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Biomedical subjects

J Aguilera

Publications and source records attributed to J Aguilera.

At least 37 records · Page 2Linked to original sources
PubMed1990

Tetanus toxin-induced protein kinase C activation and elevated serotonin levels in the perinatal rat brain.

A single intracerebral injection of tetanus toxin (TeTox) is able to produce a time-dependent translocation of Ca2(+)-phosphatidylserine-dependent protein kinase C (PKC) in close-to-term rat brain. TeTox-triggered translocation of PKC is dose- and time-dependent, can be prevented by tetanus antitoxin, and does not occur upon administration of toxin fragments B and C. TeTox-triggered PKC translocation is accompanied by a time-dependent increase in brain serotonin (5-HT). Increase of brain 5-HT is independent of monoamine oxidase inhibition by pargyline. Phorbol ester and TeTox cause a significant increase in serotonin while H-7, a kinase inhibitor, does not affect serotonin levels but abolishes the effect of TeTox. Gangliosides prevent TeTox-triggered 5-HT increase. The data are consistent with the possibility that TeTox acts effectively on the serotonergic innervation, presumably in conjunction with PKC to cause accumulation of serotonin.

Animals↗
PubMed1990

Gangliosides prevent ischemia-induced down-regulation of protein kinase C in fetal rat brain.

Complete obstruction of the maternal blood flow to fetal rats at 20 days of gestation for a period of 10 min causes a significant shift of approximately 22% in protein kinase C (PKC) activity from a cytosolic to a membrane-bound form in the fetal brain. This translocation can be entirely reversed without losses in activity by a single intraperitoneal injection into the gravid rat of either a mixture of disialo- and trisialoganglioside [polysialoganglioside (PSG)] or by GM1 (50 mg/kg of body weight) given 3 h before onset of the ischemic episode. Cessation of blood flow for 15 min followed by a reperfusion period of 24 h results in a 47% loss in total PKC activity. This down-regulation can be almost entirely prevented upon intraperitoneal administration of GM1 3 h before, but also during and even 90 min after the onset of ischemia. The PSG mixture is also effective, particularly when given 3 h before the insult. Down-regulation of PKC is accompanied by an increase in a Ca2(+)-phosphatidylserine-independent kinase [protein kinase M (PKM)] activity, which rises from 30 pmol/min/mg of protein in control animals to a maximal value of 83.1 pmol/min/mg of protein after 15 min of ischemia and 6 h of reperfusion. By 24 h, PKM activity is 46.8 pmol/min/mg of protein. Administration of GM1 blocks completely the appearance of PKM, a result suggesting that PKC down-regulation and PKM activity elevation are intimately associated events and that both are regulated by GM1 ganglioside.

Animals↗
PubMed1990

In vivo translocation and down-regulation of protein kinase C following intraventricular administration of tetanus toxin.

A single intraventricular injection into adult rats of 100 mouse lethal doses of tetanus toxin (TeTox) produces a marked intracellular redistribution of Ca2+/phosphatidylserine (PtdSer)-dependent protein kinase C (PKC) activity. Changes are particularly pronounced in hypothalamus, hippocampus, and spinal cord structures. Translocation of PKC from the inactive cytosolic compartment to a membrane-bound active form is followed by a time-dependent reduction in both total activity and enzyme protein. The down-regulation of PKC activity in the hypothalamus is accompanied by a marked increase in a Ca2+/PtdSer-independent kinase activity, predominantly in the cytosolic fraction. Our data identify PKC as a possible indirect target for TeTox and suggest that down-regulation of the enzyme may provide a clue for tetanus neurotoxicity.

Animals↗
PubMed1989

Quantum mechanical study and nuclear magnetic resonance measurements of some alpha-arylcarboxyalkyl acids as anti-inflammatory agents.

The CNDO/2 quantum mechanical conformation method of analysis, charge density and protonation energy calculations, as well as 13C and 1H NMR measurements were carried out for ibufenac, ibuprofen, methylibuprofen, and for a series of alpha-arylpropionic acids. It was found that the nature of the terminal lipophilic residue does not significantly influence the conformation of the alpha-arylcarboxyalkyl acid side chain. The preferred conformational angle, for the torsion of the phenyl-C alpha bond, was found to be 90, 120, and 180 degrees in ibufenac, ibuprofen, and methylibuprofen, respectively. This conformational angle is calculated to be the same in all the alpha-arylpropionic acids. The protonation energies of the alpha-arylpropionic acids are correlated with the anti-inflammatory activity. It was found that the smaller the protonation energy, the larger the anti-inflammatory activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Treatment of advanced epithelial ovarian cancer with a cis-dichloro-diammine platinum, cyclophosphamide, and bleomycin combination.

