Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide

BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.     

Classification and prediction of the critical heat flux using fuzzy theory and artificial neural networks

A new method to predict the critical heat flux (CHF) is proposed, based on the fuzzy clustering and artificial neural network. The fuzzy clustering classifies the experimental CHF data into a few data clusters (data groups) according to the data characteristics. After classification of the experimental data, the characteristics of the resulting clusters are discussed with emphasis on the distribution of the experimental conditions and physical mechanism. The CHF data in each group are trained in an artificial neural network to predict the CHF. The artificial neural network adjusts the weight so as to minimize the prediction error within the corresponding cluster. Application of the proposed method to the KAIST CHF data bank shows good prediction capability of the CHF, better than other existing methods.     

Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets

Adequacy of nutrient intakes of adolescents with and without phenylketonuria (PKU) and infants and children with and without maple syrup urine disease (MSUD) were assessed using 3-day diet records sorted by disease and by age of the subject. Mean intakes of all nutrients were greater than two-thirds of the Recommended Dietary Allowances (RDA) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDI) for all adolescents studied, with the exception of selenium (Se) in PKU adolescents, which averaged 27.8 micrograms. For adolescents with PKU, > 50% of the RDA or ESADDI for all nutrients was provided by elemental or modified protein hydrolysate medical foods, except for vitamin A in children aged 11-15 years and Se in children 11-18 years. Mean nutrient intakes of all infants and children were greater than two-thirds of the RDA or ESADDI for all nutrients except Se in MSUD children aged 1-11 years, where intakes ranged from 6.4 to 13.2 micrograms (21-66% of the RDA). The medical foods provided for most of the RDA and ESADDI recommendations, with the exception of Se in MSUD children.     

Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.     

Radiation-laminar free convection in a square duct with specular reflection by absorbing-emitting medium

The purpose of this work is to study the effects of specularly reflecting wall under the combined radiative and laminar free convective heat transfer in an infinite square duct. An absorbing and emitting gray medium is enclosed by the opaque and diffusely emitting walls. The walls may reflect diffusely or specularly. Boussinesq approximation is used for the buoyancy term. The radiative heat transfer is evaluated using the direct discrete ordinates method. The parameters under considerations are Rayleigh number, conduction to radiation parameter, optical thickness, wall emissivity and reflection mode. The differences caused by the reflection mode on the stream line, and temperature distribution and wall heat fluxes are studied. Some differences are observed for the categories mentioned above if the order of the conduction to radiation parameter is less than order of 10^-3 for the range of Rayleigh number studied. The differences at the side wall heat flux distributions are observed as long as the medium is optically thin. As the top wall emissivity decreases, the differences between these two modes are increased. As the optical thickness decreases at the fixed wall emissivity, the differences also increase. The difference of the streamlines or the temperature contours is not as distinct as the side wall heat flux distributions. The specular reflection may alter the fluid motion.     

Congestion pricing of multi-modal transportation systems

This paper deals with the pricing and investment decision problem of multi-modal transportation systems in which the congestion is a significant factor in the assessment of system costs. This study approaches this congestion pricing problem with a number of social welfare maximization problems, all of which have the identical structure except financial constraints. One welfare maximization problem examined in this study yields the pricing and investment decision, which can attain the first-best social optimality for multi-modal transportation systems. Other welfare maximization problems show he second-best optimal solutions that can address two policy questions in transportation economics, namely, the cross-subsidy between competing modes and peak-period congestion charges on a single highway link. Received: February 2001/Accepted: December 2001 This work was supported in part by funds from BK21 Research Division of Seoul National University for Social Infrastructure and Construction Technology.     

Cigarette smoking and submaximal exercise test duration in a biracial population of young adults: the CARDIA study

Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the Coronary Artery Risk Development in Young Adults (CARDIA) study. Compared with nonsmokers, the mean exercise test duration of smokers was 29-64 s shorter depending on race/gender group (all P < 0.001), but mean duration to heart rate 130 (beats.min-1) ranged from 20-50 s longer (P < 0.05). In each race/gender group, test duration to heart rates up to 150 was 15-35 s longer (P < 0.05) in smokers than in nonsmokers after adjustment for age, sum of skinfolds, hemoglobin, and physical activity score. The mean maximum heart rate was lower in smokers than in nonsmokers (difference ranging from 6.7 beats.min-1 in white men to 11.2 beats.min-1 lower in black women, P < 0.001), although maximum rating of perceived exertion was nearly identical in smokers and nonsmokers. Chronic smoking appears to blunt the heart rate response to exercise, so that exercise duration to submaximal heart rates is increased even though maximal performance is impaired. This may result from downloading of beta-receptors caused by smoking. Smoking status should be considered in the evaluation of physical fitness data utilizing submaximal test protocols, or else the fitness of smokers relative to nonsmokers is likely to be overestimated.     

Lysosomal enzyme and inhibitor levels in the human trabecular meshwork

PURPOSE: To examine in the human trabecular meshwork lysosomal enzymes and one inhibitor of serine proteases that actively participate in the degradation of macromolecules into low molecular weight constituents. METHODS: Using an avidin-biotin-peroxidase technique, lysosomal proteases and alpha 1-proteinase inhibitor were examined in the trabecular meshwork of 23 human eyes with donor ages ranging from 2 to 90 years. These eyes were categorized into three age groups (< or = 20, 21 to 49, and > or = 50 years). Histochemical staining for lysosomal hydrolases was also performed on frozen sections of 20 human eyes. The staining was analyzed by an image analyzer and the levels of lysosomal proteases were further measured by biochemical assays. RESULTS: The trabecular meshwork from all the eyes stained intensely against antibodies to cathepsins B and G and alpha 1-proteinase inhibitor. The staining for elastase was weaker but evident. Image analyses revealed that the staining intensity for each protease or inhibitor was similar in all age groups. The staining in the uveal meshwork appeared to be the strongest among all the trabecular meshwork regions. Biochemical assays of tissue extracts confirmed that the enzyme and inhibitor levels were comparable among the three donor age groups. Activities of two lysosomal hydrolases, acid phosphatase and acid esterase, were also found in trabecular meshwork cells of 20 eyes. No apparent difference in enzyme activities was found with increasing age, and variation related to region was not observed. CONCLUSIONS: This study demonstrated the age-independent distribution of a variety of lysosomal enzymes and a protease inhibitor in the human trabecular meshwork. The presence of these proteins suggests a possible role in the metabolic operation of the trabecular meshwork.     

Biomechanical finite element analysis of bone cemented hip crack initiation according to stem design

The purpose of this investigation was to determine the specific fracture mechanics response of cracks that initiate at the stem-cement interface and propagate into the cement mantle. Two-dimensional finite element models of idealized stem-cement-bone cross-sections from the proximal femur were developed for this study. Two general stem types were considered; Rectangular shape and Charnley type stem designs. The FE results showed that the highest principal stress in the cement mantle for each case occurred in the upper left and lower right regions adjacent to the stem-cement interface. There was also a general decrease in maximum tensile stress with increasing cement mantle thickness for both Rectangular and Charnley-type stem designs. The cement thickness is found to be one of the important fatigue failure parameters which affect the longevity of cemented femoral components, in which the thinner cement was significantly associated with early mechanical failure for shot-time period.