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Biomedical subjects

H Merz

Publications and source records attributed to H Merz.

85 records · Page 5Linked to original sources
PubMed1977

Diastereoisomeric N-tetrahydrofurfurylnoroxymorphones with opioid agonist--antagonist properties.

The two diastereoisomeric N-tetrahydrofurfurylnoroxymorphones and their hydrochlorides 1a and 1b have been prepared and studied pharmacologically; The N-(R)-tetrahydrofurfuryl derivative 1a proved to be an opioid agonist--antagonist and the N-(S)-tetrahydrofurfuryl derivative 1b a pure antagonist. As an analgesic, 1a is 25 times more potent than morphine, but it does not show morphine-like side effects in mice. In withdrawn morphine-dependent rhesus monkeys, 1a only partially suppresses abstinence. Its therapeutic ratio is exceptionally favorable compared with those of morphine and pentazocine. As antagonists, 1a and 1b have comparable potencies of 0.25 and 0.20 of that of nalorphine, respectively, in vivo. In vitro, however, 1a is 28 times (guinea pig ileum) or 6.5 times (mouse vas deferens) more potent than 1b. The antagonist properties of 1a and 1b were not anticipated according to known structure--activity relationships.

Analgesia↗
PubMed1977

[Pharmacologically active polymers. 9th communication: retard forms of morphine antagonists (author's transl)].

Acryloyl, methacryloyl, N-vinylcarbamoyl, and methacryloyl-glycyl derivatives of the morphine antagonist (--)-alpha-5,9-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphane have been synthesized. The different unsaturated derivatives were copolymerized with appropriate comonomers to yield water-soluble polymers. Pharmacological tests in mice showed a 2--30 fold increase in duration of action in comparison to the free antagonist. The binding of the antagonist to the polymers resulted in a reduced acute toxicity.

Animals↗
PubMed1975

Stereoisomeric 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphans, strong analgesics with non-morphine-like action profiles.

The eight optically active stereoisomers and the corresponding four racemic forms of 5,9-dimethyl-2'-hydroxy-2-tetrahydrofurfuryl-6,7-benzomorphan (1) have been prepared. Depending on their configurations these compounds are potent analgesics or inactive substances in mice. The analgesics attain potencies up to about a hundred times that of morphine but they do not show morphine-like side effects in mice nor do they suppress abstinence in withdrawn morphine dependent monkeys. Their therapeutic ratios are favorable and, in the case of la-1 and la-2, exceptionally good. Configuration-activity relationships are discussed. R configuration of the N-tetrahydrofurfuryl group is a major prerequisite for high analgesic potency.

Analgesia↗
PubMedDate not supplied

Cytokine expression in B-cell non-Hodgkin lymphomas.

Cytokine expression of potentially active B-cell growth factors (IL-2, IL-4, IL-6) was investigated by means of mRNA-expression in 29 cases of malignant non-Hodgkin B-cell lymphomas. Strong signals were found for IL-4 and IL-6 in two and five cases, respectively, whereas the majority of the remaining cases did not show any detectable mRNA-signals for these growth factors. Comparing these results with those of the immunohistochemistry, it could be demonstrated that at least in some of these cases the signal was due to an autocrine or paracrine phenomenon of the tumour cells.

Blotting, Northern↗
PubMedDate not supplied

Differential in vitro anti-HIV activity of natural lignans.

Two naturally occurring lignanolides, isolated from the tropical climbing shrub Ipomoea cairica, (-)-arctigenin and (-)-trachelogenin, were found to inhibit strongly replication of human immunodeficiency virus type 1 (HIV-1; strain HTLV-III B) in vitro. At a concentration of 0.5 microM, (-)-arctigenin and (-)-trachelogenin inhibited the expression of HIV-1 proteins p17 and p24 by 80-90% and 60-70%, respectively. The reverse transcriptase activity in the culture fluids was reduced by 80-90% when the cells (HTLV-III B/H9) were cultivated in the presence of 0.5 microM (-)-arctigenin or 1 microM (-)-trachelogenin. At the same concentrations, the formation of syncytia in the HTLV-III B/H9-Jurkat cell system was inhibited by the compounds by more than 80%. A series of other lignan type compounds displayed no anti-HIV activity. Studying the molecular mechanism of action of (-)-arctigenin and (-)-trachelogenin we found that both compounds are efficient inhibitors of the nuclear matrix-associated DNA topoisomerase II activity, particularly of the enzyme from HIV-1-infected cells. Our results suggest that both compounds prevent the increase of topoisomerase II activity, involved in virus replication, after infection of cells with HIV-1.

Animals↗
PubMedDate not supplied

Matrix-metalloproteinases in Hodgkin lymphoma.

BACKGROUND: Classical Hodgkin lymphomas are characterized by relatively few tumour cells and prominent proliferation of plasma cells, histiocytes, lymphocytes and eosinophils. In addition there is a varying degree of sclerosis, which is especially prominent in nodular sclerosis. These morphological peculiarities led to the idea that the interaction between tumour cells and bystander cells as well as the extracellular matrix may be important in Hodgkin lymphomas. MATERIALS AND METHODS: Thirty-four classical Hodgkin lymphomas (CHL) were analysed regarding the expression of EMMPRIN, MMP-2, -7, -9, -10 and-11 using immunohistochemistry. RESULTS: The tumour cells were positive for EMMPRIN in 100% of the cases. In 82% of CHL the Hodgkin and Reed-Sternberg cells (HRS) were negative for MMP-2. In contrast the surrounding non-neoplastic cells were MMP-2-positive in 71% of the cases. The HRS cells stained positive for MMP-7 in 68% of CHL, whereas only a few surrounding cells were positive for this marker. In all but one case (97%) the HRS cells were negative for MMP-9. However, the surrounding cells stained positive in 32%, thus resembling the staining pattern for MMP-2. Only scattered cells of both populations, HRS cells as well as bystander cells, stained for MMP-10 and -11, and no specific staining pattern was observed. CONCLUSION: Our data indicate a complex interaction between tumour cells and bystander cells with regard to metalloproteinases. The expression of EMMPRIN in the tumour cells may induce the expression of MMP-2 in the surrounding non-neoplastic cells. MMP-2 can be activated by MMP-7, which is expressed in the tumour cells. It is tempting to speculate that an interruption of this cycle could be of therapeutic benefit.

Antigens, CD↗
PubMedDate not supplied

[A sterile, regulated, pulsation-dampened precision dosing system for biomedical technics].

For sterile continuous metering of small and very small flow rates delivered by peristaltic pump, a gravimetric control system which permits a high accuracy of mass flow is described. This is achieved by a digital PI controller and a digital filter with which the very accurate signal from a high precision electronic scale is filtered. In addition proposals are made for solving the problem of refilling the reservoir and for compensating the pulsations caused by the peristaltic pump.

Biotechnology↗