Cyclodextrin (CD) complexes of cholesterol--their potential use in reducing dietary cholesterol intake.

The main objective of this investigation was to test and see if cyclodextrins, a type of molecule which form inclusion complexes, could effectively prevent the absorption of food derived cholesterol. Cyclodextrins are nontoxic and easily tolerated, having only a slight sweet taste. alpha,beta,gamma-Cyclodextrins, 2-Hydroxypropyl-beta-cyclodextrin (2-HPCD), and heptakis-O,O-dimethyl-beta-cyclodextrin (DMCD) were tested in solutions of different concentrations. These solutions were then saturated with cholesterol and the excess cholesterol was removed. The clear solutions left were then analyzed by HPLC to assess the amount of cholesterol in the solutions, and compared to a standard. DMCD gave the best results in successfully dissolving (complexing) most of the cholesterol followed by HPCD and alpha-cyclodextrin. Beta- and gamma-CD showed nearly insignificant complex formation. After administration of 10 mg of cholesterol to mice through a gastric tube, the cholesterol level increased about 125-130%, and only 15-20%, if the cholesterol was administered together with 20 mg of DMCD. That means, the DMCD formed complexes with approximately 80-85% of the cholesterol administered in the mice gastrointestinal tract.

The role of forensic experts in civil and criminal procedures in Hungary.

This short paper examines developments in expert evidentiary procedures in forensic cases in Hungary. The basis of current practice is described and certain problems arising from this are discussed.

[Medical judgement on driving capability]. / A gépjármúvezetó alkalmasságának megítélése.

Driving is an activity which puts forward the question of whether the driver is able to competently fulfill the task or not. Driving is affected or altered by age and various illnesses and the driver may not always concede that his/her driving ability is affected by these. The examination of driver capability is an important target. This can be seen especially during car accidents when the driver is examined and it is discovered that he/she is aggressive, has poor vision, old age, is epileptic, or consumed alcohol or drugs.

Distribution of inorganic elements in human autopsy tissue.

In the practice of forensic medicine, we find many of cases of death where the actual cause is not determinable with autopsy, histological or toxicological examinations. In these cases of death, we can consider cardiac dysfunction of unknown origin, in the background of which such a physiologic cardiac insufficiency occurs that cannot be detected with the previously mentioned methods. The dysfunction is possibly associated with a significant change in certain inorganic elements, primarily in the conduction system of the heart. In the absence of published data, our goal was to determine the concentration of inorganic elements in the specialized rhythm determining muscle cell groups in the heart: sinus node (SN), atrioventricular node (AV), septum (SE), left ventricle anterior wall (LVAW). With microwave technology we destroyed the muscle tissue and measured the concentration of ions (Na, Mg, K, Ca, Mn, Fe, Cu, Zn, P, S) using Inductive Completed Plasma Atom Emission Spectrometry (ICP-AES) equipment. Of the 24 cases examined, the average ion concentrations in microgram/g were the following; Sinus: Na 2602 +/- 493, Mg 120 +/- 24, K 1787 +/- 347, Ca 244 +/- 41, Mn 0.129 +/- 0.011, Fe 58 +/- 12, Cu 2.171 +/- 0.46, Zn 10.4 +/- 2.027, P 1147 +/- 227, S 2301 +/- 245; Septum: Na 1452 +/- 315, Mg 243 +/- 56, K 3269 +/- 689, Ca 105 +/- 26, Mn 0.17 +/- 0.05, Fe 74 +/- 16, Cu 3.557 +/- 0.952, Zn 25.75 +/- 8.4, P 2764 +/- 494, S 3001 +/- 523; Av: Na 2614 +/- 517, Mg 242 +/- 40.2, K 2010 +/- 395, Ca 271 +/- 27.3, Mn 0.13 +/- 0.029, Fe 54 +/- 12, Cu 2.369 +/- 0.297, Zn 15 +/- 3.2, P 1625 +/- 291, S 2535 +/- 346; Lvaw: Na 1340 +/- 201, Mg 250 +/- 37, K 3659 +/- 532, Ca 88 +/- 22, Mn 0.175 +/- 0.05, Fe 76 +/- 19, Cu 3.62 +/- 0.58, Zn 27.13 +/- 3.1, P 3025 +/- 441, S 3140 +/- 440.

