Noninvasive assessment of hepatobiliary and renal elimination of cysteinyl leukotrienes by positron emission tomography

N-Acetyl-leukotriene E4 has been identified as an endogenous, biologically less active cysteinyl leukotriene metabolite in rodents and humans. To evaluate the ratio of hepatobiliary to renal elimination of leukotrienes noninvasively by positron emission tomography (PET), we synthesized N-[11C]acetyl-leukotriene E4 by chemical N-acetylation of leukotriene E4. After the intravenous injection of N-[11C]acetyl-leukotriene E4 in normal rats and monkey, uptake by the liver and subsequent excretion into bile were largely responsible for its rapid elimination from blood. In the Cynomolgus monkey, renal excretion of the leukotriene into urine was of additional quantitative importance. Kinetic modeling indicated a mean transit time through the liver of 17 minutes and 34 minutes in rat and monkey, respectively; the corresponding hepatic excretion half-times amounted to 8.5 minutes and 16 minutes. In a mutant rat strain deficient in the hepatobiliary excretion of cysteinyl leukotrienes across the canalicular membrane, the apparent mean liver transit time was 54 minutes, and the hepatic excretion half-time was 29 minutes, indicating prolonged organ storage and metabolism. After transport from the liver back into the circulating blood of omega-oxidized and beta-oxidized metabolites of N-[11C]acetyl-leukotriene E4, renal excretion compensated for the impairment of hepatobiliary elimination in the transport mutant. Metabolite analyses in urine after intravenous injection of N-[3H]acetyl-leukotriene E4 indicated the extensive inactivation of N-acetyl-leukotriene E4 by beta-oxidation from the omega-end in the mutants. A similar shift from hepatobiliary to renal cysteinyl leukotriene elimination was monitored in rats with cholestasis due to bile duct obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy

BACKGROUND: Proliferative activities of tumors are thought to be prognostic features of malignant tumors, but their value as measured by proliferating cell nuclear antigen (PCNA) labeling remains unclear in gastric cancer. METHODS: PCNA labeling rates (LR) were quantified in 121 paraffin-embedded biopsy specimens from primary tumors by immunocytochemistry. RESULTS: Immunohistochemical analyses have demonstrated that PCNA presents an intense staining in the nuclei of tumor cells and mucous neck cells of gastric glands. The PCNA LR ranged from 12% to 79% (mean +/- standard deviation), and a significant correlation was found between bromodeoxyuridine labeling indices and PCNA LR: PCNA LR were closely associated with tumor size, serosal invasion, and nodal involvement. The patients with tumors with high PCNA LR (greater than 40%) were dead significantly earlier than were those with tumors with low PCNA LR: When the PCNA LR and all the clinicopathologic parameters were entered into a Cox regression model, PCNA LR emerged as an independent prognostic factor. CONCLUSION: These results indicate that PCNA LR may be a potentially useful prognostic factor for gastric cancer.     

Mixing in processing of thermoplastics by extrusion

Translated from Khimicheskoe i Neftyanoe Mashinostroenie, No. 8, pp. 9–11, August, 1993.     

Superior activity of a thromboxane receptor antagonist as compared with aspirin in rat models of arterial and venous thrombosis

We determined the effects of aspirin and a novel thromboxane A2/prostaglandin endoperoxide (TP)-receptor antagonist, BMS-180291, on thrombosis and bleeding times in skin and mesenteric arteries. In anesthetized rats, occlusive thrombosis was induced in the carotid artery by topical application of ferrous chloride and in the vena cava by blood flow stasis combined with either infusion of thromboplastin or hypotonic saline. Aspirin (1, 10, and 50 mg/kg) did not reduce arterial or venous thrombus weight significantly. BMS 180,291 (150 micrograms/kg/min) decreased arterial thrombus weight and hypotonic saline-induced caval thrombus weight by 58 and 57%, respectively. BMS-180291 lacked antithrombotic activity at a lower dose (50 micrograms/kg/min) and failed to inhibit thromboplastin-induced caval thrombosis. BMS-180291 (150 micrograms/kg/min) significantly reduced arterial thrombus weight by 40% when plasma epinephrine concentration was increased to 5 ng/ml. BMS-180291 and aspirin produced increases of only < or = 30% in bleeding times. These results demonstrate that BMS-180291 has antithrombotic activity in experimental aspirin-resistant arterial and venous thrombosis. Both aspirin and BMS-180291 have only modest effects on small artery hemostasis in rats.     

