Contribution of vascular rejection to progression of transplant coronary disease as assessed by serial intravascular ultrasound.
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Biomedical subjects
Publications and source records attributed to S Nissen.
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Clinicians have long used the size of the lumen and the angiogram as a predictor of coronary events. However, cardiovascular disease is not a disease of the lumen but a disease of the vessel wall. In early stages, atherosclerosis outwardly remodels the external elastic membrane; only late in the disease process does luminal narrowing occur, enabling angiographic detection. This has profound implications for drug therapy, because approximately 70% of patients present with acute myocardial infarction (MI) or sudden death, not angina as the first symptom of coronary disease. Intravascular ultrasound (IVUS) can provide detailed images of the artery and is the only technique currently available that enables physicians to routinely visualize coronary plaques. Due to its sensitivity in measuring plaque volume and content, IVUS may be a useful surrogate marker to evaluate the atherosclerotic process in smaller numbers of patients than required for conventional clinical endpoint trials.
beta-Hydroxy-beta-methyl butyrate(HMB) has been shown to counteract many of the negative effects of intensive animal production methods and results in increased growth and protection against diseases. In the present study, the effect of HMB on the immunocompetence cell activity in rainbow trout (Oncorhynchus mykiss) and carp (Cyprinus carpio) was examined. Pronephric phagocytes and lymphocytes were isolated from the fish and grown in culture medium (RPMI-1640) containing either 0, 0.1, 1, 5, 10, 25, 50 or 100 microg HMB/ml of medium. The effects of HMB on the respiratory burst activity (RBA) stimulated by phorbol myristate acetate (PMA), the potential killing activity (PKA) and lymphocyte proliferation stimulated by either concanavalin A (Con-A) or lipopolysaccharide (LPS) were examined. The addition of HMB to the culture medium increased the RBA by up to 84% (p<0.01) over that of cells grown without HMB. Similarly, the PKA of the phagocytes was also increased with HMB addition to the medium by up to 140% (p<0.01) over that of cells grown without HMB. Lymphocyte proliferation stimulated by both ConA and LPS was also increased approximately two-fold (p<0.01) when HMB was added to the culture medium at concentrations between 10 and 100 microg HMB/ml in both rainbow trout and carp. The greatest effects of HMB on RBA and PKA activities were observed at a concentration >50 microg HMB/ml while lymphocyte proliferation was maximally stimulated at 25 microg HMB/ml. In conclusion, the current study shows that HMB could potentially improve immunocompetence cell activity in fish through increased cell proliferation and functionality.
BACKGROUND: The high standard of hygiene required in using contact lenses requires regular sterilization, for which the application of a hydrogen peroxide system or storage in liquids containing antimicrobial agents are regarded as the most effective procedures. An approach to avoiding contamination could be to provide the lenses themselves with antimicrobial properties. For this purpose contact lenses equipped with a silver layer were examined for their effect on bacteria. MATERIALS AND METHODS: The antimicrobial efficacy of a silver layer on Weflex 55 hydrogellenses (watercontent 55%, nonionic) was investigated. The lenses were incubated at 37 degrees C for 1 h in suspensions (10(8) CFU/ml) with Pseudomonas aeruginosa or Staphylococcus aureus and were rinsed afterwards. The detachment of the adherent bacteria took place by shaking the lenses in the presence of glass beads (diameter 0.5 mm). Samples of these suspensions were taken, and microbial counts were performed before and after incubation of the contaminated lenses for 6 h and 24 h in a sterile solution of sodium chloride (0.9%, w/v). RESULTS: Lenses with a silver layer showed markedly fewer test organisms than did unprepared lenses. However, this effect was detectable only when the contaminated lenses were kept in sodium chloride solution (0.9%) for several hours. After incubation for 67 at 25 degrees C the microbial numbers of P. aeruginosa were diminished by about 4 log steps, and those of S. aureus by about 1 log step. Particularly in the case of P. aeruginosa the antimicrobial property of the silver layer was very effective. The microbial numbers of this species, which can cause serious infections of the eyes, were reduced after 24 h by more than 6 log steps. However, S. aureus showed a reduction of only 1.5 log steps. These results reflect the antimicrobial effect of silver ions which are dissolved from depots in the surfaces of the lenses only in traces because of their low dissolution properties. CONCLUSIONS: These first investigations of preserved contact lenses indicate a new possibility for reducing lens-induced infections of the eyes. Due to the weak efficacy against the gram-positive species S. aureus a silver layer probably cannot replace other sterilization procedures completely, but it may represent an additional protection from contamination. Side effects to the eyes due to the negligible toxicity of oligodynamics silver concentrations, such are known to occur with high silver concentrations, should be not expected, but possible allergic reactions caused by the silver-ions should be investigated.
