Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

Science.gov (United States)

Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

2012-09-01

Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.

Directory of Open Access Journals (Sweden)

Valentina Bizzarro

Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we have evaluated whether Annexin A1 derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions. Using normal human skin fibroblasts WS1 in low glucose (LG or high glucose (HG we observed the enrichment of Annexin A1 protein at cell movement structures like lamellipodial extrusions and interestingly, a significant decrease in levels of the protein in HG conditions. The analysis of the translocation of Annexin A1 to cell membrane showed lower levels of Annexin A1 in both membrane pool and supernatants of WS1 cells treated with HG. Wound-healing assays using cell line transfected with Annexin A1 siRNAs indicated a slowing down in migration speed of cells suggesting that Annexin A1 has a role in the migration of WS1 cells. In order to analyze the role of extracellular Annexin A1 in cell migration, we have performed wound-healing assays using Ac2-26 showing that peptide was able to increase fibroblast cell migration in HG conditions. Experiments on the mobilization of intracellular calcium and analysis of p-ERK expression confirmed the activity of the FPR1 following stimulation with the peptide Ac2-26. A wound-healing assay on WS1 cells in the presence of the FPR agonist fMLP, of the FPR antagonist CsH and in the presence of Ac2-26 indicated that Annexin A1 influences fibroblast cell migration under HG conditions acting through FPR receptors whose expression was slightly increased in HG. In conclusion, these data demonstrate that (i Annexin A1 is involved in migration of WS1 cells, through interaction with FPRs; (ii N- terminal peptide of Annexin A1 Ac2-26 is able to stimulate direct migration of WS1 cells in high glucose treatment possibly due to the increased receptor expression observed in hyperglycemia conditions.

Interleukin-6 stimulates Akt and p38 MAPK phosphorylation and fibroblast migration in non-diabetic but not diabetic mice.

Directory of Open Access Journals (Sweden)

Tsubame Nishikai-Yan Shen

Full Text Available Persistent inflammatory environment and abnormal macrophage activation are characteristics of chronic diabetic wounds. Here, we attempted to characterize the differences in macrophage activation and temporal variations in cytokine expression in diabetic and non-diabetic wounds, with a focus on interleukin (IL-6 mRNA expression and the p38 MAPK and PI3K/Akt signaling pathways. Cutaneous wound closure, CD68- and arginase-1 (Arg-1-expressing macrophages, and cytokine mRNA expression were examined in non-diabetic and streptozotocin-induced type 1 diabetic mice at different time points after injury. The effect of IL-6 on p38 MAPK and Akt phosphorylation was investigated, and an in vitro scratch assay was performed to determine the role of IL-6 in primary skin fibroblast migration. Before injury, mRNA expression levels of the inflammatory markers iNOS, IL-6, and TNF-α were higher in diabetic mice; however, IL-6 expression was significantly lower 6 h post injury in diabetic wounds than that in non-diabetic wounds. Non-diabetic wounds exhibited increased p38 MAPK and Akt phosphorylation; however, no such increase was found in diabetic wounds. In fibroblasts from non-diabetic mice, IL-6 increased the phosphorylation of p38 MAPK and levels of its downstream factor CREB, and also significantly increased Akt phosphorylation and levels of its upstream factor P13K. These effects of IL-6 were not detected in fibroblasts derived from the diabetic mice. In scratch assays, IL-6 stimulated the migration of primary cultured skin fibroblasts from the non-diabetic mice, and the inhibition of p38 MAPK was found to markedly suppress IL-6-stimulated fibroblast migration. These findings underscore the critical differences between diabetic and non-diabetic wounds in terms of macrophage activation, cytokine mRNA expression profile, and involvement of the IL-6-stimulated p38 MAPK-Akt signaling pathway. Aberrant macrophage activation and abnormalities in the cytokine m

Analysis of amenorrhea after transcatheter uterine artery embolization for uterine fibroids

International Nuclear Information System (INIS)

Chen Xiaoming; Li Yong; Lu Ligong; Hu Baoshan; Luo Pengfei; Du Juan; Zuo Yuewei; Hu Xiaoping; Hong Danhua

2005-01-01

Objective: To investigate the causes of amenorrhea after transcatheter uterine artery embolization (TUAE) for uterine fibroids. Methods: Two hundreds thirty-one cases of uterine fibroids with the range of age from 29 to 51 years (mean, 39.5 years) underwent TUAE between April 1999 and May 2004. TUAE was performed by injecting lipiodol-pingyangmycine emulsion (LPE) into bilateral uterine arteries, followed by administration of gelatin sponge particles in 186 of 231 patients. LPE was prepared with pingyangmycine 8-16 mg and ultra fluid lipiodol 6-20 ml. Results: Amenorrhea occurred in 2 of 231 (0.87%) patients respectively at 3 and 4 months after TUAE. Premature ovarian failure was proved to be etiology of amenorrhea in one patient because her serum estradiol (E 2 ) became decreased and serum follicle-stimulating hormone (FSH) level increased. This woman had normal amenorrhea later after receiving estrogen-progestogen sepuential therapy for 12 months. Another patient's amenorrhea was proved to be associated with endometrial atrophy after TUAE by hysteroscope. Conclusion: Amenorrhea caused by premature ovarian failure and endometrial atrophy may occur in a tiny minority of women undergoing TUAE. (authors)

Msx homeobox genes critically regulate embryo implantation by controlling paracrine signaling between uterine stroma and epithelium.

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Shanmugasundaram Nallasamy

Full Text Available The mammalian Msx homeobox genes, Msx1 and Msx2, encode transcription factors that control organogenesis and tissue interactions during embryonic development. We observed overlapping expression of these factors in uterine epithelial and stromal compartments of pregnant mice prior to embryo implantation. Conditional ablation of both Msx1 and Msx2 in the uterus resulted in female infertility due to a failure in implantation. In these mutant mice (Msx1/2(d/d, the uterine epithelium exhibited persistent proliferative activity and failed to attach to the embryos. Gene expression profiling of uterine epithelium and stroma of Msx1/2(d/d mice revealed an elevated expression of several members of the Wnt gene family in the preimplantation uterus. Increased canonical Wnt signaling in the stromal cells activated β-catenin, stimulating the production of a subset of fibroblast growth factors (FGFs in these cells. The secreted FGFs acted in a paracrine manner via the FGF receptors in the epithelium to promote epithelial proliferation, thereby preventing differentiation of this tissue and creating a non-receptive uterus refractory to implantation. Collectively, these findings delineate a unique signaling network, involving Msx1/2, Wnts, and FGFs, which operate in the uterus at the time of implantation to control the mesenchymal-epithelial dialogue critical for successful establishment of pregnancy.

Stromal progesterone receptors mediate induction of Indian Hedgehog (IHH) in uterine epithelium and its downstream targets in uterine stroma.

Science.gov (United States)

Simon, Liz; Spiewak, Kerry A; Ekman, Gail C; Kim, Jaeyeon; Lydon, John P; Bagchi, Milan K; Bagchi, Indrani C; DeMayo, Francesco J; Cooke, Paul S

2009-08-01

Uterine receptivity to embryo implantation depends on appropriate progesterone (P4) and estrogen stimulation. P4 rapidly stimulates production of the morphogen Indian hedgehog (IHH) in murine uterine epithelium as well as downstream molecules in the hedgehog pathway such as Patched homolog 1 (PTCH1) and nuclear receptor subfamily 2, group F, member 2 (NR2F2) in uterine stroma. Studies using IHH-null mice indicate that IHH is obligatory for the normal P4 response in the uterus. To determine whether IHH induction in uterine epithelium is mediated through P4 receptor (PR) in epithelium (E) and/or stroma (S), we produced tissue recombinants using uteri from neonatal PR knockout (ko) mice and wild-type (wt) mice containing PR in S and/or E or lacking PR altogether using a tissue recombinant methodology and assessed their response to P4. In tissue recombinants containing wt-S (wt-S + wt-E and wt-S + ko-E), P4 induced Ihh mRNA expression at 6 h that was 6-fold greater than in oil-treated controls (P Ihh mRNA expression was unaffected by P4 in ko-S + ko-E and ko-S + wt-E grafts despite epithelial PR expression in the latter. Nr2f2 and Ptch1 mRNA expression was similar in that it was stimulated by P4 only in recombinants containing stromal PR. These results indicate that stromal PR is both necessary and sufficient for P4 stimulation of epithelial IHH as well as downstream events such as PTCH1 and NR2F2 increases in stroma.

Study on the correlation of MLCK and FAP expression with uterine fibroid cell proliferation and invasion

Directory of Open Access Journals (Sweden)

Wei Lin1

2017-06-01

Full Text Available Objective: To study the correlation of myosin light chain kinase (MLCK and fibroblast activation protein (FAP expression with uterine fibroid cell proliferation and invasion. Methods: Uterine fibroids samples and normal uterine muscle samples next to fibroids that were surgically removed in Wuhan Red Cross Hospital between May 2014 and January 2017 were chosen, fluorescence quantitative PCR kits were used to deterct MLCK and FAP mRNA expression, and enzyme-linked immunosorbent assay kits were used to determine proliferation and invasion gene protein expression. Results: MLCK and FAP mRNA expression in uterine fibroids samples were significantly higher than those in normal uterine muscle samples, and Survivin, Livin, Bcl-2, Snail, N-cadherin and MMP2 protein expression were significantly higher than those in normal uterine muscle samples; Survivin, Livin, Bcl-2, Snail, N-cadherin and MMP2 protein expression in uterine fibroids samples with high MLCK and FAP expression were significantly higher than those in uterine fibroids samples with low MLCK and FAP expression. Conclusion: Highly expressed MLCK and FAP in uterine fibroids can promote the proliferation and invasion of uterine fibroids.

Uterine artery embolization for uterine fibroids: mid-long term follow up

International Nuclear Information System (INIS)

Guo Wenbo; Yang Jianyong; Chen Wei; Zhuang Wenquan; Li Lijuan; Zhu Yunxiao

2006-01-01

Objective: To evaluate the mid-long term effects of uterine fibroids embolization. Methods: Uterine artery embolization (UAE) was performed in 110 patients with uterine fibroids with follow up of 48-72 months. All the patients were examined with transvaginal color ultrasound. 51 cases were embolized with mixed liquor of lipiodol and pingyangmycin and another 59 cases with polyvinyl alcohol particles (350-700 μm, in diameter). The mid-long term clinical effects, complications, change of serum sexual hormone, pregnancy and delivery after UAE were observed. Results; Bilateral uterine artery embolization was performed in 110 cases with following outcomes in improvements of menorrhagia in 93/94 (98.9%) and the bulked-related symptoms in 26/26 (100%), decrease of the volumes of uterus 51.5% ± 3.1% (t value 2.861, P<0.01) and fibroids 64.2% ± 6.6% (t value 2.664, P<0.01). No statistical differences in serum levels of luteinizing, follicle stimulating hormone and estradiol before and after the uterine artery embolization were found. All events included abdominal pain in 6/110 (5.5%), fever in 90/110 (81.8%), colporrhagia in 95/110 (86.4%), haematuria in 11/110 (10.0%), non-targeted embolization of bladder in 1/110 (0.9%), transient amenorrhea in 3/110 (2.7%), permanent amenorrhea due to ovarian failure in 3/110 (2.7%), failure of embolization in 1/110 (0.9%) and recurrence after uterine fibroids embolization in 4/110 (3.6%). There were 7 times of pregnancies in 5 patients, including 4 times of deliveries in 4 patients, and one patient accepted artificial abortion 3 times, but with no fibroids recurrences or enlargement under ultrasound follow up. Conclusion: The mid-long term effects of uterine fibroids embolization are positive, stable and safe, but with a low recurrence rate slight ovarian functional change and still safe for pregnancy and delivery. (authors)

Uterine arterial embolization to treat uterine leiomyoma

International Nuclear Information System (INIS)

Wang Huali; Han Lu; Wang Feng

2002-01-01

Objective: To assess the clinical effects of uterine arterial embolization on uterine leiomyoma. Methods: The authors treated 21 patients with uterine leiomyoma by Seldinger's uterine arterial embolization. The 4.0 F Cobra catheter was laced into the double uterine arteries with Polyvinyl Alcohol Foam (PVA) particles as the embolization. At 3 and 6 months postoperatively, the authors investigated the effects of the embolization. Results: After uterine arterial embolization, the volume of uterine leiomyoma decreased and menorrhagia was under controlled. The symptoms of anemia and oppression were relieved. The physiologic functions of ovary and uterus were preserved completely. Conclusions: Uterine arterial embolization is an effective and less invasive way to treat uterine leiomyoma

Cerium oxide nanoparticles stimulate proliferation of primary mouse embryonic fibroblasts in vitro

Energy Technology Data Exchange (ETDEWEB)

Popov, Anton L., E-mail: antonpopovleonid@gmail.com [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Popova, Nelly R. [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Selezneva, Irina I. [Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Pushchino State Institute of Natural sciences, Pushchino, Moscow region (Russian Federation); Akkizov, Azamat Y. [Kabardino-Balkarian State University, Nalchik (Russian Federation); Ivanov, Vladimir K. [Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Moscow (Russian Federation); National Research Tomsk State University, Tomsk (Russian Federation)

2016-11-01

The increasing application of cell therapy technologies in the treatment of various diseases requires the development of new effective methods for culturing primary cells. The major limitation for the efficient use of autologous cell material is the low rate of cell proliferation. Successful cell therapy requires sufficient amounts of cell material over a short period of time with the preservation of their differentiation and proliferative potential. In this regard, the development of novel, highly efficient stimulators of proliferative activity in stem cells is a truly urgent task. In this paper we have demonstrated that citrate-stabilized cerium oxide nanoparticles (nanoceria) enhance the proliferative activity of primary mouse embryonic fibroblasts in vitro. Cerium oxide nanoparticles stimulate cell proliferation in a wide range of concentrations (10{sup −3} M–10{sup −9} M) through reduction of intracellular levels of reactive oxygen species (ROS) during the lag phase of cell growth and by modulating the expression level of the major antioxidant enzymes. We found the optimal concentration of nanoceria, which provides the greatest acceleration of cell proliferation in vitro, while maintaining the levels of intracellular ROS and mRNA of antioxidant enzymes in the physiological range. Our results confirm that nanocrystalline ceria can be considered as a basis for effective and inexpensive supplements in cell culturing. - Highlights: • Citrate-stabilized cerium oxide nanoparticles are shown to stimulate proliferation of primary embryonic cells in vitro. • Some of mechanisms involved in stimulating of the proliferation by CeO{sub 2} have been uncovered. • The most effective (optimal) concentration of CeO{sub 2} nanoparticles for stimulation of proliferation was determined.

The effect of Centella asiatica, vitamins, glycolic acid and their mixtures preparations in stimulating collagen and fibronectin synthesis in cultured human skin fibroblast.

Science.gov (United States)

Hashim, Puziah

2014-03-01

Centella asiatica (Linn.) Urban is well known in promoting wound healing and provides significant benefits in skin care and therapeutic products formulation. Glycolic acid and vitamins also play a role in the enhancement of collagen and fibronectin synthesis. Here, we evaluate the specific effect of Centella asiatica (CA), vitamins, glycolic acid and their mixture preparations to stimulate collagen and fibronectin synthesis in cultured human fibroblast cells. The fibroblast cells are incubated with CA, glycolic acid, vitamins and their mixture preparations for 48 h. The cell lysates were analyzed for protein content and collagen synthesis by direct binding enzyme immunoassay. The fibronectin of the cultured supernatant was measured by sandwich enzyme immunoassay. The results showed that CA, glycolic acid, vitamins A, E and C significantly stimulate collagen and fibronectin synthesis in the fibroblast. Addition of glycolic acid and vitamins to CA further increased the levels of collagen and fibronectin synthesis to 8.55 and 23.75 μg/100 μg, respectively. CA, glycolic acid, vitamins A, E, and C, and their mixtures demonstrated stimulatory effect on both extra-cellular matrix synthesis of collagen and fibronectin in in vitro studies on human foreskin fibroblasts, which is beneficial to skin care and therapeutic products formulation.

Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes

DEFF Research Database (Denmark)

Grøn, Birgitte; Stoltze, Kaj; Andersson, Anders

2002-01-01

The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations...... days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When...... cells were maintained in collagen, the level of HGF and KGF was decreased mainly in skin cultures. However, in oral fibroblasts, induction after stimulation was at a similar level in collagen compared to on polystyrene. Skin fibroblasts maintained in collagen produced almost no HGF whether...

Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

Science.gov (United States)

Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

2012-06-01

Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

International Nuclear Information System (INIS)

Story, M.T.

1989-01-01

To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue

Influence of a ras oncogene on platelet-derived growth factor (PDGF)-stimulated phosphoinositide hydrolysis in murine fibroblasts

International Nuclear Information System (INIS)

Parries, G.; Racker, E.

1986-01-01

The authors have examined the effects of transfection of rat-1 fibroblasts with the ras oncogene on the metabolism of phosphatidylinositol (PI). Incubation of [ 3 H]inositol-labeled rat-1 cells with PDGF resulted in a 2- to 3-fold increase in [ 3 H]IP3 levels within 90 s. In the presence of 25 mM Li+, [ 3 H]IP1 levels were increased 8-fold after 30 min. In contrast, incubation of ras-transfected fibroblasts (EJ-2 line) with PDGF had little or no effect on the level of either [ 3 H]IP3 or [ 3 H]IP1. Similar stimulations by PDGF were observed in NIH 3T3 cells, but not in Kirsten virus-transformed or Harvey ras-transfected cell lines. On the other hand, NIH 3T3 cells transfected with v-src responded to PDGF by stimulation of PI turnover similar to the parent cell line. In NIH 3T3 cells transfected with an expression vector containing the v-Ha-ras gene under transcriptional control of the glucocorticoid-inducible mouse mammary tumor virus promoter, the PDGF stimulation of [ 3 H]inositol incorporation into PI was reduced from 10-fold in the absence of dexamethasone to 1.8-fold when the cells were pretreated for 26 h with 2 μM dexamethasone. In the parental 3T3 cells PDGF stimulation was reduced by about 40% in the presence of dexamethasone. In the absence of PDGF the rate of PI turnover (i.e., the kinetics of [ 3 H]IP1 accumulation in the presence of Li+) in EJ-2 cells was similar to that in rat-1 cells. Thus, in the presence of PDGF, the rate of PI turnover in rat-1 cells was several fold higher than in the transfected cells. These results suggest that the ras gene product (p21) may exert an inhibitory effect on PDGF-stimulated phosphoinositide metabolism

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

2016-07-08

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

International Nuclear Information System (INIS)

Fan, Rong-hui; Zhu, Xiu-mei; Sun, Yao-wen; Peng, Hui-zi; Wu, Hang-li; Gao, Wen-jie

2016-01-01

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

The effects of acoustic vibration on fibroblast cell migration.

Science.gov (United States)

Mohammed, Taybia; Murphy, Mark F; Lilley, Francis; Burton, David R; Bezombes, Frederic

2016-12-01

Cells are known to interact and respond to external mechanical cues and recent work has shown that application of mechanical stimulation, delivered via acoustic vibration, can be used to control complex cell behaviours. Fibroblast cells are known to respond to physical cues generated in the extracellular matrix and it is thought that such cues are important regulators of the wound healing process. Many conditions are associated with poor wound healing, so there is need for treatments/interventions, which can help accelerate the wound healing process. The primary aim of this research was to investigate the effects of mechanical stimulation upon the migratory and morphological properties of two different fibroblast cells namely; human lung fibroblast cells (LL24) and subcutaneous areolar/adipose mouse fibroblast cells (L929). Using a speaker-based system, the effects of mechanical stimulation (0-1600Hz for 5min) on the mean cell migration distance (μm) and actin organisation was investigated. The results show that 100Hz acoustic vibration enhanced cell migration for both cell lines whereas acoustic vibration above 100Hz was found to decrease cell migration in a frequency dependent manner. Mechanical stimulation was also found to promote changes to the morphology of both cell lines, particularly the formation of lamellipodia and filopodia. Overall lamellipodia was the most prominent actin structure displayed by the lung cell (LL24), whereas filopodia was the most prominent actin feature displayed by the fibroblast derived from subcutaneous areolar/adipose tissue. Mechanical stimulation at all the frequencies used here was found not to affect cell viability. These results suggest that low-frequency acoustic vibration may be used as a tool to manipulate the mechanosensitivity of cells to promote cell migration. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of polyhexamethylene guanidine phosphate on human gingival fibroblasts.

Science.gov (United States)

Vitt, Anton; Slizen, Veronica; Boström, Elisabeth A; Yucel-Lindberg, Tülay; Kats, Anna; Sugars, Rachael V; Gustafsson, Anders; Buhlin, Kåre

2017-10-01

Polyhexamethylene guanidine phosphate (PHMG-P) was compared to chlorhexidine (CHX) in order to determine potential cytotoxic and immune-modulatory effects on human gingival fibroblasts. Cytotoxic effects of PHMG-P and CHX on human gingival fibroblasts were assessed using cell viability assay at various time points and concentrations. The effects of PHMG-P and CHX on the secretion of prostaglandin (PG) E 2 , interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP)-1 by non-stimulated or IL-1β stimulated fibroblasts were evaluated by enzyme-linked immunosorbent assays. PHMG-P concentration 0.00009% led to the total loss of fibroblast viability within 24 h, whereas inhibition of fibroblast viability by CHX occurred at significantly higher concentrations of 0.0009% (p PHMG-P led to loss of fibroblast viability after 5 min, whilst cells exposed to 0.005% CHX survived 30 min of treatment (p PHMG-P or CHX at concentrations of 0.000045 or 0.0.00009% resulted in significantly decreased PGE 2 , IL-6, IL-8 and MMP-1 levels. PHMG-P or CHX alone did not affect the baseline secretion of PGE 2 , IL-6, IL-8 or MMP-1 by gingival fibroblasts. Cytotoxic effects on gingival fibroblasts were triggered by both PHMG-P and CHX at concentrations below those used in clinical practice. The tested antiseptics did not cause inflammation and reduced IL-1β-induced secretion of inflammatory mediators and collagenase by gingival fibroblasts, which suggests anti-inflammatory properties.

N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

LENUS (Irish Health Repository)

Burke, John P

2012-02-01

BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn\\'s disease (CD). Transforming growth factor-beta (TGF-beta) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-beta and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho\\/ROCK, ERK-1\\/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-beta induced N-cadherin in a dose-dependent manner which was inhibited by Rho\\/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-beta or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn\\'s stricture formation.

Regulation of HGF and SDF-1 expression by oral fibroblasts--implications for invasion of oral cancer.

Science.gov (United States)

Daly, Aisling J; McIlreavey, Leanne; Irwin, Chris R

2008-07-01

Invasion and metastasis of oral squamous cell carcinoma (OSCC) is dependent on signals received from stromal fibroblasts present in the surrounding connective tissue. The aim of this study was to investigate the regulation of expression of two important signaling molecules--HGF and SDF-1--by both stromal fibroblasts and their 'activated' form, myofibroblasts, and to determine the role of these two factors in stimulating OSCC cell invasion in vitro. Fibroblasts and myofibroblasts produced similar levels of HGF and SDF-1. IL-1alpha and OSCC cell conditioned medium both stimulated HGF and SDF-1 expression, while TGF-beta(1) inhibited production of each factor. Myofibroblast-derived conditioned medium stimulated OSCC cell invasion through matrigel. Blocking antibodies to both HGF and SDF-1 reduced the level of invasion. In fibroblast-free organotypic raft cultures, addition of HGF and SDF-1 stimulated OSCC cell invasion into the underlying collagen gel, although the pattern of invasion differed from that induced by fibroblasts. Fibroblast-derived HGF and SDF-1 appear to play central roles in the reciprocal interactions between OSCC cells and underlying stromal fibroblasts leading to the local invasion of oral cancer.

Uterine endometrial stromal sarcoma located in uterine myometrium: MRI appearance

Energy Technology Data Exchange (ETDEWEB)

Ueda, M.; Otsuka, M.; Hatakenaka, M. [Dept. of Radiology, Medical Institute of Bioregulation, Kyushu University, Beppu (Japan); Torii, Y. [Dept. of Radiology, Saga Prefectural Hospital (Japan)

2000-05-01

Two cases of uterine endometrial stromal sarcoma whose main mass was located in uterine myometrium are reported. They mimicked uterine leiomyoma with cystic degeneration or uterine leiomyosarcoma. Endometrial stromal sarcoma should be suggested in the differential diagnosis of mass lesion in uterine myometrium. (orig.)

TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

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Chen, Xiao-Qing; Zhang, Dao-Liang [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-Feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhao, Liang, E-mail: zhaol_zg@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Wang, Quan-Xing, E-mail: wqxejd@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Liu, Xu, E-mail: liuxu_xk@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China)

2015-08-14

Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage.

TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

International Nuclear Information System (INIS)

Chen, Xiao-Qing; Zhang, Dao-Liang; Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang; Jiang, Wei-Feng; Zhou, Li; Zhao, Liang; Wang, Quan-Xing; Liu, Xu

2015-01-01

Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage

SIRT-1 regulates TGF-β-induced dermal fibroblast migration via modulation of Cyr61 expression.

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Kwon, Eun-Jeong; Park, Eun-Jung; Yu, Hyeran; Huh, Jung-Sik; Kim, Jinseok; Cho, Moonjae

2018-05-01

SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression. Treatment with resveratrol (RSV), a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in human dermal fibroblasts, whereas the inhibition of SIRT1 activity by nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF-β or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509 reduced the expression of Cyr61 induced by TGF-β or RSV. TGF-β, RSV, or SIRT1 overexpression enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1 increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/β-catenin signaling. SIRT1-induced Cyr61 activity is very important for human dermal fibroblasts migration.

I. Lipid metabolism stimulated by altered intracellular calcium in cultured fibroblasts. II. Regulation of the activity of rat adipose tissue lipoprotein lipase

International Nuclear Information System (INIS)

Chang Wang, Huei-Hsiang Lisa.

1988-01-01

The cell killing process of 3T3 Swiss mouse fibroblasts stimulated by Ca 2+ plus A23187, a Ca 2+ ionophore has been studied. The aim of this research is to understand the biochemical mechanism of this process, i.e, to elucidate the step involved and to characterize the enzymes involved with each steps in the lipid metabolism stimulated in cultured fibroblasts undergoing a toxic death response. Parallel 3T3 cultures biosynthetically labeled with lipid precursors were examined under Ca 2+ -mediated killing conditions. Labeled lipids were extracted and analyzed by thin-layer chromatography and autoradiography. Evidence for activation of a phosphatidylinositol-specific phospholipase C has been obtained in injured 3T3 cells labeled with [ 3 H]glycerol and [ 3 H]inositol. To simplify the system for studying the lipoprotein lipase reaction, our laboratory prepared the chromophore containing a substrate: 1,2-dipalmitoyl-3-β-2-furylacryloyltriacylglycerol (DPFATG). By using this artificial lipid we could readily investigate the lipoprotein lipase reactions, since the absorbance change directly represents the hydrolysis of the chromophoric side chain of the substrate

Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model.

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Gao, Yang; Li, Shu; Li, Qinglei

2014-08-01

In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-β (TGF-β) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-β signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-β (Tgfbr1) using anti-Müllerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-β1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stimulation of MMP-11 (stromelysin-3) expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

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Selvey, Saxon; Haupt, Larisa M; Thompson, Erik W; Matthaei, Klaus I; Irving, Michael G; Griffiths, Lyn R

2004-01-01

Matrix metalloproteinases (MMPs) are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14) and stromelysin-3 (MMP-11) are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs) were: a) treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b) grown on collagens I, IV and V; c) treated with fibronectin, con-A and matrigel; and d) co-cultured with a range of HBC (human breast cancer) cell lines of varied invasive and metastatic potential. Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms

Stimulation of MMP-11 (stromelysin-3 expression in mouse fibroblasts by cytokines, collagen and co-culture with human breast cancer cell lines

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Matthaei Klaus I

2004-07-01

Full Text Available Abstract Background Matrix metalloproteinases (MMPs are central to degradation of the extracellular matrix and basement membrane during both normal and carcinogenic tissue remodeling. MT1-MMP (MMP-14 and stromelysin-3 (MMP-11 are two members of the MMP family of proteolytic enzymes that have been specifically implicated in breast cancer progression. Expressed in stromal fibroblasts adjacent to epithelial tumour cells, the mechanism of MT1-MMP and MMP-11 induction remains unknown. Methods To investigate possible mechanisms of induction, we examined the effects of a number of plausible regulatory agents and treatments that may physiologically influence MMP expression during tumour progression. Thus NIH3T3 and primary mouse embryonic fibroblasts (MEFs were: a treated with the cytokines IL-1β, IL-2, IL-6, IL-8 and TGF-β for 3, 6, 12, 24, and 48 hours; b grown on collagens I, IV and V; c treated with fibronectin, con-A and matrigel; and d co-cultured with a range of HBC (human breast cancer cell lines of varied invasive and metastatic potential. Results Competitive quantitative RT-PCR indicated that MMP-11 expression was stimulated to a level greater than 100%, by 48 hour treatments of IL-1β, IL-2, TGF-β, fibronectin and collagen V. No other substantial changes in expression of MMP-11 or MT1-MMP in either tested fibroblast culture, under any treatment conditions, were observed. Conclusion We have demonstrated significant MMP-11 stimulation in mouse fibroblasts using cytokines, matrix constituents and HBC cell lines, and also some inhibition of MT1-MMP. Our data suggest that the regulation of these genes in the complex stromal-epithelial interactions that occur in human breast carcinoma, is influenced by several mechanisms.

Platelets stimulate fibroblast-mediated contraction of collagen gels

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Lundahl Joachim

2003-10-01

Full Text Available Abstract Background Platelets are thought to play a role in a variety of inflammatory conditions in the lung, some of which may lead to fibrosis. In the current study we tested the hypothesis that whole platelets and platelet lysate can mediate remodelling of extracellular matrix in vitro by affecting fibroblast-mediated contraction of a collagen gel. We also sought to determine to what extent platelet-derived growth factor (PDGF and transforming growth factor-β (TGF-β contribute to this effect. Methods Washed platelets, isolated from healthy blood donors, and platelet lysate (freezing and thawing, were cast together with human lung fibroblasts in three-dimensional collagen gels. The gels were then released and cultured for four days. PDGF and TGF-β1 concentrations were measured in culture supernatants by ELISA. Results Both platelets and platelet lysate augmented fibroblast-mediated gel contraction in a time and concentration dependent manner (19.9% ± 0.1 (mean ± SEM of initial area vs. 48.0% ± 0.4 at 48 hours; P 1 and PDGF-AA/AB were released in co-culture. PDGF-AA/AB had a maximum release at 24 hours whereas TGF-β1 release increased with longer culture periods. Neutralising antibodies to these mediators partially inhibited platelet-induced gel contraction. Conclusion We conclude that platelets may promote remodelling of extracellular matrix in vitro and that PDGF and TGF-β partially mediate this effect, also indicating a role for other mediators. The findings may be an important mechanism in regulating repair processes after injury.

Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts

DEFF Research Database (Denmark)

Dabelsteen, S; Wandall, H H; Grøn, B

1997-01-01

Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is expres......Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF m......RNA is expressed in periodontal ligament fibroblasts, and that the expression is increased upon serum stimulation. Fibroblasts from human periodontal ligament, from buccal mucosa, from gingiva, and from skin were established from explants. Alkaline phosphatase activity was used as an indicator of the periodontal...

