Biomedical subjects

K Mewes

Publications and source records attributed to K Mewes.

21 records · Page 2Linked to original sources

PubMed1982

Superior colliculus activation by retinal nicotinic ganglion cells: a 2-deoxyglucose study.

Systemic injection of the acetylcholinesterase inhibitor, di-isopropylfluorophosphate, in rats causes a marked increase in glucose use in the superficial layers of the superior colliculus. This activation of the superior colliculus is largely a retinal effect. Furthermore, since this response can be blocked by intraocular as well as systemic injections of mecamylamine, it is postulated that retinal nicotinic receptors are involved.

Animals↗

PubMedDate not supplied

Encoding of motor parameters by corticomotoneuronal (CM) and rubromotoneuronal (RM) cells producing postspike facilitation of forelimb muscles in the behaving monkey.

This paper compares the properties of corticomotoneuronal (CM) and rubromotoneuronal (RM) cells identified by postspike facilitation (PSF) of rectified EMG activity in the awake monkey. The postspike effects of CM and RM cells in flexors and extensors of the wrist and fingers have been determined, as have the discharge properties of these cells in relation to alternating ramp-and-hold wrist movements. The characteristics of postspike facilitation and postspike suppression (PSS) were similar for RM and CM cells. The magnitude of RM-PSF was weaker than CM-PSF and RM cells showed a stronger preference for facilitation of extensor muscles than CM cells. As with CM cells, the onset of discharge in RM cells preceded the onset of EMG activity in their target muscles. Tonic discharge related to static torque was more prominent in CM cells, whereas phasic discharge was more prominent in RM cells; however, many RM cells showed some tonic activity weakly related to static torque. We conclude that CM and RM cells share many common features; however, RM cells are concerned primarily with the dynamics of muscle contraction.

Animals↗

PubMedDate not supplied

Evidence for oxidative activation of mitoxantrone in human, pig, and rat.

A new metabolite of mitoxantrone in human, rat, and pig urine has been discovered by means of HPLC. The metabolite has been isolated by preparative HPLC from patient urine and is characterized by tandem mass spectrometry and UV-visible spectroscopy as 8,11-dihydroxy-4-(2-hydroxyethyl)-6-[[2-[(2-hydroxyethyl)amino]ethyl] amino]-1,2,3,4,7,12-hexahydronaphtho-[2,3-f]-chinoxaline-7,1 2-dione. Final structural proof has been obtained by independent synthesis. The new metabolite is a product of the enzymatic oxidation of the phenylenediamine substructure of mitoxantrone. An important biological consequence of the oxidative biotransformation is the possibility of covalent binding to intracellular targets via a highly electrophilic intermediate. Thus, alkylation may be an important mode of action of mitoxantrone. Incubation of mitoxantrone with horseradish peroxidase/hydrogen peroxide in the presence of glutathione led to the formation of two glutathione conjugates of mitoxantrone. Their structures have been elucidated by combination of IonSpray (Sciex, Canada) ionization and tandem mass spectrometry. Radioactive mitoxantrone, synthesized from sodium [14C]cyanide, was used to determine interspecies variations between human and rat. The collected rat urine was analyzed by HPLC using a radioactivity monitoring detector and revealed significant differences in the biotransformation of mitoxantrone in rat compared to human. The main metabolites thus far described in human urine are not observed in rat urine.

Animals↗