The effects of supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were examined in a resistance training study. Thirty-nine men and 36 women between the ages of 20-40 y were randomized to either a placebo (P) supplemented or HMB supplemented (3.0 g HMB/d) group in two gender cohorts. All subjects trained three times per week for 4 wk. In the HMB group, plasma creatine phosphokinase levels tended to be suppressed compared to the placebo group following the 4 wk of resistance training (HMB:174. 4 +/- 26.8 to 173.5 +/- 17.0 U/L; P:155.0 +/- 20.8 to 195.2 +/- 23.5 U/L). There were no significant differences in strength gains based on prior training status or gender with HMB supplementation. The HMB group had a greater increase in upper body strength than the placebo group (HMB:7.5 +/- 0.6 kg; P:5.2 +/- 0.6 kg; P = 0.008). The HMB groups increased fat-free weight by 1.4 +/- 0.2 kg and decreased percent fat by 1.1% +/- 0.2% while the placebo groups increased fat-free weight by 0.9 +/- 0.2 kg and decreased percent fat by 0.5% +/- 0.2% (fat-free weight P = 0.08, percent fat P = 0.08, HMB compared to placebo). In summary, this is the first short-term study to investigate the roles of gender and training status on the effects of HMB supplementation on strength and body composition. This study showed, regardless of gender or training status, HMB may increase upper body strength and minimize muscle damage when combined with an exercise program.
The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.
The effect of a high dose of 3-hydroxy-3-methylbutyrate (HMB, a leucine catabolite) on protein metabolism was investigated in growing male lambs fed on hay and concentrate. Concentrate was supplemented with either Ca(HMB)2 (4 g/kg) or Ca(CO3)2 in experimental (HMB) and control groups respectively. Both groups consisted of six 2-month old lambs. Three complementary methods to study protein metabolism were carried out consecutively 2.5 months after beginning the dietary treatment: whole body phenylalanine fluxes, postprandial plasma free amino acid time course and fractional rates of protein synthesis in skeletal muscles. Feeding a high dose of HMB led to a significant increase in some plasma free amino acids compared with controls. Total, oxidative and non-oxidative phenylalanine fluxes were not modified by dietary HMB supplementation. Similarly, an acute infusion of HMB, in the control group, did not change these fluxes. In skeletal muscles, fractional rates of protein synthesis were not affected by long-term dietary supplementation with HMB. Taken together our results showed that administration of a high dose of HMB to lambs was able to modify plasma free amino acid pattern without any effect on whole-body protein turnover and skeletal muscle protein synthesis.
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The effects of dietary supplementation with the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) were studied in two experiments. In study 1, subjects (n = 41) were randomized among three levels of HMB supplementation (0, 1.5 or 3.0 g HMB/day) and two protein levels (normal, 117 g/day, or high, 175 g/day) and weight lifted for 1.5 h 3 days/wk for 3 wk. In study 2, subjects (n = 28) were fed either 0 or 3.0 g HMB/day and weight lifted for 2-3 h 6 days/wk for 7 wk. In study 1, HMB significantly decreased the exercise-induced rise in muscle proteolysis as measured by urine 3-methylhistidine during the first 2 wk of exercise (linear decrease, P < 0.04). Plasma creatine phosphokinase was also decreased with HMB supplementation (week 3, linear decrease, P < 0.05). Weight lifted was increased by HMB supplementation when compared with the unsupplemented subjects during each week of the study (linear increase, P < 0.02). In study 2, fat-free mass was significantly increased in HMB-supplemented subjects compared with the unsupplemented group at 2 and 4-6 wk of the study (P < 0.05). In conclusion, supplementation with either 1.5 or 3 g HMB/day can partly prevent exercise-induced proteolysis and/or muscle damage and result in larger gains in muscle function associated with resistance training.