Loteprednol etabonate, a new soft steroid is effective in a rabbit acute experimental model for arthritis.

UNLABELLED: Loteprednol etabonate, a new soft steroid designed for use as a local therapeutic, was compared to dexamethasone in rabbit experimental model for arthritis. METHODS: Joint inflammation was induced by local injection of antigen into the patellofemoral articulation in sensitized rabbits. Co-administration of either dexamethasone or loteprednol etabonate directly into the joint effectively blocked the inflammatory response. Both the synovial fluid cellular content and synovium histology were examined. The steroid treatments prevented the adverse inflammatory effects of antigen action. These results, together with previous studies showing decreased systemic activity of the soft steroid, indicate that the loteprednol etabonate could provide a therapeutic advantage over currently used intra-articular steroids for alleviating rheumatoid arthritis.

The appraisal of narcotic drugs in Hungary.

Hungary has a serious problem, historically significant and currently of increasing size, partly due to changes in trafficking routes. This paper outlines the development of measures to counter the situation, emphasising the provision of forensic laboratory services with the aid of the United Nations Drug Control program. An attempt is made to quantify more precisely permitted amounts of a drug for personal use.

[Granulocyte function and lipid peroxidation in untreated patients with hyperlipoproteinemia]. / Granulocyta funkciók és a lipidperoxidáció alakulása kezelésben nem részesült hyperlipoproteinaemias betegekben.

The fatty acid composition in free fatty acid and phospholipid fraction of plasma in untreated mildly hyperlipidemic patients were determined. The general trend was an increase in saturation in both free and phospholipid fractions of plasma in patients compared with that of healthy controls. Furthermore, arachidonic acid, precursor of formation of prostaglandins and leukotrienes was detected in significantly lower amount in plasma of mildly and untreated hyperlipidemic patients. These fatty acid abnormalities were connected with the increased lipidperoxidation in plasma lipids and in both resting and stimulated granulocytes.

[Measuring breath alcohol levels]. / A kilégzett levegó alkoholtartalmának mérése.

The authors review the breath alcohol measurement method based on infrared absorptiometry and its literature. In a comparative study a person's breath alcohol content was measured by either Siemens Alcomat or Seres Ethylometer instrument in routine road-blocks controls and in experiments and was compared to his/her blood alcohol level. Using the conversion factor of 2100:1 there was a high correlation between the breath and blood alcohol levels using either instrument. Despite using a single method either Siemens Alcomat or Seres Ethylometer 679-TH instrument can be recommended for evidential breath alcohol testing of driving under the influence of alcohol in routine road-blocks controls.

Relative abundance of some free fatty acids in plasma of uremic patients: relationship between fatty acids, lipid parameters, and diseases.

The unesterified fatty acid patterns in plasma of predialytic (PHD) and hemodialysis (HD) patients were determined. The HD patients were divided into three groups: (1) HD without cardiovascular disease (HD-norm); (2) HD with cardiomyopathy (HD-CAD), and (3) HD with hyperlipidemia (HD-hyp). The relative abundance of saturated fatty acids (SFAs) was greater in the plasma of HD-norm and HD-CAD patients (73.3 and 70.0%, respectively) than that in controls (62.6%), and the relative abundance of monounsaturated fatty acids (MUFAs) was significantly greater in the plasma of HD-hyp patients than that in controls (38.9 vs. 21.6%, p < 0.01). In all HD patients the relative concentration of polyunsaturated fatty acids (PUFAs) was lower than in controls. There were no significant differences in the fatty acid patterns of PHD patients. In conclusion, the relative abundance of SFAs and MUFAs in plasma of HD patients is associated with their concomitant lipid disorders and cardiomyopathy, while the low relative abundance of PUFAs was common in all HD patients.

