[Research on the"Association of Han medicine of State of Manchuria"].

The"Association of Han medicine of State of Manchuria"was a puppet TCM academic society founded by the Puppet Manchukuo government, with well-organization system and widespread scope. During its period, though some efforts were made to promoting the TCM academic progress, improving the quality of TCM doctors, developing TCM clinic, education, academic research and administration, its essence was still a tool for the puppet government to controlling, transforming and utilizing TCM.

Genetic variation in the G-50T polymorphism of the cytochrome P450 epoxygenase CYP2J2 gene and the risk of younger onset type 2 diabetes among Chinese population: potential interaction with body mass index and family history.

BACKGROUND: Cytochrome P450 (CYP) 2J2 is a regulatory enzyme in the biosynthesis of biologically active CIS-epoxyeicosatrienoic acids (EETs). EETs have been suggested to modulate PPAR-gamma and PPAR-alpha transcription activity and play a role in stimulus-secretion coupling in pancreatic beta cells. Genetic abnormalities in the expression of CYP2J enzymes may play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our objective was to investigate CYP2J2 G-50T polymorphism (rs890293) in association with insulin resistance markers and T2DM in a Chinese population. METHODS: A total of 1 747 Chinese T2DM patients and 994 non-diabetic subjects were studied. The CYP2J2 G-50T polymorphism was determined by a restriction fragment-length polymorphism polymerase chain reaction. RESULTS: Neither the CYP2J2 genotype distribution nor allele frequency differed between the control subjects and the T2DM patients. However, among diabetics, subjects with a younger age at diagnosis (AAD; <40 years) had significantly higher T variant frequency than those with an AAD>/=40 years. When diabetic patients were stratified by their AAD in 10-year intervals, the trend was significantly linear among age grades. A significant interaction between the CYP2J2 T variant and younger onset diabetic subjects with positive family diabetes history, and BMI>/=27 kg/m (2) were observed to have the highest risk of diabetes and younger onset diabetics with the T variant had higher homeostasis model assessment estimate of insulin resistance (HOMA-IR) and HOMA-beta values than their GG genotype counterparts. Plasma concentrations of stable EET metabolites were significantly lower in individuals with the G-50T SNP in younger onset diabetics. CONCLUSION: These data suggest that age of onset, family history, and obesity may modify the association between the CYP2J2 G-50T polymorphism and T2DM risk. CYP2J2 G-50T polymorphism may contribute to the pathogenesis of T2DM, partially by effects on insulin resistance, in patients with younger onset T2DM.

Purification, characterization, and molecular cloning of an outer layer protein of carp fertilization envelope.

An outer layer protein of carp fertilization envelope (FE), FEO-1, was purified from carp oocytes. The cDNAs encoding FEO-1 were cloned. The mature protein of FEO-1 is 21 kDa in molecular weight and contains 177 amino acid residues whose sequence has 58% identity to the outer layer protein of chick vitelline membrane. In situ hybridization and immunocytochemistry show that FEO-1 is expressed in oocytes and liver. In oocytes, FEO-1 is stored in the cortical granules. During cortical reaction, it is exocytosed to the perivitelline space and then gradually added to the outer layer of FE (FE(o)). FEO-1 first appears as discrete deposits along FE(o), then merges to form a continuous layer. The thickness of FE(o) increases as cortical reaction proceeds. In addition to FEO-1, FE(o) contains cystatin, fibroin-like substance (FLS), and cathepsin-like substance (CLS) as well. They are stored in the cortical granules and are exocytosed to FE(o) simultaneously with FEO-1 during cortical reaction. In FE(o), FEO-1 is present in monomer form and can be completely extracted by sodium dodecyl sulfate (SDS)-mercaptoethanol (MSH). On the other hand, the cystatin, FLS, and CLS present in FE(o)are cross-linked together. They are partially extracted by SDS-MSH but can be completely extracted by guanidium thiocyanate-lauroylsarcosine.

Nitric oxide donors enhance calcitonin gene-related peptide-induced elevations of cyclic AMP in vascular smooth muscle cells.