Twenty-five consecutive patients with previously untreated stage III (18) and IV (7) epithelial ovarian carcinoma underwent maximum surgical tumor reduction followed by cyclophosphamide, cisplatinum, and bleomycin chemotherapy, given 5 days every 3 weeks for a total of 6-8 courses. Patients were then submitted to second-look surgery, and complete responders to a 1-year additional chemotherapy with L phenylalanine mustard and hexamethylmelamine. The median survival is 23 months for the whole group, and 31+ months for 13 patients found in microscopically assessed complete remission (CR) at the time of second-look surgery. The possible significance of these results and of the addition of bleomycin to a well-known combination are discussed, together with the limitations of a phase II study.

Adult↗
PubMed1987

Tetanus intoxication causes an increment of serotonin in the central nervous system.

Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform throughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.

5-Hydroxytryptophan↗
PubMed1986

[Induction of objective responses by an anticancer chemotherapy based on the prolonged combination of bleomycin and cisplatin. 1062 cases].

A cis-platin + bleomycin combination, sometimes associated with a third cytostatic drug, was administered for prolonged periods to 1062 cancer patients previously subjected to a wide variety of treatments. The objective response rate was about 70% in localized squamous cell and anaplastic bronchial carcinoma and 40% in bronchial adenocarcinoma and metastatic squamous cell carcinoma. Cancers of the head and neck responded in 70% of the cases before irradiation and in 30% after irradiation. Other epidermoid tumours responded objectively in the proportion of 45%, as did 58% of metastatic and refractory breast cancers. These results were not clearly improved by any of the other cytostatic drugs used concomitantly, and the combination alone was less toxic. The high response rate obtained is attributed to a synergistic effect of cis-platin and bleomycin administered for prolonged periods.

Adult↗
PubMed1985

[Inhibition of DNA repair, major objective of anticancer chemotherapy. Apropos of 680 cases with continuous platin bleomycin combination].

Six hundred and eighty seven cases of cancers of various sites, essentially of squamous structure are presented. Their treatment consisted of a combination of cisplatinum, given 5 days in a row every 3 weeks and of continuously infused bleomycin, also 5 days every 3 weeks. Objective (greater than 50 p. 100) regressions were seen in 70 p. 100 of cases, a significantly greater proportion than obtained by other chemotherapies or by cisplatinum and bleomycin given for one day. This difference is attributed to the fact that bleomycin, a potent inhibitor of type II DNA polymerase, inhibits DNA repair. The authors evaluate the extent of DNA repair to be about 80 p. 100 of all the lesions created by platinum salts and consider DNA repair to be a major limitation of cytostatic therapy, often neglected in the design of chemotherapy protocols.

Adenocarcinoma↗
PubMed1984

High-dose cyclophosphamide and high-dose 5-fluorouracil. A new first-line regimen for advanced breast cancer.

Thirty consecutive patients with metastatic breast cancer previously untreated by chemotherapy were given high-dose cyclophosphamide (Cytoxan) and high-dose 5-fluorouracil (5-FU) as first-line therapy. Cyclophosphamide, 1200 mg/m2 was administered intravenously (IV) on day 1 and 5-FU, 600 mg/m2 IV on days 1 through 5. Cycles were repeated every 21 days or on hematologic recovery. Twenty-eight of the 30 patients achieved a remission (16 partial, and 12 complete), i.e., a response rate of 93%, and a complete response rate of 40%. The actuarial survival rate at 43 months was 52% for the population as a whole, and 68% for patients who achieved a complete response. Hematologic toxicity was relatively severe and the initial doses had to be reduced by 20% in all patients between the second and fifth courses. No deaths due to either infection or bleeding were seen due largely to intensive supportive care. It is concluded that increasing the doses of a small number of drugs of proven efficacy may be more useful than increasing the number of drugs given in lower doses. Furthermore, this approach spares other effective drugs for second-line therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Bleomycin and cis-platinum with or without mitomycin C in 110 previously untreated patients with head and neck cancer.

