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Biomedical subjects

R Villa

Publications and source records attributed to R Villa.

At least 73 records · Page 4Linked to original sources
PubMed1994

[The importance of measuring plasma carcinoembryonic antigen in small-cell anaplastic carcinoma].

The clinical value of the serum biomarker carcinoembryonic antigen (CEA) was evaluated prospectively in 118 patients with small cell lung cancer (SCLC) entered chemotherapy protocol between 1986 and 1992. Five quantitative categories were determined: less than 2.5 ng/ml and 2.6-5.0 ng/ml (the standard normal), 5.1-20.0 ng/ml, 20.1-100 ng/ml and greater than 100 ng/ml. 70% of patients had levels less than 5 ng/ml and only 19% had levels greater than 20 ng/ml. There was no clearcut relationship of plasma CEA level to stage of disease, in which 61% of patients with extensive disease (59 patients) had levels less than 5 ng/ml and 22% of patients with limited disease (59 patients) had levels greater than 5 ng/ml. There was a modest relationship of CEA levels to presence of metastases, in that 50% of patients with metastases had levels greater than 20 ng/ml. The average survival for the pathologic and normal category was almost similar, ranging from 13.27 to 16.81 months. The correlation between disease extent and survival was more sensitive for lactate dehydrogenase (LDH) than for CEA. So CEA as a tumor marker for SCLC must be applied in conjunction with other biomarkers, particularly LDH and neuron specific enolase (NSE) and is meaningful in only a small proportion of patients.

Adult↗
PubMed1993

Flunarizine as a modulator of doxorubicin resistance in human colon-adenocarcinoma cells.

The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 micrograms/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow-cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 micrograms/ml flunarizine. Finally, in LoVo/DX cells, which normally express gp170, a 24-hr treatment with flunarizine markedly reduced the immunoreactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin-resistance in human colon-adenocarcinoma cells expressing the multidrug-resistance phenotype.

Adenocarcinoma↗
PubMed1993

Effect of intermittent mild hypoxia and drug treatment on synaptosomal nonmitochondrial ATPase activities.

Synaptosomal nonmitochondrial ATPases linked to the energy-utilizing systems were evaluated in cerebral cortex from normoxic rats and rats submitted to mild intermittent normobaric hypoxia [12 hr daily exposure to N2:O2 (90:10) mixture for 4 weeks]. The activities of Na+,K(+)-ATPase; high- and low-affinity Ca(2+)-ATPase; basal Mg(2+)-ATPase; and Ca2+, Mg(2+)-ATPase were assayed in synaptosomes and synaptosomal subfractions, namely, synaptosomal plasma membranes and synaptic vesicles. The evaluations were performed either in normoxic rats or in hypoxic rats submitted to 4-week treatment with saline (controls) or a vasodilator agent (papaverine), an energy-metabolism interfering agent (theniloxazine), a calcium blocker (nicardipine), and a lipid-metabolism interfering agent (phosphatidylcholine) in order to define the plasticity and the selective changes in individual ATPases. In synaptosomes from rat cerebral cortex, the enzyme adaptation to the daily mild intermittent hypoxia for 4 weeks was characterized by an increase in the activity of Mg(2+)-ATPase, concomitant with a decrease in the activities of Na+,K(+)-ATPase, high-affinity Ca(2+)-ATPase, and Ca2+, Mg(2+)-ATPase. In hypoxic rats the enzyme adaptation to the 4-week treatment with phosphatidylcholine was characterized by an increase in Ca2+, Mg(2+)-ATPase activity and a decrease in Mg(2+)-ATPase activity. The action involves the enzymatic form located in the synaptic plasma membranes. In hypoxic rats the adaptation to the 4 week treatment with nicardipine was characterized by an increase in high-affinity Ca(2+)-ATPase activity, while the 4-week-treatment with theniloxazine induced an increase in Na+,K(+)-ATPase activity. The actions of both nicardipine and theniloxazine were related to the enzymatic forms located in the synaptic plasma membranes. The effects on the biophase induced by the sequential cycles of hypoxia/normoxia and the treatment with the various agents tested should also be related to the changes induced in the activity of some synaptosomal ATPases.

Adenosine Triphosphatases↗
PubMed1993

Pharmacokinetic profile of sulphamonomethoxine-trimethoprim in horses after intravenous, intramuscular and oral administration.

