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Biomedical subjects

G Becher

Publications and source records attributed to G Becher.

At least 37 records · Page 2Linked to original sources
PubMed1998

Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Frühblühermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P<0.001); IgE was not significantly different. Eosinophil cationic protein remained unchanged with STI, but significantly increased with placebo in the pollen season (P=0.003). STI was well tolerated. In conclusion, STI was shown to be efficacious and safe for the treatment of patients with tree-pollen rhinoconjunctivitis.

Adolescent↗
PubMed1997

[Breath condensate as a method of noninvasive assessment of inflammation mediators from the lower airways].

The detection of mediators from the lower airways still depends on invasive or provoking sampling techniques like bronchoalveolar lavage (BAL) or induced sputum, respectively. Both methods affect the specimen itself. In contrast, the breathing condensate opens the possibility to get native specimens from lower airways during breathing at rest. The breathing condensate was obtained by freezing of exhaled air. The equipment was developed in the FILT Res. Soc. Ltd.. The method is applied for a patent. Leukotriene B4 and Leukotriene C4D4E4F4 were measured in the exhalation of asthmatics, patients with different airway disorders and healthy volunteers. In an additional study the condensate was obtained before and after of a non-specific bronchial challenge test. In asthmatics a close correlation between leukotriene concentration of the condensate and the degree of asthmatic disease according to "International Consensus Report" was found, but no correlation to lung function tests. Within a bronchial challenge test applying histamine the release of leukotrienes was shown to be more sensitive to the challenge test than a lung function test. The results of the study indicate new diagnostic possibilities in lung diseases using the detection of non volatile substances in the exhaled air.

Asthma↗
PubMed1996

Determination of aluminium in samples from bone and liver of elderly Norwegians.

Recent reports associating aluminium with several skeletal and neurological disorders in humans suggest that exposure to aluminium may pose a health hazard. In connection with an epidemiological study on aluminium and Alzheimer's disease, information on the body burden of aluminium was needed. Aluminium is stored in the body mainly in bone and soft tissues such as the liver. Therefore, an analytical procedure was developed for the determination of aluminium in the head of femur and the liver using graphite furnace atomic absorption spectrometry. Problems in such analyses are associated with low levels of aluminium, risk of contamination during sample preparation, inhomogeneity of the sample tissues, and complexity of the matrices. Bone samples gave poorer repeatability compared to liver samples and up to four replicate analyses were performed. In the analyses of the digested bone samples, severe chemical interference occurred when these either contained much dissolved bone mineral or had a high A1 concentration. It is possible that this interference is brought about by formation of aluminium phosphate in the graphite tube. The analytical results for bones are given relative to ash weight because the samples sometimes contained a lot of fat. The ash weight of the bone tissue varied between 8 and 69 per cent. The material consisted of 84 samples of head of femur and 95 liver samples from deceased elderly Norwegians. Two cases had high A1 levels in bone (16.8 and 18.0 mg/kg ash weight) and liver (10 and 22.7 mg/kg dry weight) tissues. The remaining cases showed about ten to fifteen-fold variation of the A1 level in both liver (0.4 - 5.7 mg/kg) and bone (0.5 - 5.8 mg/kg). There was no correlation between the level in liver and bone when the two cases with the highest levels were excluded.

Aged↗
PubMed1996

PCDDs, PCDFs, and PCBs in human blood in relation to consumption of crabs from a contaminated Fjord area in Norway.

Consumption of fish and shellfish from contaminated areas may be an important source of human exposure to persistent organohalogen compounds such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). We determined concentrations of 2,3,7,8-substituted PCDDs and PCDFs and 19 PCB congeners in whole blood samples from three groups of men, 40-54 years of age, with different consumption levels of crabs from a fjord area in southern Norway polluted with organochlorine compounds from a magnesium production plant. A significant increase of many PCDD/PCDF congeners was found in the blood when comparing the referents, moderate-, and high-intake groups. The greatest difference was observed for several of the PCDFs that are characteristic for the contamination of the marine biota of the fjord. PCBs, in general, play a minor role in the contamination of the fjord by the magnesium production process, except for the highly chlorinated congeners such as PCB-209. Nevertheless, almost all PCBs increased from the referents to the high-intake group. However, the relative concentrations of several highly chlorinated PCBs (particularly PCB-209) in blood are unexpectedly low compared to their abundance in crabs, indicating low uptake of these congeners. The exposure to PCDDs/PCDFs from crab consumption calculated from individual body burdens of these compounds were in good agreement with the intake estimated from previously measured concentrations in crabs, reported fishing sites, and consumption. Almost all subjects in the high-intake group exceeded the tolerable weekly intake of 35 pg TEQ/kg body weight/week proposed by a Nordic Expert Group.

Adult↗
PubMed1995

PCDDs, PCDFs, and PCBs in human milk from different parts of Norway and Lithuania.