Drinking habits of medical students call for better integration of teaching about alcohol into the medical curriculum.

A study was conducted with medical students to observe their drinking habits and alcohol misuse. The students completed questionnaires composed of AUDIT and SMAST questions. A significant proportion (33%) of students drank more than the recommended safe limit and screened positive at the AUDIT cut-off score of 11. The high scores of DSM-III criterion questions indicate that problem drinking on college campuses continues to be a significant public health concern. Our opinion is that prevention of alcohol misuse should be started at medical universities. The medical school curriculum must integrate education about alcohol. First the attitude of medical professionals should be changed so that we can achieve results in alcohol misuse prevention in society as a whole.

Effect of different columns and internal standards on the quality assurance of the gas chromatographic determination of blood ethanol.

Quality assurance is an essential requirement of clinical and forensic laboratories, especially in the determination of ethanol. Opinions differ as to whether normal gas chromatographic methods should be used with modified procedures, or whether different chromatographic strategies should be adopted, the choice being based entirely on practical considerations. We have evaluated the influence on the blood ethanol determination of the frequently used glass and steel columns, as well as the use of isopropanol and tert-butanol as internal standards. All the different combinations of column type and standard provided accurate and reliable results with no significant deviation. Standardization of the analytical procedure is therefore unnecessary, but international ethanol standards should be analysed sequentially to test the method and the staff performing the analyses in the different laboratories.

[Importance of evaluating clinical symptoms of alcoholic intoxication]. / A klinikai tünetek megítélésének jelentösége az alkoholos befolyásoltság megállapításakor.

The authors studied the relationship between the blood alcohol concentration and the categories of alcohol intoxication established by means of examining the clinical signs of intoxication in a drinking test, and by analyzing the reports on driving while intoxicated (DWI). In the drinking test the relative increase of viso-motor reaction time was an accurate indicator of the blood alcohol levels. In almost half of the cases there was no correlation between the clinical signs and the blood alcohol concentration. When alcohol and medicine was used in combination a more severe intoxication was frequently assumed. Therefore, if the reported intoxication based on clinical signs indicates a more severe intoxication than that correlating with the blood alcohol concentration, the toxicologic analysis of the blood samples are unconditionally necessary.

Change of alcohol dehydrogenase activity in sera after alcoholism treatment.

Increased metabolic alcohol tolerance was found in chronic non-cirrhotic alcoholics after alcoholism treatment with disulfiram. This increased metabolic alcohol tolerance is connected with an increased activity of alcohol dehydrogenase due to the healing of hepatic tissue damage. This increase in alcohol dehydrogenase activity can help in monitoring the effectiveness of treatments for alcoholic liver disease.

Ethanol elimination in man under influence of hepatoprotective silibinin.

The effect of a single dose of hepatoprotective silibinin on blood alcohol elimination was investigated. Neither influence on the blood alcohol curve, nor detectable increase in the beta 60 value was found, although biochemical considerations suggest such an effect. Though silibinin has a protective effect on chronic alcohol liver injury, it does not influence acute alcohol elimination, and is therefore not suitable for use as a "sobering-up" agent.

Novel soft steroids: effects on cell growth in vitro and on wound healing in the mouse.

Evaluation of three "soft" steroids is described. The test compounds were compared with the standard anti-inflammatory steroids betamethasone and prednicarbate in two studies. Soft steroids are designed based on the "inactive metabolite approach" to be rapidly inactivated by predictable metabolism after performing their therapeutic function. Consequently, lower circulating (peripheral) levels of potentially harmful steroids result, and undesirable systemic and local side effects are minimized. The soft and standard steroids behaved similarly in an in vitro cell culture model, whereas in a whole animal study the advantages of the soft steroids were evident.

