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Biomedical subjects

G Becher

Publications and source records attributed to G Becher.

At least 73 records · Page 4Linked to original sources

[Experimental study on the significance of arachidonic acid metabolism in the pathogenesis of bronchial asthma with an in vivo model in the guinea pig].

In anaesthetized artificially ventilated guinea-pigs from two breeds were produced histamine-induced bronchoconstrictions after pretreatment with acetylsalicylic acid (ASS) and/or para-amino-methylbenzoic acid (PAMBA). It was detected a distinct but adverse action of ASS on the intensity of bronchoconstriction in both animal groups. PAMBA was without any effect alone but mostly inhibited ASS-action. Since PAMBA inhibits phospholipase-A2 and ASS inhibits cyclooxygenase--both key-enzymes of arachidonic acid metabolism--the findings are estimated as a hint to the role of arachidonic acid metabolism in our animal model of asthma.

Airway Resistance↗

Determination of exposure to polycyclic aromatic hydrocarbons by analysis of human urine.

A method for biological monitoring of exposure to polycyclic aromatic hydrocarbons (PAH) has been developed. The analytical procedure includes extraction of PAH and PAH metabolites from urine using commercial cartridges containing C18-modified silica, reduction of metabolites to PAH by hydriodic acid and subsequent analysis of the PAH by high performance liquid chromatography with fluorescence detection. The method is applied to urine samples from an occupationally non-exposed control group and from aluminum workers with high exposure to PAH. In the control group urine extracts from smokers show a significantly higher level of PAH than from non-smokers. The high concentrations of PAH found in the working atmospheres of aluminum plants are not reflected to a corresponding extent in the excretion of PAH in urine.

Chromatography, High Pressure Liquid↗

[Problems of documentation of malignant tumors, showing as an example lip cancer].

The TNM system allows malignant tumours to be classified according to uniform aspects and permits the collective comparison of the applied therapeutical methods. The problem is illustrated by a longitudinal study of 70 patients with lip carcinoma over a period of 6 years where only one TNM code was established. In conclusion the author recommends the documentation of 4 TNM codes per patient, which allow an exact statement about the diagnosis, optimal planning of the therapy, course, and prognosis.

Humans↗

Dioxins, PCBs and some chlorinated pesticides in human milk from the Kola Peninsula, Russia.

In 1993, 30 individual human milk samples were collected in Murmansk and Monchegorsk, and analysed for 23 polychlorinated biphenyl congeners, PCBs (IUPAC nos.) 28, 52, 66, 74, 99, 101, 105, 110, 114, 118, 128, 138, 141, 149, 153, 156, 157, 170, 180, 187, 194, 206, and 209. In addition, the following organochlorine pesticides (OCPs): hexachlorobenzene (HCB), the alpha-, beta-, gamma-isomers of hexachlorocyclohexane (HCH), the chlordanes: oxychlordane, trans-chlordane, cis-chlordane, trans-nonachlor, and cis-nonachlor, and the DDT-compounds: pp-DDE, pp-DDD, op-DDT and pp-DDT were detected. From each city, a pooled sample was made and analysed for non-ortho PCBs, dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). In addition one individual sample from Monchegorsk was analysed for PCDDs/PCDFs because of the very high levels of PCBs in this sample. High levels of pp-DDE and beta-HCH were found in Murmansk and Monchegorsk (in parenthesis) with mean levels of 1269, (892) and 853, (739) micrograms/kg milk fat respectively. Highest individual levels of pp-DDE (2816 micrograms/kg milk fat) and beta-HCH (1988 micrograms/kg milk fat) were found in Murmansk. Significant differences were found between the levels of gamma-HCH, cis-chlordane, trans-nonachlor, cis-nonachlor, pp-DDE, and the PCBs 28, 52, 74, 66, 110, 118, 105, 128, 206, and 209, between the two areas. No geographic differences in the concentrations of PCDDs/PCDFs and non-ortho PCBs in the sample pools from the two Russian areas were observed.

Adolescent↗

Heterocyclic aromatic amines in human urine following a fried meat meal.