Between November 1979 and October 1981, 110 consecutive patients with previously untreated, biopsy-proven squamous cell carcinoma of the head and neck, were treated by chemotherapy prior to scheduled surgery and/or radiotherapy. Two regimens of chemotherapy were used. The first 57 patients received cis-platinum, 20 mg/m2/day for 5 consecutive days and bleomycin 5 mg/m2/day as a continuous infusion over the same 5 days every 3 weeks (Regimen A). The next 53 patients received the same schedule and dose of cis-platinum, bleomycin 2.5 mg/m2 every 12 hours for the same 5 consecutive days and mitomycin C6 mg/m2 on day 1 of each cycle every 3 weeks (Regimen B). The number of courses administered prior to surgery and/or radiotherapy ranged from 1-4 depending on the otorhinolaryngologist's assessment of the optimal time for locoregional treatment. The overall response rate in regimen A was 78% (45/57) compared to 90% for regimen B (48/53). Complete responses were seen in 10/57 (18%) and 13/53 (25%) patients in regimens A and B, respectively. Eight of 57 patients in regimen A and 6/53 in regimen B refused further treatment and follow-up, and 7/53 patients in regimen B chose to pursue chemotherapy (in which methotrexate replaced bleomycin) rather than undergo surgery and/or radiotherapy. Five of these seven patients are surviving disease-free from 7-12 months. In regimen A, 31/57 patients are surviving with a median survival exceeding 15 months. In regimen B, 46/53 patients are surviving up to 14 months. Nausea and vomiting induced by cis-platinum were the major side effects, seen to a variable degree in all patients. No cis-platinum-induced renal toxicity was observed with the 5-day regimen and none of the patients had symptomatic bleomycin-induced pneumonitis. One patient had a bleomycin-induced skin rash which did not require discontinuation of therapy.

Adult↗
PubMed1983

Treatment of advanced ovarian cancer with cis-dichlorodiammine platinum in combination with cyclophosphamide. An E.C.O.G. pilot study.

Twenty patients with Stage III and IV carcinoma of the ovary have been treated with a combination of cyclophosphamide and cis-platinum given every 3 weeks. Regarding toxicity, this combination probably included a too-high dose of CTX (1.1 g/m2 every 3 weeks). The response rate was 75% (15/20) but with a significant duration only for those patients who achieved a complete response (7/20). It was seen that, as usual, patients who have undergone extensive reductive surgery are more likely to respond. The regimen described gives results comparable to those of more aggressive combinations but did not achieve significant control of the disease.

Aged↗
PubMed1982

[Results of several times daily treatment by cisdiamine-platinum and bleomycin. Therapeutical considerations (author's transl)].

Seventy two head and neck cancers have been treated with a combination of Cis-DDP (20 mg/m2/day) and bleomycin (6 mg/m2/day, 24 hours infusion) given for 5 days 3 courses every 3 weeks in preoperative cases and for 6 days (4 courses every 3 weeks) in non preoperative cases. Fifteen patients treated for local recurrence after irradiation experienced no significant response and their actual survival at 12 months is 22%. For the other patients the objective response rate was 78% with 10 complete responses and the projected survival at 12 months varies from 62% to 92% according to the subsequent treatment (irradiation or surgery followed by irradiation). These results are in agreement with a few reports using similar combinations; but it needs to answer new questions about possibility of surgical strategy variations in the cases of good or complete responses with such a chemotherapy.

Bleomycin↗
PubMed1982

[Advanced epithelial cancers of the ovary: results of 4 chemotherapy protocols (110 cases)].

Following surgery for epithelial carcinoma of the ovary, FIGO stages IIc, III and IV, 110 patients received chemotherapy in one of four treatment regimens (Melphalan; Cyclophosphamide-Methotrexate-Fluoro uracil; Cyclophosphamide-Cisplatinum; Cyclophosphamide-Cisplatinum-Fluoro-uracil). Melphalan alone was as effective as combination chemotherapy and less toxic. The study confirms that the survival duration is inversely correlated to the stage of the disease and to the amount of residual disease following surgery. It also confirms the role of the "second look" surgery in the evaluation of the response to chemotherapy, and in the overall management of the disease.

Adult↗
PubMed1981

[Treatment of squamous cell carcinomas with prolonged, continuous infusions of bleomycin and cisplatinum. A first series of 80 cases with 75% objective response (author's transl)].

Eighty consecutive patients with measurable and assessable squamous cell carcinoma of the head or neck, lung, oesophagus and uterine cervix received one to four courses of combined bleomycin and cis-platinum treatment. Each course lasted 5 to 6 days during which bleomycin was administered by continuous intravenous infusion and cis-platinum was given daily. If there was no evidence of toxicity or progressive disease, courses were repeated every 3 weeks to a total bleomycin dose of 150 mg/m2. A 75% objective response rate was obtained, with one case of progressive disease and no prohibitive toxic reaction. These results suggest that cytostatic drugs with low bone marrow toxicity can be given for prolonged periods and throw some doubt on the alleged resistance of squamous cell carcinomas to chemotherapy.

Bleomycin↗
PubMed1980

Dialysis pruritus: effect of cimetidine.

The effect of oral Cimetidine compared to a classic antihistaminic and to a placebo was evaluated, under the double hypothesis of its anti-PTH and anti-pruritus action, in a population of patients recently included in Hemodialysis that were asked about the incidence and intensity of pruritus according to a scored questionnaire made for this purpose. No different efficacy of Cimetidine versus the antihistaminic classic and the placebo was observed in our study.

Cimetidine↗