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Biomedical subjects

A Somogyi

Publications and source records attributed to A Somogyi.

At least 91 records · Page 5Linked to original sources
PubMed1993

Nurturing and breast-feeding: exposure to chemicals in breast milk.

All chemicals that are not normal constituents of human milk should be considered undesirable contaminants. In the present review, the following substances detected in human milk are considered: persistent organochlorine pesticides; polychlorinated biphenyls (PCB); polychlorinated dibenzodioxins (PCDD) and dibenzofurans (PCDF); polybrominated compounds; polycyclic aromatic hydrocarbons (PAH); trace elements; mycotoxins; nitrate, nitrite, nitrosamines; nicotine, caffeine, ethanol; and drugs. The levels of most of these substances found in human milk were within a range that would not constitute health hazards for breast-fed infants. For many of these, there is a comfortable safety margin. This applies also to organochlorine pesticides and PCB, particularly since, as a result of their discontinued use, the levels of these compounds have clearly declined in recent years. On the other hand, the aflatoxin burden mediated through breast milk, at least in certain tropical countries, appears to pose a definite health hazard. Detailed reference are given on the contamination of human milk with PCDD/PCDF which has to be considered as a matter of concern from the viewpoint of preventive public health. Although the low PCDD/PCDF levels found in the adipose tissue of infants indicate that there is no appreciable health risk emanating from these substances for breast-fed infants, appropriate measures to reduce the current rate of their emission into the environment have to be taken.

Body Burden↗
PubMed1991

Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man.

Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (mumol.l-1.h) and CLR (ml.min-1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml.min-1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucuronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.

Acetaminophen↗
PubMed1991

Metabolic denitrosation of N-nitroso-N-methylaniline: detection of amine-metabolites.

The enzymatic denitrosation of N-nitroso-N-methylaniline (NMA) was investigated by measuring the resulting amine metabolites when NMA was incubated with liver microsomes of PB-pretreated mice. Aniline was found to be the main amine metabolite. Small amounts of the secondary amine, N-methylaniline (MA) and its metabolite, p-methylaminophenol (p-MAP), could also be detected. Incubation of MA resulted in the formation of aniline and p-MAP. The velocity of the metabolism of MA was somewhat faster than that of NMA. On the basis of the measured Vmax values the formation of aniline from MA or from NMA proceeded at nearly identical rates. The dissociation constants as a measure of binding affinity to cytochrome (cyt.) P-450 were determined by measuring the binding spectra. NMA has one Ks of 3.1 mM, whereas MA shows two apparent Ks values, 650 microM and 25 mM, respectively. The results are discussed in relation to the enzymatic mechanism of denitrosation of NMA.

Aniline Compounds↗
PubMed1991

Left ventricular beta 1 and beta 2 adrenoceptor mRNA expression in normal and volume overloaded human heart.

STUDY OBJECTIVE: The aim was to determine gene expressions of beta 1 and beta 2 adrenoceptor subtypes (BAR-1, BAR-2) in normal and volume overloaded human heart. DESIGN: Tissue mRNA levels were determined by excess solution hybridisation using 35S-UTP labelled BAR-1 and BAR-2 cRNA probes. MATERIAL: Atrium, right and left ventricular subendocardium, and papillary muscle from donor hearts and papillary muscle from patients operated for mitral stenosis and mitral regurgitation were studied. MEASUREMENTS AND MAIN RESULTS: The basal levels of myocardial BAR-1 and BAR-2 mRNA expression were similar to the levels in human adipose tissue that have been reported previously from our laboratory (10-15 amol mRNA.micrograms-1 total nucleic acids). No differences in BAR-1 and BAR-2 mRNA expression were observed between various parts of the normal heart. In papillary muscle, BAR-1 and BAR-2 mRNA levels were 8.8 (SEM 5.1) and 10.2(6.6) amol.micrograms-1 total nucleic acids, respectively. Furthermore, no differences in BAR mRNA expression were observed between myocardium subjected to mitral stenosis as compared to normal myocardium. On the other hand, patients with mitral regurgitation expressed significantly lower levels of both BAR-1 and BAR-2 mRNA, at 4.8(1.0) (p less than 0.05) and 2.6(1.1) (p less than 0.001) amol.micrograms-1 total nucleic acids, respectively. The ratio BAR-1/BAR-2 mRNA was higher (p less than 0.01) in mitral regurgitation than in the normal heart. CONCLUSIONS: Myocardium from different parts of the normal human heart, where different pressure work is generated, express similar levels of BAR-1 and BAR-2 mRNA. With volume load a significant decrease in BAR mRNA levels was observed, which was more marked for BAR-2 mRNA. This difference in specific mRNA levels in patients with mitral regurgitation indicates an independent regulation of the expression of these two receptor subtypes.

