Sweat Sodium Related to Amount of Sweat after Sweat Test in Children with and without Cystic Fibrosis

ABSTRACT. The sweat concentration of sodium was found to be inversely correlated with the amount of sweat obtained after a sweat test according to the method of Gibson & Cook in children without and with cystic fibrosis. Reference intervals for sweat sodium overlapped for the two groups but two-dimensional reference distributions for the amount of sweat (range 20-440 mg) correlated with its sodium content were completely separated. The establishment of similar distributions in centres carrying out sweat tests could serve to assess the performance of this investigation at local level.     

Cost and health consequences of reducing the population intake of salt

STUDY OBJECTIVE: The aim was to estimate health and economic consequences of interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g per person in the Norwegian population. Health promotion (information campaigns), development of new industry food recipes, declaration of salt content in food and taxes on salty food/subsidies of products with less salt, were possible interventions. DESIGN: The study was a simulation model based on present age and sex specific mortality in Norway and estimated impact of blood pressure reductions on the risks of myocardial infarction and stroke as observed in Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure (range 1-4) was assumed through the actual interventions. The cost of the interventions in themselves, welfare losses from taxation of salty food/subsidising of food products with little salt, cost of avoided myocardial infarction and stroke treatment, cost of avoided antihypertensive treatment, hospital costs in additional life years and productivity gains from reduced morbidity and mortality were included. RESULTS: The estimated increase in life expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost of the interventions was minus $118 millions (that is, cost saving) in the base case. Sensitivity analyses indicate that the interventions would be cost saving unless the systolic blood pressure reduction were less than 2 mm Hg, productivity gains were disregarded or the welfare losses from price interventions were high. CONCLUSION: Population interventions to reduce the intake of salt are likely to improve the population's health and save costs to society.     

Dose-related increases in quantitative values for altered hepatocytic foci and cytochrome P-450 levels in the livers of rats exposed to phenobarbital in a medium-term bioassay

The dose-response relationship between liver tumor promoting activity and cytochrome P-450 (CYP) induction by phenobarbital sodium (PB) was investigated using the liver medium-term bioassay system of Ito. Two weeks after a single dose of N-nitrosodiethylamine (DEN) (200 mg/kg body weight, i.p.), rats were given PB at dietary levels of 500, 250, 125, 60, 30, 15 and 8_parts per million (ppm) for 6 weeks. All rats were subjected to partial hepatectomy at week 3, and were killed at week 8. Quantitative values for glutathione S-transferase placental form positive hepatocytic (GST-P⁺) foci were increased in the high dose groups dose-dependently. In contrast, the values in the low dose groups were rather lower than that of the control. CYP2B1, 2C6 and 3A2 were predominantly immunostainable in hepatocytes around the central vein. While Western blotting revealed CYP2B1 and 2C6 proteins to be increased with strict dose-dependence, CYP3A2 was only elevated at high doses. Thus, a good correlation between increase of GST-P⁺ foci and CYP3A2 induction was observed, as well as with CYP2B1 and 2C6 in high dose groups.     

Permeability of the round window membrane

Summary Cefmetazole sodium, a cephamycin antibiotic, was shown to pass through the round window membrane into the inner ear of the guinea pig. The concentration of the drug in the inner ear fluid indicated that a larger amount of the drug reached the inner ear through the round window membrane than when administered intraperitoneally.This study was supported by a Research Grant for Specific Diseases from the Ministry of Health and Welfare's Acute Profound Deafness Research Committee of Japan     

Interleukin-1beta converting enzyme (caspase-1) in intestinal inflammation

An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1 polarizing cytokine IL-12. Recent studies provide evidence for the participation of IL-18 in the pathogenesis of IBD: IL-18 expression is increased in inflamed lesions of Crohn's disease patients and neutralization of IL-18 in different models of experimental colitis resulted in a dramatic amelioration of disease severity. IL-18 and IL-1beta are cleaved and thereby activated by the interleukin-1beta converting enzyme (ICE). Activation of ICE also occurs during different types of infectious colitis, and ICE expression and subsequent release of IL-1beta and IL-18 significantly contribute to intestinal inflammation. ICE knockout mice as well as mice treated with the ICE inhibitor pralnacasan are protected against experimental mucosal inflammation. Thus, inhibition of ICE represents an intriguing new target that requires further investigation in animal models.     

Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity

Imidazoacridinones (IA) are a class of antitumor agents which includes C-1311, an interesting drug in clinical trials. This study investigated the mechanism of IA binding to DNA for a series of 13 analogs that differ in their cytotoxic potency. Using C-1311 as a model compound, crystallographic, spectroscopic and biochemical techniques were employed to characterize drug-DNA interactions. X-ray crystallographic analysis revealed a planar structure of imidazoacridinone core that is capable of intercalative DNA binding. Accordingly, C-1311 binding to DNA followed 'classical' pattern observed for intercalation, as proved by the DNA topoisomerase I-unwinding experiments, with relatively weak binding affinity (K(i)=1.2 x 10(5)M(-1)), and the binding site size of 2.4 bp. Other IA also bound to DNA with the binding affinity in the range of 10(5)M(-1) and binding site size of 2-3 bp, suggesting a prevalence of the intercalative mechanism, similar to C-1311. Considerable DNA binding affinity was displayed by all the highly cytotoxic derivatives. However, none of the analyzed drug-DNA binding parameters was significantly correlated with IA biological activities such as cell growth, DNA and RNA synthesis inhibition, or tumor growth inhibition, which suggests that the IA ability to non-covalently bind to DNA is not crucial for their biological activity. These results show that the ability to intercalate into DNA is a prominent attribute of IA, although factors other than intercalative binding seem to be required for the biological activities of IA drugs.     

Cutaneous response to irritants

We evaluated the role of pre-existing dermatitis in the response to irritants by patch testing the skin of 40 healthy volunteers and the uninvolved skin of 480 subjects for 2 days. These latter were affected by active atopic dermatitis, psoriasis, eczema with positive and negative patch test reactions, urticaria and generalized pruritus. A first panel containing 15 micro L of aq. solutions of disodium laureth sulfosuccinate (NaLSS) 5% and 10%, potassium cocoate (KCC) 5%, potassium oleate (KOL) 5%, zinc coleth sulphate (ZnCS) 5%, sodium mireth sulphate (NaMS) 5%, sodium cocoamphoacetate (NaCCAA) 3% and 5%, was simultaneously applied to 1 site on the upper back. The results, scored by visual assessment, were compared to those observed when testing on the opposite side a second panel containing 15 micro L of aq. solutions of 3 well-known irritants, benzalkonium chloride (BAK) 1%, sodium lauryl sulphate (SLS) 1%, and dimethylsulphoxide (DMSO) 10%. Whilst the substances of the first panel and DMSO gave, on the whole, a scarce number of positive responses in all the tested groups, more evident differences in number, percent and mean intensity of the positive responses to BAK and SLS were found between the different groups. Although some of them seemed statistically significant, when the same values were evaluated by means of chi2 and Student t-test, they did not differ in a statistically significant way from the values found in healthy subjects. The results of this study seem to indicate that the substances of the first panel have a chemical structure that makes them quite safe in real-life conditions. In contrast, BAK and SLS have chemical properties that condition the number and intensity of the responses, making the role exerted by the pre-existing dermatosis quite marginal. In particular, there is no proof that the healthy skin of active atopic subjects is the most susceptible to the irritating effects of the tested substances.     

Assessment of irritant skin reactions using electrical impedance--a comparison between 2 laboratories

To assess interlaboratory variability in the measurement of skin electrical impedance (IMP), we evaluated irritant reactions to sodium lauryl sulfate (SLS) (2%) and nonanoic acid (NAA) (40%) in 2 laboratories. We studied the patch test responses in 40 healthy male and female volunteers between 20 and 30 years of age (20 in each laboratory) with an instrument for measuring IMP. 2 other bioengineering methods and visual scoring were also used to facilitate further illumination of any findings. A strict protocol including all details of the measurement procedure was carefully implemented in both laboratories. The skin reactions were evaluated at 23 h and at 3, 7 and 14 days after exposure. Our findings show that both irritants caused distinct dynamic responses detectable with the bioengineering techniques. Interestingly, the IMP baseline values varied between the 2 laboratories. Moreover, at early stages in the development of irritation (day 1), the irritants induced changes in IMP indices in the opposite direction, which accords with the concept of various IMP patterns of contact dermatitis caused by different irritants. Although the absolute values of IMP differed in both laboratories, the dynamic response patterns were the same.