Fish consumption and school grades in Swedish adolescents: a study of the large general population.

AIM: To study the associations between fish intake and academic achievement as cognitive parameter among Swedish adolescents. METHODS: In 2000, a questionnaire including respiratory items, socioeconomic conditions and dietary information was mailed to all schoolchildren (n = 18 158), aged 15 and living in Västra Götaland region of Sweden. The questionnaire was returned by 10 837 subjects. One year later, the total school grades for each subject who had completed the questionnaire and who included their full personal identification number were obtained from the national registers. Multiple linear regression models were applied to evaluate the association between fish intake and academic grades among 9448 schoolchildren, while adjusting for potential confounders, e.g. parents' education. RESULTS: Grades were higher in subjects with fish consumption once a week compared with subjects with fish consumption of less than once a week (reference group) [increment in estimate 14.5, 95% confidence interval (CI) 11.8-17.1]. Grades were even higher in subjects with fish consumption of more than once a week compared with the reference group (increment in estimate 19.9, 95% CI 16.5-23.3). In the model stratified for parents' education, there were still higher grades among subjects with frequent fish intake in all educational strata (p < 0.01). CONCLUSION: Frequent fish intake among schoolchildren may provide benefits in terms of academic achievement.

Comparison of confidence procedures for type I censored exponential lifetimes.

In the model of type I censored exponential lifetimes, coverage probabilities are compared for a number of confidence interval constructions proposed in literature. The coverage probabilities are calculated exactly for sample sizes up to 50 and for different degrees of censoring and different degrees of intended confidence. If not only a fair two-sided coverage is desired, but also fair one-sided coverages, only few methods are quite satisfactory. A likelihood-based interval and a third root transformation to normality work almost perfectly, but the chi 2-based method that is perfect under no censoring and under type II censoring can also be advocated.

On-line capillary electrophoresis with mass spectrometry detection for the analysis of carbohydrates after derivatization with 8-aminonaphthalene-1,3,6-trisulfonic acid.

Capillary electrophoresis (CE) with mass spectrometry (MS) detection is an ideal tool for analytical use, which combines a nano quantity assay with mass determination. Carbohydrate analysis has always been a challenge because of the inherent structural complexity and the lack of a chromophore, unless derivatization is used. Here we use the derivatization of carbohydrates with a fluorophore, 8-aminonaphthalene-1,3,6-trisulfonic acid (ANTS). This chromophore has two advantages, first, it facilitates UV and fluorescence detection and, second, it introduces negative charge to the analyte, which enhances zone electrophoretic separation. In this study, CE combined with negative ion electrospray MS (ESI-MS) was evaluated for the on-line analysis of ANTS labeled carbohydrates and cellulose fragments. The CE system was connected to the MS by a sheath-liquid electrospray arrangement. The ANTS reagent and Dextrin-15, which contains oligomers of maltose, were used as model samples for ESI-MS optimization in flow-injection-MS and CE-MS modes, respectively. Various sheath-liquid compositions regarding organic modifier (isopropanol, methanol, or acetonitrile) and electrolyte (acetic acid-formic acid, ammonium acetate, or triethylamine) were studied. The response as well as the analyte charge state distribution was found to be dependent on the composition and the orifice voltage. Low-pH conditions with isopropanol as organic modifier were sensitive, stable, and the most favorable for analysis.

Synthesis of 8-methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol (Isoaaptamine) and analogues.

8-Methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol, isoaaptamine, a PKC inhibitor isolated from sponge was synthesized. The synthesis parallels a synthesis of 8,9-dimethoxybenzo[de][1,6]naphthyridine, aaptamine, but uses a nitromethyl substituent as a precursor of the key 5-(2-aminoethyl)-1H-quinolin-4-one intermediate. The quinolone intermediates were prepared by thermolysis (220-240 degrees C) of anilinomethylene derivatives of Meldrum's acid. The quinolone intermediates were N-methylated prior to cyclization to the benzo[de][1,6]naphthyridine derivatives. Aaptamine and several analogues of aaptamine and isoaaptamine were prepared including 9-demethylaaptamine, 1-methyl-8-demethylaaptamine, 1-methylaaptamine, and the 8,9-methylenedioxy analogues of aaptamine and 1-methylaaptamine.

