Histology and histopathology Vol.22, nº 2 (2007)

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  • Publication
    Open Access
    Chronic ethanol feeding alters the epithelial cell proliferation and apoptosis in rat gastric mucosa
    (Murcia : F. Hernández, 2007) Ge, Y. B.; Du, J.; Fan, L.L.; Li, Y.C.; Gu, L.
    We developed a chronic drinking rat model to investigate the long-term effects of ethanol feeding on cell proliferation and apoptosis in rat stomach. Adult male Sprague-Dawley (SD) rats received either an isocaloric control or drinking water containing 6% (v/v) ethanol as their only water intake for 1, 3, 7, 14 and 28 days. At the end of each feeding period, animals were sacrificed and the stomach was dissected for the sample preparation. The cell proliferation and apoptosis in gastric mucosa of rats in different groups were analyzed by flow cytometer, immunohistochemistry and computer image analysis. In the flow cytometric study, compared with the control, the cell apoptosis in gastric mucosa of the rats was enhanced during the exposure to the ethanol in 3rd to 28th day. Otherwise the cell proliferation was increased in 3rd to 14th days, and decreased in 28th days, respectively. The results were confirmed by immunohistochemistry and computer image analysis studied. This finding suggested that short-term chronic adequate alcohol intake may enhance the cell turnover of gastric mucosa. Long-term stimulus with the low concentration ethanol may cause the impairment of the cell turnover function of the gastric mucosa and may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.
  • Publication
    Open Access
    Chromosome instability and kinetochore dysfunction
    (Murcia : F. Hernández, 2007) Tomonaga, T.; Nomura, F.
    Chromosomal instability (CIN) has been recognized as a hallmark of human cancer and is caused by continuous chromosome missegregation during mitosis. Proper chromosome segregation requires a physical connection between spindle microtubules and centromeric DNA and this attachment occurs at proteinaceous structures called kinetochore. Thus, defect in kinetochore function is a candidate source for CIN and the generation of aneuploidy. Recently, a number of kinetochore components have been shown to be mutated and/or aberrantly expressed in human cancers, which suggests an important role of kinetochore for CIN and carcinogenesis. In this article, we will discuss about how kinetochore dysfunction causes CIN and might lead to the development of cancer.
  • Publication
    Open Access
    Differential distribution of transforming growth factor beta and receptors in the hyper or hypoproliferative gastric mucosa of developing and adult rats
    (Murcia : F. Hernández, 2007) Alvares, E.P.; Jordão, L.R.; Gama, P.
    Transforming growth factor ß (TGFß) isoforms are known for their antiproliferative effect on epithelial cells in vitro, but the role of each isoform in vivo is poorly understood, mainly when non-pathological conditions are considered. We correlated the presence and distribution of isoforms and receptors to physiological changes in gastric cell proliferation in developing and adult rats. We used fasting to induce either the hyper (14-day-old pups) or hypoproliferation (60-day-old rats) of the gastric epithelium. In 14-d-old pups fasting reduced only TGFß3 labelling in the gland. Conversely, in 60-d-old rats there was an increase of TGFß1 and TGFß3 immunolabelled cells. Receptors were detected at both ages. Therefore, the changes induced by fasting in the constitutive TGFß expression can be correlated to the differential epithelial proliferation in the stomach of developing and adult rats. These results suggest that one of the functional roles of TGFß in vivo is to locally regulate cell proliferation.
  • Publication
    Open Access
    Development of new RNAi therapeutics
    (Murcia : F. Hernández, 2007) Liu, G.; Wong-Staal, F.; Li, Q.X.
    RNAi-mediated gene inactivation has become a cornerstone of the present day gene function studies that are the foundation of mechanism and target based drug discovery and development, which could potentially shorten the otherwise long process of drug development. In particular, the coming of age of “RNAi drug” could provide new promising therapeutics bypassing traditional approaches. However, there are technological hurdles need to overcome and the biological limitations need to consider for achieving effective therapeutics. Major hurdles include the intrinsic poor pharmacokinetic property of siRNA and major biological restrictions include off-target effects, interferon response and the interference with endogenous miRNA. Recent innovations in nucleic acid chemistry, formulations and delivery methods have gradually rendered it possible to develop effective RNAi-based therapeutics. Careful design based on the newest RNAi/miRNA biology can also help to minimize the potential tissue toxicity. If successful with systemic application, RNAi drug will no doubt revolutionize the whole drug development process. This review attempts to describe the progress in this area, including applications in preclinical models and recent favorable experience in a number of human trials of local diseases, along with the discussion on the potential limitations of RNAi therapeutics.
  • Publication
    Open Access
    Immunohistochemical analyses on serum proteins in nephrons of protein-overload mice by in vivo cryotechnique
    (Murcia : F. Hernández, 2007) Zhou, D.S.; Ohno, N.; Terada, N.; Li, Z.; Morita, H.; Inui, K.; Yoshimura, A.; Ohno, S.
    Immunohistochemical analyses on local distributions of serum proteins in living mouse kidneys are usually difficult to examine with conventional preparation methods. By using our “in vivo cryotechnique” combined with freeze-substitution, we have checked immunolocalizations of the serum proteins in nephrons of bovine serum albumin (BSA)-overload mice, and compared them with those obtained by the conventional preparation methods. In two days of daily BSA-injected mice, the immunolocalization of BSA could be observed in Bowman’s space and urinary tubules with their overt proteinuria, where another endogenous mouse albumin was similarly immunolocalized. The leakage of BSA and mouse albumin in Bowman’s space and their reabsorption into proximal tubules were detected in 55% of nephrons, where no leakage of immunoglobulin G1 (IgG1) was detected. However, the leakage of IgG1, in addition to BSA and mouse albumin, was detected in the other nephrons. By carefully examining immunolocalizations of BSA and IgG1, they were obviously different from those obtained by the conventional preparation methods without normal blood circulation into the kidneys. The immunolocalizations of both BSA and mouse serum proteins could be directly analyzed with the “in vivo cryotechnique”, suggesting that functional damage to glomerular filtration barriers are different at early stages of the BSA-overload mouse model, depending on each nephron of living mice.