PubMed HealthSearch

Biomedical subjects

H Brunner

Publications and source records attributed to H Brunner.

At least 37 records · Page 2Linked to original sources

Lithium discriminates between muscarinic receptor subtypes on guinea pig hippocampal neurons in vitro.

In CA3 pyramidal neurons of guinea pig hippocampal slices an outward current activated by the GABAB agonist, baclofen (0.3 microM, Ibac) was reduced by low concentrations of carbachol (Cch, 0.1-0.3 microM). The effect of Cch desensitized suggesting that the receptor subtype involved in this muscarinic effect of Cch was of the M1 subtype. The receptor subtype was also characterized by its equilibrium dissociation constant for pirenzepine (10 nM) as an M1 receptor. Li+ applied extracellularly (1 mM) or intracellularly blocked the suppression of Ibac by Cch without affecting the Cch blockade of a current termed IAHP, which is mediated by M2 receptors. While the effect of intracellular Li+ application was immediate, it developed very slowly with extracellular application. Since Li+-salts are used effectively in the treatment of mania and depression, the selective effect of Li+ on M1-mediated muscarinic neurotransmission might be important for the cholinergic hypothesis of affective disorders.

Animals

Detection of methadone in human hair by gas chromatography/mass spectrometry.

Determination of methadone in human hair by gas chromatography/mass spectrometry was described. Helium as carrier gas, a 30-m bonded phase-fused silica DB-1 capillary column and splitless injection at 230 degree C temperature were used. The concentrations of methadone and its metabolites were measured in addition by radioimmunoassay (RIA). Both methods GC/MS and RIA showed the presence of methadone in human hair.

Gas Chromatography-Mass Spectrometry

Absorption and tissue distribution of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in the rat.

A defined mixture of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) was parenterally administered to rats and absorption and tissue distribution were measured: 1) Toluene/DMSO (1 + 2; v/v) proved to be a convenient vehicle for the subcutaneous administration of the various PCDDs and PCDFs. Seven days after application the rate of absorption was 90% of the administered dose or even higher for almost all of the PCDDs/PCDFs in the mixture. In a few cases only (e.g. OCDD) the rate was found to be 84-89%; 2) Seven days after subcutaneous administration all 2378-substituted congeners were found in the liver, whereas only a few non-2378-substituted congeners could be measured in minor quantities. The 2378-substituted congeners also predominated in adipose tissue; however, most of the non-2378-substituted congeners were also detected; 3) The amount deposited within the liver as percentage of the administered dose differed for the various 2378-substituted PCDDs and PCDFs, ranging from less than 10% for OCDD or 2378-T4CDF, and between 60 and close to 100% for 12378-P5CDD or the H6CDDs. Therefore, the concentration ratio (liver/adipose tissue) was also found to be very different, ranging from less than 3 in the case of 2378-T4CDD or 2378-T4CDF to greater than 40 in the case of 1234678-H7CDD, 23478-P5CDF, 123678-H6CDF, or 1234678-H7CDF; 4) Studies performed at the time period of ongoing absorption (13-14 h after injection) provided the first evidence that some of the non-2378-substituted congeners do reach substantial concentrations in hepatic tissue shortly after administration; 5) Subsequent to intraperitoneal injection of the same PCDD/PCDF mixture the concentrations within the liver were found to be almost identical with that found after subcutaneous injection. In contrast, much higher concentrations of the congeners were found in (abdominal) adipose tissue; 6) In the liver of untreated rats of the same strain no T4CDDs/T4CDFs or P5CDDs/P5CDFs were detectable under our experimental conditions.

Animals

Elimination of various polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs and PCDFs) in rat faeces.

A defined mixture (of a composition characteristic of that present in incinerator fly ash) of polychlorinated dibenzo-p-dioxins and -furans (PCDDs and PCDFs) was subcutaneously administered to rats and the elimination of the unchanged congeners via faeces was measured. 1) All congeners administered could be found in faeces. 2) The rates of elimination via faeces were rather different for the different congeners. 3) The most toxic congeners, 2378-T4CDD and 12378-P5CDD, were present in unmetabolized form in faeces to less than 4% and less than 8% of the administered dose within the first week. Thus, parenteral administration clearly minimizes contamination of the animal quarters when compared with corresponding oral dosing. 4) The rate of unchanged elimination was apparently especially pronounced for the higher chlorinated PCDDs and PCDFs. The highest excretion rate was found for 1234678-H7CDD (up to 30% of administered dose). 5) No obvious differences were observed in the rates of elimination of the unchanged substances via faeces of the 2378-substituted or the non-2378-substituted isomers.

Animals

Effects of (-)baclofen on inhibitory neurons in the guinea pig hippocampal slice.