Concentrations of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) as well as 16 polychlorinated biphenyls (PCBs) have been determined in pooled samples of breast milk from 10-12 mothers living in three different geographical areas in both Norway and Lithuania. The results indicate no apparent dependency of the PCDD/PCDF levels, expressed as toxic equivalents (TEQs), and total PCB levels on the geographical residence of the donors within a country. This confirms the findings from a corresponding Norwegian study in 1985/1986 where individual samples from the same areas were analyzed. Teh total TEQs, including dioxin-like PCBs, ranged from 31 to 42 pg TEQs/g fat in Norway and from 45 to 49 pg TEQs/g fat in Lithuania. The mean concentration of PCDDs/PCDFs in teh Norwegian samples (10.4 pg TEQs/g fat) was slightly lower than in the Lithuanian samples (14.8 pg TEQs/g fat). Dioxin-like PCBs were found to contribute two to three times more to the total TEQs than the PCDDs and PCDFs. Major contributors among the dioxin-like PCBs were PCBs 126, 156, 114, 118, and 170. Comparison of the present data with those obtained in the Norwegian study in 1985/1986 shows that for PCDDs/PCDFs the mean TEQ levels have decreased by about 37% in the 7-yr time span, while the levels of total PCBs, as determined by packed-column gas chromatography, have remained unchanged or only slightly decreased. Future studies are necessary to confirm this potential temporal trend.

Animals↗
PubMed1994

Determination of planar PCBs by combining on-line SFE-HPLC and GC-ECD or GC/MS.

A method for determining non-ortho- and mono-ortho-substituted polychlorinated biphenyls (PCBs) in biological samples has been developed. High selectivity was obtained by on-line coupling of supercritical fluid extraction (SFE) and high-performance liquid chromatography (HPLC). Gas chromatography (GC) with electron capture detection or high-resolution mass spectrometry was utilized for quantitative determinations. Group separation of different PCB congeners was achieved on a (2-(1-pyrenyl)ethyl)dimethylsilylated silica column. Compared with off-line HPLC, the on-line coupling to SFE resulted only in a minor reduction in column efficiency. The average recoveries of the planar non-ortho-substituted PCB congeners 77, 126, and 169 from crab hepatopancreas were 71-101%, with the highest recovery for PCB-169. For human blood serum and milk, the recoveries of the three congeners ranged from 35 to 57% (serum) and from 76 to 87% (milk), with the lowest recovery for PCB-169. The relative standard deviations of the complete analyses were determined to be 5-16%. The recoveries of the on-line SFE-HPLC technique were compared to those of conventional solvent extraction and off-line HPLC. For crab hepatopancreas, the two methods gave approximately the same result, but for blood serum, slightly higher recovery of the native non-ortho-substituted PCBs was obtained using SFE-HPLC. The present method demonstrates the high speed and selectivity which were obtained by on-line SFE-HPLC as a sample preparation technique prior to GC analyses for the determination of a group of highly toxic PCBs, usually found in very low concentrations compared to the bulk of the PCB congeners.

Animals↗
PubMed1994

Congener-specific determination of polychlorinated biphenyls and organochlorine pesticides in human milk from Norwegian mothers living in Oslo.

Human milk samples from 28 mothers at Oslo City Hospital, Norway, were collected in 1991 and analyzed for individual polychlorinated biphenyl (PCB) congeners, IUPAC numbers 28, 74, 99, 101, 105, 114, 118, 128, 138, 141, 153, 156, 157, 170, 180, 194, and 206, plus selected non-ortho-substituted compounds, IUPAC numbers 77, 126, and 169. Sum DDTs (sum of concentrations of DDT and related compounds), hexachlorobenzene (HCB), oxychlordane, transnonachlor, and sum hexachlorocyclohexanes (HCHs) (sum of concentrations of alpha-HCH, beta-HCH, and gamma-HCH) were also determined. The mean levels of sum DDTs, HCB, oxychlordane, transnonachlor, and sum HCHs were 338, 41, 9, 19, and 36 ng/g, respectively, in human milk fat. p,p'-DDE and beta-HCH accounted for 81 and 93% of sum DDTs and sum HCHs, respectively. The mean level of sum PCBs (sum of mean concentrations of 20 individual congeners) was 372 ng/g milk fat. A very good correlation was found between sum PCBs and PCB-153 (r = .97). Sum PCBs determined on a capillary column was found to account for 62-79% of total PCBs calculated by using the packed column method used in previous human milk surveys in Norway. Comparison with previous results revealed that the mean sum PCB, HCB and sum DDT levels were decreased by 70, 65, and 75%, respectively during the past 9 yr. The contribution of individual PCDD/PCDF (earlier Norwegian study) and non- and mono-ortho-substituted PCB congeners to the total calculated toxic equivalent values was assessed, and the PCBs were found to constitute a major part of the TCDD equivalents in human milk, with PCB-126 as the main contributor.