The binding capacity of calcium beta-hydroxy-beta-methylbutyrate (calcium HMB), compared to other binders, was investigated in an in vitro study. Fifty milliequivalents of either calcium HMB, calcium acetate, calcium carbonate, aluminum hydroxide gel or non-gel aluminum hydroxide was added to a phosphate solution, titrated (HCl or NaOH), shaken and centrifuged to four different pH levels at 37 degrees C (simulating the gastrointestinal milieu). The difference in phosphate concentration between that of the initial and that of the supernatant represented from the bound phosphate in the precipitate. After 4 h at a pH of 6 (representing the intestinal condition after a meal), the binding percentage was: calcium acetate = 95.6%, calcium HMB = 92.6%, calcium carbonate = 46.4%, aluminum hydroxide gel = 33.4% and non-gel aluminum hydroxide = 17.8%. There was no significant difference (p > 0.05) between calcium HMB and calcium acetate. These results suggest that calcium HMB is an efficient phosphate binder in vitro, which may predict its effective role in vivo.
Cytokine production by endothelial cells is known to occur after the reception of signals such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). In the present study, we demonstrate cytokine release and upregulation of adhesion molecule expression of human endothelial cells derived from umbilical cord veins in response to stimulants. The cells were exposed to the plant lectin phytohemagglutinin A (PHA), the viral inducers Newcastle disease virus (NDV) and Sendai virus, and the nucleic acid analog polyinosinic/polycytidylic acid (polyI:C). All stimulants induced expression of IL-1 beta and IL-6. The titers of these cytokines were comparable to those obtained in human leukocytes, whereas no TNF-alpha release was detectable. A further feature of activation was upregulation of intercellular adhesion molecule 1 (ICAM-1), which was analyzed after contact with these stimulants. These experiments revealed an increased expression of ICAM-1 in response to all stimulants tested. A major part of our studies was devoted to the ability of endothelial cells to produce interferons as an important function of a number of cell types in response to viral infections. To ensure stimulation of the cells, the inducers NDV, Sendai virus, and polyI:C were analyzed. Expression of interferon (IFN) was not detected, although viral inducers mediated the release of IL-1 beta and IL-6, suggesting that endothelial cells are quite responsive to these stimulants. In conclusion, these findings show that the ability of endothelial cells to secrete cytokines is not restricted to mediators of the immune system, such as IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Beta-hydroxy-beta-methyl butyrate (HMB), a compound formed during catabolism of leucine, was fed to 256 crossbred steers as 0 or .03% of diet dry matter. Effects on performance, carcass characteristics, and tissue composition were measured. Groups of 32 steers per diet were slaughtered after 105, 119, 133, and 147 d on feed. The HMB was fed to each group only during the final 82 d they were fed. Averaged across slaughter date, animal performance was not altered by HMB; however, an interaction between HMB and time on feed was detected. Feeding HMB increased (P < .01) daily gain of steers slaughtered at 105 d but decreased (P < .01) daily gain of steers slaughtered at 147 d. Steers fed HMB had numerically higher marbling scores that resulted in a trend toward higher carcass quality grades. Steers receiving HMB tended to have less (P < .08) s.c. fat and fewer steers with yield grades of 4 or greater (1.6 vs 4.7%). Supplementation of HMB to feedlot steers tended to increase (P < .07) the ratio of intramuscular fat to subcutaneous fat. Steers fed HMB had higher (P < .001) blood plasma concentrations of HMB (3.06 vs 1.70 mg/L) and lower (P < .03) blood plasma concentrations of cholesterol (108.4 vs 118.7 mg/dL). Feeding HMB tended to increase (P < .10) lipid content of the longissimus muscles of those steers slaughtered at 105 d.