The pharmacokinetic profile of a sulphamonomethoxine-trimethoprim (SMM-TMP) combination was investigated in five horses. The combination was administered intravenously, intramuscularly and orally at a constant dose of 20 mg SMM plus 4 mg TMP kg-1 bodyweight. Following intravenous administration both drugs dispersed rapidly with distribution half-lives of about 12 minutes for SMM and about 18 minutes for TMP. Elimination half-lives for intravenous, intramuscular and oral administration were closely similar, indicating that elimination was independent of administration route. Bioavailability of the drugs in aqueous solution was good: about 72 per cent and 84 per cent for SMM and about 84 per cent and 98 per cent for TMP following intramuscular and oral administration, respectively. It is concluded that SMM-TMP administered orally once a day at 20 mg and 4 mg kg-1 bodyweight, respectively, maintains therapeutic concentrations, whereas twice daily intramuscular administration would be more effective for treating systemic infections in the horse than the once a day regimen usually adopted in veterinary practice.

Absorption↗
PubMed1993

Differential effect of 9 beta-chloro-16, 16-dimethyl prostaglandin E2 (nocloprost) on the radiation response of human normal fibroblasts and colon adenocarcinoma cells.

The possible influence of 9 beta-chloro-16,16-dimethyl prostaglandin E2 (nocloprost) on the effect of 137Cs gamma irradiation was investigated comparatively in human normal fibroblasts and colon adenocarcinoma cells. By itself, the compound did not influence the proliferation of cells of either cell type or the clonogenic capacity of carcinoma cells. Moreover, nocloprost did not induce any DNA strand breakage, as evaluated by neutral elution, in cells of either cell type. A 2-h incubation with nocloprost before irradiation induced an enhancement of fibroblast survival after an exposure of 10 Gy. This protective effect was not observed in adenocarcinoma cells under the same treatment conditions. The amount of double-strand breaks induced by 50 Gy was reduced in normal cells but not in tumor cells exposed to the prostaglandin analog before irradiation. Moreover, incubation with nocloprost for 2 h after irradiation remarkably enhanced the rate of rejoining of DNA breaks in fibroblasts but not in adenocarcinoma cells. Overall, these findings indicate a specific radioprotective effect of nocloprost in normal cells and no influence of the compound on the cytotoxic effect of ionizing radiation on colon adenocarcinoma cells.

Adenocarcinoma↗
PubMed1992

Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells.

The ability of lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian-cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24-hr post-incubation with 300 microM lonidamine significantly potentiated the activity of a 1-hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4-fold in the sensitive line and 5-fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links. Our results suggest that lonidamine can positively modulate the anti-tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients.

Cell Cycle↗
PubMed1992

Cyclophosphamide, epirubicin, etoposide, cis platinum (CEVP) in combination with radiotherapy: evaluation of a protocol adopted for 6 years in 148 cases of small cell lung cancer.

The present study was carried out with the purpose of assessing and evaluating the responsiveness of small cell lung cancer (SCLC) to combined treatment (i.e., chemotherapy and radiotherapy). This approach was applied to all patients observed in our Institution during the last 6 years with the exclusion of patients more than 65 years old, with Karnofsky performance status less than 60, and with concomitant non-neoplastic diseases. One hundred and forty-eight patients were selected and treated with a combination chemotherapy regimen including cyclophosphamide, etoposide, epirubicin and cisplatinum. For patients with limited disease, treatment consisted of 3 cycles of chemotherapy (induction), followed by radiation therapy and then by another 3 cycles of chemotherapy (consolidation). For those with extensive disease, treatment consisted only of 6 consecutive cycles of chemotherapy. Results, besides showing the good activity and tolerability of the chemotherapeutic regimen employed (which induced 80% overall response), indicated that some prognostic factors such as the number of metastatic sites, brain and liver involvement and performance status are essential in determining the outcome of response and, particularly, of survival. In addition, the efficacy and tolerability of the combination chemotherapy-radiotherapy were confirmed, as was the evidence of a synergistic pharmacologic effect between cis-platinum and etoposide.

Adult↗
PubMed1992

[Coin lesions: 5 years of percutaneous needle aspiration].

197 patients with either malignant (No. 175) or infections (No. 22) chest coin lesions had lung aspirations using fine-needles, 18 to 22 gauge. All the patients previously had flexible fiberoptic bronchoscopy with negative results. A positive diagnosis of malignancy was established in 138 (70%), with identification of cell type in 51 (37%), and of infectious disease in 11 (50%). The procedure's sensitivity for malignant lesions was 79.3% and the specificity was 96.5%. Complications were minimal (hemoptysis and pneumothorax), although some patients had COPD and hypoxemia.

Adult↗
PubMed1990

In vitro activity of 4'-iodo-4'-deoxydoxorubicin on human colo-rectal cancer as measured by a short-term antimetabolic assay.

A short-term antimetabolic assay based upon the inhibition of incorporation of nucleic acid precursors was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound doxorubicin (DX) on human colo-rectal carcinoma specimens. IDX showed a marked dose-dependent effect, with frequencies of activity consistently greater than those of DX at all concentrations. The minimal dose required to induce a significant antimetabolic effect for IDX was 1/10 that for DX.

