Confirmation of an influence of the inherited Lp(a) variation on serum insulin and glucose levels

Previously reported analyses on three different series of people suggested that fasting serum insulin levels are lower in males with (high levels of) serum Lp(a) lipoprotein (Lp(a+)) than in males without detectable Lp(a) lipoprotein (Lp(a-)). The same was observed during an oral glucose tolerance test. Also, blood glucose concentrations tended to be lower in males with high levels of Lp(a) lipoprotein than in those in whose serum no Lp(a) lipoprotein could be detected. In this paper, we present data which appear to confirm the previously reported results. A significant correlation was found between the fasting triglyceride level and the sum of insulin values determined during the oral glucose tolerance test in healthy Lp(a-) but not in Lp(a+) individuals. The present data, together with those previously reported on an effect of the Lp(a) locus on serum lipid levels and on propensity to contract coronary heart disease, indicate that the genetically determined Lp(a) lipoprotein may be of considerable clinical importance.     

Induced fit binding of aldose reductase inhibitors to AKR1B10

AKR1B10 is a recently identified NADP+ dependent aldo–keto reductase. It is strongly over expressed in lung and hepatic carcinomas as well as in colorectal and uterine cancers. AKR1B10 has 71% sequence identity with aldose reductase, the latter plays an important role in diabetic complications. The enzyme also exhibits substrate-specificity and inhibitor-sensitivity similar to aldose reductase. Various aldose reductase inhibitors show induced fit phenomenon in aldose reductase. It is reported that the selective ALR2 inhibitor, zopolrestat, also inhibits wild type AKR1B10. In this study, we have performed the induced fit docking of a few aldose reductase inhibitors in crystal structure of AKR1B10 (i.e., 1ZUA). This study elucidates the binding mode of various aldose reductase inhibitors in AKR1B10 and provides insights for the design of more selective and specific inhibitors.     

Modeling complex genetic and environmental influences on comorbid bipolar disorder with tobacco use disorder

Background  

Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD.     

Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor

Lp(a) lipoprotein shares the apoB antigen with low density lipoprotein (LDL). The Lp(a) antigen is unique for Lp(a) lipoprotein. Fibroblast association (i.e. plasma membrane binding plus intracellular accumulation), plasma membrane binding, intracellular accumulation and degradation of 125I-Lp(a) lipoprotein were studied in strains from subjects with or without autosomal dominant hypercholesterolemia (HC). Subjects without HC (non-HCs) have cell surface receptors for low density lipoprotein (LDL receptors). On the average, HC heterozygotes have half-normal LDL receptor activity and "receptor-negative" HC homozygous cell strains lack functional receptors. Fibroblast processing of 125I-Lp(a) lipoprotein was compared to fibroblast processing of 125I-LDL. LDL receptor-dependent processing of 125I-LDL was saturated at about 50 microgram apo 125I-LDL.ml-1 in non-HC fibroblasts. 125I-Lp(a) lipoprotein was, however, largely processed independently of receptor mechanisms by non-HC cells (highest concentration examined 150 microgram apo 125I-Lp(a) lipoprotein . ml-1). Lp(a) lipoprotein did not interfere with 125I-LDL for fibroblast association, but inhibited 125I-LDL degradation. The interference with 125I-LDL degradation was time dependent. Only slightly higher 125I-Lp(a) lipoprotein processing values were found in non-HC and HC heterozygous strains than in "receptor-negative" HC homozygous strains. However, non-HC cells had more than tenfold higher 125I-LDL processing values than "receptor-negative" HC homozygous cells.     

Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects

Rødningen OK, Leren TP, Røsby O, Tonstad S, Ose L, Berg K. Haplotype analysis at the low density lipoprotein receptor locus in normal and familial hypercholesterolemia Norwegian subjects.
Clin Genet 1993: 44: 214–220. © Munksgaard, 1993
We have performed haplotype analysis at the low density lipoprotein receptor (LDLR) locus in order to investigate the molecular genetics of familial hypercholesterolemia (FH) in Norway. Haplotypes were constructed using 7 restriction fragment length polymorphisms (RFLPs) in 194 subjects from 48 unrelated Norwegian FH families. Hypercholesterolemia co-segregated with haplotypes at the LDLR locus in all 48 families. Unambiguous haplotypes could be established for 190 independent chromosomes from 51 FH heterozygotes and 44 healthy normal subjects. A total of 20 different haplotypes was found. The most frequent haplotype was haplotype 3, which accounted for 32.4% or 43.1% of the normal and defective haplotypes, respectively. Haplotype 2 was significantly more frequent among the defective alleles than among the normal alleles (33.3% and 5.8%, respectively, p<0.0001). Thus, haplotypes 2 and 3 accounted for 76.4% of the defective haplotypes. More data are needed to determine the possible existence of founder genes in the Norwegian population. Haplotypes 1, 2, 3, 5 and 8 accounted for 88.2% of the normal haplotypes. Based upon the cumulative heterozygosity index, the SphI, NcoI and 3' ApaLI RFLPs are the most informative markers in the Norwegian population.     