Three trials were conducted to test whether feeding the leucine metabolite beta-hydroxy-beta-methyl butyrate (HMB) would increase fat content of sows' milk and pig weight gain. All sows received a basal diet and were assigned at random to receive either 2 g of CaCO3/d (control) or 2 g of Ca(HMB)2/d (HMB), which was top-dressed to the basal diet. Treatment began 3 to 4 d before farrowing. In Trials 1, 2, and 3 there were 4, 19, and 11 pairs of sows, respectively. In a combined analysis that included all three trials, milk fat at d 1 was increased by 41% (P = .01) and pig weight at d 21 was increased by 7% (P = .01) for sows fed diets containing HMB compared with sows fed control diets. Sows fed HMB lost more backfat (P = .03); however, sows receiving HMB had more (P < .05) backfat depth at farrowing than control sows. At weaning there was no difference in backfat depth between the treatment groups. Sows fed HMB tended to consume less feed (P = .07) than control sows. In Trials 2 and 3, data were collected on the subsequent reproductive cycles of the sows. A combined analysis of the data revealed no differences in sow performance when sows previously fed the diet containing HMB were compared with sows previously fed the control diet. In conclusion, beta-hydroxy-beta-methyl butyrate, when fed to sows at 2 g/d, resulted in an increase in fat percentage of sow's milk and pig performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Experiments were conducted to determine whether the leucine catabolite beta-hydroxy-beta-methylbutyrate (HMB) could influence protein metabolism in broilers. In Experiment 1, HMB was fed at either .01 or .05% of the diet. beta-Hydroxy-beta-methylbutyrate did not improve feed conversion or BW gain; however, broilers fed HMB at .01% in a diet formulated to meet NRC (1984) recommendations had no mortality (P < .03) from 0 to 21 d of age. In Experiment 2, HMB fed at .003, .01, .03, and .09% of the diet had no significant affect on growth or carcass yield of the broilers when compared with control-fed broilers. In Experiment 3, HMB fed at .001, .003, and .01% of the diet had no effect on broiler growth. In Experiment 4, HMB was fed at .01% of the diet in combination with an antibiotic and coccidiostat (GP). Use of GP increased (P < .01) BW, feed conversion, and carcass yield when compared with the control broilers. In Experiment 5, HMB was fed at .1% of the diet, and effects of sex and GP were examined. beta-Hydroxy-beta-methylbutyrate decreased (P < .01) mortality by 72% in the male broilers. In a combined analysis, HMB fed at .01% of the diet (Experiments 1, 2, and 3) increased breast yield (P < .05) and reduced mortality by 56% (P < .04) from 0 to 21 d of age. In a combined analysis, HMB fed at .003% of the diet (Experiments 2 and 3) increased 42-d BW (P < .02) and hot (P < .04) and chilled (P < .05) carcass yields. In conclusion, across all HMB dosages mortality of male broilers was decreased from 6.37 to 4.39% (-31%, P < .04) by feeding HMB, with the pattern of death suggesting that HMB decreased the incidence of sudden death syndrome in these broilers.
Coronary intravascular ultrasound imaging has been found to be the most sensitive method for detecting postcardiac transplantation coronary vasculopathy. Techniques for this type of imaging have been well established for adult patients, but coronary intravascular ultrasound imaging in young children has not been previously reported. We describe the cases of 2 children, ages 8.5 years and 9 months, respectively, who had confusing clinical pictures after cardiac transplantation. Currently available imaging equipment and techniques were used in these children to visualize the coronary arteries. The results of ultrasound imaging were considered helpful in determining future treatment for these 2 pediatric patients.
The kinetics of 3-methylhistidine (3MH) metabolism in four crossbred lambs were studied. Each lamb was injected with an intravenous dose of 3-[2H3]methylhistidine (d3-3MH) and the stable isotope disappearance in plasma and appearance in both urine and muscle were measured. Immediately after the administration of tracer there was a phase of rapid disappearance of tracer from the plasma, which was followed by a more gradual decrease in d3-3MH from the plasma during the last 4 d of the experiment. A minimum of three exponentials was required to describe the plasma decay curve adequately. The kinetic model of 3MH in the whole animal was constructed by using the SAAM/CONSAM computer modelling program. Two different configurations of a three-compartment model are described: (1) a simple three-pool model, in which plasma kinetics were entered into pool 1 out of which they had one undefinable exit; (2) a plasma-urinary three-pool model with two exits, in which the urinary kinetics were entered as an exit out of pool 1 and required a second exit out of pool 3 to produce an adequate fit. In addition, muscle kinetics from biopsies of the longissimus dorsi were entered into either pool 2 or 3 using the plasma-urinary model. Steady-state mass and transport rate values were obtained for each model construct described, and a de novo production rate corresponding to a fractional breakdown rate of myofibrillar protein of approximately 5%/d was also calculated. The model predicted that only 15% of 3MH was excreted in urine as free 3MH, which is consistent with current knowledge of 3MH excretion in sheep. The simple three-pool plasma kinetic model, therefore, could be used to estimate, by a relatively simple injection-sampling technique, the extent of muscle protein turnover in lambs.
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The initial lymphatics of the human skin do not possess a basal lamina, but a subendothelial fibrous network, of which we do not know the biochemical and immunohistological composition. We investigated the wall of blood vessels and initial lymphatics in normal human skin for the presence of fibronectin by immunoelectron microscopy. We found discontinuous linear subendothelial diaminobenzidine (DAB) reaction products in both blood vessels and lymphatics. In addition fibronectin could be found at the anchoring fibrils of the initial lymphatics.