Adult↗
PubMed1991

Genotoxic effects of the drinking water mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in mammalian cells in vitro and in rats in vivo.

The potent bacterial mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]- furanone) (MX), which is formed during chlorination of drinking water and accounts for about one third of the Ames mutagenicity of tap water, has been studied with respect to its genotoxicity in vitro and in vivo. Treatment with 30-300 microM MX (1 h) induced DNA damage in a concentration-dependent manner in suspensions of rat hepatocytes, as measured by an automated alkaline elution system. The effect was similar in hepatocytes from PCB-induced and uninduced rats. DNA damage was induced in V79 Chinese hamster cells and in isolated rat testicular cells, at the same concentration level as in hepatocytes. Pretreating testicular cells with diethylmaleate, which depletes 85% of cellular glutathione, had no significant effect on the DNA damage induced by MX. The treatment conditions used in the alkaline elution experiments were not cytotoxic to any of the cell types used, as determined by trypan blue exclusion. V79 cells exposed to 2-5 microM MX (2 h) showed an increased frequency of sister-chromatid exchanges (SCE) whereas no significant effect on HGPRT mutation induction was observed. Higher concentrations (greater than 10 microM, 2 h) apparently blocked cell division. The data indicate that MX can react directly with DNA or that MX is metabolized to an ultimate mutagen via some enzyme which is common in mammalian cells. The in vivo experiments showed no evidence of genotoxicity after intraperitoneal (18 mg/kg, 1 h) or oral (18, 63 or 125 mg/kg, 1 h) administration of MX, as measured by alkaline elution, in any of the following organs: the pyloric part of the stomach, the duodenum, colon ascendens, liver, kidney, lung, bone marrow, urinary bladder and the testes. In conclusion, MX is a direct-acting genotoxicant in vitro but no in vivo genotoxicity was detected.

4-Nitroquinoline-1-oxide↗
PubMed1991

Formation of a glutathione conjugate and a semistable transportable glucuronide conjugate of N2-oxidized species of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rat liver.

We have previously shown that 2-hydroxamino-1-methyl-6-phenylimidazo[4,5-b]pyridine(2-h ydroxamino-PhIP) is the principal metabolite leading to mutations in Salmonella typhimurium TA98 and DNA damage in mammalian cells. In rat hepatocytes this metabolite can be further conjugated to 2-(N-beta-D-glucuronopyranosyl (hydroxamino)-1-methyl-6-phenylimidazo[4, 5-b]pyridine[N(OH)-gluc-PhIP]. Its rate of formation was increased in hepatocytes from polychlorinated biphenyl (PCB)-pretreated animals. This metabolite is the main metabolite of PhIP in bile and it is hydrolyzed both by human and rat intestinal bacteria. Smaller amounts are excreted into urine. The evidence for the proposed structure is based on 1H- and 13C-NMR, beta-glucuronidase-lability giving 2-hydroxamino-PhIP upon hydrolysis and on the results obtained by using biochemical enzyme inhibitors. N(OH)-gluc-PhIP may be important for genotoxic lesions and tumors of 2-amino-1methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in extrahepatic tissue. In hepatocytes and bile from PCB-pretreated rats a PhIP-glutathione conjugate, 2-glutathionyl-1-methyl-6-phenylimidazo[4,5-b]pyridine (GSH-PhIP) was also found. The evidence for the proposed structure is based on 1H-NMR and high-resolution mass spectrometry. The metabolite can also be produced by a direct nucleophilic substitution of the nitro group in 2-nitro-PhIP by glutathione (GSH) in vitro. The metabolite did not form from 2-hydroxamino-PhIP and GSH either directly or in the presence of glutathione S-transferase. The formation of GSH-PhIP in rat liver and isolated cells only at a high rate of 2-hydroxamino-PhIP formation (PCB-treated animals) indicates that 2-nitro-PhIP may be formed in the liver during such N-oxidation of PhIP.

Animals↗
PubMed1990

[Diagnosis of lung function in bronchial asthma].

Chronic obstructive airway diseases have only slight demand on lung function diagnostics according to the number of methods and technical level. But we have the demand of a high rate of lung function, more than in all other lung diseases. The expiratory peak flow (PEF) seems to be a suitable parameter for daily control.

Adult↗
PubMed1989

Characterisation of metabolites of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline formed after incubation with isolated rat liver cells.