Adolescent↗
PubMed1990

Determination of endogenous concentrations of N1-methylnicotinamide in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic assay for the determination of endogenous plasma and urine concentrations of N1-methylnicotinamide was developed. N1-Methylnicotinamide and N1-ethylnicotinamide (internal standard) are reacted with acetophenone in a strong base at 0 degree C, formic acid is added, and the reaction mixture is heated in a boiling water bath, resulting in the formation of fluorescent derivatives. These derivatives were chromatographed on a C18 reverse-phase column using a mobile phase of acetonitrile-triethylamine and 0.01 M heptanesulfonic acid adjusted to pH 3.2. Fluorescent detection was achieved using 366-nm excitation and 418-nm emission filters. Precision and accuracy were generally greater than 90%, interfering peaks did not cochromatograph, and the limit of quantification was 2 ng/ml in plasma using a 0.2-ml sample. The method was used to examine the concentrations of endogenous N1-methylnicotinamide in the plasma of 36 subjects with various pathology. The mean concentration was 18 ng/ml and the range was 6.2 to 116.7 ng/ml. The assay represents a marked improvement on previous methods and is suitable for routine clinical monitoring.

Acetophenones↗
PubMed1990

Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum.

Experiments reported here were designed to investigate the effect of silibinin (extracted from Silybum marianum) on human polymorphonuclear leukocyte (PMN) motility and on leukocyte immobilizing activity of lymphokine (leukocyte inhibitory factor, LIF), formyl-Met-Leu-Phe (fMLP), calcium ionophore A-23187 and human sera inactivated by heat (HI-S). In the in vitro experiments, silibinin (1-10 micrograms/ml) failed to influence the random motility of unstimulated PMNS in agarose droplet assay, but enhanced the motility of the PMNs immobilized by fMLP, calcium ionophore, LIF or by autologous human sera. In the in vivo study, silibinin (Legalon-70) two hours after the administration was effective in enhancing spontaneous motility of leukocytes obtained from health volunteers which action could be regarded as a consequence of the decrease of leukocyte immobilizing activity being present in normal human plasma.

Blood↗
PubMed1990

Amiloride disposition in geriatric patients: importance of renal function.

1. The absorption and disposition of the potassium sparing diuretic amiloride were determined in nine elderly patients aged 71 to 87 years and in eight young (25 to 38 years) subjects following oral administration of 5 mg amiloride HCl daily to steady-state. 2. The maximum and steady-state plasma amiloride concentrations were significantly (P less than 0.05 and P less than 0.001) higher in the elderly patients. The renal clearance of amiloride was lower in the elderly than in young subjects (102 +/- 36 ml min -1 vs 300 +/- 64 ml min-1, P less than 0.001) as was the urinary excretion of amiloride (36 +/- 13 vs 62 +/- 18% of the dose, P less than 0.01). 3. The steady-state plasma amiloride concentration correlated significantly (r2 = 0.61, P less than 0.001) with amiloride renal clearance and with creatinine clearance (r2 = 0.59, P less than 0.001). There was a very strong positive correlation between renal amiloride clearance and creatinine clearance (r2 = 0.76, P less than 0.001). The slope of the regression line was 2.5 indicating substantial proximal tubular secretion of amiloride. 4. Sodium and potassium excretion, along with urine volume were significantly (P less than 0.05) lower in the elderly (by 39, 45 and 34% respectively). 5. The disposition of amiloride was highly dependent on renal function, with higher plasma amiloride concentrations in the elderly reflecting diminished renal function. The dose of amiloride should be titrated to individual response, and the lower potassium excretion in the elderly patients suggests that the dose of amiloride could be reduced in this group of patients.

Adult↗
PubMed1990

Late effect of tobanum and tobanum + furosemide therapy on the glucose tolerance of patients and on the insulin response to oral glucose doses.

