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Biomedical subjects

L Keso

Publications and source records attributed to L Keso.

At least 19 recordsLinked to original sources
PubMed1996

Biochemical and chemical characterization of phenylglyoxal bis(guanylhydrazone), an aromatic analogue of mitoguazone.

Since little has been known about the properties of aromatic analogues of the antineoplastic agent methylglyoxal bis(guanylhydrazone) (MGBG), an investigation was performed on phenylglyoxal bis(guanylhydrazone) (PhGBG). PhGBG competitively inhibited yeast adenosylmethionine decarboxylase (AdoMetDC) with a Ki of 65 microM. As compared to MGBG (Ki 0.23 microM), PhGBG is a much weaker inhibitor, being even weaker than the unsubstituted congener glyoxal bis(guanylhydrazone) (GBG, Ki 18 microM). PhGBG inhibited porcine kidney diamine oxidase (DAO) non-competitively, being a more potent inhibitor (Ki 0.12 microM) than GBG (Ki 0.17 microM) or MGBG (Ki 0.33 microM). Thus, PhGBG has an unfavourably high ratio of Ki(AdoMetDC)/Ki(DAO) for potential use for selectively inhibiting polyamine biosynthesis. This does not exclude the possibility that PhGBG or other aromatic congeners might have therapeutic value since the corresponding ratio of the antileukaemic congeners GBG and MGBG is also high as compared to many aliphatic non-antileukaemic analogues. The pKa1 and pKa2 values of PhGBG dication were found to be 6.39 +/- 0.02 and 8.64 +/- 0.02 respectively, their difference being distinctly larger than in the case of GBG or its C-alkylated analogues. This may result from decreased stability of the dication form, caused by the resonance effect or possibly by the inductive effect of the phenyl group. The species distribution of PhGBG (proportion of free base 5.5%, predominant species the monocation) at 37 degrees C resembles that of GBG and MGBG but is clearly different from that of non-antileukaemic C-alkylated analogues. These similarities suggest that PhGBG and its derivatives may be worth antitumour screening. Depending on the conditions used in the crystallization, three different types of crystals of PhGBG sulphate were obtained. Crystallography indicated that, in two of the types, the crystal consisted exclusively of the anti-anti isomer, i.e. the same isomer as has been observed in the case of GBG and its C-alkylated congeners. One crystal type, however, consisted of a different geometrical isomer (anti-syn), suggesting that PhGBG may isomerize more easily than its aliphatic analogues. Previous concepts on the isomerism of GBG and C-alkylated bis(guanylhydrazones) thus cannot be generalized to aromatic congeners. A theory based on resonance, inductive and hyperconjugative effects and electron transfers is presented that is capable of explaining the formation of the two geometrical isomers of PhGBG that were experimentally observed. A similar theory, based on hyperconjugation of C-F bonds, is presented that is capable of explaining the previous finding of the formation of the anti-syn isomer of trifluoromethylglyoxal bis(guanylhydrazone) (CF3GBG). Like that of CF3GBG, the anti-syn isomer of the PhGBG dication is stabilized by an internal hydrogen bond. The lack of structural rigidity may affect the biological properties of PhGBG, e.g. its ability to inhibit AdoMetDC.

Animals↗
PubMed1990

Serum lipids and lipoproteins in alcoholic women during pregnancy.

The concentrations of triglyceride, cholesterol, phospholipids, and proteins in the major lipoprotein fractions (very-low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoproteins [HDL] HDL2 and HDL3) were monitored in 20 pregnant women who chronically abused alcohol and in 15 abstinent pregnant women. Five of the alcohol users gave birth to infants with fetal alcohol syndrome (FAS). Lipoproteins were fractionated by sequential flotation from samples taken at 16, 20, 24, 28, 32, 36, and 40 weeks of gestation and 6 to 8 weeks after delivery. In abstinent women, concentrations of VLDL and LDL triglyceride, cholesterol, phospholipids, and proteins increased in late gestation. Concentrations of HDL2-cholesterol, phospholipids, proteins, and total HDL2 were increased during the 16th to 28th weeks, but HDL3 remained unchanged. Alcohol abuse clearly reduced the normal increase in total and LDL-cholesterol, as well as in LDL phospholipids, proteins, and total LDL during the 24th to 40th weeks. LDL changes were most pronounced in alcoholic women who later produced FAS infants. Alcohol abuse also increased HDL3. Furthermore, in alcohol users, the normal increase in VLDL was accentuated, especially so in women with FAS infants, and that of HDL2 was reduced. The significance of the changes found remains obscure, but they may be related to impaired function of the fetoplacental unit.

Alcoholism↗
PubMed1990

Comparative value of self-report and blood tests in assessing outcome amongst alcoholics.