The metabolism of 14C-labelled 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was studied in suspensions of hepatocytes isolated from PCB-pretreated rats. The metabolites found after incubation of IQ/MeIQ (0.1 mM) with PCB-pretreated hepatocytes for 3 h were separated into three principal groups: ethyl acetate-extractable metabolites (2-4%), water soluble metabolites (94-98%) and covalently bound metabolites (0.4-0.5%). The water soluble metabolites were separated by HPLC. The metabolites were evaluated by beta-glucuronidase lability, sulphate incorporation and compared with glucuronides formed by microsomes. Mass spectroscopy and proton NMR were also run. The major metabolites formed were a N2-sulphamate, an O-sulphate in position 5 for IQ and 5 for MeIQ and an O-glucuronide in the same position. The MeIQ N2-sulphamate was much less abundant than the IQ N2-sulphamate. When compared with hepatocytes from uninduced rats, it was found that primarily the formation of ring-hydroxylated conjugates increased after PCB-pretreatment. The major ethyl acetate-extractable metabolites were the N2-acetyl derivatives and an unidentified metabolite. A small peak representing the 5-hydroxy-IQ or 5-hydroxy-MeIQ could also be seen in the HPLC chromatogram of the ethyl acetate extractable metabolites. All major water soluble products described in hepatocytes were also found in urine and bile of uninduced rats exposed to IQ/MeIQ in vivo.

Animals↗
PubMed1989

Metabolism of the food carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in isolated rat liver cells.

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was transformed to at least 10 metabolites in suspensions of hepatocytes isolated from Aroclor 1254 treated rats. Combining biochemical data such as effects on MeIQx metabolism of metabolic modulators and incorporation of radioisotopic sulfur with UV, mass and 1H-NMR spectroscopy, we elucidated the structures of six metabolites. About 40% of the MeIQx was transformed to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxalin-4(or5)-yl sulfate. Other oxygenated metabolites were 2-amino-8-hydroxymethyl-3-methylimidazo[4,5-f]quinoxalin-4(or 5)-yl sulfate and 2-amino-4(or5)-beta-D-glucuronopyranosyloxy-3,8-dimethyli midazo[4,5-f] quinoxaline. Evidence was obtained that a glutathione conjugate was formed. This metabolite, and the other oxygenated metabolites were probably formed in P-450 catalyzed reactions. Two metabolites, 2-beta-D-glucuronopyranosylamino-3,8-dimethylimidazo[4,5-f]q uinoxaline and the N-(3,8-dimethylimidazo[4,5-f]quinoxaline-2-yl) sulfamate, were direct conjugates of MeIQx.

Animals↗
PubMed1989

4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate--a major metabolite of the food mutagen 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) in the rat.

Isolated rat hepatocytes (4 X 10(6) cells/ml metabolized the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP) (100 microM) to at least eight different metabolites in a 4 h duration. The major metabolite formed was 4-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate (4'-PhIP sulfate). Its rate of formation was increased in hepatocytes from PCB pretreated animals in comparison to hepatocytes from untreated animals. One of the other metabolites was the unconjugated derivative of the sulfate (4'-OH-PhIP). This metabolite was also found after in-vitro incubations of rat liver microsomes from PCB or beta-naphthoflavone pretreated animals. The evidence for the proposed structure of the major metabolite is based on [1H]NMR and UV spectroscopy, incorporation of radiolabelled sulfate and arylsulfatase-lability. The formation of 4'-PhIP sulfate was inhibited by the P-450 inhibitors alpha-naphthoflavone and metyrapone and when incubated in sulfate-free medium added the sulfotransferase inhibitor pentachlorophenol. 4'-PhIP sulfate was also the major metabolite of PhIP in the urine of exposed rat.

Animals↗
PubMed1989

[Short scientific report. Vitamin C lessens superoxide anion(O2)-induced bronchial constriction].

An in vivo model of acute lung damage provoked by free oxygen radicals in guinea pigs was introduced. Bronchial and pulmonary response was induced by tracheal instillation of Xanthine-Oxidase (XO)-Xanthine solution. The response was measured as a decrease of tidal volume during unchanged artificially ventilation. It was found that ascorbic acid pretreatment was effective to diminish the XO-induced reaction.

Animals↗
PubMed1989

Failure of ambroxol to influence the allergen induced bronchial constriction in sensitized guinea pigs.

The action of ambroxol was tested in an in vivo guinea pig asthma model. Ambroxol, a compound with antiallergic properties effects the mediator releasing cells in vitro and surfactant secretion from alveolar type II cells. This paper deals with the action of ambroxol in an in vivo asthma model in guinea pigs. Ovalbumin sensitized guinea pigs were artificially ventilated by negative chest wall pressure, using a tank respirator. Breathing parameters were measured pneumotachographically. The experimental animals were treated with 50 mg/kg ambroxol i.p. for 5 days; control animals received saline only. The results indicate that pretreatment with ambroxol had no significant effect on the allergic bronchial constriction, while in vitro ambroxol effects on mediator releasing cells and surfactant production point to antiallergic properties. An explanation of the failure of allergenic preventing effects of ambroxol in vivo may be its insufficient concentration in the tissue.

Allergens↗