Intracellular recordings were made from electrophysiologically identified inhibitory neurons in the dentate hilus. (-)Baclofen (0.1-0.5 mumol/l), applied by the bath, strongly hyperpolarized inhibitory neurons, reduced their input resistance and induced outward currents under voltage clamp at holding potentials of -60 mV in cells recorded with KCl-filled electrodes. Increasing the (-)baclofen concentration (up to 1 mumol/l) did not increase the amplitude of the outward current, but increased its duration. (-)Baclofen depressed Cl-dependent IPSPs evoked by perforant path stimulation in inhibitory neurons, granule cells and CA3 neurons. In the case of inhibitory neurons and CA3 neurons, depression of IPSPs, membrane hyperpolarization and increase in membrane conductance concurred. All effects were blocked by BaCl2 (1 mmol/l) in the superfusate. In the case of granule cells, depression of IPSPs by (-)baclofen outlasted an only small membrane hyperpolarization, conductance increase or outward current. High concentrations (up to 10 mumol/l) of (-)baclofen depressed evoked IPSPs of granule cells for an extended period of time, but the other effects remained small and transient. IPSPs elicited in granule cells by microdrop application of glutamate to the dentate hilus were also blocked by (-)baclofen, but spontaneous IPSPs were only reduced in amplitude. We suggest that the blockade of GABAA receptor-mediated IPSPs of hippocampal neurons by the GABAB receptor agonist (-)baclofen can be explained by a K-dependent hyperpolarization of inhibitory neurons.

Animals

Reduced proliferative response of mouse spleen cells to mitogens during infection with Salmonella typhimurium or Listeria monocytogenes.

A significant reduction in the mitogenic responsiveness (uptake of 3H-thymidine) of murine spleen cells to concanavalin A, phytohemagglutinin or lipopolysaccharide was observed during infection with virulent Salmonella typhimurium. The decreased response to mitogens could be observed independent of the immunity to typhimurium (Ity) genotype, i.e. in CBA/J mice and C3H/HeJ mice (Ityr) as well as in C57BL/6 mice (Itys). Because reduced responsiveness was demonstrated in C3H/HeJ mice, which are susceptible to S. typhimurium infection but are unresponsive to lipopolysaccharide, it is concluded that the two phenomena are not correlated with one another. A similar decrease in response to mitogens was shown in mice infected with Listeria monocytogenes. Reduction in mitogenic responsiveness was directly correlated with the number of viable bacteria detected in the spleen cell suspension. Decreased lymphoproliferation could be observed as early as 2 days after infection and lasted 3 weeks in sublethally infected mice. The question remains whether or not the reduced responsiveness indicates an enhanced susceptibility to infection or merely represents a high degree of activation of defense mechanisms.

Animals

[Tetrahydrocannabinols in hair of hashish smokers].

The study investigates the presence of tetrahydrocannabinols in the head hair and the pubic and axillary hair. The hair samples were obtained from hashish smokers. The concentrations were determined by radioimmunoassay and reflect total tetrahydrocannabinols and metabolites. The values found ranged from 0.4 ng/mg hair up to 3.8 ng/mg hair. The presence of the drug in the hair samples was also demonstrated by GC/MS.

Accidents, Traffic

Isolation of unusually composed sialyl-compounds from hemofiltrate.

Sialyl compounds are essential components of various biological fluids but relatively little is known about their occurrence in the extracellular fluid of patients with end-stage renal disease. As we have developed a macropreparative method for concentrating and desalting a wide range of fractions from diluted biological fluids we have been able to isolate and identify 5 sialooligosaccharides, 3 sialosugarphosphates, 2 monosialoglycopeptides and 1 disialoglycopeptide. The structures have been elucidated predominantly by one and two-dimensional NMR spectroscopy, enzymatic degradation and FAB mass spectrometry. The accumulation of these compounds in uremic sera may be of particular interest as they may interact in the molecular biology of diseases typically associated with the uremic state, e.g., immune deficiency, neurological disorders, receptor binding abnormalities, complement system disturbances and cell membrane alterations.

Carbohydrate Conformation

[The De Barsy syndrome].

De Barsy syndrome is defined by the combination of a progeroid aspect, cutis laxa, cornea clouding, growth retardation, mental retardation and athetoid movements. The clinical symptoms of a male infant are described and compared with all other cases reported in literature. The aetiology of this syndrome is unclear; inheritance is probably autosomal recessive.

Athetosis

Effect of ganglion blockade with pentolinium on circulating neuropeptide Y levels in conscious rats.

The vasoconstrictor peptide, neuropeptide Y (NPY), is present in perivascular noradrenergic neurons of all mammals studied and may be important in the regulation of blood pressure. High plasma levels of NPY have been measured in the rat. To investigate partially the source and factors controlling the release of the circulating peptide, the effect of pentolinium tartrate administration has been studied in conscious rats. Pentolinium given as a bolus (5 mg/kg) followed by an infusion of a further 5 mg/kg/30 min produced a highly significant reduction in blood pressure of more than 40 mm Hg, when compared to either basal values or control animals treated with saline. Pentolinium treatment resulted in significantly lower plasma neuropeptide Y levels (31.0 +/- 6.7 fmol/ml) compared with those of control animals (78.6 +/- 8.2 fmol/ml). Circulating catecholamines were also significantly reduced in those animals receiving pentolinium. These results are compatible with circulating NPY arising from the sympathetic nervous system, with release being controlled by the mechanisms already established for catecholamines.

Animals