In a search for suitable biomarkers for human dietary exposure to heterocyclic aromatic amines (HAAs), we have investigated the concentrations of three common fried food mutagens in food and urine after consumption of a fried meat meal. In this connection we developed a method for the determination of HAAs and have investigated the common fried red meat HAAs 2-amino-1-methyl-6-phenylimidazo[4,5-beta]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx). Eight volunteers participated in the study, each consuming a meal of fried minced beef patties (295 g), boiled potatoes, and a green salad. Urine was collected for two 12-hr periods prior to and following the meal. HAAs were determined in cooked meat and in untreated and acid hydrolysed urine by a series of liquid/liquid extractions, followed by Blue cotton adsorption and finally by a novel derivatized technique for gas chromatography-mass spectrometry (GC-MS). The primary amino groups were derivatized by acylation with heptafluorobutyric acid anhydride, and the resulting amide methylated using diazomethane. Phenolic hydroxyl groups were also methylated by this procedure, making it possible to detect hydroxylated HAAs, possible metabolites or constituents of the fried meat. 4'-Hydroxy-PhIP ¿2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-beta]pyridine¿ (4'-OH-PhIP) was indeed found in meat as well as in urine. The contents of PhIP, MeIQx and DiMeIQx in meat were 4.0 +/- 2.6, 3.5 +/- 0.9 and 0.3 +/- 0.1 ng g-1 (mean +/- SD, n = 4), from which the mean amounts ingested were calculated to be 1180, 1030 and 90 ng, respectively. Total amounts of HAAs in the 0-24-hr post-meal untreated urine (and percent of ingested dose) were 6-23 ng PhIP (0.5-2%) and 10-63 ng MeIQx (1-6%). In hydrolysed urine, the levels of HAAs were higher, totalling 24-100 ng PhIP (2-8.5%) and 133-329 ng of MeIQx (13-32%). DiMeIQx was below detection limit in all urine samples. Judged from our study, there were rather large inter-individual variations in the amounts of excreted HAAs, possibly caused by variations in the activities of enzymes taking part in HAA metabolism.

Adult↗

Determination and quantification of urinary metabolites after dietary exposure to acrylamide.

It is known that heat-treated carbohydrate-rich foods may contain high levels of acrylamide (AA) and up to 4000 microg kg-1 in potato crisps and 2000 microg kg-1 in French fries have been reported. In order to obtain more information on the human exposure to and metabolism of AA, a method for the determination of known urinary metabolites from the dietary exposure of AA using solid-phase extraction and liquid chromatography with positive electrospray MS/MS detection was developed. The validated assay range was from 8.6 to 342.9 microg l-1. The urinary metabolites were synthesized and their structures determined by NMR and MS. To test the method, a pilot study was conducted in which all urine during 48 h starting with 24 h fasting was collected. The two urinary metabolites, N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine (MA-GA3) and N-acetyl-S-(3-amino-3-oxopropyl)cysteine (MA-AA), were found to be above the detection limit. Fasting during 1 day caused about a 50% decrease in the total level of the metabolites, but after 1 day of a normal diet, the metabolite levels increased back to pre-fasting levels. The total amount of AA in the form of urinary metabolites excreted over the period was estimated to be about 40 microg AA day-1 for the average non-smoker.

Acrylamide↗

Fluorescence properties and base pair stability of oligonucleotides containing 8-aza-7-deaza-2'-deoxyisoinosine or 2'-deoxyisoinosine.

The fluorescence and the base pairing properties of 8-aza-7-deaza-2'-deoxyisoinosine (1) are described and compared with those of 2'-deoxyisoinosine (2). The corresponding phosphoramidites (11, 12) are synthesized using the diphenylcarbamoyl (DPC) residue for the 2-oxo group protection. The nucleosides 1 and 2 base pair with 2'-deoxy-5-methylisocytidine in DNA duplexes with antiparallel chain orientation and with 2'-deoxycytidine in a parallel DNA. These base pairs are less stable than the canonical dA-dT pair and that of 2'-deoxyinosine (4) with 2'-deoxycytidine. The fluorescence of the nucleosides 1 and 2 is quenched (approximately 95%) in duplex DNA. The residual fluorescence is used to determine the Tm-values, which are found to be the same as determined UV-spectrophotometrically.

Base Pairing↗

Pyrazolo[3,4-d]pyrimidine nucleic acids: adjustment of the dA-dT to the dG-dC base pair stability.

