Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.     

THE EFFECT OF SOME α2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

1. The effects of graded doses of the α₂-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the α₂-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.     

免疫调节剂对小鼠实验性单纯疱疹性角膜炎发病的影响

实验组小鼠腹腔分别注射免疫调节剂胸腺五肽(TP5)或环孢霉素(CsA),对照组注射生理盐水(NS),尔后角膜感染单纯疱疹病毒(HSV),造成小鼠实验性单纯疱疹性角膜炎模型。用裂隙灯显微镜观察小鼠角膜上皮、角膜实质、角膜新生血管、结膜和眼睑的病变变化情况。结果:种毒唇4～6天,TP5组角膜上皮和角膜实质病变比NS组严重,差异有显著性,而CsA无此作用。三组小鼠新生血管形成程度差异无显著性。且均在第8天出现高峰。TP5组和CsA组的结膜和眼睑病变,比NS组严重。因此,在临床上,应根据不同病种和不同情况,慎重使用免疫调节剂。     

消化性溃疡中医辨证分型与胃液微量元素 前列腺素E_2及IgG的关系

为了探讨消化性溃疡中医辨证分型与胃液生化、免疫成分的关系,笔者将胃镜确诊的65例患者进行辨证分型,并同步检测其胃液常量元素、微量元素、前列腺素E_2-(PGE_2)、IgG等指标。结果发现,肝胃不和型胃液镁、铜、锌含量低于正常值,IgG高于正常值;脾虚胃热型胃液钠、铜、锌、PGE_2、IgG低于正常值,而钙含量高于正常值;脾胃虚寒型铜、锌、PGE_2低于正常值,而IgG无差异。说明消化性溃疡辨证分型有其客观生化、免疫基础。     

Can past academic criteria predict students at risk of future failure?

A significant minority of medical and dental students fail their undergraduate courses. Early warning systems (EWSs) have been developed in some areas of higher education to predict 'at-risk' students at an early remedial stage. An attempt is made to develop an EWS to predict failure in the bacteriology component of the Batchelor of Dental Surgery course at Manchester Dental School. A system based on class tests and previous end-of-year performance is derived which is used to predict those students likely to fail or fall in the bottom 20-25% in their finals examination. The predictors are combined by a simple equal weights method, which is found to have the same predictive power as using multiple regression. Failure was correctly predicted in 60% of cases, at the expense of 71% false alarms. The high number of false alarms reflects the low failure rate rather than the lack of predictive information. The need for effective cross-validation of EWSs is discussed; many previous studies have not been tested on independent data.     

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

CT angiography in carotid stenosis

Purpose: Prospective evaluation of the accuracy of CT angiography (CTA) with different postprocessing for extracranial carotid artery in comparison with DSA. Method: one hundred patients were studied with standarized CTA. For postprocessing, MPR, MIP, and 3D reconstruction based on segmentation with upper and lower threshold were used. Intravascular density profiles were considered. All CTA studies were correlated with intra-arterial angiography. The degree and classification of stenoses was determined using the guidelines established by the NASCET collaborators. Results: Measurement of stenosis was possible by MPR in 82.5 %, by MIP in 85 %, and 3D in 100 %. Correct classification was found in 65.5 % for MPR, 66 % for MIP and 88.5 % for 3D. The sensitivity for severe stenoses was 74 % for MPR, 82 % for MIP, and 93 % for 3D. The specificity of these methods was 98 %, 96 %, and 97 %, respectively. All carotid occlusions were correctly identified, no carotid artery was wrongly classified as occluded. Conclusions: CT angiography allows reliable examinations in carotid artery stenoses and occlusions. 3D reconstruction based on threshold segmentation is superior to MPR and MIP. In some circumstances, e.g., carotid occlusion, further investigation by invasive procedures is not necessary.      

Quantitative structure-activity relationships in MAO-inhibitory 2-phenylcyclopropylamines: Insights into the topography of MAO-A and MAO-B

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno ⁻, m⁻, p⁻ isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows: pI₅₀=0.804 Π² Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI₅₀=1.815 π-0.825 Π² R+0.900 Es²+0.869 Es³+0.796 Es⁴−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group, a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position, and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.     

Heterocyclic amines: evaluation of their role in diet associated human cancer

1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.     

家兔实验性减压病时血浆中血拴素A_2及前列环素含量的变化

实验观察了“安全”减压和不适当减压条件下家兔减压病(DCS)的发病情况、Doppler超声以及血浆中TxB_2和6-keto-PGF_(1a)的变化;还观察了消炎痛对DCS的预防怍用。结果显示:减压愈不当,DCS发病愈重,Doppler超声气泡探测仪检测到的级别愈高。血浆TxB_2、6-keto-PGF_(1α)值在濒死动物中明显升高(P<0.01);存活动物中,TxB_2经历了下降、再恢复的过程(P<0.01),而6-keto-PGF_(1α)值未见明显变化。消炎痛在抑制血浆TxB_2升高的同时,有效地降低了DCS发病率。此结果表明:TxA_2、PGI_2参与了重型DCS的发病过程,消炎痛的顶防作用与抑制花生四烯酸代谢物的生成有关。