RHPP⁺, were present in blood and urine of haloperidol-treated schizophrenics and that the concentrations of RHPP⁺ exceeded those of HPP⁺. In this study, we examined pathways for formation of RHPP⁺ in subcellular fractions of human liver (n=5) and brain (basal ganglia;n=5). The major pathway was reduction of HPP⁺ (20 µM) to RHPP⁺ in cytosol (0.17–0.39 and 0.03–0.07 µM RHPP⁺/g cytosolic protein per h in liver and brain, respectively). The reactions were inhibited significantly by menadione and in brain also by daunorubicin. The inhibition profile, cytosolic location and strict NADPH dependence suggest that the enzymes involved are ketone reductases. A second pathway was oxidation of reduced haloperidol (50 µM), a major metabolite of haloperidol in blood and brain, to RHPP⁺. In liver microsomes, 0.17–0.63 µmol RHPP⁺ was formed /g microsomal protein per h. A potent inhibitor of the pathway was ketoconazole (IC₅₀, 0.8 µM), which suggests that P-450 3A isozymes could be involved. In brain mitochondria but not microsomes, reduced haloperidol (120 µM) was oxidised to RHPP⁺ at a small but significant rate (0.005–0.020 µmol RHPP⁺/g mitochondrial protein per h) which was not attenuated by SKF 525A, quinidine, ketoconazole, or monoamine oxidase inhibitors. Further studies are warranted to establish the biological importance of these metabolites in vivo.     

Vasodilating effects of carbon monoxide

The vasodilator effects of carbon monoxide (CO) were studied in an isolated perfused rat thoracic aorta preparation. Thoracic aortas from male Sprague-Dawley laboratory rats were dissected free of surrounding tissue, cannulated proximally, and tethered to in situ length. The vessels were perfused with oxygenated Krebs-Henseleit (KH) solution at 37 degrees C in a constant flow system with a circumferentially-applied, pulsatile (300/min), basal "systolic" pressure of 100 mm Hg. Aortas were precontracted with high-potassium (K+) or norepinephrine (NE). Changes in perfusion pressure were indicative of changes in vascular resistance induced by the test gas mixtures. Oxygen (O2) content of the perfusate was kept constant, while CO and nitrogen (N2) were altered. CO (2.5, 5 and 10%) dilated both K+-contracted and NE-contracted aortas in a dose-dependent manner. A significant vasodilation in response to 5% CO (24.5% of maximal), but not to 5% N2, was obtained in the K+-contracted aortas. After the endothelium was removed chemically, the aortas continued to dilate in response to CO. These results suggest that CO has a direct vasorelaxant effect on vascular smooth muscle which is nonspecific and is not endothelium-dependent.     

Crosslinked polyimide foams derived from poly(imidepropylene oxide) copolymers

A new route for the synthesis of high glass transition temperature, thermally stable polymer foams has been developed, using compositionally asymmetric microphase-separated block copolymers where the minor component (poly(propylene oxide)) is thermally labile and the major component (polyimide) is thermally stable. The minor component decomposes to low molecular weight species upon heating, and the decomposition products diffuse out of the film, leaving behind pores embedded in a matrix of the thermally stable component. In this study, the polyimide block was crosslinked with ethynyl functionalities to obtain a stable porous structure. The decomposition of the propylene oxide in the block copolymer was studied by thermogravimetric, dynamic mechanical and thermomechanical analyses. Mild conditions were required to avoid rapid depolymerization of the propylene oxide and plasticization of the polyimide matrix. The foams showed pore sizes with diameters up to a micrometer in size as well as the expected reduction in the mass density.     

Duodenal carcinoid tumor: report of a case diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy with immunocytochemical correlation

Fine-needle aspiration biopsy is a reliable and accurate method for the endoscopic diagnosis of gastrointestinal malignancies and it is particularly well suited for evaluation of submucosal lesions. We report the cytopathologic findings of a case of malignant carcinoid tumor of a 44-year-old male who presented with melena and a nonhealing duodenal ulcer. Endoscopic ultrasound examination revealed a submucosal lesion in the pyloric region. Fine-needle aspiration revealed abundant cellularity with tumor cells arranged in sheets and loose groups and dispersed single cells in a clean background. Papillary fragments, capillaries cuffed by tumor cells, and rosette formation were also noted. The cells were moderate in size, round to oval, with a small subpopulation of spindle-shaped cells. The nuclei were uniform, round to oval, with smooth nuclear borders. The chromatin pattern was finely granular with a salt-and-pepper appearance. The cytoplasm of the cells was small to moderate in amount, pale, and showed fine granularity. The differential diagnosis included a neuroendocrine neoplasm vs. an epithelioid gastrointestinal stromal tumor. The tumor cells were focally positive for chromogranin and negative for CD34, supporting the diagnosis of a neuroendocrine neoplasm. The differential diagnosis of primary gastrointestinal carcinoid tumors from gastrointestinal stromal tumors can be very difficult in cytologic material. In cases when diagnostic material is scant, or only present on one smear, the use of smear division and cell transfer in order to perform immunocytochemical stains may be of considerable value to confirm the neuroendocrine nature of the neoplasms.     

Biomedical applications of tunable diode laser spectrometry: Correlation between breath carbon monoxide and low level blood carboxyhemoglobin saturation

Tunable diode laser spectrometry was used to measure breath carbon monoxide (CO) concentrations in nonsmoking subjects. Corresponding blood carboxyhemoglobin (COHb) saturations between physiological levels and levels after 1 and 8 hours exposure to 9 ppm CO, the maximum permissible concentration in the air under federal regulations, were also determined. A good linear correlation between breath CO and blood COHb saturation for low levels representing ambient conditions was established, with a correlation coefficient better than 0.999 for the means and 0.945 for the individual data points. Similar studies on the other compounds of concern are also possible using tunable diode laser spectrometry, requiring only a breath sample and with no sample preparation. This technique will facilitate fast, noninvasive environmental health effect and biomedical studies.