Histology and histopathology Vol.23,nº10 (2008)
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- PublicationOpen AccessInvolvement of pro-apoptotic and anti-apoptotic factors in the early development of the human pituitary gland(Murcia : F. Hernández, 2008) Saraga-Babic, Mirna; Bazina, Mirna; Vukojevic, Katarina; Bocina, Ivana; Stefanovic, VedranThe spatial and temporal pattern of appearance of pro-apoptotic caspase-3 and p53 proteins, and anti-apoptotic bcl-2 protein was investigated in the developing pituitary gland of 6 human embryos 5-8- weeks old, using morphological and immunohistochemical techniques. Their dynamic appearance was analyzed in the Rathke's pouch (future adenohypophysis), mesenchyme, and in the developing neurohypophysis. In the 5th and 6th week, caspase-3 positive cells appeared in the Rathke's pouch (5%) and stalk (11%), in the mesenchyme, but not in the neurohypophysis. In the 6th and 7th week, apoptotic cells were more numerous in the caudal part of the Rathke's pouch due to its separation from the oral epithelium. Pro-apoptotic p53 protein was detected in all parts of the pituitary gland throughout the investigated period. Nuclear condensations characterized cells positive to caspase-3 and p53 proteins. Apoptotic cells displayed condensations of nuclear chromatin on an ultrastructural level as well. While caspase-3 dependent pathway of cell death participated in morphogenesis of the adenohypophysis and associated connective tissue, p53-mediated apoptosis most likely participates in morphogenesis of all parts of the gland, including neurohypophysis. The anti-apoptotic bcl-2 protein was also detected in all parts of the developing gland. With advancing development, the positivity to bcl-2 protein increased in the cells of the adenohypophysis, while it decreased in the neurohypophysis. Bcl-2 protein probably prevented cell death in all parts of the gland and enhanced cell differentiation. The described pattern of appearance of the investigated pro-apoptotic and antiapoptotic factors might be important for normal morphogenesis and function of the pituitary gland.
- PublicationOpen AccessAllopurinol attenuates L-NAME induced cardiomyopathy comparable to blockade of angiotensin receptor(Murcia : F. Hernández, 2008) Kasal, Daniel Arthur B.; Fritsch Neves, Mario; Oigman, Wille; Mandarim-de-Lacerda, Carlos A.It is widely recognized that L-NAME exposed rats develop myocardial fibrosis and hypertrophy. The aim of this study was to evaluate the contribution of xanthine oxidase (XO) to these phenomena using allopurinol, isolated or associated with olmesartan. Thirty adult male Wistar rats were divided into 5 groups (n=6) and studied for 5 weeks: L group (LNAME, 40mg/kg/day); L+A group (L-NAME and allopurinol, 40 mg/kg/day); L+O group (L-NAME and olmesartan, 15mg/kg/day); L+A+O group (L-NAME, allopurinol, and olmesartan); and control group. LNAME caused arterial hypertension and cardiomyocyte hypertrophy. Hypertension was prevented by olmesartan, but not by allopurinol. There was an increase of left ventricular mass index in the L-NAME group that was prevented by allopurinol, olmesartan and by the combination of both. The increase in mean cardiomyocyte transversal area caused by L-NAME was prevented by the allopurinol and olmesartan combination, or by olmesartan used as monotherapy, but not by allopurinol alone. There was a reduction in the myocardial vascularization index caused by L-NAME which was abolished by allopurinol or by olmesartan, but not by the association. L-NAME caused a reduction in the total number of cardiomyocyte nuclei. This was prevented by olmesartan alone or associated with allopurinol, but not by allopurinol alone. We conclude that XO has an important contribution to adverse cardiac remodeling in L-NAME exposed animals. Moreover, allopurinol acts without interfering with L-NAME induced hypertension. The protective action of this drug is comparable to the results obtained with olmesartan. Antioxidative mechanisms are proposed to account for the pressure independent effects of allopurinol.
- PublicationOpen AccessNucleolus, The ribosome factory(Murcia : F. Hernández, 2008) Cmarko, Dusan; Smigova, Jana; Minichova, Lucía; Popov, AlexeyThe nucleolus is a nuclear compartment and represents the most obvious and clearly differentiated nuclear structure seen in the microscope. Within nucleoli most events of ribosome biogenesis, such as ribosomal RNA synthesis, processing, and ribosome subunit assembly, take place. Several lines of evidence now show that the nucleolus has also numerous nonribosomal functions. This review is focused on the recent progress in our knowledge of how to correlate the known biochemical processes taking place in the nucleolus with nucleolar structures observed in the microscope. We still lack detailed enough information to understand fully the organization and regulation of the processes taking place in the nucleolar sub-structures. However, the present power of microscopy techniques should allow for an in situ description of the organization of nucleolar processes at the molecular level in the years to come.
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- PublicationOpen AccessAkt pathway as a target for therapeutic intervention in HNSCC(Murcia : F. Hernández, 2008) Moral, Marta; Paramio, Jesús M.Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide. One frequent alteration found in this type of cancer is overactivation of the PI3K/PTEN/mTOR pathway, of which protein kinase B (PKB)/Akt is a central key element, controlling important cellular processes such as metabolism, cell size, proliferation and apoptosis, ultimately regulating cell growth and survival. Thus, drugs that target Akt directly or elements of the pathway are plausible candidates for cancer treatment. Accordingly, numerous clinical trials in various phases are being performed for these drugs. In this review, we discuss the tumorigenic capacity of Akt and focus on its role in HNSCC, paying special attention to the current efforts in treating this cancer in a more specific, Akttargeted way, based on its primordial role in this type of cancer.
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