The study group consisted of 73 employed alcoholics, who were directed to inpatient treatment. They were evaluated (structured interview, GGT, and MCV) before the treatment period and 8 months after the termination of the treatment. Patients with diseases or medications influencing the laboratory tests were not included in the study group. According to the structured interview 72.6% of the patients were drinking in a controlled manner (less than 40 g/d ethanol) during the 2-month period prior to the follow-up evaluation. According to the laboratory data 52.1% of the patients had been drinking in a controlled manner (i.e. both GGT and MCV values were normal). With the interview and laboratory data combined 39.7% of the patients had been drinking in a controlled manner. Thus the drinking outcome was strongly influenced by the selection of the variables used to measure the outcome. It is recommended that no studies should be carried out about the drinking outcome of alcoholism treatment without the use of laboratory markers as a part of the evaluation.

Adult↗
PubMed1990

Inpatient treatment of employed alcoholics: a randomized clinical trial on Hazelden-type and traditional treatment.

The first randomized clinical trial on the Hazelden-type of treatment showed that this AA-oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment. One hundred forty-one employed alcoholics were randomized to either Hazelden-type treatment (N = 74) or to traditional-type treatment (N = 67). The treatment groups were highly comparable. The bimonthly follow-up lasted one year. According to the COPES-questionnaire (short form), the treatment at the Hazelden-type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional-type institute. In accordance the treatment drop-out rate was 7.9% at Hazelden-type institute and 25.9% at traditional-type institute (p less than 0.02). The participation in outpatient treatment was significantly better after the Hazelden-type treatment. The proportion of those abstinent (admitted ethanol consumption, 0 g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden-type institute during the last (8-12 months) follow-up period (26.3% vs. 9.8%, p = 0.05). Fourteen percent of the Hazeldon-type institute patients and 1.9% of the traditional-type institute patients stayed abstinent during the whole 1-year follow-up period (p less than 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden-type treatment obtained better results in 1-year abstinence rate than a more traditional-type treatment.

Adult↗
PubMed1990

Laboratory tests in the follow-up of treated alcoholics: how often should testing be repeated?

The study group consisted of 60 male and 13 female alcohol-dependent employed patients who participated in inpatient treatment for alcoholism. They were followed up bimonthly for eight months after the treatment period. The results with GGT, ASAT, ALAT, MCV and the combination of GGT and MCV were studied with respect to the effect of taking the tests once (at eight months), twice (once every four months) or four times (bimonthly). According to our definition, the treatment outcome was good when the laboratory test values were within the normal range during the whole follow-up period. The differences in observed outcome (at eight months after treatment) were small whether one took the tests once at the end of the follow-up period or up to four (i.e. bimonthly) times. Nevertheless, there were some differences between the laboratory markers. To get the most accurate picture of drinking during the follow-up period one should repeat the test bimonthly with ASAT or ALAT, once every four months with GGT (or combined GGT and MCV), and once after eight months with MCV. When the time course of relapses is important for the study the more frequent test taking is also indicated.

Adult↗
PubMed1989

Laboratory markers as compared to drinking measures before and after inpatient treatment for alcoholism.

A study group, consisting of 60 male and 13 female alcohol-dependent patients, participated in an inpatient treatment for alcoholism. They were interviewed about their alcohol use before the treatment period and bimonthly for 8 months after it. It was found that the correlations between laboratory markers and average daily alcohol intake are very low (range, -0.01-0.23) in alcoholics with high alcoholic intake level (before the treatment period). It was also found that the correlations between the laboratory tests and the drinking measures after the initial assessment undergo large changes. The correlation between GGT and average daily alcohol intake before the treatment period was 0.07 (p = NS) and 2 months after the treatment period 0.55 (p less than 0.001). The long period of abstinence, the change to a lower level of alcohol consumption, and improved accuracy of reporting alcohol intake were probably causative in this change. GGT proved to have the highest correlations with the drinking measures during the follow-up and MCV before the treatment period. The frequency measure, number of drinking days, gave consistently higher correlations with the laboratory markers than the measure of drinking amount, average daily alcohol intake. Laboratory markers, GGT and MCV, are well suited for outcome evaluation of drinking behavior of alcoholics after inpatient treatment for alcoholism or other comparative periods of abstinence.

Adult↗
PubMed1988

Adenosine and the regional differences in adipose tissue metabolism in women.

