scholarly journals Doxazosin and Carvedilol Treatment Improves Hepatic Regeneration in a Hamster Model of Cirrhosis

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Sandra Alejandra Serna-Salas ◽  
Yesenia Danyeli Navarro-González ◽  
Sandra Luz Martínez-Hernández ◽  
Luis Fernando Barba-Gallardo ◽  
Esperanza Sánchez-Alemán ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cirrhosis ◽  
Morphological Changes ◽  
The Other ◽  
Hepatic Tissue ◽  
Hepatic Regeneration ◽  
Ki 67 ◽  
Hamster Model ◽  
Proliferation Markers ◽  
Other Hand

Regulation of the mechanisms of fibrosis is an important goal in the treatment of liver cirrhosis. One mechanism is the participation of hepatic stellate cells in fibrogenesis when activated by catecholamines. Consequently, α/β adrenoblockers are proposed as an alternative treatment for chronic liver lesions such as fibrosis and/or cirrhosis and for possible liver regeneration. We herein analyzed the effect of doxazosin and carvedilol treatments during the regeneration of tissue in a hamster model of liver cirrhosis. Tissue samples were examined by H&E and PAS to evaluate tissue damage and with Sirius red to assess collagen fiber content. ALT, AST, albumin, and total proteins were examined by spectrophotometry. Determination of the levels of α-SMA and TGF-β in hepatic tissue was examined by Western blot and of the expression of TIMP-2, MMP-13, α-FP, HGF, CK-7, and c-Myc was examined by qPCR. Treatment with doxazosin or carvedilol prompted histological recovery and reduced collagen fibers in the livers of cirrhotic hamsters. The expression of TIMP-2 decreased and that of MMP-13 increases in animals treated with adrenoblockers with respect to the group with cirrhosis. Additionally, the concentration of α-SMA and TGF-β declined with both drugs with respect to placebo p<0.05. On the other hand, each drug treatment led to a distinct scenario for cell proliferation markers. Whereas doxazosin produced no irregularities in α-FP, Ki-67, and c-Myc expression, carvedilol induced an increment in the expression of these markers with respect to the intact. Hence, doxazosin and carvedilol are potential treatments for the regression of hepatic cirrhosis in hamsters in relation to the decrease of collagen in the hepatic parenchyma. However, at regeneration level we observed that doxazosin caused slight morphological changes in hepatocytes, such as its balonization without affecting the hepatic function, and on the other hand, carvedilol elicited a slight irregular expression of cell proliferation markers.

scholarly journals Extraordinary morphological changes in valve morphology during the ontogeny of several species of the Australian ostracod genus Bennelongia (Crustacea, Ostracoda)

2013 ◽  
Author(s):  
Patrick De Deckker ◽  
Koen Martens
Keyword(s):  
Adult Stage ◽  
Morphological Changes ◽  
The Other ◽  
Left Valve ◽  
Ventral Region ◽  
Valve Morphology ◽  
Other Hand ◽  
Early Instar ◽  
Juvenile Stages

Ostracods belonging to the genus Bennelongia differ much in valve morphology between adults and juveniles. Adult valves are asymmetrical, characterised by a beak-like feature in the antero-ventral region of the left valve, and, with some notable exceptions, mostly have smooth or weakly-ornamented valves. Juvenile specimens, on the other hand, have valves that are almost symmetrical, with no beak-like feature and are often heavily ornamented.We have examined the last 3 - 4 juvenile stages of 6 Bennelongia species from 5 different lineages, in order to decipher the types of external valve ornamentation and their recurrences during ontogeny and across lineages. It is clear that ornamentation is more prevalent at the early instar stages compared to the last 2 pre-adult stages, and especially when compared to the adult stage itself.We also examined the surprising presence of a calcified inner lamella with a prominent inner list in the pre-adult stages of Bennelongia species, that is usually absent in juveniles of other ostracods, thus questioning if heterochronic processes have provided an intermediate valve morphology between the simple (normal) cypridinid juvenile state and the heavily derived and modified state of adult Bennelongia.We discuss the possible (speculative) functionality of the ornamentation in juveniles.