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

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Toshiki Hirakawa

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs, the expression of insulin-like growth factor-1 (IGF1 and IGF1 receptor (IGF1R was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9 was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2 and hypoxia (1% O2. IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

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Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

2011-08-01

Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

Uterine artery embolization to treat uterine fibroids

International Nuclear Information System (INIS)

Machan, L.; Martin, M.

2001-01-01

The first reported application of uterine artery embolization, in 1979, was to treat life-threatening hemorrhage after a failed hysterectomy. Since then, uterine artery embolization has been used very successfully to control acute or delayed post-partum hemorrhage, post-surgical hemorrhage and hemorrhage from ectopic pregnancy, to treat uterine arteriovenous malformations and as prophylaxis before high-risk surgery, such as cesarean delivery in women with placenta previa. In contrast to these proven but underutilized applications, uterine embolization for fibroids has, in a short time, achieved significant notice in the lay press and is being widely offered. Ravina and colleagues, first reported uterine fibroid shrinkage after embolization for the treatment of acute bleeding. Since then, his group has performed over 100 procedures with up to a 6-year follow-up. The cumulative clinical success rate for the treatment of abnormal uterine bleeding due to fibroids is reported to be approximately 85% and for treatment of pain or pressure symptoms, about 75%. Six-month follow-up sonography reveals an average reduction of fibroid size of approximately 40%. However, to date, no studies have compared patients who undergo embolization with a nontreatment cohort or with surgical intervention. (author)

Uterine artery embolization to treat uterine fibroids

Energy Technology Data Exchange (ETDEWEB)

Machan, L.; Martin, M. [Univ. of British Columbia Hospital, Dept. of Radiology, Vancouver, BC (Canada)

2001-06-01

The first reported application of uterine artery embolization, in 1979, was to treat life-threatening hemorrhage after a failed hysterectomy. Since then, uterine artery embolization has been used very successfully to control acute or delayed post-partum hemorrhage, post-surgical hemorrhage and hemorrhage from ectopic pregnancy, to treat uterine arteriovenous malformations and as prophylaxis before high-risk surgery, such as cesarean delivery in women with placenta previa. In contrast to these proven but underutilized applications, uterine embolization for fibroids has, in a short time, achieved significant notice in the lay press and is being widely offered. Ravina and colleagues, first reported uterine fibroid shrinkage after embolization for the treatment of acute bleeding. Since then, his group has performed over 100 procedures with up to a 6-year follow-up. The cumulative clinical success rate for the treatment of abnormal uterine bleeding due to fibroids is reported to be approximately 85% and for treatment of pain or pressure symptoms, about 75%. Six-month follow-up sonography reveals an average reduction of fibroid size of approximately 40%. However, to date, no studies have compared patients who undergo embolization with a nontreatment cohort or with surgical intervention. (author)

PAMPs and DAMPs stimulate the expression of pro-inflammatory cytokines in vitro in a fibroblast cell-line from rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Ingerslev, Hans-Christian; Ossum, CarlobG.; Nielsen, Michael Engelbrecht

The recognition of PAMPs by immune cells relies on conserved PRRs such as TLRs, NLRs and RLRs leading to activation of NFκB signalling pathways. These receptors are activated upon stimulation by different ligands such as bacterial or viral components. The binding of ligands to the receptors...... in this evolutionary lineage of the bony fishes. The expression of TLR-3 and -9 receptors were significantly up-regulated following physical damage of muscle tissue as well as in stimulated fibroblasts, where LPS induced both TLR-3 and -9, supernatant from sonicated cells only TLR-9 while debris caused no induction...

Evodiamine attenuates TGF-β1-induced fibroblast activation and endothelial to mesenchymal transition.

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Wu, Qing-Qing; Xiao, Yang; Jiang, Xiao-Han; Yuan, Yuan; Yang, Zheng; Chang, Wei; Bian, Zhou-Yan; Tang, Qi-Zhu

2017-06-01

The aim of this study is to investigate the effect of evodiamine on fibroblast activation in cardiac fibroblasts and endothelial to mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs). Neonatal rat cardiac fibroblasts were stimulated with transforming growth factor beta 1 (TGF-β1) to induce fibroblast activation. After co-cultured with evodiamine (5, 10 μM), the proliferation and pro-fibrotic proteins expression of cardiac fibroblasts were evaluated. HUVECs were also stimulated with TGF-β1 to induce EndMT and treated with evodiamine (5, 10 μM) at the same time. The EndMT response in the HUVECs was evaluated as well as the capacity of the transitioned endothelial cells migrating to surrounding tissue. As a result, Evodiamine-blunted TGF-β1 induced activation of cardiac fibroblast into myofibroblast as assessed by the decreased expressions of α-SMA. Furthermore, evodiamine reduced the increased protein expression of fibrosis markers in neonatal and adult rat cardiac fibroblasts induced by TGF-β1. HUVECs stimulated with TGF-β1 exhibited lower expression levels of CD31, CD34, and higher levels of α-SMA, vimentin than the control cells. This phenotype was eliminated in the HUVECs treated with both 5 and 10 μM evodiamine. Evodiamine significantly reduced the increase in migration ability that occurred in response to TGF-β1 in HUVECs. In addition, the activation of Smad2, Smad3, ERK1/2, and Akt, and the nuclear translocation of Smad4 in both cardiac fibroblasts and HUVEC were blocked by evodiamine treatment. Thus, evodiamine could prevent cardiac fibroblasts from activation into myofibroblast and protect HUVEC against EndMT. These effects may be mediated by inhibition of the TGFβ pathway in both cardiac fibroblasts and HUVECs.

Therapeutic efficacy of uterine arterial embolization for intractable uterine hemorrhage

International Nuclear Information System (INIS)

Liu Lang; Lu Lianwei; Ke Mengjia; Zhao Ru'en; Zeng Shaolan

2010-01-01

Objective: To evaluate the therapeutic efficacy of uterine arterial embolization (UAE) for intractable uterine hemorrhage. Methods: 16 patients with intractable uterine hemorrhage underwent bilateral UAE after failed conventional conservative treatment. Results: Uterine hemorrhage ceased within 12 hours in 15 patients (93.8%) after bilateral super-selective UAE. Internal iliac artery embolization was performed on one patient (6.2%) and hysterectomy was eventually carried out because of recurrent hemorrhage. Conclusion: UAE is a rapid and effective treatment method obviating hysterectomy for intractable uterine hemorrhage. (authors)

Uterine contraction induced by Ghanaian plants used to induce abortion

DEFF Research Database (Denmark)

Larsen, Birgitte HV; Soelberg, Jens; Kristiansen, Uffe

2016-01-01

Ethnomedicinal observations from the time of the Atlantic slave trade show women in Ghana historically used plants as emmenagogues (menstruation stimulants) and to induce abortion. This study investigates the effect of four of these plants on uterine contraction. The historically used plants were...

Boron nitride nanotube-mediated stimulation modulates F/G-actin ratio and mechanical properties of human dermal fibroblasts

Science.gov (United States)

Ricotti, Leonardo; das Neves, Ricardo Pires; Ciofani, Gianni; Canale, Claudio; Nitti, Simone; Mattoli, Virgilio; Mazzolai, Barbara; Ferreira, Lino; Menciassi, Arianna

2014-02-01

F/G-actin ratio modulation is known to have an important role in many cell functions and in the regulation of specific cell behaviors. Several attempts have been made in the latest decades to finely control actin production and polymerization, in order to promote certain cell responses. In this paper we demonstrate the possibility of modulating F/G-actin ratio and mechanical properties of normal human dermal fibroblasts by using boron nitride nanotubes dispersed in the culture medium and by stimulating them with ultrasound transducers. Increasing concentrations of nanotubes were tested with the cells, without any evidence of cytotoxicity up to 10 μg/ml concentration of nanoparticles. Cells treated with nanoparticles and ultrasound stimulation showed a significantly higher F/G-actin ratio in comparison with the controls, as well as a higher Young's modulus. Assessment of Cdc42 activity revealed that actin nucleation/polymerization pathways, involving Rho GTPases, are probably influenced by nanotube-mediated stimulation, but they do not play a primary role in the significant increase of F/G-actin ratio of treated cells, such effect being mainly due to actin overexpression.

Sialylation regulates myofibroblast differentiation of human skin fibroblasts.

Science.gov (United States)

Sasaki, Norihiko; Itakura, Yoko; Toyoda, Masashi

2017-04-18

Fibroblasts are key players in maintaining skin homeostasis and in orchestrating physiological tissue repair and skin regeneration. Dysfunctions in fibroblasts that occur with aging and the senescent process lead to the delayed healing observed in elderly people. The molecular mechanisms leading to fibroblast dysfunction during aging and the senescent process have not yet been clarified. Previously, changes in patterns of glycosylation were observed in fibroblasts in aging and the senescent process, but the effect of these changes on the function of fibroblasts has not been well documented. Here, we investigated whether changes in glycosylation during the process to senescence may have functional effects on fibroblasts. The changes in cell surface glycans on skin fibroblasts during the process to senescence were examined in early-passage (EP) and late-passage (LP) skin fibroblasts by fluorescence-activated cell sorting analysis using lectins. The contributors to the changes in cell surface glycans were examined by real-time polymerase chain reaction or Western blot analysis. The effects of changes in glycosylation on proliferation, migration, induction of cellular senescence, and myofibroblast differentiation induced by transforming growth factor (TGF)-β1 stimulation were examined in EP fibroblasts. The changes in glycosylation were performed by GalNAc-α-O-benzyl or sialidase treatment. A decrease in sialylation of glycoproteins and an increase in sialidase NEU1 were observed in LP fibroblasts. The reduction of sialylation did not have any effect on proliferation, migration, or induction of cellular senescence. On the other hand, myofibroblast differentiation was inhibited by the reduction of sialylation, indicating that sialylation is important for myofibroblast differentiation. The localization of CD44 in lipid rafts, which is required for myofibroblast differentiation, was inhibited by the reduction of sialylation. Furthermore, reduced myofibroblast

Super selective uterine arterio-embolization in treating uterine myoma

International Nuclear Information System (INIS)

Gu Yaqin; Wang Jiangu; Shang Jinyun; Zhang Jian; Zhang Rulan; Tan Yuedi; Zhao Zehua; Xu Chongsen

2001-01-01

Objective: To study the clinical efficacy of super selective uterine arterio-embolization in treating uterine myoma. Methods: From February to August 2000, 28 cases of uterine myomas were under-gone bilateral arterio-embolization of tumor feeding vessels. Results: The successful rate of embolization catheterization reached 100%. B-mode ultrasound examination revealed the following during 1-6 months after the procedure, with an average shrinkage of 25% in volume for all cases in the first month follow up, complete disappearance of tumor in 8 cases and with an average shrinkage of 68% volumetrically for the other 20 cases, together with conspicuous decrease in volume of menstruation. Conclusions: Interventional treatment for uterine myoma is definite effective especially in submucosal uterine myoma

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

Science.gov (United States)

Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

2013-01-01

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

Directory of Open Access Journals (Sweden)

Elaine Hatanaka

Full Text Available The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

Uterine Artery Anatomy Relevant to Uterine Leiomyomata Embolization

International Nuclear Information System (INIS)

Gomez-Jorge, Jackeline; Keyoung, Andrew; Levy, Elliot B.; Spies, James B.

2003-01-01

To categorize the anatomic variants of uterine arteries, and determine the incidence of menopausal symptoms where the tubo-ovarian branches were seen prior to embolization. Between July 1997 and June 2000, 257 (n = 257) uterine fibroid embolizations were performed at our institution. Arteriograms were retrospectively evaluated. Uterine arteries were classified into groups: type I (the uterine artery as first branch of the inferior gluteal artery), type II (the uterine artery as second or third branch of the inferior gluteal artery), type III (the uterine artery, the inferior gluteal and the superior gluteal arteries arising as a trifurcation), type IV (the uterine artery as first branch of the hypogastric artery), inconclusive, or not studied. Tubo-ovarian branches were recorded if visualized prior to and/or after embolization. Menopausal symptoms were recorded (n = 175 at 3 months, n = 139 at 6 months, n = 98 at 1 year, n = 22 at 2 years) using written questionnaires. Five hundred and fourteen uterine arteries (n = 514) were evaluated. There were 38% classifiable types, 23% inconclusive, and 39% not studied. Classification was as follows: type I, 45%; type II, 6%; type III, 43%; type IV, 6%. Among 256 patients, tubo-ovarian arteries were seen in 36 prior to embolization, but not afterwards. In this group, 25 patients reported transient menopausal symptoms (hot flashes, amenorrhea). Five patients did not report any menopausal symptoms. Six patients did not answer the questionnaires. Type I is the most common type of anatomy, followed by type III. The tubo-ovarian arteries may be visualized prior to and/or after embolization. The embolization was monitored to avoid embolization of the tubo-ovarian branches. Menopausal symptoms were transient all patients when the tubo-ovarian branches were seen prior to embolization

Emmprin, released as a microvesicle in epithelioid sarcoma, interacts with fibroblasts.

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Aoki, Mikiko; Koga, Kaori; Hamasaki, Makoto; Egawa, Nagayasu; Nabeshima, Kazuki

2017-06-01

Emmprin (extracellular matrix metalloproteinase inducer, CD147) is a glycosylated transmembrane protein, consisting of two immunoglobulin domains, that stimulates the production of matrix metalloproteinases (MMPs) by tumor-associated fibroblasts. These effects play important roles in tumor invasion and metastasis. However, the precise mechanisms by which emmprin acts on fibroblasts have not been fully elucidated, especially in sarcoma cells. Previously, we demonstrated that emmprin, expressed in conditioned medium collected from the epithelioid sarcoma cell line (FU-EPS-1), stimulates MMP-2 production via interactions with fibroblasts. In this study, we used microvesicles derived from sarcoma cells, and determined whether emmprin exists in the microvesicles, which enhance the production of MMP-2 via fibroblasts. Microvesicles released from FU-EPS-1 cells were shown to contain full-length emmprin, identified as a 45-kDa protein characterized by polylactosamine glycosylation. Microvesicles collected from FU-EPS-1 cells transfected with emmprin-specific siRNA or transduced with shRNA displayed significantly reduced MMP-2 production by fibroblasts compared with those from control-transfected cells. Our findings show that emmprin is released through microvesicle shedding in sarcoma cells, and emmprin in microvesicles regulates MMP-2 production by influencing the activity of fibroblasts located at sites distant from the tumor cells.

Abnormal uterine bleeding

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Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www. ...

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

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Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

2015-06-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

Leptin and Pro-Inflammatory Stimuli Synergistically Upregulate MMP-1 and MMP-3 Secretion in Human Gingival Fibroblasts.