Vasorelaxant effects of calcitonin gene-related peptide (CGRP) are dependent on endothelium-derived nitric oxide (NO) in some arteries. The mechanism involved is still not clear. In the present study, we used NO donors (sodium nitroprusside (SNP) and 6-(2-hydroxy-1-methyl-2-nitrisohydrazino)-N-methyl-1-hyxanamine (NOC-9)), cyclic GMP elevator (brain natriuretic peptide (BNP)) and a selective type III (cyclic GMP-inhibited) phosphodiesterase (PDE) inhibitor 5-(4-acetamidophenyl)pyrazin-2(1H)-one (SK&F94120) to investigate involvement of NO, cyclic GMP and type III PDE in CGRP-induced accumulation of cyclic AMP in cultured rat aortic smooth muscle cells. SNP (10 microM), NOC-9 (10 microM) and BNP (1 microM) all increased intracellular cyclic GMP to similar levels (2- to 2.5-fold above basal) and caused significant enhancement of CGRP (10 nM)-induced cyclic AMP accumulation similar to that caused by 10 microM SK&F 94120. The data are therefore consistent with our hypothesis that the mechanism of endothelium-dependent vasorelaxation effect of CGRP involves cyclic GMP-mediated inhibition of type III PDE and subsequent accumulation of cyclic AMP in smooth muscle cells.

Interleukin-1beta causes different levels of nitric oxide-mediated depression of contractility in different positions of rat thoracic aorta.

Interleukin-1beta (IL-1beta) can be synthesized by macrophages, endothelial cells and vascular smooth muscle cells when stimulated by bacterial lipopolysaccharide (endotoxin) during septic shock. The IL-1beta levels in the blood vessel wall are also elevated in atherosclerosis. IL-1beta can cause induction of inducible nitric oxide synthase (iNOS) expression in vascular smooth muscle cells and produce vasorelaxation, hypotension and ultimately tissue damage. We studied the depressions of vascular smooth muscle contractions at 3 hours after exposure to IL-1beta in different positions of rat thoracic aorta. The data show that the aortic rings from the cranial end of rat thoracic aorta had little response to IL-1beta (0.5 and 1.0 ng/ml) while those from the caudal end of thoracic aorta had larger depressant response. S-methylisothiourea sulfate (SMT), an iNOS inhibitor, completely blocked the depression of contraction caused by IL-1beta in intact aortic rings. If the endothelium was removed from the aortic rings before exposure to IL-1beta, all rings from different parts of the thoracic aorta showed an equal amount of vasodepression. Thus, the difference in the depressant response of IL-1beta in different portions of thoracic aorta is endothelium-dependent and involves induction of NOS.

Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.

The objective of the present study was to investigate the specific drug targeting of anticarcinogenic drugs, such as camptothecin (CA), after intravenous (i.v.) injection by incorporation into solid lipid nanoparticles (SLN). A CA loaded SLN suspension consisted of 0.1% (w/w) camptothecin, 2.0% (w/w) stearic acid, 1.5% (w/w) soybean lecithin and 0.5% (w/w) polyoxyethylene-polyoxypropylene copolymer (Poloxamer 188) was prepared by high pressure homogenization. In vitro drug release was investigated in pH 7.4 phosphate-buffered saline at 37 degrees C. The concentrations of camptothecin in various organs were determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after i.v. administration of CA-SLN and a camptothecin control solution (CA-Sol). The results showed that the CA-SLN had an average diameter 196.8 nm with a Zeta potential of -69.3 mV and in vitro drug release was achieved for up to a week. In tested organs, the AUC/dose and the mean residence times (MRT) of CA-SLN were much higher than those of CA-Sol, especially in brain, heart and reticuloendothelial cells containing organs. The brain AUC ratio of CA-SLN to CA-Sol was the highest among the tested organs. These results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity.

Calcitonin gene-related peptide causes long-term inhibition of contraction in rat thoracic aorta through a nitric oxide-dependent pathway.

Calcitonin gene-related peptide (CGRP) is released into the circulation during pathogenesis of endotoxin and septic shock and appears to partly mediate vascular problems of shock. To explore the function of CGRP during shock, we investigated long-term action of CGRP, alone or in combination with interleukin-1beta (IL-1beta), another shock mediator, in isolated rings of rat thoracic aorta. CGRP or IL-1beta, by themselves, caused significant long-term (3 h) depression of contraction, while the combination of CGRP and IL-1beta had no synergistic effects. Dose-response curves to phenylephrine were significantly decreased and shifted to the right when aortic rings were incubated with 1 microM CGRP for 1 h followed by 2 h incubation without CGRP. Inducible nitric oxide synthase (iNOS) inhibitors, S-methylisothiourea sulfate (SMT) and N(G)-nitro-L-arginine (L-NNA), completely eliminated long-term depressant effect of CGRP. Our results suggest pathology of septic shock may involve long-term inhibition of vascular contraction mediated by CGRP via expression of iNOS.