About morphological changes in the kidney in children with infections and some other diseases

1930 ◽  
Vol 26 (2) ◽  
pp. 121-132
Author(s):  
Yu. V. Makarov
Keyword(s):  
Scarlet Fever ◽  
Morphological Changes ◽  
The Other ◽  
Histological Changes ◽  
Other Hand ◽  
Renal Changes ◽  
The One

The issue of pathological and histological changes in the kidneys in children with various infections and other diseases cannot be considered sufficiently researched and worked out. Only in certain infections (scarlet fever) has much attention been paid to the study of the kidneys. Most of the works on the issue of interest to us date back to the time when, on the one hand, insufficient importance was attached to the early dissection of corpses and the freshness of the material, which, as is now known, is of particular importance for the histology of the kidney, on the other hand, such interpretation of the detected changes, which do not correspond to the views and concepts of modern nephropathology; Finally, those changes in views on some diseases that have occurred to date, for example, in the issue of disorders of digestion and nutrition in infants, dictate the need for a different approach to the study of renal changes in these diseases.

scholarly journals Bmi-1 Immunohistochemical Expression in Endometrial Carcinoma is Correlated with Prognostic Activity

Medicina ◽  
2020 ◽  
Vol 56 (2) ◽  
pp. 72
Author(s):  
Kayo Horie ◽  
Chihiro Iseki ◽  
Moe Kikuchi ◽  
Keita Miyakawa ◽  
Mao Yoshizaki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endometrial Carcinoma ◽  
Human Cancer ◽  
Hot Spot ◽  
Rank Correlation ◽  
Cyclin A ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Spearman’S Rank Correlation ◽  
Gynecology And Obstetrics

Background and objectives: B-lymphoma Mo-MLV insertion region 1 (Bmi-1) is a stem cell factor that is overexpressed in various human cancer tissues. It has been implicated in cancer cell proliferation, cell invasion, distant metastasis, and chemosensitivity, and is associated with patient survival. Several reports have also identified Bmi-1 protein overexpression in endometrial carcinoma; however, the relationship between Bmi-1 expression and its significance as a clinicopathological parameter is still insufficiently understood. Accordingly, the present study aimed to clarify whether immunohistochemical staining for Bmi-1 in human endometrial carcinoma and normal endometrial tissues can be used as a prognostic and cell proliferation marker. Materials and Methods: Bmi-1 expression was assessed in endometrioid carcinoma (grade 1–3) and normal endometrial tissues (in the proliferative and secretory phases) by immunohistochemistry; protein expression was evaluated using the nuclear labeling index (%) in the hot spot. Furthermore, we examined other independent prognostic and proliferation markers, including the protein levels of Ki-67, p53, and cyclin A utilizing semi-serial sections of endometrial carcinoma tissues. Results: The expression of the Bmi-1 protein was significantly higher in all grades of endometrial carcinoma than in the secretory phase of normal tissues. Moreover, Bmi-1 levels tended to be higher in G2 and G3 tissues than in G1 tissue, without reaching significance. Bmi-1 expression showed no notable differences among International Federation of Gynecology and Obstetrics (FIGO) stages in endometrial carcinoma. Furthermore, we observed a significant positive relationship between Bmi-1 and Ki-67, cyclin A, or p53 by Spearman’s rank correlation test, implying that high Bmi-1 expression can be an independent prognostic marker in endometrial carcinoma. Conclusions: Our study suggests that Bmi-1 levels in endometrial carcinoma tissues may be useful as a reliable proliferation and prognostic biomarker. Recently, the promise of anti-Bmi-1 strategies for the treatment of endometrial carcinoma has been detected. Our results provide fundamental data regarding this anti-Bmi-1 strategy.

Clonal Effect Of Lenalidomide On Akt Activation In Low-Risk MDS Patients With Del(5q)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5227-5227
Author(s):  
Matilde Y Follo ◽  
Carlo Finelli ◽  
Cristina Clissa ◽  
Sara Mongiorgi ◽  
Carmen Baldazzi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Erythroid Differentiation ◽  
Low Risk ◽  
The Other ◽  
Normal Cells ◽  
Akt Phosphorylation ◽  
Other Hand ◽  
5Q Deletion

