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Biomedical subjects

J Molnar

Publications and source records attributed to J Molnar.

101 records · Page 6Linked to original sources
PubMedDate not supplied

Comparative investigation of antipyrine half-life and induction of cytochrome P-450 dependent monooxygenases in rats treated with phenylurea herbicides.

The short-term effect of three substituted phenylurea herbicides has been investigated on antipyrine plasma half-life in rats. Isoproturon was ineffective, while chlortoluron and diuron decreased the half-life significantly. There was a close correlation between antipyrine half-lives and induction of hepatic cytochrome P-450 dependent benzo(a)pyrene monooxygenase, 7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase.

Animals↗
PubMedDate not supplied

Cardiac and cardiopulmonary disorders in patients with ankylosing spondylitis and rheumatoid arthritis.

One hundred patients suffering from ankylosing spondylitis (AS) and one hundred patients suffering from rheumatoid arthritis (RA) were examined by clinical, non-invasive cardiological, radiological and laboratory methods to determine the prevalence of their cardiac and cardiopulmonary disorders. Fourteen patients with AS and 24 patients with RA had several valvular abnormalities. Among the patients not having any valvular abnormality, systolic dysfunction of the myocardium was detectable in 15 and 11 cases respectively, and cor pulmonale was diagnosed in 16 and 7 cases respectively. Conduction disturbances were demonstrated in 17 patients suffering from AS and in 14 patients suffering from RA.

Adult↗
PubMedDate not supplied

Fibronectin in alkali burns of the rabbit cornea.

Alkali burns of the cornea were made bilaterally in 16 albino rabbits. The eyes were then treated four times a day in a masked fashion with a solution either of fibronectin (250 micrograms/ml) plus gentamicin (1.5 mg/ml) or of gentamicin (1.5 mg/ml) plus hydroxypropyl methylcellulose (Tears Naturale). The eyes were examined daily in a masked manner for evidence of a corneal epithelial defect. On days 6-14, the fibronectin-treated eyes had more healed corneal defects (p less than 0.05, McNemar's test for matched pairs) than the control eyes. Fibronectin aided the healing of corneal alkali burns by decreasing the peeling back of the healing epithelium and by allowing re-epithelialization if peeling back had occurred. These properties of fibronectin helped to preserve a stable, intact corneal surface.

Animals↗
PubMedDate not supplied

Effects of tricyclic compounds on membrane binding of bivalent cations, activities of acetylcholinesterase and some tissue proteases.

A tricyclic compound tetrahydroaminoacridine is known to improve the cognitive function in Alzheimer's disease. The possible mechanism of action of acridine and structurally related tricyclic compounds was studied on the bivalent cation content of bacterial membrane, rat brain acetylcholinesterase and some tissue proteases in model experiments. Acridine orange and disubstituted chlorpromazine (CPZ) derivatives lowered Ca2+ and Mg2+ binding and membrane polarization in the simplest biological membrane (E. coli), as revealed by reactor neutron activation analysis. Acetylcholinesterase (AChE) was inhibited by CPZ, 3,7,8-trihydroxy-CPZ, acridine orange partially saturated desipramine, imipramine, trans-clopenthixol and tetrahydrocannabidiolic at 10(-4) to 10(-5). A metalloproteinase, MMP-7-ase, was inhibited by tetrahydrocannabidiolic acid, 3,7,8-trihydroxy-CPZ, acridine orange but other tissue proteinases, ATN-ase and cathepsin B, were less sensitive to these compounds. (ATN-ase is an acetyltyrosine-p-nitroanilide splitting enzyme, a serine protease). The chelate complex forming ability and electron donor capacity of the compounds may play a role in the biological effects tested. It is assumed that compounds which do not displace bivalent cations in membranes may exert an inhibitory effect on AChE, and that metalloproteinase enzymes may be promising for the treatment of degenerative brain diseases.

Alzheimer Disease↗
PubMedDate not supplied

Antiplasmid and carcinogenic molecular orbitals of benz[c]acridine and related compounds.

Effect of K- and L- molecular orbital regions on expression of antiplasmid and carcinogenic activity was studied with various benz[c]acridine derivatives, tricyclic compounds (acridine orange, phenothiazines) and dibenzoazepine (imipramine). Antiplasmid compounds showed the out-of-phase of molecular orbital in the L-region. On the other hand, mutagenic and carcinogenic compounds showed the out-of-phase in the L-region, and their energy was accumulated in the K-region of the molecular orbitals. The present study suggests that the molecular orbitals responsible for the expression of antiplasmid and carcinogenic effects might be basically different.

Acridines↗
PubMedDate not supplied

Immunomodulation activity of phenothiazines, benzo[a]phenothiazines and benz[c]acridines.