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Rachel C Williams

Full Text Available Gingival fibroblast-mediated extracellular matrix remodelling is implicated in the pathogenesis of periodontitis, yet the stimuli that regulate this response are not fully understood. The immunoregulatory adipokine leptin is detectable in the gingiva, human gingival fibroblasts express functional leptin receptor mRNA and leptin is known to regulate extracellular matrix remodelling responses in cardiac fibroblasts. We therefore hypothesised that leptin would enhance matrix metalloproteinase secretion in human gingival fibroblasts.We used in vitro cell culture to investigate leptin signalling and the effect of leptin on mRNA and protein expression in human gingival fibroblasts. We confirmed human gingival fibroblasts expressed cell surface leptin receptor, found leptin increased matrix metalloproteinase-1, -3, -8 and -14 expression in human gingival fibroblasts compared to unstimulated cells, and observed that leptin stimulation activated MAPK, STAT1/3 and Akt signalling in human gingival fibroblasts. Furthermore, leptin synergised with IL-1 or the TLR2 agonist pam2CSK4 to markedly enhance matrix metalloproteinase-1 and -3 production by human gingival fibroblasts. Signalling pathway inhibition demonstrated ERK was required for leptin-stimulated matrix metalloproteinase-1 expression in human gingival fibroblasts; whilst ERK, JNK, p38 and STAT3 were required for leptin+IL-1- and leptin+pam2CSK4-induced matrix metalloproteinase-1 expression. A genome-wide expression array and gene ontology analysis confirmed genes differentially expressed in leptin+IL-1-stimulated human gingival fibroblasts (compared to unstimulated cells were enriched for extracellular matrix organisation and disassembly, and revealed that matrix metalloproteinase-8 and -12 were also synergistically upregulated by leptin+IL-1 in human gingival fibroblasts.We conclude that leptin selectively enhances the expression and secretion of certain matrix metalloproteinases in human gingival

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

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Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

2010-01-01

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

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Filomena M Carvalho

2010-01-01

Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

Uterine arterial embolization for uterine leiomyoma: efficacy and clinical outcome

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Park, Jeong Seon; Lee, Do Yon; Kim, Yong Tae; Park, Ki Hyun; Park, Yong Won; Cho, Jae Sung; Kim, Myung Jun; Won, Je Hwan; Kang, Byung Chul

1999-01-01

To determine the efficacy and clinical outcome of uterine arterial embolization as a new approach to the management of uterine leiomyomas. Uterine arterial embolization was performed in 21 patients aged 26-62(mean, 42) years. Twenty of these had menorrhagia, dysmenorrhea, and mass-related symptoms (low abdominal discomfort, backache, urinary frequency, etc.) and one was diagnosed incidentally. Bilateral uterine arteries were selected individually and polyvinyl alcohol and/or gelfoam was used as an embolic material. Nineteen patients were followed up after embolization. Seventeen (89.5 %)reported satisfactory improvement of symptoms and follow-up sonography three months later showed a 58.5 % reduction in mean myoma volume. In 17 patients (89.5 %), the menstrual cycle returned to normal. All patients experienced pain after the procedure and other complications were vaginal bleeding (26.3 %) and fever (23.8 %). Uterine arterial embolization represents a new approach to the management of uterine leiomyoma-related symptoms. Further investigations and long-term follow-up are, however, enquired

Uterine arterial embolization for uterine leiomyoma: efficacy and clinical outcome

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Park, Jeong Seon; Lee, Do Yon; Kim, Yong Tae; Park, Ki Hyun; Park, Yong Won; Cho, Jae Sung; Kim, Myung Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of); Won, Je Hwan [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Kang, Byung Chul [Ewha Womans Univ. College of Medicine, Seoul (Korea, Republic of)

1999-09-01

To determine the efficacy and clinical outcome of uterine arterial embolization as a new approach to the management of uterine leiomyomas. Uterine arterial embolization was performed in 21 patients aged 26-62(mean, 42) years. Twenty of these had menorrhagia, dysmenorrhea, and mass-related symptoms (low abdominal discomfort, backache, urinary frequency, etc.) and one was diagnosed incidentally. Bilateral uterine arteries were selected individually and polyvinyl alcohol and/or gelfoam was used as an embolic material. Nineteen patients were followed up after embolization. Seventeen (89.5 %)reported satisfactory improvement of symptoms and follow-up sonography three months later showed a 58.5 % reduction in mean myoma volume. In 17 patients (89.5 %), the menstrual cycle returned to normal. All patients experienced pain after the procedure and other complications were vaginal bleeding (26.3 %) and fever (23.8 %). Uterine arterial embolization represents a new approach to the management of uterine leiomyoma-related symptoms. Further investigations and long-term follow-up are, however, enquired.

Induction of growth stimulation in skin fibroblasts from retinoblastoma donors after ionizing radiation

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Diatloff-Zito, C.; Macieira-Coelho, A.; Turleau, C.; Cabanis, M.O.; Grouchy, J. de

1983-01-01

Skin fibroblasts from normal children and two children with a 13q14 deletion retinoblastoma (Rb) were submitted to fractionated doses of γ radiations. Irradiation reduced the population doublings in normal fibroblasts and the decline was inversely related to the dose. An increase in population doublings was obtained with one of the Rb cell lines. Foci appeared in the irradiated culture of the other Rb donor. It is suggested that fibroblasts from patients with Rb are able to express some phenotypical properties of transformed cells, perhaps related to factors rendering them more susceptible to carcinogens [fr

Uterine artery embolization with Pingyangmycin lipiodol emulsion for treatment of symptomatic uterine fibroids

International Nuclear Information System (INIS)

Li Yanhao; Liu Biao; Zeng Qingle; Jiang Zhongpu; Chen Yong; Huang Weilang; Shen Qi; Zhao Zhongqing

2000-01-01

Objective: To evaluate the effectiveness and side effects of uterine arterial embolization with Pingyangmycin(a homogenous bleomycin) lipiodol emulsion(PLE) for symptomatic uterine fibroids. Methods: Uterine arterial embolization with PLE was performed in 25 patients. The improvement of symptoms and uterine size changes were followed up in 3-18 months(mean 6 months) after the procedure. Results: All but 2 cases were successfully treated bilaterally. Super-selective angiography showed enlargement of uterine artery, accompanied by tortuous branches. The uterine size was increased. The uterus itself was significantly stained and emptied slowly. Coagulation necrosis was found in resected fibroids after embolization in 3 patients. One month after the procedure, a mean 40% reduction of uterine volume was obtained in 18 followed-up cases. The clinical symptoms were relieved significantly. The main side effects were hypogastric pain(13/25),which was intense in 6 cases. Conclusion: Uterine arterial embolization with PLE is a good non-surgical therapy in symptomatic uterine fibroids with mild side effects

Electrophysiological and functional effects of sphingosine-1-phosphate in mouse ventricular fibroblasts

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Benamer, Najate [UMR CNRS/Universite de Poitiers No. 6187, Pole Biologie Sante Bat B36, BP 633, 1 rue Georges Bonnet, 86022 Poitiers (France); Fares, Nassim [Laboratoire de Physiologie, Faculte de Medecine, Universite Saint Joseph, Beyrouth (Lebanon); Bois, Patrick [UMR CNRS/Universite de Poitiers No. 6187, Pole Biologie Sante Bat B36, BP 633, 1 rue Georges Bonnet, 86022 Poitiers (France); Faivre, Jean-Francois, E-mail: Jean-Francois.Faivre@univ-poitiers.fr [UMR CNRS/Universite de Poitiers No. 6187, Pole Biologie Sante Bat B36, BP 633, 1 rue Georges Bonnet, 86022 Poitiers (France)

2011-04-29

Highlights: {yields} In cardiac fibroblasts, SUR2/Kir6.1 channel is activated by S1P via the S1P3R. {yields} S1P increases cell proliferation through SUR2/Kir6.1 activation. {yields} S1P decreases collagen and IL-6 secretion through SUR2/Kir6.1 activation. {yields} S1P stimulates fibroblast migration independently from SUR2/Kir6.1 channel. -- Abstract: The aim of this study was to characterize the effects of sphingosine-1-phosphate (S1P) on cardiac ventricular fibroblasts. Impacts of S1P on fibroblast excitability, cell migration, proliferation and secretion were characterized. The patch-clamp technique in the whole-cell configuration was used to study the S1P-induced current from mouse ventricular fibroblasts. The expression level of the S1P receptor during cell culture duration was evaluated by western-blot. Fibroblast proliferation and migration were quantified using the methylene blue assay and the Boyden chamber technique, respectively. Finally, fibroblast secretion properties were estimated by quantification of the IL-6 and collagen levels using ELISA and SIRCOL collagen assays, respectively. We found that S1P activated SUR2/Kir6.1 channel and that this effect was sensitive to specific inhibition of the S1P receptor of type 3 (S1P3R). In contrast, S1P1R receptor inhibition had no effect. Moreover, the S1P-induced current increased with cell culture duration whereas S1P3R expression level remained constant. The activation of SUR2/Kir6.1 channel by S1P via S1P3R stimulated cell proliferation and decreased IL-6 and collagen secretions. S1P also stimulated fibroblast migration via S1P3R but independently from SUR2/Kir6.1 channel activation. This study demonstrates that S1P, via S1P3R, affects cardiac ventricular fibroblasts function independently or through activation of SUR2/Kir6.1 channel. The latter effect occurs after fibroblasts differentiate into myofibroblasts, opening a new potential therapeutic strategy to modulate fibrosis after cardiac

Electrophysiological and functional effects of sphingosine-1-phosphate in mouse ventricular fibroblasts

International Nuclear Information System (INIS)

Benamer, Najate; Fares, Nassim; Bois, Patrick; Faivre, Jean-Francois

2011-01-01

Highlights: → In cardiac fibroblasts, SUR2/Kir6.1 channel is activated by S1P via the S1P3R. → S1P increases cell proliferation through SUR2/Kir6.1 activation. → S1P decreases collagen and IL-6 secretion through SUR2/Kir6.1 activation. → S1P stimulates fibroblast migration independently from SUR2/Kir6.1 channel. -- Abstract: The aim of this study was to characterize the effects of sphingosine-1-phosphate (S1P) on cardiac ventricular fibroblasts. Impacts of S1P on fibroblast excitability, cell migration, proliferation and secretion were characterized. The patch-clamp technique in the whole-cell configuration was used to study the S1P-induced current from mouse ventricular fibroblasts. The expression level of the S1P receptor during cell culture duration was evaluated by western-blot. Fibroblast proliferation and migration were quantified using the methylene blue assay and the Boyden chamber technique, respectively. Finally, fibroblast secretion properties were estimated by quantification of the IL-6 and collagen levels using ELISA and SIRCOL collagen assays, respectively. We found that S1P activated SUR2/Kir6.1 channel and that this effect was sensitive to specific inhibition of the S1P receptor of type 3 (S1P3R). In contrast, S1P1R receptor inhibition had no effect. Moreover, the S1P-induced current increased with cell culture duration whereas S1P3R expression level remained constant. The activation of SUR2/Kir6.1 channel by S1P via S1P3R stimulated cell proliferation and decreased IL-6 and collagen secretions. S1P also stimulated fibroblast migration via S1P3R but independently from SUR2/Kir6.1 channel activation. This study demonstrates that S1P, via S1P3R, affects cardiac ventricular fibroblasts function independently or through activation of SUR2/Kir6.1 channel. The latter effect occurs after fibroblasts differentiate into myofibroblasts, opening a new potential therapeutic strategy to modulate fibrosis after cardiac physiopathological injury.

Differential expression of caveolin-1 in human myometrial and uterine leiomyoma smooth muscle.

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Zhou, Yu; Ren, Yuanyuan; Cui, Lihua; Li, Zongjin; Zhu, Yingjun; Lin, Wanjun; Wang, Yuebing

2014-11-01

Uterine leiomyomas, the most common neoplasms of the female genital tract, are benign tumors of the uterus arising from the smooth muscle cells (SMCs) of the myometrium with an involvement of estrogen. Caveolin-1 (Cav-1), a major protein component in caveolae membrane lipid rafts, is down-regulated in several estrogen-related cancer cells, and overexpression of Cav-1 inhibits proliferation of cancer cells and vascular SMCs as well. Therefore, we hypothesize that Cav-1 is down-regulated in human uterine leiomyoma. Western blot using tissues from clinical patients showed that Cav-1 expression was significantly lower or undetectable in uterine leiomyoma compared with their matched myometrium (P leiomyomas was also significantly lower as detected by reverse transcription-quantitative polymerase chain reaction analysis (P = .001). To further study the underlying mechanism, we performed primary cell culture, and found that the expression of Cav-1 remained low in cultured leiomyoma SMCs (P = .009). Serum withdrawal did not change Cav-1 expression in leiomyoma SMCs, but increased expression in myometrial SMCs (P = .006). 17-β estradiol inhibited the expression of Cav-1 protein (P = .047) and mRNA (P = .007) in leiomyoma SMCs, whereas it stimulated expression in myometrial SMCs (P = .043). 17-β estradiol, although activating the mitogen-activated protein kinase pathway in both SMCs, did not stimulate their proliferation. We conclude that human uterine leiomyomas in vitro express low levels of Cav-1, which may result from estrogen inhibition. This effect of estrogen may contribute to the pathogenesis of uterine leiomyoma. Further studies in vivo are needed to verify these results. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical application of uterine artery embolization in treating uterine scar pregnancy

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Li Tonghuai; Zheng Hongfeng

2011-01-01

Objective: To evaluate uterine artery embolization in treating uterine scar pregnancy. Methods: During the period from November 2007 to February 2010, 11 patients with uterine scar pregnancy were encountered in authors' hospital. All the patients had a history of lower uterine segment cesarean section. Four patients had to receive an emergency uterine artery embolization due to acute massive vaginal bleeding. The other 7 patients received intravenous chemotherapy with MTX (0.4 mg/kg/day, every 5 days as a treatment course). Emergency uterine artery embolization had to be carried out in three patients as they developed acute massive vaginal bleeding (blood loss ≥ 100 ml/hour) during the course of chemotherapy, while subsequent uterine artery embolization was performed in the remaining 4 patients after they had completed two courses of treatment when their blood HCG showed no significant decrease. The clinical results were analyzed. Results: Remarkable decrease in serum HCG was seen in all 11 patients after interventional management. The vaginal bleeding in 7 patients was significantly reduced within half an hour after uterine artery embolization. The uterus together with intact fertility was successfully preserved in all 11 patients. Conclusion: For the treatment of uterine scar pregnancy complicated by massive vaginal bleeding (blood loss ≥ 500 ml/24 h) and/or abnormal elevation of serum HCG (blood β-HCG ≥ 20000 IU/L), ectopic pregnancy with the mass diameter ≥ 5 cm, uterine artery embolization treatment is very safe and effective. This technique can well preserve female patient's uterus and fertility ability. It is of value to employ this treatment in clinical practice. (authors)

Selective uterine artery embolization: its application in treating symptomatic uterine leiomyomas

International Nuclear Information System (INIS)

Zhang Guofu; Han Zhigang; Hu Pei'an; Wang Shijia; Tian Xiaomei; Zhou Yan; He Beiyi; Wang Jing

2010-01-01

Objective: To discuss the feasibility and safety of uterine artery embolization(UAE) for the treatment of symptomatic uterine leiomyomas. Methods: During the period of Jan. 2005-June 2009, UAE was performed in 85 patients with uterine leiomyomas in the authors' hospital. The main symptoms included hypermenorrhea, delayed menstruation and pelvic pressure symptoms. The bilateral uterine arteries were embolized with polyvinyl alcohol particles (diameter 500-710 μm) and Gelfoam. The technical success rate and the clinical results were observed. The patients were followed up for 6-36 months. Results: The technical success rate of bilateral uterine artery embolization was 100%. No serious complications occurred. During the follow-up period, menses returned to regular cycle in all patients and the hemoglobin concentration rose up to normal level in patients with anemia. The sizes of uterine leiomyomas were decreased by 57.5% after 6 months of the procedure. Conclusion: UAE is an effective and less-invasive treatment for symptomatic uterine leiomyomas with reliable results and fewer complications. This technique can greatly avoid unnecessary uterectomy and, thus, preserve the fertility of the female patients.(authors)

Stimulation of human gingival fibroblasts viability and growth by roots treated with high intensity lasers, photodynamic therapy and citric acid.

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Karam, Paula Stephania Brandão Hage; Ferreira, Rafael; Oliveira, Rodrigo Cardoso; Greghi, Sebastião Luiz Aguiar; de Rezende, Maria Lúcia Rubo; Sant'Ana, Adriana Campos Passanezi; Zangrando, Mariana Schutzer Ragghianti; Damante, Carla Andreotti

2017-09-01

The aim of this study was to compare the effect of root biomodification by lasers, citric acid and antimicrobial photodynamic therapy (aPDT) on viability and proliferation of human gingival fibroblasts (FGH). Groups were divided in control (CC - only cells), and root fragments treated by: scaling and root planing (positice control - SC), Er:YAG (ER-60mJ,10pps,10Hz,10s,2940nm), Nd:YAG (ND-0.5W,15Hz,10s,1640nm), antimicrobial photodynamic therapy (PDT-InGaAIP,30mW,45J/cm 2 ,30s,660nm,toluidine blue O), citric acid plus tetracycline (CA). Fibroblasts (6th passage, 2×10 3 ) were cultivated in a 24-h conditioned medium by the treated root fragments. Cell viability was measured by MTT test at 24, 48, 72 and 96h. In a second experiment, FGH cells (10 4 ) were cultivated on root fragments which received the same treatments. After 24, 48, 72h the number of cells was counted in SEM pictures. In addition, chemical elements were analyzed by energy dispersive spectroscopy (EDS). Data was analyzed by two-way ANOVA (first experiment), repeated measures ANOVA (second experiment) and ANOVA (EDS experiment) tests complemented by Tukey's test (pplaning stimulated fibroblast viability while Er:YAG and Nd:YAG treated root surfaces presented higher number of cells. Copyright © 2017. Published by Elsevier Ltd.