The distribution of the maximum likelihood estimator in up-and-down experiments for quantal dose-response data.

Standard maximum likelihood logistic or probit regression has been used in biopharmaceutical practice for inference about tolerance threshold distributions in situations where subjects (patients) have been allocated doses according to an up-and-down design. For example, a steeper dose-response curve than expected was reported in one such study. This article demonstrates that the maximum likelihood estimator systematically and considerably exaggerates the regression parameter with moderately large sample sizes. Thus a probable explanation for finding a steeper curve than expected is the method used to analyze the experiment, that is, the bias in the maximum likelihood estimator. An additional consequence of this bias is that the mean/median/ED50 are estimated with a misleading precision. In particular, confidence intervals are much too narrow. As a conclusion, we warn against conventional logistic or probit regression in combination with up-and-down designs.

Bis-cationic heteroaromatics as macrofilaricides: synthesis of bis-amidine and bis-guanylhydrazone derivatives of substituted imidazo[1,2-a]pyridines.

A series of guanylhydrazone, amidine, and hydrazone derivatives of 2-phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial activity against Acanthocheilonema viteae and Brugia pahangi in jirds. Compounds with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6-Bis-amidines show some activity but are more toxic; 4'- or 6-monosubstituted compounds are inactive. 2,6-Bis-substituted compounds lacking the phenyl ring are inactive. 4',6-Bis-substituted compounds having additional double bonds inserted between the heterocyclic ring and the phenyl ring or between the substituent and the ring system show reduced activity.

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.

Carbamates of (hydroxyphenoxy)methyl heteroaromatic salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds.

A series of N,N-dimethylcarbamates of 2-[(2'-, 3'-, and 4'-hydroxyphenoxy)methyl] heteroaromatic salts has been prepared. Pyridine, imidazole, quinoline, benzimidazole, and imidazo-[1,2-alpha]pyridine derivatives were included. Most of the compounds are inhibitors of electric eel acetylcholinesterase and also show prophylactic activity toward a 2LD50 dose of soman in mice.

Carbamate derivatives of 2-arylimidazo[1,2-a]pyridinium salts as acetylcholinesterase inhibitors and protective agents against organophosphorus compounds.

A series of 2-arylimidazo[1,2-a]pyridinium salts with (N,N-dimethylcarbamoyl)oxy or (N-methylcarbamoyl)oxy groups at the 3'- or 4'-position on the phenyl substituent and various substituents on the imidazo[1,2-a]pyridine ring have been synthesized. The compounds show in vitro inhibitory activity against electric eel acetylcholinesterase (AChE), type III, and several of the compounds show protective effects toward the organophosphorus AChE inhibitor soman in mice. The possible structural relationship of these compounds to physostigmine and pyridostigmine is considered.

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution.

The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation.

A new dextran 40-based solution for liver preservation.

UW solution is at present the most efficient solution for preservation of livers for transplantation. We have developed an alternative solution based on dextran instead of hydroxyethyl starch and without raffinose, allopurinol, magnesium sulfate, insulin, penicillin, or dexamethasone, which all are used in UW solution. In addition, 62.5 mM potassium in UW solution is replaced with sodium. We tested this new solution for liver preservation using the isolated perfused rabbit liver. We found that livers preserved in the UW solution for 24 or 48 hr lost 11.6 +/- 2.6% and 16.8 +/- 2.0% of the prepreservation weight, respectively, as a sign of organ shrinkage (P less than 0.001). In contrast, no change in liver weight was observed after preservation in the new dextran-based solution. Similarly, no change in total tissue water of the rat liver slices was seen after preservation in the new solution. Furthermore, livers preserved for 24 hr in the UW solution or the new solution produced the same amount of bile as unpreserved livers. However, after preservation in the UW solution for 48 hr, bile production was reduced by 65% (P less than 0.05). In contrast, livers preserved for 48 hr in the new solution showed no reduction in bile production. We conclude that our new solution significantly improves long-term liver preservation, and with this modified solution, 48-hr preservation may be safe.