Abstract Lenalidomide is an immunomodulating drug currently used in the treatment of del(5q) low-risk MDS patients, where it can suppress the del(5q) clone and restore a normal erythropoiesis. The exact molecular mechanisms underlying the effect of Lenalidomide in del(5q) MDS are not completely clear, although Akt phosphorylation is inhibited in Lenalidomide-sensitive del(5q) cell lines (Gandhi et al, 2006). On the other hand, the activation of the Akt/mTOR pathway has been demonstrated in CD34+ cells from high-risk MDS (Follo et al, 2007), which show alterations on stem cell proliferation, differentiation and apoptosis. These processes are important also in low-risk MDS, that usually show a stable disease but can evolve towards a worse clinical status, characterized by an increased cell proliferation. In this study we firstly investigated the effect of Lenalidomide in 6 patients with del(5q) MDS (IPSS: Low or Int-1). Given the limited number of cells, we analyzed bone marrow total mononuclear cells. As for Akt phosphorylation, we analyzed its localization along with RPS14, in order to specifically detect the del(5q) clone. On the other hand, by Real-Time PCR analyses, we assessed the expression of Globin genes, to evaluate the effect of the drug on erythropoiesis. In addition, we analyzed the effect of Lenalidomide on two cell lines with a different 5q status, one bearing a normal 5q chromosome and one showing the 5q deletion, to further investigate the effect of this drug on cell cycle, erythroid differentiation and inositide signalling pathways. Clinically, 4/6 del(5q) MDS patients showed a favourable response to Lenalidomide. At a molecular level, these cases showed an activation of erythropoiesis, in that Beta-Globin levels increased, as compared with baseline. Moreover, these subjects also displayed a specific phosphorylation of Akt. Interestingly, Akt resulted to be specifically activated in cells not showing the 5q deletion, whereas it was down-regulated in del(5q) cells. The two non responder patients early discontinued Lenalidomide for adverse events, and for these patients neither a clinical assessment of Lenalidomide effect, nor a molecular analysis, were possible. As for cell lines, ongoing analyses are showing that Lenalidomide specifically inhibits the growth of the del(5q) clone, blocking cells in G1 phase. On the other hand, Akt phosphorylation specifically increases in cells with a normal 5q chromosome. Taken together, our data show a specific activation of erythropoiesis in del(5q) low-risk MDS patients responding to Lenalidomide. In addition, our results indicate that Akt is specifically phosphorylated in normal cells without the del(5q), leading to hypothesize that Lenalidomide has a double effect: it can induce apoptosis in clonal del(5q) cells, but it also supports the proliferation and erythroid differentiation of normal cells, as also described in non-del(5q) MDS (Ebert et al, 2008). Therefore, our findings might contribute to elucidate the molecular mechanisms of Lenalidomide and possibly pave the way for the development of innovative therapeutic targeted strategies in MDS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Plasmin Promotes Keratinocyte Migration and Phagocytic-killing Accompanied by Suppression of Cell Proliferation which may Facilitate Re-epithelialization of Wound Beds

2004 ◽  
Vol 11 (3-4) ◽  
pp. 233-240 ◽  
Author(s):  
Imre Szabo ◽  
Miklos Simon ◽  
Janos Hunyadi
Keyword(s):  
Cell Proliferation ◽  
The Other ◽  
Epidermal Keratinocytes ◽  
Thymidine Uptake ◽  
Hacat Keratinocytes ◽  
Chemotactic Migration ◽  
Cell Functions ◽  
Other Hand ◽  
Phagocytic Killing

Abstract Keratinocytes were shown to induce the activation of plasminogen activator resulting in the formation of plasmin and the initiation of proteolysisin vitro. Activation of surface bound plasminogen may localize protease activity in the pericellular microenvironment and play a role in inducing both a conformational change and cell locomotion. Plasmin, however, can induce non-proteolytic effects on certain cell functions in a variety of cell lineages. In the present study we examined the effects of plasmin on keratinocytes with a focus on its role in the process of re-epithelialization, which included studies of cell migration, phagocytic-killing and cell proliferation. Migration of freshly isolated human epidermal keratinocytes was analyzed utilizing the agarose gel assay in the presence of 10% human serum. Plasmin at the concentration of 25 U/l induced a 160% increase in the chemotactic migration of keratinocytes that was completely blocked by the plasmin inhibitor α2-antiplasmin (Serpin). In the absence of serum, plasmin also induced a reversible chemotactic migration of HaCaT keratinocytes as determined utilizing the microchemotaxis assay. Dose-response analysis showed a bi-phasic effect of plasmin with a maximum increase of 52% in keratinocyte chemotaxis at a concentration of 25 U/l. HaCaT cells on the other hand, showed no detectablein vitrochemokinesis by plasmin. Phagocytic-killing of Candida albicans by freshly isolated epidermal keratinocytes was enhanced in the presence of 25 U/l plasmin which was also reversible by the addition of Serpin. Spontaneous proliferation of HaCaT keratinocytes as determined by3H-Thymidine uptake on the other hand, was reduced by 47 and 13% in cultures with 25 U/l plasmin for 24 and 48 h respectively, in a Serpin reversible manner. These data suggest that plasmin-induced chemotactic migration of epidermal keratinocytes is accompanied by enhanced phagocytic-killing coupled with suppression of proliferation of these cells which may facilitate re-epithelialization following skin injury.

