[Contribution to the diagnosis and clinical picture of malignant reticulosis of the skin].
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Aged↗
Biomedical subjects
M Gerlach
Publications and source records attributed to M Gerlach.
The effect of silyl substituted methotrexate in the treatment of experimental allergic encephalomyelitis in rats mediated by T-line cells.
The effect of methotrexate and of silyl-methotrexate were compared in the treatment of experimental allergic encephalomyelitis (EAE) mediated by T-line lymphocytes. It was demonstrated that, during the first three days after cell transfer, no difference between methotrexate and its silyl derivative could be seen. At a time when the cytotoxic lymphoblasts must have penetrated the blood brain barrier, only silyl methotrexate was able to prevent severe paralysis and death of the animals. It is suggested that the effect of N,N,O,O-Tetrakis (t-butyldimethylsilyl)-methotrexate, (N-4-N-(2,3-bis-t-butyldimethylsilyl-amino-6-pteridinyl-methyl)- methylamino-benzoyl-glutamic acid-bis-(t-butyldimethylsilyl)-ester), depends on the increased lipid solubility and permeability of the blood brain barrier of silylated drugs.
Animals↗
Influence of neuromelanin on oxidative pathways within the human substantia nigra.
Neuromelanin (NM) is a dark-coloured pigment produced in the dopaminergic neurons of the human substantia nigra (SN). The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by directly inactivating free radical species or via its ability to chelate transition metals, such as iron. Increased tissue iron, however, may saturate iron-chelating sites on NM and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. The death of NM-pigmented neurons in Parkinson's disease (PD) is associated with both a measurable increase in tissue iron concentrations and indices of free radical mediated damage, suggesting that NM is involved in the aetiology of this disorder. As yet, it is unknown whether NM in the parkinsonian brain differs to that found in healthy tissue and thus may fulfil a different role within this tissue.
Binding Sites↗
Expression, but not activity, of neuronal nitric oxide synthase is regionally increased in the alcoholic brain.
The regional distribution of nitric oxide synthase (NOS) was investigated in alcoholic post-mortem brains compared with brains of non-alcoholic control individuals. Total enzyme activity in 28 brain regions was determined using the [(3)H]l-citrulline formation assay, whereas Western blot analyses were used for semi-quantitative measurement of the neuronal isoform of NOS (nNOS). In the alcoholic brain, nNOS protein expression was increased in the following regions: frontal cortex (85%), the cingulate gyrus (294%), the nucleus accumbens (54%), the entorhinal cortex (85%) and the thalamus (51%). These increases were, however, not associated with higher total NOS activity. Interestingly, nNOS protein content was increased in the frontal cortex and the nucleus accumbens, brain regions which are suggested to be involved in the dopaminergic mesolimbic reward system. It is concluded that upregulation of signal transduction pathways, such as the adenosine 3',5'-monophosphate and the protein kinase C-dependent pathway, due to stimulation of G-protein-coupled neurotransmitter receptor regulation, as a form of functional tolerance, could be responsible for increased nNOS protein expression, and downregulation of NOS enzyme activity in these brain regions.
Adult↗
Pro- and antioxidative properties of cortical tissue preparations from human brain exhibiting NMDA-receptor characteristics.
The effects of cortical tissue preparations (CTP) from human brain on the production of reactive oxygen species (ROS) has been investigated with several biochemical model reactions. As indicators for ROS, fragmentation of the methionine derivatives, alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC), yielding ethene have been used. With these systems we have shown that production of OH-radical-type oxidants by the xanthine oxidase (XOD)-system is strongly stimulated by CTP. This activity is due to intrinsic iron ions since ethene formation from KMB is stimulated by EDTA, inhibited by desferrioxamine (Desferal) and also visible with heat-denatured CTP. CTP by themselves have no XOD activity. 3-Hydroxykynurenine (3HK) is another possible substrate for XOD but produces H2O2 without XOD-catalysis, whereas allopurinol is not inhibiting. CTP contain measurable NAD(P)H oxidoreductase activity, producing OH- radical- type oxidants at the expense of NADPH and (to a lesser extent) NADH as electron donors, shown as redox-cycling of 2-methyl-5-hydroxy-1,4-naphthoquinone, plumbagin. Ethene formation from KMB is also driven by both morpholinosydnonimine (SIN) or ONOOH. The reaction driven by SIN is stimulated by CTP and inhibited by catalase, SOD and hemoglobin. Since ethene release from KMB driven by ONOOH is inhibited by CTP the mechanisms driving KMB fragmentation are different for SIN and ONOOH. Furthermore CTP contain approx. 4 U catalase activity per mg protein and very weak peroxidase (POD) activity shown as ACC fragmentation yielding ethene in the presence of both H2O2 and KBr or NaCl. Since ACC binds to CTP and both compounds, ACC and KMB are natural products, present in food (ACC) or synthesized from methionine in vivo (KMB), these compounds may represent protecting agents in systems where reactive oxygen species are formed. One might even speculate that the production of ethene at these membrane receptor sites may have biological functions, since ethene is known to possess anaesthetic activities.
Antioxidants↗