Some non-differentiation-induction benzo[a]phenothiazines and mutagenic benz[c]acridines more potently inhibited the mitogen-induced blast transformation of human-peripheral blood lymphocytes than differentiation-induction and non-mutagenic counterparts and phenothiazines. Differential absorption spectrophotometry revealed tight complex formation between these drugs and bacterial endotoxin or mitogens. All of these compounds only slightly affected antibody dependent cellular cytotoxicity and natural killer cell activity, but significantly inhibited the endotoxin-or heat-killed Staphylococcus aureus induced tumor necrosis factor production by human mononuclear cells. Pretreatment of mice with these drugs protected them from lethal E. coli infection. Quantumchemical analysis suggests a correlation between the biological activity of these compounds and some molecular orbital parameters such as the charge at C7, and the ratio of polar/total surface areas.

Acridines↗
PubMedDate not supplied

Reversal of multidrug resistance by amitriptyline in vitro.

Amitriptyline, a tricyclic antidepressant, was able to reverse the multidrug resistance efflux pump of human colon cancer subline SW 620 and multidrug resistant (mdr) mouse lymphoma cells by decreasing rhodamine 123 efflux. The inhibitory effect of amitriptyline on the efflux pump was dose dependent. An investigation was made of the effects of mouse tumour necrosis factor (TNF) alpha and interferon (IFN) gamma on the efflux pump activity of mdr cells together with amitriptyline compared to the par cells (mdr-). After long-term cytokine pretreatment of mdr cells, the amitriptyline was more effective, due to some synergism between the amitriptyline and TNF-alpha.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Diverse mutagenicity of methylbenz[c]acridines in the direct Ames' Salmonella mutagenicity assay.

The mutagenicity of eleven methylbenz[c]acridines (methyl-B[c]ACRs) was examined by the direct Ames' Salmonella mutagenicity assay on the standard tester strains of TA97a, TA98, TA100 and TA102, each of which is specific to a certain type of mutation. The Benz[c]acridines (B[c]ACRs) studied in this investigation were substituted with one to three methyl group(s) at the 5, 7, 8, 9, 10 and 11 position(s) of B[c]ACR. A certain degree of mutagenic activity was observed by all methyl-B[c]ACRs on at least one of the tester strains, indicating that even non-carcinogenic methyl-B[c]ACRs showed mutagenicity in the assay. Meanwhile, 7,10-dimethyl-B[c]ACR and 7,9,10-trimethyl-B[c]ACR significantly increased the number of back-mutant colonies. However, monomethyl-B[c]ACRs, 7-methyl-B[c]ACR and 10-methyl-B[c]ACR did not increase back-mutation except for TA102 and TA100, respectively. The induction of 7-methyl substituent on B[c]ACR appears to play a key role in frameshift (+1 and -1), base-pair substitution, and single base substitution mutation of the strains in the presence of additional methyl substituent(s) at C-9 and/or C-10 position(s) of D ring of B[c]ACR.

Acridines↗
PubMedDate not supplied

Trifluoperazine and its metal complexes inhibit the Moloney leukemia virus reverse transcriptase.

Reverse transcriptase plays an essential role in the early steps of the replicative cycle of retroviruses. Because of the resistance against nucleoside analogue inhibitors such as 3'-azido-2',3'-dideoxythymidine, the importance of the investigation of non-nucleoside analogue inhibitors is increasing. We have investigated the influence of trifluoperazine (TFP--a species of phenothiazines) and its newly prepared TFP-metal complexes (TFP-VO(IV), TFP-Cu(II), TFP-Ni(II), TFP-Pd(II), TFP-Sn(IV)). The compounds were tested on Moloney murine leukemia virus reverse transcriptase assay. The inhibitory effect of metal complexes was higher than that of TFP. TFP-VO(IV) showed higher effectiveness compared the added effect of parent tricyclic chemical and metal. Therefore we concluded that the improved biological action depends on the formation of metal complexes. This phenothiazine and its metal coordination complexes could become a new non-nucleoside analogue group of compounds inhibiting the retrovirus replication.

Animals↗
PubMedDate not supplied

Nitric oxide production and MDR expression by human brain endothelial cells.

The endothelium both initiates and responds to a cascade of events triggered by cytokines. Enhanced formation of NO, especially by inducible nitric oxide- synthase (i NOS), is largely stimulated by tumor necrosis factor (TNF). Nitrogen oxides are reactive intermediate molecules functioning in neural transmission, and vasodilatation. The aim of our study was to investigate the effect of TNF and Staphylococcus aureus, a TNF inducing agent on the NO production of brain endothelial cells in vitro. The effect of the same agent was investigated on the MDR expression of endothelial cells. Both TNF and Staphylococcus aureus resulted in enhanced NO production. Western blot analysis showed enhanced expression of iNOS, which could be inhibited by pentoxifylline, an inhibitor of TNF synthesis. Flow cytometric analysis revealed that the brain capillary endothelial cells exerted P-glycoprotein expression, which was not influenced by TNF. However, the mdr function itself in these cells was decreased by TNF. Cultured endothelial cells are excellent tools for the investigation of the possible connection between the NO production and MDR function, and for the estimation the effect of different agents influencing these activities, which might be important in blood-brain barrier function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