Cell Proliferation and Inflammation on Biopsy Samples With Multifocal Atrophic Gastritis Before and 1 Year After Helicobacter pylori Eradication

2005 ◽  
Vol 129 (11) ◽  
pp. 1451-1456
Author(s):  
Jeannette Guarner ◽  
Jeanine Bartlett ◽  
Roslyn Seitz ◽  
Toni Whistler ◽  
Roberto Herrera-Goepfert ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Helicobacter Pylori ◽  
T Lymphocytes ◽  
Intestinal Metaplasia ◽  
Eradication Therapy ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Helicobacter Pylori Eradication ◽  
Biopsy Specimens ◽  
H Pylori

Abstract Context.—Results of clinical trials that have assessed whether gastric cancer is preventable with Helicobacter pylori eradication therapy remain inconclusive. These trials have used atrophy, intestinal metaplasia, and dysplasia as histopathologic end points that reflect possible preneoplastic lesions. Trial results would be more compelling if cell proliferation and inflammatory markers improved simultaneously with histopathologic lesions. Objective.—To study the presence of cell proliferation markers and type of inflammatory cells in biopsy specimens with gastritis, atrophy, and intestinal metaplasia before and 1 year after H pylori therapy and to determine if immunohistochemistry can be used to study these. Design.—We evaluated 12 subjects with gastritis and 16 with gastritis and multiple foci of atrophy and intestinal metaplasia by using immunohistochemical assays for tumor suppressor protein p53, proliferation marker Ki-67, cell cycle regulator cyclin D1, T and B lymphocytes, macrophages, and TUNEL (terminal deoxynucleotide transferase deoxyuridine triphosphate nick end labeling) assay for apoptosis. The biopsy specimens were selected from a randomized clinical trial that studied improvement of histopathologic gastric lesions after H pylori eradication. Results.—Groups of surface epithelial cells that expressed p53 and Ki-67 were observed more often in subjects with atrophy and intestinal metaplasia compared with those with gastritis alone. T lymphocytes in the lamina propria were frequently observed 1 year after treatment in subjects with atrophy and intestinal metaplasia. Conclusions.—Immunohistochemical assays for cell proliferation and inflammatory cell markers showed different distribution patterns in these gastric biopsy specimens. The presence of T lymphocytes and groups of cells that expressed proliferation markers in subjects with multiple foci of atrophy and intestinal metaplasia needs further study.

scholarly journals Neonatal and Juvenile Ocular Development in Sprague-Dawley Rats: A Histomorphological and Immunohistochemical Study

2017 ◽  
Vol 55 (2) ◽  
pp. 310-330 ◽  
Author(s):  
Vanessa Vrolyk ◽  
Julius Haruna ◽  
Marie-Odile Benoit-Biancamano
Keyword(s):  
Cell Proliferation ◽  
Morphological Changes ◽  
Harderian Gland ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Ocular Tissue ◽  
Sprague Dawley ◽  
Ki 67 ◽  
Rapid Phase ◽  
Free Zone ◽  
Sd Rats

As in many altricial species, rats are born with fused eyelids and markedly underdeveloped eyes. While the normal histology of the eyes of mature rats is known, the histomorphological changes occurring during postnatal eye development in this species remain incompletely characterized. This study was conducted to describe the postnatal development of ocular structures in Sprague-Dawley (SD) rats during the first month of age using histology and immunohistochemistry (IHC). Both eyes were collected from 51 SD rats at 13 time points between postnatal day (PND)1 and PND30. Histologic examination of hematoxylin and eosin-stained sections was performed, as well as IHC for cleaved-caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) to evaluate apoptosis, and IHC for Ki-67 and phospho-histone-H3 to evaluate cell proliferation. Extensive ocular tissue remodeling occurred prior to the eyelid opening around PND14 and reflected the interplay between apoptosis and cell proliferation. Apoptosis was particularly remarkable in the maturing subcapsular anterior epithelium of the lens, the inner nuclear and ganglion cell layers of the developing retina, and the Harderian gland, and was involved in the regression of the hyaloid vasculature. Nuclear degradation in the newly formed secondary lens fibers was noteworthy after birth and was associated with TUNEL-positive nuclear remnants lining the lens organelle-free zone. Cell proliferation was marked in the developing retina, cornea, iris, ciliary body and Harderian gland. The rat eye reached histomorphological maturity at PND21 after a rapid phase of morphological changes characterized by the coexistence of cell death and proliferation.

scholarly journals Cell proliferation markers in the transplanted canine transmissible venereal tumor

2011 ◽  
Vol 63 (6) ◽  
pp. 1345-1352 ◽  
Author(s):  
F.G.A. Santos ◽  
L. Moro ◽  
G.D. Cassali ◽  
T.A. Paixão ◽  
P.P. Campos ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Mitotic Index ◽  
Proliferative Activity ◽  
The Other ◽  
Proliferation Markers ◽  
Proliferative Phase ◽  
Tumoral Cells ◽  
Argyrophilic Protein ◽  
Regressive Phase

Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT) on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10% buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67). Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.

Sign in / Sign up

Export Citation Format

Share Document