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.     

Correlates of alcohol use and misuse in fourth-grade children: psychosocial, peer, parental, and family factors

To determine level of alcohol use/misuse and to examine correlates of these behaviors, 1,314 fourth-grade students were surveyed. The questionnaire included 55 items concerning tolerance of deviance, deviant self-image, self-efficacy, susceptibility to peer pressure, personal and peer approval of alcohol use, peer adjustment, parent nurturance and monitoring, family adjustment, parental permissiveness, peer use of alcohol, and exposure to alcohol. The items were factor analyzed and indices constructed. The indices generally had acceptable alpha coefficients (alpha = .61-.91); two exceptions were peer adjustment (alpha = .51) and parental permissiveness (alpha = .42). Tolerance of deviance, deviant self-image, susceptibility to peer pressure, personal and peer approval, peer use and exposure by peers, and parental permissiveness were positively correlated with alcohol use/misuse. Self-efficacy, child-parent interactions, family adjustment, and peer adjustment were negatively correlated with alcohol use/misuse. Implications for the design of family-based alcohol use/misuse prevention programs are discussed.     

The use of low-osmolar contrast agents: technological change and defensive medicine

The escalating cost of medical care in the United States, especially in the past decade, has resulted in efforts to identify the factors contributing to rising costs. One factor often assumed to cause higher medical costs is the physician's fear of liability for not using the latest available technology. In this article, we report the results of a case study we conducted to better understand the relationship between the introduction and use of one particular technology, low-osmolar contrast agents, and liability concerns. Our study suggests that both clinicians and administrators are primarily guided by the medical benefits of low-osmolar contrast agents, and that liability concerns, although widespread, are of secondary importance. The inability to control this and similar technologies is likely to put a far greater strain on the nation's health care resources than is the practice of defensive medicine. These findings may be helpful to health policy makers, physicians, administrators, and legislators considering choices for health care reform in general and for medical liability reform in particular.     

Evolution of the serum amyloid A (SAA) protein superfamily

The serum amyloid A (SAA) superfamily comprises a number of genes and proteins characterized from a range of mammalian species. The majority of members described to date are dramatically induced during the acute-phase response, suggesting an important short-term beneficial role in the response to tissue injury and inflammation. However, important disease associations have also been proposed for certain SAAs during chronic inflammation. The nomenclature of many of the superfamily members has been the result of comparisons with previously reported sequences implying disease association and/or functional relatedness between such members. The evolutionary relationships of the SAA superfamily members have been investigated by comparisons at both the amino acid and the nucleotide level. The results indicate that all members of the superfamily within a species have been undergoing concerted evolution. This has important implications in ascribing functions and disease associations to individual SAA superfamily members and indicates that designations should not be based on the extent of amino acid identity alone but should be made only following direct experimental observation of the proteins themselves.     

THE PROGRESSION OF BENDING FATIGUE IN MONEL K500

Abstract— A comparison was made at room temperature of the fatigue sequence in Monel K 500 (N05500), both between the different states of solution heat treated, aged, and overaged, and with nickel that had been studied previously. The test mode was reversed bending and monitoring was by Nomarski interference contrast microscopy, in conjunction with sequential microhardness measurements. It was found that variations in Monel between the heat treated states were minor in comparison to differences with nickel. In Monel, the fatigue resistance was relatively poor because of ready intergranular, as well as transgranular, cracking. To achieve a significant life, the stress level had to be kept well below the yield strength, low enough to delay the onset of visible slip, for cracking would follow promptly. This meant that, in contrast to nickel, stress levels high enough to invoke strain hardening and obvious secondary slip led to exceedingly short lives. Also, inclusions mattered, slip occurring preferentially in their vicinity.