Uterine-sparing Laparoscopic Resection of Accessory Cavitated Uterine Masses.

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Peters, Ann; Rindos, Noah B; Guido, Richard S; Donnellan, Nicole M

2018-01-01

To demonstrate surgical techniques utilized during uterine-sparing laparoscopic resections of accessory cavitated uterine masses (ACUMs). ACUMs represent a rare uterine entity observed in premenopausal women suffering from dysmenorrhea and recurrent pelvic pain. The diagnosis is made when an isolated extra-cavitated uterine mass is resected from an otherwise normal appearing uterus with unremarkable endometrial lumen and adnexal structures. Pathologic confirmation requires an accessory cavity lined with endometrial epithelium (and corresponding glands and stroma) filled with chocolate-brown fluid. Adenomyosis must be absent. Although the origin of ACUMs is currently unknown, the most common presentation is a 2-4 cm lateral uterine wall mass at the level of the insertion of the round ligament. Hence it has been hypothesized that gubernaculum dysfunction may be responsible for duplication or persistence of paramesonephric tissue leading to ACUM formation as a new Müllerian anomaly. A stepwise surgical tutorial describing 2 laparoscopic ACUM resections using a narrated video (Canadian Task Force classification III). An academic tertiary care hospital. In this video, we present 2 patients who underwent uterine-sparing laparoscopic resections of their ACUM in order to preserve fertility (Case 1) or avoid the complications and surgical recovery time of a total laparoscopic hysterectomy (Case 2). Case 1 is a 19-year-old, gravida 0, para 0 woman with dysmenorrhea and recurrent pelvic pain who presented for multiple emergency room and outpatient evaluations. Transvaginal ultrasonography was unremarkable except for a 28×30×26mm left lateral uterine mass with peripheral vascular flow that was initially felt to be a leiomyoma or rudimentary uterine horn. MRI imaging, however, demonstrated this mass to be more consistent with an ACUM. This was based on the lack of communication between the lesion and the main uterine cavity exhibited by high T2 signal (compatible with

Effect of clomiphene citrate on uterine hemodynamics in women with unexplained infertility

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Omran E

2018-04-01

Full Text Available Eman Omran, Mohamed El-Sharkawy, Akmal El-Mazny, Mohamed Hammam, Wafaa Ramadan, Dina Latif, Dalia Samir, Sherine Sobh Department of Obstetrics and Gynecology, Kasr Al-Ainy Hospital, Cairo University, Cairo, Egypt Purpose: The aim of the study was to evaluate the effect of clomiphene citrate on uterine artery blood flow using pulsed Doppler and endometrial and subendometrial micro vascularization using 3D power Doppler in unexplained infertility. Patients and methods: In a prospective observational study at a university teaching hospital, the mid-luteal (peri-implantation endometrial thickness and volume, uterine artery pulsatility index (PI and resistance index (RI, endometrial and subendometrial vascularization index (VI, flow index (FI, and vascularization flow index (VFI, and serum estradiol and progesterone levels were compared between natural and clomiphene citrate stimulated cycles in the same group of 50 patients with unexplained infertility. Statistical analysis was done using paired t-test to compare different study variables. Results: The primary outcome, which was the endometrial flow index, was significantly lower in the stimulated cycles (mean ± SD: 23.89±7.96 vs 27.49±8.73, mean difference (95% CI: -3.6 (-2, -5.9; P=0.03. The mean ± SD of endometrial thickness (10.92±3.04 vs 12.46±3.08 mm; P=0.01, volume (4.57±1.28 vs 5.26±1.32 cm3; P=0.009, endometrial VI (0.86±0.15 vs 0.95%±0.21%; P=0.02, VFI (0.25±0.08 vs 0.31±0.12; P=0.004, subendometrial VI (1.93±0.68 vs 2.26%±0.75%; P=0.02, FI (26.81±9.16 vs 30.73±9.87; P=0.04, and VFI (0.68±0.18 vs 0.79±0.21; P=0.006 were significantly lower in the stimulated cycles. However, there were no significant differences in the uterine artery PI (P=0.12 and RI (P=0.08 or serum estradiol (P=0.54 and progesterone (P=0.37 levels between natural and stimulated cycles. Conclusion: Peri-implantation endometrial perfusion is significantly lower in clomiphene citrate stimulated

Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.

Science.gov (United States)

Shukla, Vasudha; Barnhouse, Victoria; Ackerman, William E; Summerfield, Taryn L; Powell, Heather M; Leight, Jennifer L; Kniss, Douglas A; Ghadiali, Samir N

2018-01-01

The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.

Uterine Cancer—Patient Version

Science.gov (United States)

Uterine cancers can be of two types: endometrial cancer (common) and uterine sarcoma (rare). Endometrial cancer can often be cured. Uterine sarcoma is often more aggressive and harder to treat. Start here to find information on uterine cancer treatment, causes and prevention, screening, research, and statistics.

Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

Science.gov (United States)

Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

2016-10-01

Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (PLucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

Uterine Cancer

Science.gov (United States)

... is pregnant. There are different types of uterine cancer. The most common type starts in the endometrium, ... the uterus. This type is also called endometrial cancer. The symptoms of uterine cancer include Abnormal vaginal ...

Uterine Necrosis after Uterine Artery Embolization for Symptomatic Fibroids

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Steve Kyende Mutiso

2018-01-01

Full Text Available Introduction. Uterine artery embolization (UAE is a minimally invasive intervention that is used in the treatment of fibroids. UAE can lead to complications including postembolization syndrome, postprocedure pain, infection, endometrial atrophy leading to secondary amenorrhea, and uterine necrosis. Uterine necrosis after UAE is very rare and hence poses a clinical dilemma for any clinician in its identification and management. We document a case of uterine necrosis after UAE and conduct a literature review on its causation, clinical features, and management principles. Case. A patient presented one month after UAE with abdominal pain and abdominal vaginal discharge. Her work-up revealed features of possible uterine necrosis with sepsis and she was scheduled for a laparotomy and a subtotal hysterectomy was performed. She was subsequently managed with broad spectrum antibiotic and recovered well. Conclusion. Uterine necrosis after UAE is a rare occurrence and we hope the documentation of this case will add to the body of knowledge around it. Theories that explain its occurrence include the use of small particles at embolization, the use of Contour-SE a spherical poly-vinyl alcohol, and lack of collateral supply to the uterus. Its symptoms may be nonspecific but unremitting abdominal pain is invariably present. Finally although conservative management may be successful at times, surgical management with hysterectomy will be required in some cases. The prognosis is good after diagnosis and surgical management.

Identification of specific gene expression profiles in fibroblasts derived from middle ear cholesteatoma.

Science.gov (United States)

Yoshikawa, Mamoru; Kojima, Hiromi; Wada, Kota; Tsukidate, Toshiharu; Okada, Naoko; Saito, Hirohisa; Moriyama, Hiroshi

2006-07-01

To investigate the role of fibroblasts in the pathogenesis of cholesteatoma. Tissue specimens were obtained from our patients. Middle ear cholesteatoma-derived fibroblasts (MECFs) and postauricular skin-derived fibroblasts (SFs) as controls were then cultured for a few weeks. These fibroblasts were stimulated with interleukin (IL) 1alpha and/or IL-1beta before gene expression assays. We used the human genome U133A probe array (GeneChip) and real-time polymerase chain reaction to examine and compare the gene expression profiles of the MECFs and SFs. Six patients who had undergone tympanoplasty. The IL-1alpha-regulated genes were classified into 4 distinct clusters on the basis of profiles differentially regulated by SF and MECF using a hierarchical clustering analysis. The messenger RNA expressions of LARC (liver and activation-regulated chemokine), GMCSF (granulocyte-macrophage colony-stimulating factor), epiregulin, ICAM1 (intercellular adhesion molecule 1), and TGFA (transforming growth factor alpha) were more strongly up-regulated by IL-1alpha and/or IL-1beta in MECF than in SF, suggesting that these fibroblasts derived from different tissues retained their typical gene expression profiles. Fibroblasts may play a role in hyperkeratosis of middle ear cholesteatoma by releasing molecules involved in inflammation and epidermal growth. These fibroblasts may retain tissue-specific characteristics presumably controlled by epigenetic mechanisms.

Uterine arterial methotrexate infusion and embolization in the treatment of uterine adenomyosis

International Nuclear Information System (INIS)

Xie Jingyan; Wang Suzheng; Chen Jingfang; Xuan Yinghua; Lou Wensheng; Gu Jianping

2008-01-01

Objective: To study the efficacy of treating different types of uterine adenomyosis with transcatheter local infusion of methotrexate (MTX) combined with uterine arterial embolization under guidance of digital subtraction angiography (DSA). Methods: 33 cases were primarily screened out according to clinical symptoms and color Doppler and then further diagnosis as diffuse or local adenomyosis were undertaken with super selective uterine arterial angiography. The patients were then treated with uterine arterial local infusion (50 mg MTX)and embolization with PVA microsphere (diameter 450-650 μm), individually. Finally, the comparison between the preoperative and postoperative menstruation volumes, the degrees of dysmenorrheal, uterine sizes and the levels of sexual hormones of diffuse and local adenomyosis was carried out. Results: The uterine arterial local infusion of MTX combined with embolization showed no chemotherapeutic side effects. In all cases, there were decrease of menstruation amount, alleviated dysmenorrhea, reduction of uterine size, and the efficacy was more evident in diffuse adenomyosis (P<0.05). Conclusions: Micro-invasive interventional technique combined with drug therapy is promising for diffuse and local adenomyosis especially for the former. (authors)

Characteristics of estrogen-induced peroxidase in mouse uterine luminal fluid

International Nuclear Information System (INIS)

Jellinck, P.H.; Newbold, R.R.; McLachlan, J.A.

1991-01-01

Peroxidase activity in the uterine luminal fluid of mice treated with diethylstilbestrol was measured by the guaiacol assay and also by the formation of 3H2O from [2-3H]estradiol. In the radiometric assay, the generation of 3H2O and 3H-labeled water-soluble products was dependent on H2O2 (25 to 100 microM), with higher concentrations being inhibitory. Tyrosine or 2,4-dichlorophenol strongly enhanced the reaction catalyzed either by the luminal fluid peroxidase or the enzyme in the CaCl2 extract of the uterus, but decreased the formation of 3H2O from [2-3H]estradiol by lactoperoxidase in the presence of H2O2 (80 microM). NADPH, ascorbate, and cytochrome c inhibited both luminal fluid and uterine tissue peroxidase activity to the same extent, while superoxide dismutase showed a marginal activating effect. Lactoferrin, a major protein component of uterine luminal fluid, was shown not to contribute to its peroxidative activity, and such an effect by prostaglandin synthase was also ruled out. However, it was not possible to exclude eosinophil peroxidase, brought to the uterus after estrogen stimulation, as being the source of peroxidase activity in uterine luminal fluid

ENDOVASCULAR HEMOSTASIS IN UTERINE BLEEDING IN PATIENTS WITH UTERINE LEIOMYOMA

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M. M. Damirov

2017-01-01

Full Text Available We report results of treatment for 72 patients with uterine leiomyoma (LM of various sizes and location, who had arrived with excessive uterine bleeding. All patients underwent urgent or urgently-delayed endovascular hemostasis by performing uterine arteries embolization (UAE. We analyzed clinical features of the disease after UAE in various sizes of tumors and studied immediate and long-term results of UAE in patients with LM.

Uterine Artery Embolization to Treat Uterine Adenomyosis with or without Uterine Leiomyomata: Results of Symptom Control and Health-Related Quality of Life 40 Months after Treatment

International Nuclear Information System (INIS)

Froeling, V.; Scheurig-Muenkler, C.; Hamm, B.; Kroencke, T. J.

2012-01-01

Purpose: To evaluate the clinical outcome for uterine adenomyosis with or without uterine leiomyomata 40 months after uterine artery embolization (UAE). Methods: Forty women aged 39–56 years (median 46 years) with symptomatic uterine adenomyosis and magnetic resonance imaging findings of uterine adenomyosis with or without combined uterine leiomyomata underwent UAE. Self-perceived changes in clinical symptoms were assessed, and residual symptom severity and health-related quality of life (HRQOL) after UAE were evaluated. Clinical failure was defined as no symptomatic improvement or second invasive therapy after UAE. Results were stratified by the extent of uterine adenomyosis at baseline magnetic resonance imaging. Results: Patients were followed for a median of 40 months (range 5–102 months). UAE led to symptomatic control after UAE in 29 (72.5%) of 40 patients while 11 women underwent hysterectomy (n = 10) or dilatation and curettage (n = 1) for therapy failure. No significant difference between women with pure uterine adenoymosis and women with uterine adenomyosis combined with uterine leiomyomata was observed. Best results were shown for UAE in uterine adenomyosis with uterine leiomyomata predominance as opposed to predominant uterine adenomyosis with minor fibroid disease (clinical failure 0% vs. 31.5%, P = 0.058). Throughout the study group, HRQOL score values increased and symptom severity scores decreased after UAE. Least improvement was noted for women with pure adenomyosis. Conclusions: UAE is clinically effective in the long term in most women with uterine adenomyosis. Symptomatic control and HRQOL were highest in patients with combined disease of uterine adenomyosis but leiomyomata predominance.

Cleaved CD147 shed from the surface of malignant melanoma cells activates MMP2 produced by fibroblasts.

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Hatanaka, Miho; Higashi, Yuko; Fukushige, Tomoko; Baba, Naoko; Kawai, Kazuhiro; Hashiguchi, Teruto; Su, Juan; Zeng, Weiqi; Chen, Xiang; Kanekura, Takuro

2014-12-01

Cluster of differentiation 147 (CD147)/basigin on the malignant tumor cell surface is critical for tumor proliferation, invasiveness, metastasis, and angiogenesis. CD147 expressed on malignant melanoma cells can induce tumor cell invasion by stimulating the production of matrix metalloproteinases (MMPs) by surrounding fibroblasts. Membrane vesicles, microvesicles and exosomes have attracted attention, as vehicles of functional molecules and their association with CD147 has been reported. Cleaved CD147 fragments released from tumor cells were reported to interact with fibroblasts. We investigated the intercellular mechanisms by which CD147 stimulates fibroblasts to induce MMP2 activity. CD147 was knocked-down using short hairpin RNA (shRNA). The stimulatory effect of CD147 in cell culture supernatants, microvesicles, and exosomes on the enzymatic activity of MMP2 was examined by gelatin zymography. Supernatants from A375 control cells induced increased enzymatic activity of fibroblasts; such activity was significantly lower in CD147 knock-down cells. Cleaved CD147 plays a pivotal role in stimulating fibroblasts to induce MMP2 activity. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Factor XIIIa is expressed by fibroblasts in fibrovascular tumors.

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Nemeth, A J; Penneys, N S

1989-10-01

Factor XIIIa (FXIIIa), a blood and intracellularly produced coagulation factor, has been found in a variety of cell types including fibroblast-like mesenchymal cells, and has been shown to stimulate the proliferation of fibroblasts and some neoplastic cells in vitro. We have already shown that the dendritic fibroblasts composing the fibrous papule contain this factor. We hypothesized that histopathologically similar fibrovascular tumors may also express FXIIIa and, in this report, show that the large stellate fibroblasts found in acquired digital fibrokeratomas, angiofibromas (adenoma sebaceum of Pringle), and oral fibroma (oral fibrous hyperplasia) also express FXIIIa. We postulate that FXIIIa, possibly acting as a growth factor, may be a common denominator in the pathogenesis of these tumors. Another possibility is that these tumors may be the consequence of a local overproduction of FXIIIa in response to an, as yet, unidentified stimulus.

