Biomedical subjects

M M Alonso

Publications and source records attributed to M M Alonso.

6 recordsLinked to original sources

PubMed2003

New benzo(b)thiophenesulphonamide 1,1-dioxide derivatives induce a reactive oxygen species-mediated process of apoptosis in tumour cells.

In this work, we describe the process of cell death induced by a series of new benzo(b)thiophenesulphonamide 1,1-dioxide derivatives (BTS) that have been selected as candidate antineoplastic drugs. Human leukaemic CCRF-CEM cells incubated with BTS undergo a typical apoptotic process that includes cell shrinkage, phosphatidylserine translocation to the cell surface, mitochondrial dysfunction, caspase activation, chromatin condensation and internucleosomal DNA degradation. Mitochondrial alterations included dissipation of the mitochondrial membrane potential, oxidation of the phospholipid cardiolipin, release of cytochrome c and uncoupling of the mitochondrial respiratory chain, leading to a decrease of the intracellular ATP pool. Activation of caspase-8, -9 and -3 takes place during BTS-induced apoptosis. Either the addition of the specific caspase-8 inhibitor Z-IETD-fmk, or the overexpression of the antiapoptotic protein Bcl-2 significantly prevented BTS-induced apoptosis, suggesting the involvement of both caspase-8-regulated and mitochondria-dependent signalling pathways in this process. BTS induce a significant increase in the production and accumulation of intracellular reactive oxygen species (ROS) that can be observed within minutes after drug addition. Moreover, cytochrome c release, caspase-3 activation and cell death can be completely abrogated by a previous incubation with the antioxidant N-acetyl-cysteine. These results suggest that ROS are essential mediators in BTS-induced apoptosis.

Antineoplastic Agents↗

PubMed2001

New cytotoxic benzo(b)thiophenilsulfonamide 1,1-dioxide derivatives inhibit a NADH oxidase located in plasma membranes of tumour cells.

A series of benzo(b)thiophenesulfonamide 1,1-dioxide derivatives (BTS) have been designed and synthesized as candidate antineoplastic drugs. Several of these compounds have shown in vitro cytotoxic activity on leukaemic CCRF-CEM cells. The cytotoxic BTS, but not the inactive ones, were able to inhibit a tumour cell-specific NADH oxidase activity present in the membrane of CCRF-CEM cells.

Antineoplastic Agents↗

PubMed2000

Comparison of immunologic restoration and virologic response in plasma, tonsillar tissue, and cerebrospinal fluid in HIV-1-infected patients treated with double versus triple antiretroviral therapy in very early stages: The Spanish EARTH-2 Study. Early Anti-Retroviral Therapy Study.

The objective of antiretroviral therapy is to obtain an almost complete and durable suppression of viral replication in all compartments to facilitate recovery of the immune system. We assessed the virologic effect in plasma, tonsillar tissue, and cerebrospinal fluid (CSF) in 94 HIV-1-infected patients with CD4 counts >500 x 106 cells per liter and viral load >5000 copies/ml randomly assigned to triple antiretroviral therapy (two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor) versus double therapy (two NRTIs). We also analyzed the immunologic recovery in this cohort of patients. Lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to HIV-1 specific antigens, and other immunophenotypic markers were analyzed. The proportion of patients who achieved a decrease in HIV RNA levels to <200 copies/ml was significantly greater in the triple therapy group than in the two drug groups (p =.0002 for each pair-wise difference). At week 52, tonsillar tissue HIV RNA from 5 patients treated with triple therapy was lower than the limit of detection, whereas the mean +/- standard error in patients with double therapy (n = 5) was 5.03 +/- 0.34 copies/mg/tissue. In all 10 patients, CSF viral load (VL) was <20 HIV-1 RNA copies/ml at week 52. CSF cell counts and protein levels tended to decrease after 52 weeks of antiretroviral therapy. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n = 9] and stavudine plus lamivudine [n = 12]) had evidence of M184V mutation. None of the 10 samples of patients receiving triple therapy could be amplified because of low HIV RNA levels. The mean increase in CD4 cells at week 52 was greater in the stavudine and lamivudine and indinavir group than in the double-treatment arms (186 versus 67 and 102, respectively; p =.03). In patients treated with triple therapy, the increase in naive T cells (CD4 and CD8) was greater than in patients treated with double therapy. Markers of activation decreased further in patients treated with the regimen that included protease inhibitors. Proliferative responses to HIV-1 p24 antigen were never recovered after double or triple therapy. Our study suggests that even in very early stages of HIV-1 disease only therapy with two NRTIs and one protease inhibitor reduces plasma, lymphoid tissue, and CSF VL to undetectable levels. HIV-1-related immune system abnormalities improved but were still defective after 1 year of antiretroviral therapy.

Adult↗

PubMed1994

[The psychologists in Argentina. Quantitative data].

A partial report from a study dealing with Psychology's current status in Argentina is presented. Pursuant to this preliminary study 36,128 psychologists have taken their degree at both State and private universities in Argentina--between 1956, when the first Department of Psychology was created, and 1992. So, over a 32.5-million population (as per the 1991 census), there is a psychologist every 897 inhabitants, or 111 psychologists every 100,000 inhabitants. According to psychologists' geographical distribution, the highest density is to be found in the capital city of Buenos Aires (one psychologist every 246 inhabitants) while the lowest density is to be found in the Province of Chaco (one psychologist every 17,465 inhabitants). During year 1993, a total of 26,726 students have been studying Psychology at the different Argentine universities: Of these, 6,858 have taken their Psychology degree during this academic year. A great majority of psychologists work in the clinical field, being Psychoanalysis their prominent theoretical orientation. Ladies psychologists supposedly account for 85% of the overall number of psychologists. Psychological Associations have 24,878 active psychologists recorded, of which a great majority work in the clinical field.

Argentina↗

PubMed1992

DNA ploidy of primary and metastatic squamous cell head and neck cancers.

Regional metastases are a major determinant in the treatment outcome of patients with squamous cell carcinoma of the head and neck. Metastases do not respond as well to cytotoxic therapy as do primary tumors. DNA diploid tumors or tumor components also respond poorly to intermittent cytotoxic therapy. In our series of 497 patients with squamous cell carcinoma of the head and neck, the percentage of pure DNA diploid tumors and the mean DNA indexes in 497 primary tumors and 82 regional metastases were 34% and 1.54 and 50% and 1.34, respectively. Paired comparisons were performed in 61 patients and revealed a statistically significant increase in the frequency of DNA diploid tumors (27.4% to 41.2%) in associated lymph node metastases. The clinical observation that patients with squamous cell carcinoma of the head and neck and regional lymph node metastases have a poorer prognosis and a poorer response to cytotoxic therapy may in part be explained by the increased incidence of DNA diploid tumors in their regional lymph nodes, and the poorer response of such tumors to cytotoxic therapy.

Carcinoma, Squamous Cell↗

PubMed1989

Serum interleukin 2 (IL-2) levels and prolactin bioactive/radioimmunoassay ratios of women at risk for breast cancer.

In a cohort of women at high risk for developing breast cancer we have observed that 74% of the women with prolactin BA/RIA ratios over 1.4 had detectable levels of IL-2 in their serum (990 +/- 400 mU/ml) and the IL-2 levels were correlated with the prolactin BA/RIA ratio (R = 0.79; P greater than 0.004). Women with BA/RIA ratios were either approximately 1.0 or less than 0.55 had lower levels of serum IL-2 (177 +/- 70 and 130 +/- 40 mU/ml, respectively). Detectable levels of serum IL-2 were found in 58% of those women with BA/RIA ratios of 1.0 and 55% of those with BA/RIA ratios less than 0.55.

Adolescent↗