Synthesis and evaluation of 2-diazo-3,3,3-trifluopropanoyl derivatives of colchicine and podophyllotoxin as photoaffinity labels: reactivity, photochemistry, and tubulin binding.

Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2-diazo-3,3,3-trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, and N-DTFP-deacetylthiocolchicine was shown to competitively inhibit tubulin-colchicine binding with a Ki of 4-5 microM. The tubulin off-rate of this analog was similar to that of podophyllotoxin, rather than to the relatively irreversibly bound colchicine. Photochemical solvent insertion reactions of the labels were investigated. Radioactive samples of the two most active labels were prepared and used in initial protein-labeling experiments, during which the fractional occupancy of tubulin and extent of covalent incorporation were determined. A rearrangement of DTFP amides was encountered which is relevant to the utility of this moiety for use in synthesis of photoaffinity labels.

Petite mutagenesis in Saccharomyces cerevisiae by a series of bis-cationic trypanocidal drugs.

A group of bis-cationic imidazo[1,2-a]pyridinium salts and related compounds, some of which exhibit in vivo trypanocidal activity, have been investigated for induction of petite mutagenesis in Saccharomyces cerevisiae. All of the compounds which are active trypanocides induce mutagenesis. There appears to be a correlation between trypanocidal activity and mutagenic activity which may have its structural origin in the spatial separation of the cationic centers.

The function of a colloid in liver cold-storage preservation.

The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function.

Characterization of posttranslational modifications in neuron-specific class III beta-tubulin by mass spectrometry.

Class III beta-tubulin, isolated from adult bovine brain, is resolved into at least seven charge variants on isoelectric focusing gels. To identify the posttranslational modifications responsible for this heterogeneity, a mixture of brain tubulins was treated with cyanogen bromide and the C-terminal fragments from the class III beta-tubulin isoforms were then isolated by binding them to the monoclonal antibody TuJ1. Combined use of tandem mass spectrometry and both subtractive and automated Edman degradation chemistry on the isolated peptides indicates that many of the isoforms differ by phosphorylation at Ser-444 plus attachment of one to six glutamic acid molecules to the side chain of the first glutamate residue, Glu-438, in the C-terminal sequence Tyr-Glu-Asp-Asp-Glu-Glu-Glu-Ser-glu-Ala-Gln-Gly-Pro-Lys.

The functional effects of suppression of hypothermia-induced cell swelling in liver preservation by cold storage.

It is known that cellular edema and functional impairment develop during anaerobic cold storage of organs. The extent of both is related to the storage time and the composition of the preservation solution used. We studied hypothermia-induced cell swelling and its effect on liver function after cold storage preservation with either Eurocollins (EC), a number of modified EC solutions in which glucose was replaced by various concentrations of raffinose, or UW solution. After 24 h storage, tissue swelling as determined by total tissue water (TTW) in rat liver tissue slices was most pronounced in slices incubated in Eurocollins, whereas the TTW was only moderately increased in slices stored in modified Eurocollins containing 90 to 120 mM raffinose. In contrast, slices incubated in UW solution had a TTW equal to normal rat liver tissue. Furthermore, intact rabbit livers preserved with Eurocollins had an increase in the whole organ weight, while there was no weight change after preservation with the modified solution containing 120 mM raffinose (M120). In contrast, a pronounced weight loss was observed after preservation with UW solution. After cold storage, the livers were reperfused for 2 h at 38 degrees C in an isolated perfusion circuit (IPL) with an acellular perfusate. Bile flow was significantly greater in livers preserved in M120 than in those preserved with the conventional Eurocollins. However, the bile flow in the livers stored in M120 was inferior to that in the livers preserved with UW solution, which in turn was equal to that in control livers. The release of alanine-aspartate-aminotransferase into the perfusate was higher in livers preserved with Eurocollins, with or without modification, than in the livers preserved with UW solution.(ABSTRACT TRUNCATED AT 250 WORDS)