A comparison between electrical uterine monitor, tocodynamometer and intra uterine pressure catheter for uterine activity in labor.

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Hadar, Eran; Biron-Shental, Tal; Gavish, Oz; Raban, Oded; Yogev, Yariv

2015-08-01

We aimed to evaluate the performance of a non-invasive EMG electrical uterine monitor (EUM) versus tocodynamometry (TOCO) by comparing both to internal uterine pressure catheter (IUPC). Prospective observational trial. Uterine activity was recorded continuously and simultaneously, in women during active term labor, with TOCO, EUM and IUPC. Uterine activity tracings were analyzed by three blinded physicians. Overall, 385 tracings from 43 women were analyzed. A similar rate of interpretable tracings between physicians was demonstrated for EUM (87%; 95% CI 80.9-92.7%) and IUPC (94.8%; 95% CI 83.4-96.3%), with a significantly lower rate for TOCO (67.5%; 95% CI 59.4-76.8%, p TOCO versus IUPC (-3.34 ± 4.97). There is a high variability between the timing of TOCO contractions as compared to IUPC (4.74 ± 10.03 seconds), while a gap of 8.46 ± 4.24 seconds was detected for EUM. The sensitivity, positive predictive value and false positive rate for individual contraction identification by TOCO and EUM are 54.0%, 84.4%, 15.6% and 94.2%, 87.6%, 12.4%, respectively. EUM is efficient as IUPC for uterine activity assessment and both techniques are superior in comparison to external tocodynamometry. Our results support the use of non-invasive EMG technology to monitor uterine activity.

Anti-fibrotic effects of theophylline on lung fibroblasts

International Nuclear Information System (INIS)

Yano, Yukihiro; Yoshida, Mitsuhiro; Hoshino, Shigenori; Inoue, Koji; Kida, Hiroshi; Yanagita, Masahiko; Takimoto, Takayuki; Hirata, Haruhiko; Kijima, Takashi; Kumagai, Toru; Osaki, Tadashi; Tachibana, Isao; Kawase, Ichiro

2006-01-01

Theophylline has been used in the management of bronchial asthma and chronic obstructive pulmonary disease for over 50 years. It has not only a bronchodilating effect, but also an anti-inflammatory one conducive to the inhibition of airway remodeling, including subepithelial fibrosis. To date however, whether theophylline has a direct inhibitory effect on airway fibrosis has not been established. To clarify this question, we examined whether theophylline affected the function of lung fibroblasts. Theophylline suppressed TGF-β-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited fibroblast proliferation stimulated by FBS and TGF-β-induced α-SMA protein. A cAMP analog also inhibited TGF-β-induced COL1 mRNA expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of theophylline on TGF-β-induced COL1 mRNA expression. These results indicate that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP-PKA pathway

Use of fertility drugs and risk of uterine cancer: results from a large Danish population-based cohort study

DEFF Research Database (Denmark)

Jensen, Allan; Sharif, Heidi; Kjaer, Susanne K

2009-01-01

and 1998. In a case-cohort study, rate ratios and 95% confidence intervals were used to assess the effects of 4 groups of fertility drugs on overall risk of uterine cancer after adjustment for potentially confounding factors. Through mid-2006, 83 uterine cancers were identified. Ever use of any fertility......Some epidemiologic studies have indicated that uterine cancer risk may be increased after use of fertility drugs. To further assess this association, the authors used data from a large cohort of 54,362 women diagnosed with infertility who were referred to Danish fertility clinics between 1965...... drug was not associated with uterine cancer risk (rate ratio (RR) = 1.10, 95% confidence interval (CI): 0.69, 1.76). However, ever use of gonadotropins (follicle-stimulating hormone and human menopausal gonadotropin) increased uterine cancer risk (RR = 2.21, 95% CI: 1.08, 4.50); the risk was primarily...

Laparoscopic uterine surgery as a risk factor for uterine rupture during pregnancy.

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An-Shine Chao

Full Text Available The incidence of uterine rupture through a previous cesarean scar (CS is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes. Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%, 13 through a non-cesarean scar (non-CS ruptures, 59%, whereas the remaining two (9% were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76% occurred after a previous laparoscopic myomectomy, one (8% following a hysteroscopic myomectomy, and two (16% after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024. Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy.

Laparoscopic uterine surgery as a risk factor for uterine rupture during pregnancy.

Science.gov (United States)

Chao, An-Shine; Chang, Yao-Lung; Yang, Lan-Yan; Chao, Angel; Chang, Wei-Yang; Su, Sheng-Yuan; Wang, Chin-Jung

2018-01-01

The incidence of uterine rupture through a previous cesarean scar (CS) is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes). Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%), 13 through a non-cesarean scar (non-CS ruptures, 59%), whereas the remaining two (9%) were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76%) occurred after a previous laparoscopic myomectomy, one (8%) following a hysteroscopic myomectomy, and two (16%) after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL) requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024). Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy.

Laparoscopic uterine surgery as a risk factor for uterine rupture during pregnancy

Science.gov (United States)

Chao, An-Shine; Chang, Yao-Lung; Yang, Lan-Yan; Chao, Angel; Chang, Wei-Yang; Su, Sheng-Yuan

2018-01-01

The incidence of uterine rupture through a previous cesarean scar (CS) is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes). Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%), 13 through a non-cesarean scar (non-CS ruptures, 59%), whereas the remaining two (9%) were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76%) occurred after a previous laparoscopic myomectomy, one (8%) following a hysteroscopic myomectomy, and two (16%) after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL) requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024). Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy. PMID:29787604

Effect of storage media on the proliferation of periodontal ligament fibroblasts

International Nuclear Information System (INIS)

Lauer, H.C.; Mueller, J.G.; Gross, J.; Horster, M.F.

1987-01-01

The effect of storage media, which are routinely used in replantation, upon the proliferative capacity of periodontal ligament fibroblasts, was compared with the effect of a tissue culture medium. The periodontal tissue was obtained from mandibular central incisors of White New Zealand rabbits. The experiments were performed in fibroblasts derived during second subculture. The storage media were physiologic salt solution, Ringer's solution and Rivanol; the tissue culture medium was alpha-minimum essential medium without nucleosides. The incubation period was 1 hour. [ 3 H]-thymidine incorporation and cell counts were taken to indicate changes in the proliferative capacity of the fibroblasts. The tissue culture experiments showed that the proliferative ability of the periodontal ligament fibroblasts was dependent upon the composition of the storage medium. Physiologic salt solution, Ringer's solution and Rivanol were unable to maintain the metabolism of the fibroblasts. alpha-MEM medium, however, was capable of stimulating proliferation of the periodontal ligament fibroblasts

Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

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Gen Kuroyanagi

2014-10-01

Full Text Available It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2 on osteoprotegerin (OPG synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK, and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation.

Effect of eosinophils activated with Alternaria on the production of extracellular matrix from nasal fibroblasts.

Science.gov (United States)

Shin, Seung-Heon; Ye, Mi-Kyung; Choi, Sung-Yong; Kim, Yee-Hyuk

2016-06-01

Eosinophils and fibroblasts are known to play major roles in the pathogenesis of nasal polyps. Fungi are commonly found in nasal secretion and are associated with airway inflammation. To investigate whether activated eosinophils by airborne fungi can influence the production of extracellular matrix (ECM) from nasal fibroblasts. Inferior turbinate and nasal polyp fibroblasts were stimulated with Alternaria or Aspergillus, respectively, for 24 hours and ECM messenger RNA (mRNA) and protein expressions were measured. Eosinophils isolated from healthy volunteers were stimulated with Alternaria or Aspergillus for 4 hours then superoxide, eosinophil peroxidase, and transforming growth factor β1 were measured. Then activated eosinophils were cocultured with nasal fibroblasts for 24 hours, and ECM mRNA expressions were measured. Alternaria strongly enhanced ECM mRNA expression and protein production from nasal fibroblasts. Alternaria also induced the production of superoxide, eosinophil peroxidase, and transforming growth factor β1 from eosinophils, and activated eosinophils enhanced ECM mRNA expression when they were cocultured without the Transwell insert system. Eosinophils activated with Alternaria enhanced ECM mRNA expression from nasal polyp fibroblasts. Alternaria plays an important role in tissue fibrosis in the pathogenesis of nasal polyps by directly or indirectly influencing the production of ECM from nasal fibroblasts. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Single versus double-layer uterine closure at cesarean: impact on lower uterine segment thickness at next pregnancy.

Science.gov (United States)

Vachon-Marceau, Chantale; Demers, Suzanne; Bujold, Emmanuel; Roberge, Stephanie; Gauthier, Robert J; Pasquier, Jean-Charles; Girard, Mario; Chaillet, Nils; Boulvain, Michel; Jastrow, Nicole

2017-07-01

Uterine rupture is a potential life-threatening complication during a trial of labor after cesarean delivery. Single-layer closure of the uterus at cesarean delivery has been associated with an increased risk of uterine rupture compared with double-layer closure. Lower uterine segment thickness measurement by ultrasound has been used to evaluate the quality of the uterine scar after cesarean delivery and is associated with the risk of uterine rupture. To estimate the impact of previous uterine closure on lower uterine segment thickness. Women with a previous single low-transverse cesarean delivery were recruited at 34-38 weeks' gestation. Transabdominal and transvaginal ultrasound evaluation of the lower uterine segment thickness was performed by a sonographer blinded to clinical data. Previous operative reports were reviewed to obtain the type of previous uterine closure. Third-trimester lower uterine segment thickness at the next pregnancy was compared according to the number of layers sutured and according to the type of thread for uterine closure, using weighted mean differences and multivariate logistic regression analyses. Of 1613 women recruited, with operative reports available, 495 (31%) had a single-layer and 1118 (69%) had a double-layer closure. The mean third-trimester lower uterine segment thickness was 3.3 ± 1.3 mm and the proportion with lower uterine segment thickness cesarean delivery is associated with a thicker third-trimester lower uterine segment and a reduced risk of lower uterine segment thickness <2.0 mm in the next pregnancy. The type of thread for uterine closure has no significant impact on lower uterine segment thickness. Copyright © 2017 Elsevier Inc. All rights reserved.

Uterine sarcoma Part I—Uterine leiomyosarcoma: The Topic Advisory Group systematic review

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Kuo-Chang Wen

2016-08-01

Full Text Available Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Primary uterine inertia in four labrador bitches.

Science.gov (United States)

Davidson, Autumn P

2011-01-01

Uterine inertia is a common cause of dystocia in the bitch and is designated as primary (i.e., uterine contractions fail to ever be initiated) or secondary (i.e., uterine contractions cease after a period of time but before labor is completed). The etiology of primary uterine inertia is not well understood. The accurate diagnosis of primary uterine inertia requires the use of tocodynamometry (uterine monitoring). Primary uterine inertia has been postulated to result from a failure of luteolysis resulting in persistently elevated progesterone concentrations. In this study, primary uterine inertia was diagnosed in a series of four bitches in which luteolysis was documented suggesting some other etiopathogenesis for primary uterine inertia.

Cell proliferation in vitro modulates fibroblast collagenase activity

International Nuclear Information System (INIS)

Lindblad, W.J.; Flood, L.

1986-01-01

Collagenase enzyme activity is regulated by numerous control mechanisms which prevent excessive release and activation of this protease. A primary mechanism for regulating enzyme extracellular activity may be linked to cell division, therefore they have examined the release of collagenase by fibroblasts in vitro in response to cellular proliferation. Studies were performed using fibroblasts derived from adult rat dermis maintained in DMEM containing 10% newborn calf serum, 25 mM tricine buffer, and antibiotics. Cells between subculture 10 and 19 were used with enzyme activity determined with a 14 C-labelled soluble Type I collagen substrate with and without trypsin activation. Fibroblasts, trypsinized and plated at low density secreted 8.5 fold more enzyme than those cells at confluence (975 vs. 115 dpm/μg DNA). This diminution occurred gradually as the cells went from logrithmic growth towards confluence. Confluent fibroblast monolayers were scraped in a grid arrangement, stimulating the remaining cells to divide, without exposure to trypsin. Within 24-48 hr postscraping enzyme levels had increased 260-400%, accompanied by enhanced incorporation of 3 H-thymidine and 3 H-uridine into cell macromolecules. The burst of enzyme release began to subside 12 hr later. These results support a close relationship between fibroblast proliferation and collagenase secretion

Dysfunctional Uterine Bleeding (DUB) (For Teens)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Abnormal Uterine Bleeding (AUB) KidsHealth / For Teens / Abnormal Uterine Bleeding (AUB) ... Print en español Sangrado uterino anormal What Is Abnormal Uterine Bleeding? Abnormal uterine bleeding (AUB) is the name doctors ...

The clinical application of uterine arterial embolization with dextran microspheres in treating uterine leiomyomas

International Nuclear Information System (INIS)

Xu Qiang; Huang Youhua; Shi Hongjian; Shen Tao; Zhou Huaming; Wu Xiaosong; Jiang Lei; Chen Jing; Chu Jumei

2011-01-01

Objective: To prospectively investigate the clinical application of bilateral uterine arterial embolization with dextran microspheres in treating uterine leiomyomas. Methods: A total of 60 patients with uterine leiomyomas, encountered in the authors' hospital during the period from Jan. 2003 to Dec. 2010, were enrolled in this study. The patients were randomly divided into study group and control group with 30 cases in each group. Patients in the study group received bilateral uterine artery embolization by using dextran microspheres (Sephadex, g-50, 100-300 μm) as embolic agents, while patients in control group received bilateral uterine artery embolization by using KMG (500-700 μm) as embolic agents. Before and after the treatment, all patients were kept under observation for the menstrual flow, the size of the uterine and the leiomyoma and the changes in sex hormone level. The hospitalization costs were recorded. The results were compared between the two groups. Results: The technical success rate of catheterization and embolization procedure was 100% in both groups. After the therapy, the volumes of both the uterine and the leiomyoma were significantly decreased, but no significant difference in the size reduction existed between the two groups (both P.0.05). The clinical symptoms were markedly improved in all patients. The sex hormone level showed no obvious changes. No serious complications occurred. The hospitalization cost of the study group was significantly lower than that of the control group (P<0.05). Conclusion: For the treatment of uterine leiomyomas, uterine artery embolization with dextran microspheres is very effective and safe. Moreover, the hospitalization cost is lower. Therefore, it is of value to use this technique in clinical practice. (authors)

Expression and prognostic value of lactate dehydrogenase-A and -D subunits in human uterine myoma and uterine sarcoma.

Science.gov (United States)

Song, Ke-Juan; Yu, Xiao-Ni; Lv, Teng; Chen, Yu-Long; Diao, Yu-Chao; Liu, Su-Li; Wang, Yan-Kui; Yao, Qin

2018-04-01

This study aimed to determine the expression of lactate dehydrogenase (LDH)-A and LDH-D in patients with uterine myoma, cellular leiomyoma (CLM), and uterine sarcoma and to evaluate their prognostic significance. Protein expression levels of LDH-A and LDH-D were determined in tissue samples from 86 patients (26 uterine myoma, 10 CLM, 50 uterine sarcoma) by immunohistochemistry and their associations with clinicopathologic parameters and outcomes were analyzed in patients with uterine sarcoma. The positivity rates for LDH-A and LDH-D were significantly higher in patients with uterine sarcoma compared with those with uterine myoma or CLM (P sarcoma were classified as having uterine leiomyosarcoma (LMS), malignant endometrial stromal sarcoma, and malignant mixed Mullerian tumor, with 5-year overall survival rates of 59%, 71%, and 29%, respectively (P sarcoma. Furthermore, the overexpressions of LDH-A and LDH-D in uterine sarcoma patients may contribute to further understanding of the mechanism of LDH in tumor metabolism in uterine sarcoma. Positive expression of LDH-A in patients with LMS may act as a potential prognostic biomarker in these patients.