The pyrazolo[3,4-d]pyrimidine-4,6-diamine nucleosides 2b-d stabilize the dA-dT base pair significantly when the dA-residue is replaced. Oligonucleotide duplexes incorporating 2b-d show a 4-6 degrees C Tm increase per modification. The 7-bromo compound 2b harmonizes the stability of the dA-dT vs. the dG-dC pair. According to this the stability of such duplexes depends no longer on the base pair composition of a DNA molecule.

Base Pairing↗

[Breath condensate--a medium obtained by a noninvasive method for the detection of inflammation mediators of the lung].

Collection of exhaled condensate (freezing of expired air under conditions of spontaneous breathing) is a non-invasive method permitting the collection of material originating from the lung and the lower respiratory tract so that it can be used for diagnostic examinations. In order to be able to evaluate the diagnostic evidence of exhaled condensate samples in cases of respiratory disease of the calf, leukotriene B4 (LTB4) in bovine exhaled condensate was determined. The influence of the breathing pattern and body temperature on the quantity of condensate to be collected was tested in a total of 49 exhaled condensate samples. It became obvious that the exhaled condensate quantity obtained per time unit is dependent on the ventilation volume per time unit (minute volume). In exhaled condensate samples from 35 clinically healthy calves, LTB4 concentrations of less than 250 pg/mL exhaled condensate were detected. A total of 14 exhaled condensate samples from 7 calves was analyzed before and after experimental respiratory infection with Pasteurella multocida D. In parallel to the analysis of LTB4 in exhaled condensate, the lung function of the calves was examined by means of impulse oscilloresistometry. The increase of LTB4 in the exhaled condensate post infection correlated significantly (p < or = 0.05) with decreases of respiratory reactance. The determination of LTB4 concentrations in exhaled condensate seems to be suitable, in principle, for the detection of inflammations in the respiratory system of the calf. Further studies are needed for the evaluation of the diagnostic validity of the method.

Animals↗

A test hierarchy for anti-bronchoconstrictory lipoxygenase inhibitors: in vitro and in vivo experimental tests.

A test hierarchy for potential antiasthmatic lipoxygenase inhibitors was developed which includes besides molecular and cellular test systems, the arachidonic acid-(AA)-induced contraction of lung strips and ovalbumin-induced bronchoconstriction of sensitized guinea pigs. Nordihydroguaiaretic acid, butylated hydroxyanisole, benoxaprofen, BW 755C, salicylhydroxamic acid, FLM 5011 and other substances inhibit to a different extent the AA-induced contraction of lung strips and show anti-bronchoconstrictory activities in the ovalbumin-sensitized guinea pig.

Animals↗

Influence of bilateral subnodular vagotomy and section of retrotracheal plexus on allergic bronchial constriction in guinea pigs.

A bilateral subnodular vagotomy and a tracheal dissection with immediate readaptation (n = 18) or one of both (n = 8) was performed on ovalbumin sensitized guinea pigs. Control animals got a shame operation (n = 13). About one week later the animals were narcotized by ethylurethane 1.3 g per kg b.w. intraperitoneally and received a tracheotomy with insertion of a tracheal cannula and an additional insertion of a flexible catheter into the right jugular vein. Then the animals were artificially ventilated in a tank respirator by rhythmical exposure to a negative chest wall pressure, the ventilator settings were f = 20 per min, I: E = 1: 1, and rectangular pressure = -2 kPa. Breathing parameters were measured pneumotachographically. Flow, tidal volume, ECG and ventilation pressure were recorded with a 12-channel UV-light recorder. After the recording of initial parameters an intratracheal bolus-instillation of 0.5 mg/kg b.w. ovalbumin was given and 5 min later, a second ovalbumin bolus i.v. of 1 mg/kg b.w. Mean minimal tidal volumes reached after i.t. OA-provocation were: 17.6 +/- 19 in controls, 39.7 +/- 30 after vagotomy and tracheotomy, 40.5 +/- 20 after vagotomy alone, and 27.6 +/- 18 after tracheotomy alone. We found a significant inhibition of allergic bronchial constriction by bilateral vagotomy. The dissection of the retrotracheal plexus by tracheotomy was without significant effect on the allergic response. The investigation could demonstrate the significance of vagotomy on asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