Comparison of bivalirudin with heparin versus abciximab with heparin for primary percutaneous coronary intervention in “Real World” practice

ObjectiveWe aimed to carry out a “real world” comparison of bivalirudin plus unfractionated heparin (UFH) versus abciximab plus UFH in patients undergoing primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI).MethodsWe included patients who had abciximab or bivalirudin during their PPCI in our unit between Sept 2009 and Nov 2011.ResultsThe study included 516 and 484 patients in the bivalirudin and abciximab group respectively. There were more women in the bivalirudin group (29% vs 20%, p 0.001), while cardiogenic shock (6.4% vs 10.1%, p 0.04) and thrombectomy device use (76.6% vs 82%, p 0.04) were lower in the bivalirudin group.The primary composite end point of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding was similar between the bivalirudin and abciximab groups (7.8% vs 9.5%, OR 0.8, 95% CI 0.5 to 1.2, p 0.4). There was also no difference in in-hospital mortality (4.1% vs 4.3%, p 0.9), 30-day mortality (5.2% vs 6.4%, p 0.5), 1-year mortality (9.1% vs 9.9%, p 0.7), 30-day stent thrombosis (1% vs 0.4%, p 0.5) and non-CABG bleeding (2.7 vs 3.7%, p 0.4) between the bivalirudin and abciximab group respectively. On Cox proportional hazard analysis after adjusting for all the co-variates, the use of bivalirudin was not a predictor of 30-day mortality (HR 1.13, 95% CI 0.7–1.9, p 0.7).ConclusionIn this “real-world” observational study, there was no significant difference in the clinical outcome of PPCI for patients who had abciximab or bivalirudin after initial pre-treatment with UFH.     

Variability and determinants of wood dust and resin acid exposure during wood pellet production: measurement strategies and bias in assessing exposure-response relationships

Production of wood pellets is a relatively new and expanding industry in which the exposure profiles differ from those in other wood-processing industries like carpentries and sawmills where there are lower levels of wood dust. Sixty-eight personal exposure measurements of wood dust (inhalable and total dust) and resin acids were collected for 44 participants at four production plants located in Sweden. Results were used to estimate within- and between-worker variability and to identify uniformly exposed groups and determinants of exposure. In addition, overexposure, whether the risk of the long-term mean exposure of a randomly selected worker exceeding the occupational exposure limit is acceptably low, was calculated as well as the underestimation of the exposure-response relationship (attenuation). Greater variability in exposure between work shifts than between workers was observed with the within-worker variation accounting for 57-99% of the total variance in the individual-based model. Several uniformly exposed groups were detected but were mostly associated with a between-worker variation of zero which is an underestimation of the between-worker variation but an indication of uniformly exposed groups. Cleaning was identified as a work task that increases exposure slightly; so reducing workers' exposure during this operation is advisable. The levels of wood dust were high and were found to pose unacceptable risks of overexposure at all plants for inhalable dust and at three out of four plants for total dust. These findings show that exposure to dust needs to be reduced in this industry. For resin acids, the exposure was classed as acceptable at all plants. According to an individual-based model constructed from the data, the level of attenuation was high, and thus there would be substantial bias in derived dose-response relationships.     

Adaptation of canine pancreatic enzymes to diet composition

1. Lipase, protease and amylase activity in canine pancreatic juice were determined during the feeding of basal, high fat, high protein and high carbohydrate diets for 3-week periods.2. The level of lipase in pancreatic juice was significantly augmented by increasing the dietary intakes of fat (P < 0.05) and carbohydrate (P < 0.05) but was not affected by increasing the protein intake.3. Protease activity was highly augmented by increasing the intake of protein (P < 0.01), was less strongly augmented by increasing carbohydrate (P < 0.10), but was not affected by the level of dietary fat ingested.4. Enzyme activities in canine pancreatic juice were modified by the nature of the diet on which the animals were maintained and the response for a given enzyme may be influenced by more than one dietary constituent.     

Treatment of the exposed Achilles tendon using negative pressure wound therapy: a case report

Exposed tendons after burn injury create a surgical challenge for the treating physician. This is particularly true with regard to the exposed Achilles tendon. This case report reviews the nature of this challenge and traditional solutions, and describes the use of negative pressure wound therapy to facilitate coverage of the Achilles tendon. This therapy may provide a more appropriate therapeutic option for dealing with tendon exposure after severe burns.     

Sensory factors which affect the acceptance of raw and heated defatted soybeans by rats

The acceptability of heated soybean meal (HS) compared to raw soybean flakes (RS) was studied by means of diet selection in free choice situations. The selection by rats of diets containing HS over those containing RS was shown in short- and long-term preference tests. Texture did not seem to be an important factor in the acceptability difference between HS and RS. Rats selected a less nutritious diet containing RS + sodium saccharin (appealing taste) over a diet containing HS + sucrose octaacetate (aversive taste) for an initial 6 to 7 days, suggesting that post-ingestional factors did not markedly affect the acceptability during that period. However, after this initial period, the rats selected the diet of higher nutritive value, even though it had added sucrose octaacetate. Preference tests before and after producing anosmia indicated that RS contains an aversive odor(s) which could be removed by vacuum treatment. Heated soybean meal was found to contain an appealing taste stimulus (i) which could also be removed by vacuum treatment.