THE EFFECTIVENESS OF COMBINATION OF OXYTOCIN AND ENDORPHIN MASSAGE ON UTERINE INVOLUTION IN PRIMIPAROUS MOTHERS

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Nurmala Sari

2017-10-01

Full Text Available Background: One of the puerperal complication is uterine subinvolution that can cause bleeding to maternal death. Oxytocin massage can stimulate oxytocin hormone that plays a role in the process of uterine involution. Endorphine massage can increase the release of oxytocin and endorphine hormone that give a sense of calm and comfort. It also increases production of oxytocin hormone that can improve the process of uterine involution. Objective: To prove the effectiveness of a combination of oxytocin massage and endorphine massage to uterine involution in primiparaous mothers during postpartum period. Methods: This was a quasy-experimental study with pretest-posttest with control group design. Total samples were 44 normal postpartum mothers selected using purposive sampling technique, which were randomly assigned in four groups, namely: 1 oxytocin massage group, 2 endorphin massage group, 3 combined oxytocin-endorphin massage group, and 4 control group. The data were analyzed using univariate, bivariate and One Way Anova to test the effectiveness of the intervention. Results: There were statistically significant differences of fundal height before and after intervention among the four groups (p=<0.05. Conclusion: The combination of oxytocin massage and endorphine massage proved most effective in accelerating uterine involution in normal postpartum mothers.

Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

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JoAnn eTrial

2013-09-01

Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

Is a history of cesarean section a risk factor for abnormal uterine bleeding in patients with uterine leiomyoma?

Science.gov (United States)

Kinay, Tugba; Basarir, Zehra O; Tuncer, Serap F; Akpinar, Funda; Kayikcioglu, Fulya; Koc, Sevgi; Karakaya, Jale

2016-08-01

To determine whether a history of cesarean section was a risk factor for abnormal uterine bleeding in patients with uterine leiomyomas, and to identify other risk factors for this symptom. We analyzed retrospectively, the medical records of patients who underwent hysterectomies due to the presence of uterine leiomyomas during a 6-year period (2009 and 2014) at Etlik Zubeyde Hanim Women's Health Training and Research Hospital, Ankara, Turkey. Uterine leiomyoma was diagnosed based on histopathological examination of hysterectomy specimens. Demographic characteristics, and laboratory and histopathological findings were compared between patients with uterine leiomyoma with and without abnormal uterine bleeding. In total, 501 (57.9%) patients had abnormal uterine bleeding and 364 (42.1%) patients had other symptoms. A history of cesarean section was more common in patients with abnormal uterine bleeding than in those with other symptoms (17.6% versus 9.3%, p=0.001; odds ratio [OR]: 2.1; 95% confidence interval [CI]: 1.4-3.3). The presence of a submucosal leiomyoma (OR: 2.1; 95% CI: 1.5-3.1) and coexistent adenomyosis (OR: 1.6; 95% CI: 1.1-2.4) were also associated with abnormal uterine bleeding. A history of cesarean section was an independent risk factor for abnormal uterine bleeding in patients with uterine leiomyomas; submucosal leiomyoma and coexisting adenomyosis were also independent risk factors.

Effect of lectin (ScLL on fibroblasts stimulated with LPS - an in vitro study

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Manuella Verdinelli de Paula REIS

Full Text Available Abstract: The lectin (ScLL extracted from the Synadenium carinatum plant has been evaluated as an immunomodulator in diseases such as asthma, neosporosis and leishmaniasis. However, it has not yet been evaluated in the oral cavity. This study evaluated the effect of ScLL on viability, proliferation and release of IL-10 in human gingival fibroblasts (HGF stimulated with lipopolysaccharide (LPS. HGF were stimulated with LPS 1 µg/ml and treated with ScLL in concentrations of 10, 5 and 2 µg/ml for 1 and 5 h, and evaluated by flow cytometry for viability, apoptosis (initial/advanced and necrosis. The supernatant was collected to detect release of IL-10 by ELISA. The proliferation was assessed with the BrdU assay. Positive control consisted of cells maintained in Dulbecco's Modified Eagles Medium (DMEM, and the negative control, of those kept in tap water. Data were analyzed by ANOVA and Dunnett's test (α = 0.05. No significant difference was found for ScLL concentrations regarding viability or initial and advanced apoptosis (p=0.455. All the groups, including the positive control, had a significantly lower necrosis parameter than negative control at 5 h (p < 0.001. No difference was found for proliferation among the experimental groups (p = 0.832. ScLL at 5 and 2 µg/ml resulted in a lower release of IL-10 than positive and negative controls at 5 h (p = 0.047. The results indicated that ScLL concentrations tested were not cytotoxic, and had no effect on proliferation and release of IL-10 parameters. A thorough understanding of ScLL, regarding its immunomodulatory potential, may open the door to new perspectives for dentistry.

Uterine transplantation: Review in human research.

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Favre-Inhofer, A; Rafii, A; Carbonnel, M; Revaux, A; Ayoubi, J M

2018-06-01

Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation. Copyright © 2018. Published by Elsevier Masson SAS.

Study on the relationship between the growth of uterine leiomyoma and the level of hormone in serum and the content of ER and PR in uterus

International Nuclear Information System (INIS)

Liu Manhua; Cheng Ying; Guan Weiqun; Tao Qian; Zheng Yanli; Yang Qichang

2003-01-01

Objective: To study the relationship between expressions of estrogen receptor (ER) and progesterone receptor (PR) in uterine leiomyoma, its adjacent sites and myometrium with the uterine leiomyoma. Methods: Expressions of ER and PR in uterine leiomyoma, its adjacent site and myometrium were determined by immunohistochemical SP method in 30 patients with uterine leiomyoma and serum prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E 2 ), progesterone (P) and testosterone (T) concentrations were measured with radioimmunoassay, with normal cycling women served as the controls. Results: (1) contents of ER and PR were significantly higher in leiomyoma than in its adjacent site and myometrium (P 0.05). Conclusion: The growth of uterine leiomyoma is associated with strong expression of ER, PR in uterine tissue. When myometrectomy is performed, the myometrium around the leiomyoma should be cut at the same time

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

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Vaheri, Antti, E-mail: antti.vaheri@helsinki.fi [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland); Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland)

2009-06-10

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

International Nuclear Information System (INIS)

Vaheri, Antti; Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli

2009-01-01

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Induction of growth and proliferation of fibroblast cells in magnetic field

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Naghmeh Ezatti

2015-02-01

Full Text Available Background: Tissue engineering is generally defined as developing and changing the laboratory growth of molecules and cells in tissues or organs to replace and repair the damaged part of body. This study was carried out to stimulate the growth of cultured fibroblast cells by a physical electromagnetic method. Methods: First, an air-core coil was prepared and the cell culture plate was placed comfortably into the mold, then the plate containing the culture medium and human fibroblast cell along with air-core coil were placed in an incubator and then connected to the power supply. Thus, the sample underwent electromagnetic field at different times, and cell proliferation was studied by MTTassay. Results: Microscopic images indicated that the cells undergoing electromagnetic field (0.35 amps had a significant growth compared to the cells in control group in a definit range of stimulation. Conclusion: In conclusion, electromagnetic stimulation in a definite range led to cell proliferation and could be used as a positive factor in tissue engineering.

Uterine Cancer: Cancer of the Uterus

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... Subscribe To receive Publications email updates Submit Uterine cancer Cancer of the uterus (uterine cancer) is cancer ... Institute . Expand all | Collapse all What is uterine cancer? Cancer is a disease in which certain body ...

Uterine Vascular Lesions

Science.gov (United States)

Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

2013-01-01

Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

Long-term follow up after uterine artery embolization for symptomatic uterine leiomyomas

DEFF Research Database (Denmark)

Poulsen, Bente; Munk, Torben; Ravn, Pernille

2011-01-01

Uterine artery embolization is one of the established treatment options for symptomatic uterine leiomyomas, with a proven effect on the size of leiomyomas and providing short-term relief of symptoms. Only few studies have addressed long-term satisfaction with the treatment. We conducted...

Effect of low-power red light laser irradiation on the viability of human skin fibroblast

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Bednarska, K.; Rozga, B.; Leyko, W.; Bryszewska, M. [Institute of Biophysics, University of Lodz (Poland); Kolodziejczyk, K.; Szosland, D. [Diabetological Clinic, Medical Academy of Lodz (Poland)

1998-10-01

Human skin fibroblast monolayers (S-126 cell line) were exposed to laser radiation (wavelength 670 nm, power density 40 mW/cm{sup 2}). The energy densities were 2 J/cm{sup 2} and 12 J/cm{sup 2}, respectively, and the irradiation was carried out at a temperature of 22 C. For fibroblast viability evaluation, the colorimetric assay (conversion of thiazolyl blue to formazan) was used. The experiments were carried out at 37 C, in the presence of 5% CO{sub 2}, and at different time periods of incubation after irradiation (2, 4, 8 h and 1, 2, 3, 4, 5 days). The results indicated that there was a certain stimulating effect on the long-term proliferation of skin fibroblasts and that the stimulation proceeded in two stages, the first one 2 h and the second one 3 days post-irradiation. (orig.) With 4 figs., 2 tabs., 13 refs.

MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months after Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol

International Nuclear Information System (INIS)

Das, Raj; Gonsalves, Michael; Vlahos, Ioannis; Manyonda, Issac; Belli, Anna-Maria

2013-01-01

Purpose: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on 6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. Methods: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction, presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). Results: Magnetic resonance angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. Conclusion: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL scores were achieved

MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months after Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol

Energy Technology Data Exchange (ETDEWEB)

Das, Raj, E-mail: rajdas@nhs.net; Gonsalves, Michael; Vlahos, Ioannis [St George' s Healthcare NHS Trust, Blackshaw, Department of Radiology (United Kingdom); Manyonda, Issac [St George' s Healthcare NHS Trust, Department of Gynaecology (United Kingdom); Belli, Anna-Maria [St George' s Healthcare NHS Trust, Blackshaw, Department of Radiology (United Kingdom)

2013-10-15

Purpose: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on 6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. Methods: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction, presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). Results: Magnetic resonance angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. Conclusion: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL scores were achieved.

Anastomoses of the Ovarian and Uterine Arteries: A Potential Pitfall and Cause of Failure of Uterine Embolization

International Nuclear Information System (INIS)

Matson, Matthew; Nicholson, Anthony; Belli, Anna-Maria

2000-01-01

Four women with symptomatic uterine fibroids were treated by uterine artery embolization (UAE). In all cases both uterine arteries were embolized via a single femoral puncture with polyvinyl alcohol using a selective catheter technique. In three cases, the ovarian artery was not visible on the initial angiogram before embolization, but appeared after the second uterine artery had been treated. In one case of clinical failure following UAE, a repeat angiogram demonstrated filling of the fibroids from the ovarian artery. Anastomoses between uterine and ovarian arteries may cause problems for radiologists performing UAE and are a potential cause of treatment failure

Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

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Huann-Cheng Horng

2016-08-01

Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts

International Nuclear Information System (INIS)

Dudas, Jozsef; Fullar, Alexandra; Bitsche, Mario; Schartinger, Volker; Kovalszky, Ilona; Sprinzl, Georg Mathias; Riechelmann, Herbert

2011-01-01

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1β (IL1-β) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-β expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-β processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-β. IL1-β signaling was investigated by western blot and immunocytochemistry. IL1-β-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-β, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NFκBα. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-β reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-β-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-β in the tumor cells leads to IL1-β-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-β. PDL fibroblasts possess receptor for IL1-β, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-β receptor expression in

Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

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Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

2011-09-10

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

Use of fertility drugs and risk of uterine cancer: results from a large Danish population-based cohort study.

Science.gov (United States)

Jensen, Allan; Sharif, Heidi; Kjaer, Susanne K

2009-12-01

Some epidemiologic studies have indicated that uterine cancer risk may be increased after use of fertility drugs. To further assess this association, the authors used data from a large cohort of 54,362 women diagnosed with infertility who were referred to Danish fertility clinics between 1965 and 1998. In a case-cohort study, rate ratios and 95% confidence intervals were used to assess the effects of 4 groups of fertility drugs on overall risk of uterine cancer after adjustment for potentially confounding factors. Through mid-2006, 83 uterine cancers were identified. Ever use of any fertility drug was not associated with uterine cancer risk (rate ratio (RR) = 1.10, 95% confidence interval (CI): 0.69, 1.76). However, ever use of gonadotropins (follicle-stimulating hormone and human menopausal gonadotropin) increased uterine cancer risk (RR = 2.21, 95% CI: 1.08, 4.50); the risk was primarily observed after 10 years of follow-up. Furthermore, uterine cancer risk increased with number of cycles of use for clomiphene (for > or =6 cycles, RR = 1.96, 95% CI: 1.03, 3.72) and human chorionic gonadotropin (for > or =6 cycles, RR = 2.18, 95% CI: 1.16, 4.08) but not for other gonadotropins. Use of gonadotropin-releasing hormone analogs was not associated with risk. Gonadotropins, and possibly clomiphene and human chorionic gonadotropin, may increase the risk of uterine cancer, with higher doses and longer follow-up leading to greater risk.

Minimally invasive treatments of uterine fibroids

NARCIS (Netherlands)

Voogt, M.J.

2012-01-01

This thesis assesses clinical results and technical developments of two minimally invasive treatments for symptomatic uterine fibroids: uterine artery embolization (UAE) and magnetic resonance-guided high intensity focused ultrasound (MR-HIFU). Part I: Uterine artery embolization The results of a

Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

Energy Technology Data Exchange (ETDEWEB)

Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

2004-07-14

Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

Uterine transplantation: a systematic review

Directory of Open Access Journals (Sweden)

Dani Ejzenberg

Full Text Available Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

ABNORMAL UTERINE BLEEDING IN ADOLESCENTS — ENDOCRINE PROFILE CONDITION

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E. V. Sibirskaya

2014-01-01

Full Text Available Aim: The purpose of the study was to evaluate the endocrine profile condition in adolescent girls with abnormal uterine bleeding. Patients and methods: The participants of the study were 110 adolescent girls in the age between 11 and 15 years taken to hospital by emergency indication in the period between 2010–2013 years with dysfunctional uterine bleeding for the term from 3 to 48 days. In the first day of hospitalization before starting the hormonal therapy all patients underwent the physical examination, ultrasonic examination of pelvic organs and endocrine profile assessment. Concentration of follicle-stimulating hormone (FSH and luteinizing hormone (LH and the levels of mammotropic hormone, thyrotropic hormone, estradiol, progesterone and testosterone in their blood were determined. Besides that physicians assessed the complete blood count indices: hemoglobin concentration, erythrocyte number and hematocrits. Results: It was determined that the predisposing causes of abnormal uterine bleeding development in adolescents: high somatic pathology frequency, abnormalities of neuroendocrinal system and menstrual cycle. Gynecological pathology in adolescents is represented by significant disorders of menstrual function establishment expressed in the later beginning of menstruation, its intensity and duration. The authors also note the higher frequency of inflammatory diseases such as adnexitis, edeitis, vulvovaginitis and coleitis in comparison with the control group (37.3 and 30%, respectively. Another tendency was observed while studying the endocrine profile: in patients with hyperestrogenism the normal or increased content of FSH at the normal or lowered LH concentration is observed. At the same time, in patients with hypestrogenism FSH concentration at the lower limits of the age group is lowered, while LH concentration is lowered or normal. Conclusion: Abnormal uterine bleeding in adolescents in the most cases is developing in the setting

Arachidonic acid metabolism in fibroblasts derived from canine myocardium

International Nuclear Information System (INIS)

Weber, D.R.; Prescott, S.M.

