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Biomedical subjects

R Villa

Publications and source records attributed to R Villa.

88 records · Page 5Linked to original sources
PubMed1976

Muscle metabolism investigated at rest and during exercise and/or pharmacological treatment by vasodilators.

The Ruderman's preparation was utilized to investigate in situ some aspects of the muscular metabolism both at rest and during submaximal exercise upon bilateral sciatic nerve stimulation, and/or during perfusion with some vasodilators: papaverine, caffeine, nicergoline, bamethan. O2 and glucose uptake, the production of lactate and the glycogen level of the muscle were studied. The availability of acetoacetate modifies the muscular metabolism; other fuels (e.g. the ketone body itself) are probably used for energetic purposes both under basal conditions and during exercise, even in the presence of high glycogen concentrations in the tissues. Some vasodilators increase the utilization of other fuels in replacement of glycogen (e.g. nicergoline), some others increase the ulilization of glycogen itself (e.g. bamethan and caffeine), whereas others (e.g. papaverine) do not effect the biochemical parameters studied. The present data confirm the importance both of the substrate availability and of the power of drugs to interfere with some enzymatic systems which modulate the utilization of available substrates, especially during exercise.

Animals↗
PubMed1975

Mitochondrial enzymatic adaptation of skeletal muscle to endurance training.

Some mitochondrial enzymatic activities (succinate dehydrogenase, NADH cytochrome reductase, cytochrome oxidase) were studied in the gastrocnemius and soleus muscle of the rat. The modifications of the enzyme activity, induced by endurance training, were found to be functions of 1) daily work load and 2) total training time. The treatment with an effective dose of vasodilating substances (papaverine, nicergoline, dipyridamole, and bamethan) showed that 1) nicergoline, bamethan, and dipyridamole were differently able to shorten the time of appearance of the increase in the enzymatic activities; 2) however, long-term treatments with these drugs did not prove able to modify the plateau level of the enzymatic activity increase, for a given amount of endurance training; 3) the pharmacodynamic effect on enzymatic activities was in no way related to the vasodilating effect of these drugs, since the effect was not observed with papaverine. The transition from a given level of endurance training to a lower one led to a proportional decrease of the mitochondrial enzymatic activities, thus pointing out the relation between amount of training and enzymatic activity. The drugs studied were unable to modify the decrease of enzymatic activity induced by lower work load.

Adaptation, Physiological↗
PubMedDate not supplied

Effect of hyperthermia on the formation and removal of DNA interstrand cross-links induced by melphalan in primary cultures of human malignant melanoma.

In an attempt to elucidate possible mechanisms responsible for the synergistic interaction between hyperthermia and melphalan observed in melanoma cells, we investigated the effect of heat on the formation and removal of melphalan-induced DNA interstrand cross-links (DNA ISC). Cells obtained from melanoma nodal metastases of 15 patients were grown as monolayer primary cultures and their malignant nature was confirmed by specific monoclonal antibodies. Cultures were treated with melphalan for 1 h at 37 or 42 degrees C and DNA ISC were determined by alkaline elution after proteinase K digestion. Results showed an enhanced induction of DNA ISC at hyperthermic conditions. Median number of DNA lesions 6 h after treatment was significantly higher for samples treated at 42 degrees C than for those treated at 37 degrees C (185 compared with 95 rad equivalents, p = 0.01). Moreover, the concomitant hyperthermic treatment prevented the long-term removal of DNA ISC produced by melphalan in most of the tumours considered.

Cell Survival↗
PubMedDate not supplied

Combined effects of lonidamine and hyperthermia on malignant melanoma and lung carcinoma surgical specimens.

The in vitro cytotoxic activity of a 1 hr-treatment with lonidamine alone or combined with hyperthermia was investigated on primary cultures obtained from 12 human malignant melanomas and 9 lung carcinomas. The study was carried out by an antiproliferative assay based upon the inhibition of incorporation of 3H-thymidine into DNA of cells grown in agarose for 4 days. Under normothermic conditions the drug did not have any cytotoxic effect on either tumor type. Hyperthermia alone also failed to influence proliferation of melanoma and lung carcinoma cells. When the same tumors were exposed to lonidamine at 42 degrees C, there was significant enhancement of drug activity in both tumor types. There was also a synergistic interaction in a percentage of tumors, which increased as a function of drug concentration.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Cytotoxic activity of azelaic acid against human melanoma primary cultures and established cell lines.

The in vitro cytotoxic activity of azelaic acid was studied with 25 human melanoma primary cultures and with 5 established cell lines characterized by different contents of melanotic pigment. A dose-dependent antiproliferative effect was observed in both the experimental systems, even though cell lines displayed a slightly greater susceptibility to the compound, with ID50 values generally lower than those for fresh human tumors. Our results do not demonstrate a clear difference between melanotic and non-melanotic melanomas in sensitivity to azelaic acid. The early interference of azelaic acid on nucleic acid metabolism was investigated additionally with 15 human melanoma primary cultures. There were significant inhibitions of RNA and DNA synthesis in a remarkable percentage of tumors, at the highest concentrations of the compound. Moreover, cell proliferation of tumors that showed these antimetabolic effects was always significantly depressed by lower drug concentration as well as by the highest.

Antineoplastic Agents↗
PubMedDate not supplied

Absolute and relative activities of 4' -iodo-4'-deoxydoxorubicin against human colo-rectal tumors, as evaluated by a short-term in vitro assay.

A short-term antimetabolic assay based on the interference with 3H-thymidine and 3H-uridine incorporation after 3 hours of in vitro treatment was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-Iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound Doxorubicin (DX) against 44 human colorectal carcinomas. IDX had a marked dose-dependent effect, with frequencies of activity consistently greater than those of DX at all concentrations. The minimal dose of IDX required to induce a significant antimetabolic effect obtained by extrapolation from the dose-effect plots for each drug was 1/10 that of DX (2.3 micrograms/ml vs 23 micrograms/ml). When the relative activities of the two drugs on the same tumor specimen were determined, there was 71% to 86% overall agreement, depending on the concentration used. Lack of agreement was always attributed to sensitivity to IDX and resistance to the parent compound.

Colorectal Neoplasms↗
PubMedDate not supplied

Comparative in vitro sensitivity of human cholangiocarcinoma and colon adenocarcinoma cells to anticancer agents.

We comparatively investigated the sensitivity of a human cholangiocarcinoma cell line (SG231) and an adenocarcinoma cell line (WiDr) to mitoxantrone (MX), taxol (TX), mitomycin C (MMC), doxorubicin (DX), cisplatin (CDDP) and 5-fluorouracil (5FU) by the sulforhodamine B assay. The lower susceptibility of SG231 to SFU, to CDDP, to DX and to MMC than WiDr was observed, whereas the sensitivity of the two cell lines to MX and TX was similar. We also investigated the ability of a chemical modulator, lonidomine (LND), and hyperthermia to enhance the cytotoxic activity of the different drugs in the SG231 cell line. No potentiation of MX or CDDP activity was observed after a 2 hours treatment in hyperthermic conditions (42 degrees C). Conversely, a slight potentiation of a 2 hours pretreatment with MX and DX was obtained by a 24 hours post treatment with LND.

Adenocarcinoma↗