Quantitative ultrastructural analysis of hepatoprotective effects of (+)-cyanidanol-3 on alcoholic liver damage.

Biochemical considerations suggest that bioflavonoids may be effective antihepatotoxic and hepatoprotective agents. We, therefore, designed a morphometric study to examine the effect of (+)-cyanidanol-3 on ethanol-induced hepatocellular alterations. Using a stereologic point and intersection counting method we determined the volume fraction of cytoplasmic components, the surface area of cytoplasmic membranes, some parameters of mitochondria, and numerical densities of some organelles, after chronic ethanol intoxication and hepato-protective treatment of rats. Consistent with previous qualitative and quantitative descriptions, chronic ethanol feeding caused increases in parameters of mitochondria, microsome, and Golgi complex. The hepatoprotective (+)-cyanidanol-3 treatment restored most of the morphologic distortion caused by ethanol ingestion. The (+)-cyanidanol-3 treatment alone caused an elevation of the surface area of smooth endoplasmic reticulum and nonsignificant changes in mitochondrial parameters, possibly due to its inducing effect on microsomes and activating effect on mitochondrial enzymes. These data indicate that bioflavonoids could be of potential benefit in hepatotoxic or alcohol-related liver disease.

[Variabilities of kinetics of alcohol catabolism]. / Az alkoholbontás kinetikájának változékonysága.

The resorption, distribution and elimination of ethanol vary individually. The differences in the resorption deficit and elimination coefficient can be of great extent. Though the generally accepted average of resorption deficit is 20%, which is calculated with in forensic practice, this value can occasionally be a lot higher. The elimination coefficient (beta value) depends on the blood alcohol level. Beta value was found higher than 0.15%o/h, the generally accepted one, even below 1.5% blood alcohol content, above 2.5% the beta value was found to be as high as 0.33%o h. This faster rate of ethanol clearance is due to induction of alcohol elimination systems. The ethanol metabolism at higher blood alcohol levels is characterized by Michaelis-Menten kinetics.

Drug identification problems in two suicides with neuromuscular blocking agents.

Cases of suicide committed with neuromuscular blocking agents have been investigated. Both cases involved anesthesiologists who took the muscle relaxants suxamethonium chloride (Sukolin) or pipecuronium bromide (Arduan) and a rapid-acting barbiturate, 5-sec-butyl-5-ethyl-2-thiobarbituric acid (Inactin). The examinations were performed by using gas chromatography and mass spectrometry. The quantitative data obtained showed that doses useful in general anesthesiological practice were applied. Metabolites were found despite their fast metabolizing character.

Some morphometric evidence of hepatoprotective effects of (+)-cyanidanol-3.

The (+)-cyanidanol-3 is used as an antihepatotoxic and hepatoprotective drug in both men and animals against alcoholic and experimental liver injury. Histologic staining techniques give mostly qualitative or semiquantitative description of liver damages. Experiments have been carried out to determine the hepatoprotective effects of (+)-cyanidanol-3 on alcoholic liver damage (i.e., fatty liver and hepatomegaly) by morphometric measurement of the liver tissue sections. Ethanol was administered ad lib to CFY rats to cause mild alcoholic liver damage together with 200 mg/kg/day (+)-cyanidanol-3 to prevent the tissue deterioration. The changes of hepatic lobule and hepatocytes were measured morphometrically. The chronic ethanol consumption results in hepatocellular hypertrophy, a significant increase in size of the hepatocytes and a mild increase of the intralobular extrahepatocytic space as well when compared with controls. The volume of cytoplasm was increased while the parameters of nuclei were unchanged. The (+)-cyanidanol-3 prevents changes and the morphometric parameters in the treated group were almost the same as in the controls. The treatment with (+)-cyanidanol-3 alone does not affect the hepatic tissue parameters. The results show the hepatoprotective effect of (+)-cyanidanol-3 and the suitability of the morphometric method for quantitative comparison of normal and experimentally-altered liver cells.