Implementation of a quiet hour: effect on noise levels and infant sleep states

It is necessary to decrease environmental stimuli in order to provide developmentally supportive care to the very low birthweight (VLBW) infant, thereby enhancing the sleep/wake cycle and possibly physiologic stability. The purpose of this study was to determine if it was possible to decrease the noise level in the Developmental Unit, and promote sleep states in infants on the unit. After determining control noise levels and infant state, the last hour of each shift was designated a Quiet Hour. During this time, noise levels were monitored in the room in five locations. Infant sleep states were also noted. The results indicate that noise levels decreased significantly on two of the three shifts. Fewer infants were crying during the Quiet Hour than the control period (2.4 vs 14.3 percent), and more were in deep or light sleep (84.5 vs 33.9 percent). This study demonstrates that noise levels in Developmental Units can be significantly decreased, and that the decreased noise levels positively impact infant state. By enhancing sleep states, nurses can enhance the long term developmental outcome of the VLBW infant. However, the reduction of noise is highly dependent on the collaborative efforts of all health care providers within the unit.     

An experiment study of the guided bone regeneration

BMP is one of important factors in the pathophysiology of bone regeneration. Fifteen New Zealand rabbits were used in this experiment. We studied the distribution and effectiveness of endogenic BMP on a 10 mm bone defect of radius, by utilizing immunohistochemistry of BMP and quantitative computer imaging system. On the 3rd day, death of osteocytes and BMP positive blood clot were observed. The mesenchymal cells from periosteum and endoosteum, and osteoblast were also BMP positive. By quantitative study, we found there was a gradient distribution of BMP in bone defect, i.e, the value of BMP decreased gradually along the distance from the fracture ends. The maximal value of BMP was noted at the 1st week postoperation. In conclusion, two sources of endogenic BMP were found, one was from the absorption of necrotic tissue of fracture ends, the other was from the secretion of osteogenic mesenchymal cells during the process of bone regeneration. Nonunion of bone defect was caused in part by the gradient distribution of BMP. Accordingly, the concept of effective quantity of endogenic BMP was drawn rosen. It might be a new method in the treatment of bone defect by increasing the concentration of endogenic BMP and improving its distribution.     

Neurotrophins and their receptors in the adult hypo- and hyperthyroid rat after kainic acid injection: an in situ hybridization study

Thyroid hormone plays a key role in trophic events during development of the central nervous system. In spite of neurological and psychiatric symptoms associated with adult hypothyroidism, the role of thyroid hormone in mature brain function is less clear. In this paper we investigated the effect of thyroid status on kainic acid-induced up-regulation of mRNAs for members of the nerve growth factor family and related receptors in adult male rats by means of in situ hybridization. We found that in hypothyroid rats there is a dramatic attenuation of the kainic acid-induced up-regulation of mRNA levels for nerve growth factor, brain-derived neurotrophic factor and tyrosine kinase trkB in euthyroid rats. A trend to reduced c-fos mRNA up-regulation, which did not reach significance, was also found, whereas the increase in c-jun mRNA after kainic acid was similar in eu-, hypo- and hyperthyroid rats. These data indicate a severe impairment of the regulation of neurotrophin synthesis after excitotoxin administration in the hippocampus during adult hypothyroidism. Possible roles of thyroid hormone in molecular, biochemical and metabolic mechanisms of this defect are discussed.