The authors examined the effect of beta-blocker monotherapy (Tobanum tab = 5 mg cloranololum hydrochloricum) and beta-blocker + diuretic (Tobanum + Furosemide) combination therapy on glucose tolerance and insulin secretion in response to oral glucose doses in hypertensive non-diabetic patients. Twenty-six patients were examined (13 men, 13 women). The patients were followed up for 28 weeks after a 2-week drug-free period. The hypotensive dose was adjusted individually within 4 weeks. Oral glucose tolerance test and immuno-reactive insulin determination were performed concurrently before starting hypotensive therapy and on weeks 6, 14, and 28 of therapy. The results of the examinations were evaluated separately in two patient groups. Fifteen patients were given daily 10-20 mg Tobanum (Group I) while 11 patients received daily 10-20 mg Tobanum + 40-80 mg Furosemide (Group II). The glucose area of patients on Tobanum monotherapy did not change, insulin secretion decreased gradually (from 804 to 495 pmol/l). The decrease was significant (p less than 0.05). The glucose area of Tobanum + Furosemide-treated patients increased from 13.2 +/- 3.2 mmol/l to 16.1 + 4.9, the insulin secretion decreased from 1039 + 339 to 706 + 411 pmol/l during therapy (p less than 0.02 and p less than 0.05, resp.). When evaluating the results the decrease of insulin secretion is attributed to Tobanum effect while the deterioration of glucose tolerance may be correlated to the action of Furosemide on extrapancreatic metabolism.

Adrenergic beta-Antagonists↗
PubMed1990

[Morphologic and morphometric analysis of atheromatous changes in the aorta in silibinin-treated cholesterin-fed rabbits].

Authors studied the effect of Silibinin of antioxidative effect on cholesterin sclerosis of rabbits. Qualitative analysis of aorta sections, macroscopic and microscopic morphometric examination of aorta were the applied methods. Their results seem to show that Silibinin has a favourable influence on cholesterin sclerosis. According to their opinion only joint use of qualitative and quantitative macroscopic and microscopic methods can provide basis for really accurate judgment of any atheromatose change.

Animals↗
PubMed1989

Direct determination of codeine-6-glucuronide in plasma and urine using solid-phase extraction and high-performance liquid chromatography with fluorescence detection.

A sensitive and selective method was developed for the direct determination of codeine-6-glucuronide in plasma and urine using high-performance liquid chromatography (HPLC) with fluorescence detection. Codeine-6-glucuronide was synthesised and its purity estimated using acid and enzyme hydrolysis. The hydrolysis of codeine-6-glucuronide by beta-glucuronidase was incomplete and urine reduced the extent of hydrolysis. Codeine-6-glucuronide was recovered from plasma using a solid-phase extraction column and separated on a reversed-phase C18 HPLC column. The assay showed good reproducibility and accuracy (within 10%), and standard curves were linear between 32 and 1600 ng/ml in plasma and between 0.32 and 160 micrograms/ml in urine. The assay has been applied to the study of the pharmacokinetics and metabolism of codeine in patients.

Chromatography, High Pressure Liquid↗
PubMed1989

Simultaneous determination of codeine, norcodeine and morphine in biological fluids by high-performance liquid chromatography with fluorescence detection.

A novel high-performance liquid chromatographic method for the determination of codeine, norcodeine and morphine in plasma and urine has been developed. The compounds were separated on a cyano column (15 cm x 4.6 mm, 5 microns particle size) using a mobile phase of acetonitrile-triethylamine-distilled water (4:0.1:95.9, v/v) pH 3.1 and then determined by fluorescence detection. Calibration curves in the range 5-200 ng/ml for plasma and 0.1-10 micrograms/ml for urine were linear and passed through the origin. The imprecision and inaccuracy of the assay were less than 10% and the limits of detection were 2 ng/ml for all three compounds in human plasma.

Adult↗
PubMed1989

The effect of CH 402 dihydroquinoline type antioxidant on the activity of Na+-K+-ATP-ase and Mg++-ATP-ase of rat brain subcellular fractions in the presence and absence of ascorbic acid.

Authors studied the activities of Na+-K+-ATP-ase and Mg++-ATP-ase as indicators of lipid peroxidation on rat brain plasmamembrane and microsomal fraction. The CH 402 (Sodium(2,2-dimethyl-1,2-dihydroquinoline-4-yl)methane sulfonate) a synthetic, water soluble, non toxic dihydroquinoline type antioxidant proved to be effective in decreasing the membrane damage caused by ascorbic acid induced lipid peroxidation. The CH 402 did not inhibit the Na+-K+-ATP-ase and Mg++-ATP-ase activities even at a concentration of 10(-3) mol/l.

Animals↗
PubMed1989

Short term treatment of type II hyperlipoproteinaemia with silymarin.

