Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats

In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammutory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4g/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutroph il infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact ruts. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site.     

Membranous lipodystrophy

Summary The case is described of a 35-year-old housewife diagnosed as having membranous lipodystrophy (as described by Nasu et al. in 1970 and called lipomembranous polycystic osteodysplasia by Hakola in 1972). The main symptom of this patient was a slowly progressive dementia. Skeletal symptoms were not seen. The computerized tomogram of the brain showed calcification of bilateral basal ganglia and the plain roentgenograms of the bones revealed cystic radiolucent areas at the distal end of the bones of the patient's extremities. Histological examination of the curetted material from the right talus revealed a membranocystic pattern. The fatty tissue curetted from the cyst of the talus and the lysosomal enzymes of the white blood cells were biochemically normal. A possible relationship between this disease entity and connective disorders is considered.     

Effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) measurement

To retrospectively investigate the effects of indigo carmine intravenous injection on oxygen reserve index (ORi?) in 20 patients who underwent elective gynecologic surgery under general anesthesia. The study subjects were patients who underwent elective gynecologic surgery under general anesthesia between April 2016 and January 2017, and were administered a 5-ml intravenous injection of 0.4% indigo carmine for clinical purposes during surgery with ORi monitoring. Changes in ORi within 20 min after indigo carmine injection were observed. A relevant decrease in ORi was defined as ≥?10% reduction in ORi from pre-injection level. ORi rapidly decreased after indigo carmine intravenous injection in all patients. In 10 of 19 patients, ORi decreased to 0 after indigo carmine injection. The median lowest value of ORi was 0 (range 0–0.16) and the median time to reach the lowest value of ORi was 2 min (range 1–4 min) after injection. ORi values returned to pre-injection levels within 20 min in 13 of 19 patients, and the median time to return to pre-injection levels was 10 min (range 6–16 min) after injection. During ORi monitoring it is necessary to consider the rapid reduction in ORi after intravenous injection of indigo carmine.     

Regioselective hydroxylation of steroid hormones by human cytochromes P450

This article reviews in vitro metabolic activities [including Michaelis constants (K_m), maximal velocities (V_max) and V_max/K_m] and drug–steroid interactions [such as induction and cooperativity (activation)] of cytochromes P450 (P450 or CYP) in human tissues, including liver and adrenal gland, for 14 kinds of endogenous steroid compounds, including allopregnanolone, cholesterol, cortisol, cortisone, dehydroepiandrosterone, estradiol, estrone, pregnenolone, progesterone, testosterone and bile acids (cholic acid). First, we considered the drug-metabolizing P450s. 6β-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. CYP1A2 and CYP3A4, respectively, are likely the major hepatic enzymes responsible for 2-/4-hydroxylation and 16α-hydroxylation of estradiol and estrone, steroids that can contribute to breast cancer risk. In contrast, CYP1A1 and CYP1B1 predominantly metabolized estrone and estradiol to 2- and 4-catechol estrogens, which are endogenous ultimate carcinogens if formed in the breast. Some metabolic activities of CYP3A4, including dehydroepiandrosterone 7β-/16α-hydroxylation, estrone 2-hydroxylation and testosterone 6β-hydroxylation, were higher than those for polymorphically expressed CYP3A5. Next, we considered typical steroidogenic P450s. CYP17A1, CYP19A1 and CYP27A1 catalyzed steroid synthesis, including hydroxylation at 17α, 19 and 27 positions, respectively. However, it was difficult to predict which hepatic drug-metabolizing P450 or steroidogenic P450 will be mainly responsible for metabolizing each steroid hormone in vivo based on these results. Further research is required on the metabolism of steroid hormones by various P450s and on prediction of their relative contributions to in vivo metabolism. The findings collected here provide fundamental and useful information on the metabolism of steroid compounds.     

Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan

Journal of Gastroenterology - Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of...     

O-nitroso aldol synthesis: Catalytic enantioselective route to alpha-aminooxy carbonyl compounds via enamine intermediate

The approach using pyrrolidine enamine as substrate has been studied for this synthesis, and an important catalyst structural feature has been developed. After survey of pyrrolidine-based Br?nsted acid catalyst, tetrazole catalyst (3f) was found to be optimal in synthesis of aminooxy carbonyl compounds in high yields, with complete enantioselectivity not only for aldehydes but also for ketones.