Esterase activity of synthetic fragments of human adrenocorticotrophic hormone.

The anterior pituitary hormone adrenocorticotrophin (ACTH) has been extensively studied in terms of structure-function relationships and in vivo and in vitro activities of different synthetic fragments of ACTH have been characterized. Here we describe the ability of synthetic fragments of ACTH to hydrolyze a fluorogenic esterase substrate 4-methylumbelliferyloleate (MUBO). The measured esterase activities (in mumol 4-MU mol-1 s-1) were 79.7 for ACTH1-13, 385.9 for ACTH3-18, 503.0 for ACTH1-19, 1249.9 for ACTH1-24 D-ser3, and 1350 for ACTH1-24. Although the significance of the observed esterase activities in the actual molecular mechanisms of action of ACTH remains to be established it is worth noticing that the esterase activities of the different ACTH fragments closely parallel their reported ability to activate the brain lipase as well as their in vivo ability to induce steroidogenesis in adrenal cortex.     

Impact of aging on muscle blood flow in chronic heart failure.

Chronic heart failure (CHF) is manifested principally in the elderly population. Therefore, to understand the causes of exercise intolerance in CHF patients, it is imperative to resolve the effects of aging on muscle blood flow (BF) in CHF. To address this issue, we determined the muscle BF response to submaximal treadmill exercise (20 m/min, 5% grade) in young (Y(CHF): 6-8 mo, 412 +/- 11 g, n = 11) and old (O(CHF): 27-29 mo, 494 +/- 10 g, n = 8) Fischer 344 x Brown Norway rats with similar degrees of myocardial infarction-induced left ventricular (LV) dysfunction [resting LV end-diastolic pressure: Y(CHF) = 24 +/- 2, O(CHF) = 22 +/- 2 mmHg; derivative of LV pressure over time: Y(CHF) = 5,168 +/- 285; O(CHF) = 5,050 +/- 165 mmHg/s; lung weight normalized to body weight: Y(CHF) = 9.14 +/- 0.72; O(CHF) = 8.21 +/- 0.29 mg/g (all P > 0.05)]. The exercising heart rate response was blunted in O(CHF) compared with Y(CHF) rats (Y(CHF) = 454 +/- 8, O(CHF) = 395 +/- 9 beats/min; P < 0.05). BF (radiolabeled microspheres) to the total hindlimb musculature and to each of the 28 individual muscles examined was similar between Y(CHF) and O(CHF) rats under resting conditions. During exercise, BF to five of the hindlimb muscles that normally possess a majority of slow-twitch oxidative and fast-twitch oxidative glycolytic muscle fibers increased significantly less (-25 to -42%) for O(CHF) compared with Y(CHF) rats. In contrast, BF to 14 of the hindlimb muscles that normally possess a majority of fast-twitch glycolytic muscle fibers was increased (+22 to +337%) for O(CHF) vs. Y(CHF) rats, which contributed to a greater mass-specific total hindlimb BF response in O(CHF) rats (Y(CHF) = 78 +/- 5, O(CHF) = 100 +/- 11 ml.min(-1).100 g(-1); P < 0.05) and coincided with greater reductions in BF to the kidneys and splanchnic organs during exercise in O(CHF) vs. Y(CHF). In conclusion, there appears to be a profound age-related redistribution of BF from the highly oxidative to the highly glycolytic muscles of the hindlimb during exercise in O(CHF) compared with Y(CHF) rats. This phenomenon is qualitatively similar to that reported previously for healthy young and old rats.     

Intestinal Microbiota and Microbial Metabolites Are Changed in a Pig Model Fed a High-Fat/Low-Fiber or a Low-Fat/High-Fiber Diet