Colorectal Neoplasms↗
PubMed1989

Antitumor activity of hyperthermia alone or in combination with cisplatin and melphalan in primary cultures of human malignant melanoma.

The effects of heat and the interaction between hyperthermia and alkylating agents, such as cisplatin (CDDP) and melphalan (L-PAM) in human malignant melanoma biopsies have been investigated by a short-term assay based upon the inhibition of 3H-thymidine incorporation. Cell suspensions from 50 cutaneous and lymph nodal metastases were heated at 40.5 degrees C or at 42 degrees C for 1 h. There were significant antiproliferative effects due to heat in 10% of the tumors exposed to 40.5 degrees C and 34% to 42 degrees C. Thermal resistance was evident in 73% (at 40.5 degrees C) and 54% (at 43 degrees C) of tumors, and there was significant enhancement of cell growth in 17% and 12% of tumors. The combined effects of hyperthermia and drugs were studied on 36 tumors. Cell suspensions were exposed to different concentrations of CDDP or L-PAM for 1 h at 40.5 degrees C and 42 degrees C. Synergy between heat and CDDP was observed in 7% of cases treated with the lowest drug dose and 38% of cases treated with the highest (40.5 degrees C), with only a slight increase in the frequency of synergy at 42 degrees C. Synergy between heat and L-PAM was also observed in 12% to 44% of tumors at 42 degrees C as a function of drug concentration.

Antineoplastic Agents↗
PubMed1988

Comparison of an antimetabolic assay and an antiproliferative assay, both using 3H-thymidine incorporation, to test drug sensitivity of human tumors.

Two assays based on the inhibition of 3H-thymidine incorporation into DNA were used to measure either the antimetabolic or the antiproliferative effects of anticancer drugs. A direct comparison of the two assays was made with cell suspensions obtained from 11 ovarian cancers and 22 malignant melanomas. Drugs with different effects on cell cycle phases were tested by both assays, for a total of 53 drug comparisons. When the sensitivity indices specific for each system was used, a significant association (p less than 0.01) was noted between the two assays. The agreement of both assays in defining in vitro sensitivity or resistance was 100% for ovarian cancer. For melanoma, 97% of samples resistant to the antimetabolic assay were also resistant to the antiproliferative assay; whereas, only 45% of samples sensitive to the antimetabolic assay were sensitive to the antiproliferative assay.

Antimetabolites, Antineoplastic↗
PubMed1986

111In-oxine-labelled autologous leucocytes in inflammatory bowel disease: new scintigraphic activity index.

The usefulness of scintigraphy with 111In-oxine-labelled autologous leucocytes was investigated in 27 patients with inflammatory bowel disease (IBD): 16 with ulcerative colitis and 11 with Crohn's disease. Scans were performed 2-4 h (early scan) and at 24 h (late scan) after leucocyte reinjection. No false-negative results occurred in the early scan; however, in the late scan, 2 patients with Crohn's disease had a normal scintigram. A new index of activity (Il) based on the number and relative activity of abnormal 111In-leucocyte zones was used for scan quantitation. All patients with clinically active IBD had Il greater than or equal to 2. The scintigraphic index showed a significant correlation with the Harvey clinical index, especially in patients with ulcerative colitis. Our results suggest that an early scan (2-4 h) provides useful information in cases of IBD, and that Il greater than or equal to 2 is indicative of the degree of disease activity in such patients.

Adolescent↗
PubMed1984

Correction of congenital hydrocephalus in utero II: Efficacy of in utero shunting.

To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.

Amniotic Fluid↗
PubMed1982

Effects of ischemia and pharmacological treatment on subcellular fractions from neonatal rat brain.

The effects of complete ischemia and of in vivo pharmacological treatment with trimetazidine were studied on some enzymatic activities related to energy transduction: lactate dehydrogenase for anaerobic glycolysis; citrate synthase and malate dehydrogenase for the Krebs' cycle; total NADH-cytochrome c reductase and cytochrome oxidase for the electron transport chain; glutamate dehydrogenase for amino acid metabolism and acetylcholine esterase for acetylcholine metabolism. These enzymatic activities were evaluated in brains of 10-day-old rats, at three different subcellular levels: homogenate in toto, purified mitochondrial fraction, crude, synaptosomal fraction. Complete normothermic post-decapitative ischemia of 30 min duration increased the activity of cytochrome oxidase in the homogenate in toto and increased the activities of citrate synthase and malate dehydrogenase in the purified mitochondrial fraction, the activities of the enzymes evaluated in the crude synaptosomal fraction being unaffected. The i.p. treatment with trimetazidine (at the dose level of 50 mg . kg-1) was without any significant effect on the tested enzymatic activities.

Animals↗
PubMed1980

[Not Available].

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History, Modern 1601-↗
PubMed1980

[Not Available].

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Belgium↗