[P-glycoprotein, a membrane pump that represents a barrier to chemotherapy in cancer patients]. / La glicoproteína-P una bomba de membrana que representa una barrera a la quimioterapia de los pacientes con cáncer.

Multidrug resistance (MDR) in oncology is considered to be the main cause of chemotherapy failure in the treatment of patients with cancer. The resistance mechanism consists in decrease intracellular drug accumulation by P-glycoprotein (Gp-P) overexpression. This protein acts as a drug-extracting pump that needs energy in the process. The efflux takes place by mean of a pore in the cell membrane that consist in twelve segments. The activity of this pump is regulated by protein kinase C and shows homology with other transport systems. The analysis of the presence of Gp-P and the characterization of MDR phenotype in biopsy material could be important in the overcome of the resistance to cancer chemotherapy.

La glicoproteína-P una bomba de membrana que representa una barrera a la quimioterapia de los pacientes con cáncer / P-glycoprotein, a membrane pump that represents a barrier to chemotherapy in cancer patients

La resistencia oncológica a múltiples agentes antineoplásicos o MDR se considera una de las mayores causas de fallo clínico en el tratamiento quimioterápico de pacientes con cáncer. El mecanismo de resistencia consiste en una disminución en la acumulación intracelular de droga por sobreexpresión de la glicoproteína-P (Gp-P). Esta proteína actúa como una bomba extrusora de drogas, dependiente de energía. El eflujo se realiza a través de un canal que forma en la membrana plasmática, constituido por doce segmentos transmembranales. La actividad de esta bomba extrusora esta regulada por la proteína quinasa C y presenta homología con otros sistemas de transporte. El análisis de la presencia de Gp-P y la caracterización del fenotipo MDR en biopsias tumorales podría tener gran importancia en el abordamiento del problema clínico que representa la resistencia tumoral a la quimioterapia (AU)

Multidrug resistance (MDR) in oncology is considered to be the main cause of chemotherapy failure in the treatment of patients with cancer. The resistance mechanism consists in decrease intracellular drug accumulation by P-glycoprotein (Gp-P) overexpression. This protein acts as a drug-extracting pump that needs energy in the process. The efflux takes place by mean of a pore in the cell membrane that consist in twelve segments. The activity of this pump is regulated by protein kinase C and shows homology with other transport systems. The analysis of the presence of Gp-P and the characterization of MDR phenotype in biopsy material could be important in the overcome of the resistance to cancer chemotherapy (AU)

[Multidrug resistance (MDR) in oncology]. / Multirresistencia a drogas (MDR) en oncología.

Multidrug resistance or mdr is a frequent phenomenon for which tumor cells can develop, in only one step, cross-resistance to a different anticancer drugs such as antibiotics, vinca alkaloids and podophylotoxins. This is due to an extrusion of drugs out of the cells, since it is interrelated with the decrease of the intracellular concentration of the drug, compared to sensitive cells. This phenomeno of multidrug resistance (mdr) is considered one of the principal causes of failure in quimiotherapic treatment of cancer, and is associated in many cases to an hyperexpression of mdr-I gene, that codifies for a high molecular weight glycoprotein (p-170) (170-180 Kdaltons), also called p-glycoprotein (pgp). Locadet it in the cellular membrane extracts, like a pump, the quimiotherapic drugs with consumption of ATP. In humans, there are two principal genes that codify for pgp: mdr-I and mdr2/3; being the most important the mdr-I gene. The structure of p-glycoprotein consists in two symmetrical halves anchored in the cellular membrane that includes three extracellular dominances each one, and on intracellular portion with the ATP binding site. Also, has got an for extracellular carbohydrates chain. It is specially important to find drugs that reverse the multidrug resistance. Chemicals such as verapamil, nifedine, quinidine and calmodulin inhibitors are joined to pgp inhibiting it. A Cyclosporine and its non-immunosuppressors derivateds such as SDZ 280-125 and SDZ PSC 833 reverse mdr. At present it is being advancing in clinical trials, but the results are not satisfactory. Most useful chemicals are verapamil, better R-verapamil and A-cyclosporine or its non-immunosuppressors derivates. Futures possibilities are grateful. From diagnostic point of view the mains are: 1. Detection of mdr-I gene. 2. Recognition of the presence of mRNA for pgp. 3. Detection of pgp by flow cytometry or western blot. 4. Immunohistochemistry with monoclonal antibodies to pgp. 5. Rhodamine 123 to study mdr phenotype. 6. Multidrug resistance modulators in vitro. 7. pgp in vivo as a tumor marker. From therapeutic point of view: 1. To assay mdr modulators with higher power and better tolerated. 2. Reversing of mdr with in vivo MoAbs and/or immunotoxins. 3. Gene therapy. 4. New chemicals that joined to tubulin do not be extrused by pgp. 5. Drugs joined to liposomes. 6. Interpheron to increase the efficacy of MoAbs in mdr reversion. 7. Photodynamic therapy. Other possibilities can be the use of MoAbs in diagnostic (immunodetection) by PET and SPECT: and the MoAbs joined to drugs and radioisotopes.

[Captopril + hydrochlorothiazide versus captopril + nifedipine in the treatment of arterial hypertension in diabetes mellitus type II]. / Captopril + hidroclorotiazida frente a captopril + nifedipino en el tratamiento de la hipertensión arterial del diabético tipo II.

Captopril is a suitable drug to treat high blood pressure in diabetic patients. This Angiotensin-Converting Enzyme Inhibitor (ACEI) is a vasodilator without tachycardia and saline retention. Furthermore, captopril is one of antihypertensive drugs with less adverse effects. It does not induce metabolic changes, improves glucose tolerance and brake the evolution of renal insufficiency. About 50-60% of patients are under control (DBP < 90 mmHg) with captopril monotherapy. In the present paper, were included 64 women and 16 men with diabetes mellitus and mild-moderate hypertension, I-II phase WHO. The average age (mean +/- S.D.) was 66.6 +/- 9.2 years. All patients were treated with 25 mg/12 h of captopril, for one month. If blood pressure was not under control, captopril treatment enhanced to 50 mg/12 h during second month. After this period of two months, patients under control were got out of this study. 37 patients (46.25%) needed a second drug. In randomized form, 20 patients associated 25 mg HCTZ one time a day (CAP + HCTZ); and 17 patients associated 20 mg/12 h of nifedipine retard (CAP + NIF). The study continued for 4 months more. Both treatments reduced blood pressure in significant form without changes statistical significant in the heart rate, weight, glycemia, cholesterol, triglycerides, c-HDL, uric acid, creatinine, Na+ and K+ blood levels. CAP + HCTZ controlled (DBP < 90 mHg) 85% and CAP + NIF 81.25% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)