The intestinal microbiota and its metabolites appear to be an important factor for gastrointestinal function and health. However, research is still needed to further elaborate potential relationships between nutrition, gut microbiota and host’s health by means of a suitable animal model. The present study examined the effect of two different diets on microbial composition and activity by using the pig as a model for humans. Eight pigs were equally allotted to two treatments, either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for 7 weeks. Feces were sampled at day 7 of every experimental week. Diet effects on fecal microbiota were assessed using quantitative real-time PCR, DNA fingerprinting and metaproteomics. Furthermore, fecal short-chain fatty acid (SCFA) profiles and ammonia concentrations were determined. Gene copy numbers of lactobacilli, bifidobacteria (P<0.001) and Faecalibacterium prausnitzii (P<0.05) were higher in the LF pigs, while Enterobacteriaceae were more abundant in the HF pigs (P<0.001). Higher numbers of proteins affiliated to Enterobacteriaceae were also present in the HF samples. Proteins for polysaccharide breakdown did almost exclusively originate from Prevotellaceae. Total and individual fecal SCFA concentrations were higher for pigs of the LF treatment (P<0.05), whereas fecal ammonia concentrations did not differ between treatments (P>0.05). Results provide evidence that beginning from the start of the experiment, the LF diet stimulated beneficial bacteria and SCFA production, especially butyrate (P<0.05), while the HF diet fostered those bacterial groups which have been associated with a negative impact on health conditions. These findings correspond to results in humans and might strengthen the hypothesis that the response of the porcine gut microbiota to a specific dietary modulation is in support of using the pig as suitable animal model for humans to assess diet-gut-microbiota interactions.Data are available via ProteomeXchange with identifier PXD003447.     

Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study.

An increase in induced abortions in Sweden has been accompanied by an increase in the incidence of breast cancer of about 40% in women aged 20-44. To assess whether the apparent risk is real the risk of breast cancer was investigated in practically all Swedish women with a history of a legal abortion in the first trimester before the age of 30 during 1966-74 (n = 49,000). The cohort was followed up in the Swedish cancer register to identify cases of breast cancer diagnosed more than five years after the abortion until the end of 1984. The number of observed cases of breast cancer was 65 compared with an expected number of 84.5, estimated from the contemporary Swedish population with due consideration to age, giving a relative risk of 0.8 (95% confidence interval 0.58 to 0.99). Contrary to most earlier reports, this study did not indicate any overall increased risk of breast cancer after an induced abortion in the first trimester in young women.     

Correlation of exons with structural domains in alcohol dehydrogenase.

The intron/exon arrangement in the gene sequence of maize alcohol dehydrogenase has been compared to the three dimensional structure of liver alcohol dehydrogenase. The co-enzyme binding domain is separated from the catalytic domain by introns four and nine. Intron seven separates the co-enzyme binding domain into two structurally similar mononucleotide binding units. The first of these units is divided by introns five and six into three structurally similar alpha beta modules. Implications of these results for protein evolution is discussed. All splice junctions map close to or at the surface of the domains, and several of these cannot be identified by distance maps.     

Determination of free concentration of sameridine in blood plasma by ultrafiltration and coupled-column liquid chromatography

Sameridine is a new candidate drug with both local anaesthetic and analgesic properties. The free concentration of sameridine in blood plasma was determined by coupled-column liquid chromatography. Following adjustment of the pH and the temperature of the plasma samples, the free fraction was prepared by ultrafiltration. The coupled-column liquid chromatographic system consisted of a reversed-phase column, a cation-exchange extraction column and a cation-exchange analytical column. Sameridine was detected by UV determination at 205 nm and the system showed high selectivity. The limit of quantification was 1 nM and the within-day precision was 4.6% (R.S.D., n=10).     

Use of the MHC for mate choice in wild house mice (Mus domesticus)

The mechanisms maintaining natural diversity at the major histocompatibility complex (MHC) are not well understood. To increase knowledge of one potential mechanism, I examined the use of MHC genes for mate choice by wild house mice in a controlled laboratory setting. Three rearing groups of wild test mice were produced: non‐fostered control mice, mice fostered into families of an inbred laboratory mouse strain, and mice fostered into families of a second, MHC‐congenic mouse strain. Mature test mice were given a choice of two opposite‐sex stimulus mice from the two MHC‐congenic strains used for fostering, and were scored for several measures of preference. The results were non‐significant in general, but females of two rearing groups spent significantly more time with mice of one MHC‐type, and in most rearing groups, mice tended to spend more time with this same MHC‐type. Other results showed that male test mice ejaculated indiscriminantly and that female wild mice mated to ejaculation more often in longer length trials, but showed no significant preferences. In this study, fostering seemed to have little or no effect on MHC‐based mate preferences of wild house mice, and wild mice did not appear to be using the MHC to avoid inbreeding. However, some wild female mice used the MHC to choose potential mates. This revised version was published online in July 2006 with corrections to the Cover Date.