Adenosine content in abdominal and femoral adipose tissue in menstruating women was 0.38 +/- 0.10 and 0.59 +/- 0.14 nmol/g of wet weight, respectively (mean +/- SEM; N = 17). No difference in adenosine sensitivity was found between abdominal and femoral adipocytes. In lactating women, the adenosine content was lower in femoral than in abdominal adipose tissue (0.40 +/- 0.08 and 0.57 +/- 0.08 nmol/g of wet weight, respectively; N = 10). Adenosine sensitivity in femoral adipocytes was not increased during lactation. As adenosine is a locally acting insulin-like effector, these results suggest that the higher adenosine content in femoral adipose tissue in menstruating women could explain its higher lipoprotein lipase activity and tendency to accumulate fat. During lactation, the lower extracellular adenosine concentration would allow lipid mobilization preferentially from the femoral site.

Abdomen↗
PubMed1988

Fractures on chest radiographs in detection of alcoholism.

The prevalence of fractures seen on chest radiographs among alcoholics varies in various series from 36.0% to 8.7% while that for controls remains below 5%. The aim of our study was to find out whether the selection of the alcoholic subjects could account for this four-fold variation. We therefore chose two groups of alcoholics, group 1 consisting of 76 mainly unmarried or divorced lower class alcoholics who had attended the emergency department while intoxicated, and group 2 consisting of 108 mainly married middle class alcoholics with alcoholic liver cirrhosis. The control group consisted of 98 randomly chosen hospital patients. There was no significant difference between group 1 and group 2 in the prevalence of fractures detectable with chest radiography (25% and 21.3% respectively). 8.2% of the controls also had fractures. The fracture prevalence did not correlate with socioeconomic group. Married alcoholics had significantly less thoracic fractures than unmarried, divorced or widowed alcoholics as a group. The sensitivity and specificity of the fractures visible on chest radiograph as a marker for alcoholism is not sufficient to warrant its use in clinical or research work.

Adult↗
PubMed1987

Thyroid status and adenosine content of adipose tissue.

Fat-cells from hypothyroid rats lack the normal lipolytic response to catecholamines. We have suggested that this is due to increased sensitivity to the inhibitory actions of endogenous adenosine. In this paper we present evidence that thyroid hormones increase adipose-tissue adenosine contents and suggest that the increased sensitivity to adenosine in hypothyroidism is due to relief from desensitization by endogenous adenosine.

Adenosine↗
PubMed1987

Apolipoprotein A-I-binding protein from human term placenta. Purification and partial characterization.

A protein that binds to the main apoprotein, apoA-I, of human high density lipoprotein (HDL) has been isolated from human placenta. Ligand blotting after SDS gel electrophoresis indicated that the 120 kDa protein in the absence of reducing agents binds apoA-I. If gel electrophoresis was performed under reducing conditions two main bands, approx. 50 and 30 kDa that did not bind apoA-I, were evident. In an enzyme-linked immunosorbent assay the binding protein specifically bound apoA-I, delipidated or as HDL. ApoA-II, apo E and LDL did not compete with apoA-I for binding to this protein.

Apolipoprotein A-I↗
PubMed1987

Apolipoprotein E polymorphism, serum lipids and occurrence of "double pre-betalipoproteinemia' (DPBL) in subjects from two different populations.

The association between apolipoprotein E phenotype and the presence of 2 electrophoretic populations of very low density (VLDL) lipoproteins from human sera, double pre-beta(VLDL)lipoproteinemia (DPBL), was studied in 2 groups of subjects, one from Italy and one from Finland. In both populations the prevalence of DPBL was significantly higher in subjects with E4/4 and E4/3 phenotypes than in the other phenotypes not containing the E4 isoprotein. This finding suggests that the presence of a structural variant of the apo E protein, the isoprotein E4, may be causally related to the appearance of DPBL phenomenon.

Adolescent↗
PubMed1987

Employed problem drinkers: a nutritional risk group?

Nutritional assessment was made in 26 employed Finnish men drinking excessively and in 49 control men. Because of their greater alcohol consumption, daily intake of energy of case men significantly exceeded that of control men; other dietary differences were negligible. Compared with control men, case men had thicker fatfolds but reduced mean body mass and arm muscle circumference. Mean circulating levels of vitamin C and alpha-tocopherol were normal and equal in case and control men, but serum retinol was raised and beta-carotene was reduced in case men. Serum concentration and 24-h urinary excretion of selenium were significantly lower in case than in control men. Serum levels of magnesium and zinc were similar in both groups, but urinary excretions were higher in case men. Heavy drinking does not result in florid nutritional deficiencies in socially intact men, but its role in subtle nutritional alterations deserves further studies.

Adult↗
PubMed1987

Serum creatinine values and changes in alcohol consumption among alcohol dependent patients.

Serum creatinine has been shown to be significantly negatively correlated to alcohol related death. According to our study short term abstinence in employed male alcoholics is not reflected in serum creatinine values, whereas in employed female alcoholics abstinence raises serum creatinine values. Low serum creatinine values (below 80 mumol/l) were found to characterize employed male alcoholics with increased incidence of alcohol related diseases.

Adult↗