Biotransformation or drug-metabolising enzymes have an important function in the detoxication of ingested toxic, carcinogenic, or tumour promoting compounds. Enzyme activity and isoenzyme composition of three biotransformation systems: glutathione Stransferase, uridine diphosphate-glucuronosyltransferase, and cytochrome P-450 were studied in normal small and large intestinal mucosa from three kidney donors. The activity of most drug-metabolising enzymes decreases slightly from proximal to distal small intestine, whereas in the mucosa of the large intestine a sharp fall in activity was observed. The isoenzyme composition for each of the three biotransformation systems changed from the small to the large intestine. Class Alpha glutathione S-transferases were not expressed in the colon, in contrast to the small intestine where both Alpha and Pi class isoenzymes are present. In addition, with monoclonal antibodies fewer protein bands for UDP-glucuronosyltransferases and cytochrome P-450 were detected in the colon. In the small intestine both isoforms P-4504 and P-450, were present, whereas in the colon only reduced amounts of cytochrome P-4504 could be visualised. For UDP-glucuronosyltransferase, 53 and 54 kDa proteins could be detected in the small intestine, but in the colon there was only weak staining ofthe 54 kDa band. In the normal human colon enzymes are less active and there are fewer isoenzymes present in the mucosa than in the small intestine. This implies a lower level of the detoxifying potential in the colon, which might be important in regard to the high rates ofcarcinogenesis in the colon.

Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test The chylomicron remnant clearance (S,< 1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05 ±12.84 hours x [mg/L]) compared with control subjects (25.1±5.4 hoursx[mg/L]; p=0.01). Postprandial lipoprotein particle size and composition in the Sf> 1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54 ±0.09 mmol/L) than in control subjects (0.89±0.05 mmol/L; p<0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94 ±25 and 427 ±57 milliunits/mL, respectively) and control subjects (126±16 and 362±33 milliunits/mL, respectively). In FCH, a 54% reduction (p<0.05) of plasma triglycerides to 2.63±0.41 mmol/L by drug treatment resulted in an enhanced, but not normalized, clearance of chylomicron remnants (39.4±6.0 hours x [mg/L]). Univariate regression analysis revealed that in FCH subjects the changes in fasting plasma apolipoprotein C-III concentrations after therapy were significantly associated with the changes in chylomicron remnant AUC-RP (r=0.87;p=0.02). Delayed elimination of atherogenic chylomicron remnants may contribute to the increased risk of premature atherosclerosis in FCH. ( of premature atherosclerosis in FCH patients has been related to the observed lipoprotein abnormalities. However, neither elevated low density lipoprotein (LDL) concentrations nor decreased high density lipoprotein (HDL) levels are consistently found in all FCH patients. 4 Increased production of VLDL and VLDL remnants in FCH patients may be important, since remnants are atherogenic particles that contribute to premature atherosclerosis.8 " 12 We studied postprandial lipoprotein metabolism in six patients with FCH and seven normolipidemic control subjects. Because postprandial chylomicron metabolism is known to depend on fasting plasma TGs, 10 -13 apo B, 13 and HDL 2 cholesterol, 14 the FCH patients were studied both before and after lipid-lowering medication. We used the oral retinyl palmitate (RP) fat-loading test 1015 in separate studies of the elimination of chylomicrons and chylomicron remnants. Methods FCH PatientsThe six male FCH patients (aged 30-66 years) were on a low-fat, low-cholesterol diet, 16 comparable to the American Heart Association Phase I diet, and did not consume more than four alcoholic beverages per week. Patients were diagnosed as FCH when they had each of the following: 1) hyperlipidemia, defined as cholesterol and/or TG plasma concentrations >6.5 and 2.0 mmol/L, respectively, 2) at least one first-degree relative with a different lipoprotein phenotype than the index patient 5 ; 3) an elevated fasting plasma concentration of apo B (>0.9 by guest on May 9, 2018 http://atvb.ah...

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Here we report an improved, simple method to assign the human apolipoprotein (apo) E genotype and its isoforms, apo E2, apo E3, and apo E4. Genomic DNA was amplified with specific primers that included the polymorphic region of amino acids 112 and 158. Digestion of the product with Hhal resulted in unique fragments that were separated on Meta-Phor agarose instead of polyacrylamide. The pattern of unique DNA fragments obtained unequivocally characterizes the different apo E alleles.

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We studied the effect of 2 mg micronized 17 beta-estradiol replacement therapy, administered orally during 6 weeks, on postprandial lipid and retinyl palmitate (RP) metabolism. In the human postprandial state, atherogenic chylomicron remnant particles are produced. RP is incorporated into the core of newly synthesized chylomicrons and can be used as a marker of chylomicrons and chylomicron remnants. Six normolipidemic (plasma cholesterol, 5.63 +/- 0.83 mmol/L; plasma triglycerides, 1.47 +/- 0.69 mmol/L) postmenopausal women (amenorrhea > 1 yr; aged 55.5 +/- 4.0 yr) received an oral fat load (50 g/m2 fat as cream, with 60,000 IU RP/m2) before and after 6 weeks of 17 beta-estradiol treatment. Plasma RP areas under the curve decreased significantly from 27.1 +/- 15.9 to 16.6 +/- 13.2 mg/h.L-1 (P = 0.01). Fasting cholesterol concentrations in intermediate density lipoproteins decreased significantly. Fasting and postprandial plasma triglyceride levels did not change. These findings indicated that 17 beta-estradiol improved the postprandial elimination of potentially atherogenic lipoprotein remnants.

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Summary The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university‐based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping‐by‐sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo‐autosomal sexing marker (zinc‐finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats.