Biomedical subjects

Alberto Muñoz

Publications and source records attributed to Alberto Muñoz.

57 records · Page 4Linked to original sources

PubMedDate not supplied

Low thyroid hormone levels impair the perinatal development of the rat retina.

Eye development is regulated by multiple agents including hormones and growth factors. Thyroid hormone (triiodothyronine, or T(3), and the prohormone thyroxine, or T(4)) plays a crucial role in the development of the central nervous system. Here we have examined the effects of low T(3)/T(4) levels (hypothyroid status) on the developing rat retina during the perinatal stage. Eyes from control (CG) and T(3)/T(4)-deficient (HG) fetuses (E19 and E21) and newborn (P0, P3, P5 and P7) rats were obtained by administering a chemical antithyroid solution (0.02% methyl-mercaptoimidazole +1% ClOK(4)) in the tap water to the dams and their offspring, from E9 and throughout gestation until they were killed. Perinatal eyes were processed for light and electron transmission microscopy and subjected to morphological and morphometric analyses. Low T(3)/T(4) levels led to decreased retinal growth during the perinatal stage. In addition, the retinas from the HG presented fewer neuroblasts than those of their euthyroid counterparts (at E21: 705 +/- 83 cells per constant area of 4 x 10(4) microm(2) vs. 440 +/- 60 cells per constant area of 4 x 10(4) microm(2); p = 0.010). During development the index of mitosis in the retina peaked at E21, falling at the end of the 1st postnatal week. Significantly lower values were observed in the HG (at P5: 0.803 +/- 0.374 mitoses/cells % vs. 0.349 +/- 0.180 mitoses/cells %; p = 0.004). Furthermore, we have found that low T(3)/T(4) levels delayed and/or altered a series of developmental processes occurring in the retina during the perinatal stage such as layering and differentiation of several cell types. Our results demonstrate that thyroid hormone regulates rat neuroretinogenesis.

Animals↗

PubMedDate not supplied

Preradiation chemotherapy with VM-26 and CCNU in patients with glioblastoma multiforme.

AIMS AND BACKGROUND: The objective of the study was to evaluate the efficacy of combined chemoradiation in patients with newly diagnosed glioblastoma multiforme. The main end points were time to progression and overall survival. METHODS: Thirty-one patients with glioblastoma multiforme underwent surgery whenever possible and then received intravenous VM26 (120 mg/m2) and oral CCNU (120 mg/m2) for three cycles followed by radiotherapy (60 Gy). RESULTS: Surgery consisted of a complete resection in 39% of patients, partial resection in 35% and a biopsy in 26%. Sixteen patients had clinical or radiological evidence of progression during or after chemotherapy. Hematologic toxicity was mild. Forty-five percent of patients received the scheduled dose of radiation. The outcome was disappointing, with a median time to progression of 18 weeks and median survival of 37.17 weeks. CONCLUSIONS: The survival of patients with glioblastoma multiforme remains disappointing. Multimodal therapy does not seem to modify the evolution of the tumor. Stratification according to prognostic factors might detect a potential benefit of other therapeutic approaches.

Administration, Oral↗

PubMedDate not supplied

Effects of 1alpha,25-dihydroxyvitamin D3 in human colon cancer cells.

Colorectal cancer is a major health problem worldwide. Epidemiological studies and work on experimental animals strongly suggest a protective effect of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) against colon neoplasia. 1,25(OH)2D3 is a pleiotropic hormone that has multiple actions in the organism. By binding to the widely expressed high affinity vitamin D receptor (VDR) it regulates the transcription rate of many genes. Other non-genomic effects of 1,25(OH)2D3 also appear to modulate the physiology of numerous cell types. Human normal and cancer colon epithelial cells express VDR and the key enzymes involved in 1,25(OH)2D3 synthesis and degradation and are, thus, responsive to the hormone. 1,25(OH)2D3 inhibits proliferation, induces differentiation and sometimes the apoptosis of human colon cancer cells. A great variety of mechanisms and signaling pathways are involved. Since VDR mediates most, if not all, 1,25(OH)2D3 actions, the control of VDR expression is a crucial aspect of 1,25(OH)2D3 biology. Here, the molecular mechanisms underlying the actions of 1,25(OH)2D3 are reviewed and the repression of the VDR gene by the transcription factor SNAIL in human colon cancer cells is discussed. Understanding these mechanisms may provide the basis for the potential use of this hormone and its non-hypercalcemic derivatives in the prevention and treatment of colon cancer.

Animals↗