In a seven-month open clinical study on 14 type-II hyperlipidaemic outpatients, the effects of silymarin (Legalon), an antioxidant and hepatoprotective agent, were investigated. Blood lipid, lipoprotein and apolipoprotein concentrations, as well as liver and renal function parameters were measured. After determining baseline values, patients were treated with 420 mg Legalon daily for three months. After a two-month placebo period, the treatment was repeated with Legalon for a further month. In respect to the serum lipid and lipoprotein concentrations, there were no remarkable changes except that the total cholesterol and HDL-cholesterol levels slightly decreased. At the 12th week, in all cases, the apolipoprotein levels were somewhat decreased compared to the baseline values. By the significant decrease of both apo A-I and A-II values, a decrease of the total structural protein amount of HDL, and thus a relative increase in the proportion of cholesterol in HDL fraction was suggested. There were minor changes in serum protein concentration and liver function tests, but all values remained within the normal range. All of the renal function parameters remained unchanged during both treatments and the placebo periods. An additive role of Legalon in the therapy of secondary hyperlipoproteinaemia resulting from different liver diseases is discussed.

Cholesterol↗
PubMed1988

Sensitive high-performance liquid chromatographic assay for determination of amiloride in biologic fluids using an ion-pair extraction method.

The paucity of data on disposition of the potassium-retaining diuretic amiloride is mainly owing to the lack of sensitive and specific analytic methods for measuring the drug in biologic fluids. Poor lipophilicity and extremely low plasma concentrations impose severe constraints. A method is described for analysing plasma and urine concentrations of amiloride using an ion-pair extraction method and high-performance liquid chromatography (HPLC) with fluorescence detection. Amiloride and internal standard triamterene form an ion-pair with bromothymol blue at pH 7.6. The ion-pairs are extracted into diethyl ether: dichloromethane (2:1), and back-extraction into 0.1% tetrabutylammonium hydroxide liberates the drugs from their ion pairs. Analyses are performed using HPLC with a reverse-phase C18 column and a mobile phase of 11% acetonitrile and 0.5% triethylamine adjusted to pH 3. Amiloride is quantified using fluorescence detection (366-nm excitation, 418-nm emission cutoff). Retention times are 2.2 and 6.0 min for amiloride and triamterene, respectively. The sensitivity limit is 0.2 ng/ml, and recovery is 82% for amiloride and 71% for triamterene. Calibration curves are linear (range 0.25-25 ng/ml for plasma and 0.05-2.0 micrograms/ml for urine). Inter- and intraday assay variability is less than 8% and precision is within 5%. The assay is of sufficient sensitivity and specificity for the study of the pharmacokinetics of amiloride in humans.

Amiloride↗
PubMed1988

Pharmacokinetics of pholcodine in healthy volunteers: single and chronic dosing studies.

1. The pharmacokinetics of pholcodine after two single doses and after chronic administration were studied in healthy human volunteers. 2. Six subjects received single oral doses of 20 and 60 mg of pholcodine according to a balanced cross-over design with an interval of 3 weeks between the two treatments. Blood and saliva samples and all urine were collected over 168 h after each dosage administration. Subsequently, the same subjects received 20 mg pholcodine 8 hourly orally for 10 days. Blood and saliva samples and all urine were collected during an 8 h dosing interval after the last dose on day 11. 3. Plasma, saliva and urine concentrations of pholcodine were determined by a high performance liquid chromatographic assay. 4. After the single doses, pholcodine was absorbed rapidly (tmax = 1.6 +/- 1.2 h) and eliminated slowly with a mean half-life of 50.1 +/- 4.1 h. The renal clearance of pholcodine was 137 +/- 34 ml min-1 and was inversely correlated with urine pH (r = 0.60) but not with urine flow rate. 26.2 +/- 3.3% of the dose was excreted as unchanged pholcodine after both doses. The concentration of pholcodine in saliva was 3.6 times higher than in plasma. 5. After chronic administration, the pharmacokinetics of pholcodine were not statistically different from the single dose parameters. 6. Pholcodine did not appear to undergo conjugation. The plasma protein binding was 23.5%. Morphine, in unconjugated or conjugated form, was not detected in the urine of any subject after pholcodine administration.

Adult↗
PubMed1988

Inhibition of lipid peroxidation by dihydroquinoline-type antioxidant (CH 402).

The in vitro effect of a non-toxic, water soluble, low molecular weight, stable dihydroquinoline-type antioxidant, CH 402 (Na (2,2-dimethyl-1,2-dihydroquinoline-4-yl)-methane sulphonic acid) was studied on free radical reactions in brain subcellular fractions. Experiments were performed using rat and mouse brain homogenate and microsomal fractions. Non-enzymatically induced lipid peroxidation by ascorbic acid was studied in correlation with ascorbic acid and CH 402 concentrations and incubation time. Malondialdehyde production during lipid peroxidation was measured by the thiobarbituric acid test. In a concentration range of 10(-2)-10(-5) M CH 402 dose-dependently inhibited the ascorbic acid induced in vitro lipid peroxidation in mouse and rat brain subcellular fractions.

Animals↗