1986-01-01

Canine fibroblasts from normal or healing infarcted myocardium were grown in culture. The cells were morphologically indistinguishable, but the doubling time of cells from healing myocardium was 39.6 +/- 3.5 hr whereas that of normals was 24 +/- 3.7 (n=5, p 3 H]arachidonate (AA) into phospholipids. Calcium ionophore A23187 (10 μM) caused release and metabolism of [ 3 H] AA. A23187 or AA (10μM) induced production of 6-keto PGF1α, PGE2, and a hydroxy metabolite of AA. RIA of 6-keto PGF1α showed that subconfluent cells from healing myocardium produced 1202 +/- 354 pg/mg protein whereas that of normals was 551 +/- 222 (n=7, p 3 H]AA released but did not metabolize [ 3 H]AA. In coincubations, fibroblasts incorporated myocyte-derived AA. Subsequent stimulation of the fibroblasts with A23187 induced the synthesis of 6-keto PGF1α, PGE2 and a hydroxy metabolite. The fibroblast content of healing myocardium was 35-1000 times that of normal tissue (n=7). Thus even a moderate change in AA metabolism, amplified by the AA released from deteriorating myocytes, may be a significant physiologic or pathologic event

Primary cultured fibroblasts derived from patients with chronic wounds: a methodology to produce human cell lines and test putative growth factor therapy such as GMCSF

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Coppock Donald L

2008-12-01

Full Text Available Abstract Background Multiple physiologic impairments are responsible for chronic wounds. A cell line grown which retains its phenotype from patient wounds would provide means of testing new therapies. Clinical information on patients from whom cells were grown can provide insights into mechanisms of specific disease such as diabetes or biological processes such as aging. The objective of this study was 1 To culture human cells derived from patients with chronic wounds and to test the effects of putative therapies, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF on these cells. 2 To describe a methodology to create fibroblast cell lines from patients with chronic wounds. Methods Patient biopsies were obtained from 3 distinct locations on venous ulcers. Fibroblasts derived from different wound locations were tested for their migration capacities without stimulators and in response to GM-CSF. Another portion of the patient biopsy was used to develop primary fibroblast cultures after rigorous passage and antimicrobial testing. Results Fibroblasts from the non-healing edge had almost no migration capacity, wound base fibroblasts were intermediate, and fibroblasts derived from the healing edge had a capacity to migrate similar to healthy, normal, primary dermal fibroblasts. Non-healing edge fibroblasts did not respond to GM-CSF. Six fibroblast cell lines are currently available at the National Institute on Aging (NIA Cell Repository. Conclusion We conclude that primary cells from chronic ulcers can be established in culture and that they maintain their in vivo phenotype. These cells can be utilized for evaluating the effects of wound healing stimulators in vitro.

Carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Hayakawa, Norihiko

1992-01-01

There are few reports on uterine cancer in relation to radiation. This chapter discusses uterine cancer in A-bomb survivors, with special reference to the mortality rate, in a review of the literature. The Atomic Bomb Casualty Commission has first discovered 28 cases of uterine cancer among A-bomb survivors during the period 1953-1957. Since 1970, mortality rate from uterine cancer has been investigated statistically according to the T65D system. The Radiation Effect Research Foundation (RERF) has revealed 282 death cases from uterine cancer during the period 1950-1974. The RERF's data up to 1982 has revealed no radiation-dependent mortality from uterine cancer. More recent data (1950-1985) has revealed that mortality rate was increased by 22% in A-bomb survivors exposed to 1 Gy or more. When mortality of uterine cancer was investigated statistically using the 1968-1982 data for the population of the Research Institute for Nuclear Medicine and Biology, Hiroshima University, it was 1.2 times higher in the entire exposed group and 1.4 times higher in the group of proximally exposed A-bomb survivors (within 2 km from the hypocenter) than the non-exposed group, with statistically significant difference. It tended to be high in the group of distally exposed A-bomb survivors (who entered the city within 3 days after A-bombing) than the non-exposed group. When comparing the group of Hiroshima City with the group of Hiroshima Prefecture, mortality from uterine cancer was 1.3 times higher in the municipal group for proximally exposed A-bomb survivors and 1.3 times higher in the prefectural group for distally exposed A-bomb survivors and the others. Mortality rate was highest within one year after the acquisition of health handbook in the exposed group. (N.K.)

LXA4 actions direct fibroblast function and wound closure

International Nuclear Information System (INIS)

Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Leung, Kai P.; Van Dyke, Thomas E.

2015-01-01

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A 4 (LXA 4 ), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA 4 on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA 4 receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA 4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA 4 slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA 4 tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA 4 in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF-β1 up-regulates LXA 4 receptor (ALX

Connective tissue fibroblasts and Tcf4 regulate myogenesis

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Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

2011-01-01

Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

Uterine Leiomyoma: Hysterosalpingographic Appearances

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Firoozeh Ahmadi

2008-01-01

Full Text Available Uterine leiomyoma is the most common benign tumor of genital tract. The etiology of myomasis unknown. Leiomyoma shows a broad spectrum of radiographic appearances depending on thenumber, size, and location of the tumor. The diagnostic method for uterine leiomyomas is basedprimarily on the clinical situation. Despite of the varied diagnostic options such as; transvaginalsonography, sonohysterography, hysteroscopy, laparoscopy and MRI; hysterosalpingography isstill one of the valuable imaging methods for identification of uterine leiomyoma.The various features of the proved leiomyoma are illustrated in this pictorial review. The incidence,risk factors and clinical features will also be discussed briefly.

Acute puerperal uterine inversion

International Nuclear Information System (INIS)

Hussain, M.; Liaquat, N.; Noorani, K.; Bhutta, S.Z; Jabeen, T.

2004-01-01

Objective: To determine the frequency, causes, clinical presentations, management and maternal mortality associated with acute puerperal inversion of the uterus. Materials and Methods: All the patients who developed acute puerperal inversion of the uterus either in or outside the JPMC were included in the study. Patients of chronic uterine inversion were not included in the present study. Abdominal and vaginal examination was done to confirm and classify inversion into first, second or third degrees. Results: 57036 deliveries and 36 acute uterine inversions occurred during the study period, so the frequency of uterine inversion was 1 in 1584 deliveries. Mismanagement of third stage of labour was responsible for uterine inversion in 75% of patients. Majority of the patients presented with shock, either hypovolemic (69%) or neurogenic (13%) in origin. Manual replacement of the uterus under general anaesthesia with 2% halothane was successfully done in 35 patients (97.5%). Abdominal hysterectomy was done in only one patient. There were three maternal deaths due to inversion. Conclusion: Proper education and training regarding placental delivery, diagnosis and management of uterine inversion must be imparted to the maternity care providers especially to traditional birth attendants and family physicians to prevent this potentially life-threatening condition. (author)

Uterine restoration after repeated sloughing of fibroids or vaginal expulsion following uterine artery embolization

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Park, Hye Ri; Kim, Nack Keun; Lee, Mee Hwa [Pochon CHA University, Department of Obstetrics and Gynecology, Bundang CHA General Hospital, Sungnam-si, Kyonggi-do (Korea); Kim, Man Deuk; Kim, Hee Jin; Yoon, Sang-Wook [Pochon CHA University, Department of Diagnostic Radiology, Bundang CHA General Hospital, Sungnam-si, Kyonggi-do (Korea); Park, Won Kyu [Yeungnam University, Department of Diagnostic Radiology, Kyongson, Dyongbuk (Korea)

2005-09-01

The aim of our study is to present our experience with uterine restoration after repeated sloughing of uterine fibroids or transvaginal expulsion following uterine artery embolization (UAE) and to determine its safety and outcome. One hundred and twenty-four women (mean age, 40.3 years; age range, 29-52 years) with symptomatic uterine fibroids were included in this retrospective study. We performed arterial embolization with poly(vinyl alcohol) particles (250-710 {mu}m). Clinical symptoms and follow-up information for each patient were obtained through medical records. At an average of 3.5 months (range, 1-8 months) after embolization, magnetic resonance imaging examinations with T1- and T2-weighted and gadolinium-enhanced T1-weighted images were obtained for all patients. The mean follow-up duration was 120 days (90-240 days). Eight (6.5%) patients experienced uterine restoration after repeated sloughing of uterine fibroids or spontaneous transvaginal expulsion. The locations of the leiomyomas were submucosal (n=5), intramural (n=2) and transmural (n=1). The maximum diameter of the fibroids ranged from 3.5 to 18.0 cm, with a mean of 8.4 cm. The time interval from embolization to the uterine restoration was 7-150 days (mean 70.5 days). The clinical symptoms before and during vaginal sloughing or expulsion were lower abdominal pain (n=4), vaginal discharges (n=3), infection of necrotic myomas (n=2) and cramping abdominal pain (n=1). Gentle abdominal compression (n=1) and hysteroscopic assistance (n=1) were required to remove the whole fibroid. No other clinical sequelae, either early or delayed, were documented. Magnetic resonance images revealed the disappearance of leiomyomas, intracavitary rupture resulting in transformation of intramural or transmural myomas into submucosal myomas and localized uterine wall defects. Although the small size of this study precludes a strict conclusion, there appear to be few serious complications directly related to vaginal

Uterine restoration after repeated sloughing of fibroids or vaginal expulsion following uterine artery embolization

International Nuclear Information System (INIS)

Park, Hye Ri; Kim, Nack Keun; Lee, Mee Hwa; Kim, Man Deuk; Kim, Hee Jin; Yoon, Sang-Wook; Park, Won Kyu

2005-01-01

The aim of our study is to present our experience with uterine restoration after repeated sloughing of uterine fibroids or transvaginal expulsion following uterine artery embolization (UAE) and to determine its safety and outcome. One hundred and twenty-four women (mean age, 40.3 years; age range, 29-52 years) with symptomatic uterine fibroids were included in this retrospective study. We performed arterial embolization with poly(vinyl alcohol) particles (250-710 μm). Clinical symptoms and follow-up information for each patient were obtained through medical records. At an average of 3.5 months (range, 1-8 months) after embolization, magnetic resonance imaging examinations with T1- and T2-weighted and gadolinium-enhanced T1-weighted images were obtained for all patients. The mean follow-up duration was 120 days (90-240 days). Eight (6.5%) patients experienced uterine restoration after repeated sloughing of uterine fibroids or spontaneous transvaginal expulsion. The locations of the leiomyomas were submucosal (n=5), intramural (n=2) and transmural (n=1). The maximum diameter of the fibroids ranged from 3.5 to 18.0 cm, with a mean of 8.4 cm. The time interval from embolization to the uterine restoration was 7-150 days (mean 70.5 days). The clinical symptoms before and during vaginal sloughing or expulsion were lower abdominal pain (n=4), vaginal discharges (n=3), infection of necrotic myomas (n=2) and cramping abdominal pain (n=1). Gentle abdominal compression (n=1) and hysteroscopic assistance (n=1) were required to remove the whole fibroid. No other clinical sequelae, either early or delayed, were documented. Magnetic resonance images revealed the disappearance of leiomyomas, intracavitary rupture resulting in transformation of intramural or transmural myomas into submucosal myomas and localized uterine wall defects. Although the small size of this study precludes a strict conclusion, there appear to be few serious complications directly related to vaginal

Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

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François Huaux

Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

Secondary postpartum haemorrhage with uterine artery ...

African Journals Online (AJOL)

a left uterine artery PA, which measured 4 cm in diameter, with extravasation of contrast into a pocket that connected to the uterine cavity. After obtaining the patient's consent, selective left uterine artery embolisation was performed with a mixture of Gelfoam and contrast media, followed by one stainless steel coil insertion.

Cell-free assay measuring repair DNA synthesis in human fibroblasts

International Nuclear Information System (INIS)

Ciarrocchi, G.; Linn, S.

1978-01-01

Osmotic disruption of confluent cultured human fibroblasts that have been irradiated or exposed to chemical carcinogens allows the specific measurement of repair DNA synthesis using dTTP as a precursor. Fibroblasts similarly prepared from various xeroderma pigmentosum cell lines show the deficiencies of uv-induced DNA synthesis predicted from in vivo studies, while giving normal responses to methylmethanesulfonate. A pyrimidine-dimer-specific enzyme, T4 endonuclease V, stimulated the rate of uv-induced repair synthesis with normal and xeroderma pigmentosum cell lines. This system should prove useful for identifying agents that induce DNA repair, and cells that respond abnormally to such induction. It should also be applicable to an in vitro complementation assay with repair-defective cells and proteins obtained from repair-proficient cells. Finally, by using actively growing fibroblasts and thymidine in the system, DNA replication can be measured and studied in vitro

Uterine fibroids

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... Instructions Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - discharge Hysterectomy - vaginal - discharge Uterine artery embolization - discharge Images Pelvic laparoscopy Female ...

Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

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Pomari, Elena; Stefanon, Bruno; Colitti, Monica

2013-12-15

Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process. © 2013 Elsevier B.V. All rights reserved.

KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

International Nuclear Information System (INIS)

Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

2005-01-01

The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

Expression levels of novel cytokine IL-32 in periodontitis and its role in the suppression of IL-8 production by human gingival fibroblasts stimulated with Porphyromonas gingivalis

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Kazuhisa Ouhara

2012-03-01

Full Text Available Background:IL-32 was recently found to be elevated in the tissue of rheumatoid arthritis and inflammatory bowel disease. Periodontitis is a chronic inflammatory disease caused by polymicrobial infections that result in soft tissue destruction and alveolar bone loss. Although IL-32 is also thought to be associated with periodontal disease, its expression and possible role in periodontal tissue remain unclear. Therefore, this study investigated the expression patterns of IL-32 in healthy and periodontally diseased gingival tissue. The expression of IL-32 in cultured human gingival fibroblasts (HGF as well as effects of autocrine IL-32 on IL-8 production from HGF were also examined.Methods:Periodontal tissue was collected from both healthy volunteers and periodontitis patients, and immunofluorescent staining was performed in order to determine the production of IL-32. Using real-time PCR and ELISA, mRNA expression and protein production of IL-32 in HGF, stimulated by Porphyromonas gingivalis (Pg, were also investigated.Results:Contrary to our expectation, the production of IL-32 in the periodontitis patients was significantly lower than in the healthy volunteers. According to immunofluorescent microscopy, positive staining for IL-32 was detected in prickle and basal cell layers in the epithelium as well as fibroblastic cells in connective tissue. Addition of fixed Pg in vitro was found to suppress the otherwise constitutive expression of IL-32 mRNA and protein in HGF. However, recombinant IL-32 in vitro inhibited the expression of IL-8 mRNA by HGF stimulated with Pg. Interestingly, anti-IL-32 neutralizing antibody upregulated the IL-8 mRNA expression in non-stimulated HGF, indicating that constitutive expression of IL-32 in HGF suppressed IL-8 mRNA expression in the absence of bacterial stimulation.Conclusion:These results indicate that IL-32 is constitutively produced by HGF which can be suppressed by Pg and may play a role in the downregulation

A patient-preference cohort study of office versus inpatient uterine polyp treatment for abnormal uterine bleeding.

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Cooper, Natalie A M; Middleton, Lee; Smith, Paul; Denny, Elaine; Stobert, Lynda; Daniels, Jane; Clark, T Justin

2016-01-01

Uterine polyps can cause abnormal bleeding in women. Conventional practise is to remove them under general anaesthesia but advances in technology have made it possible to perform polypectomy in the office setting. We conducted a patient-preference study to explore women's preferences for treatment setting and to evaluate the effectiveness and treatment experience of women undergoing uterine polypectomy. Three hundred ninety-nine women with abnormal uterine bleeding who were found to have uterine polyps at diagnostic hysteroscopy were recruited. Office polypectomies were performed in office hysteroscopy clinics, and inpatient procedures were undertaken in operating theatres. Three hundred twenty-four of 399 (81 %) expressed a preference for office treatment. There was no difference found between office treatment and inpatient treatment in terms of alleviating abnormal uterine bleeding as assessed by patients and in improving disease-specific quality of life. Acceptability was lower and patient pain scores were significantly higher in the office group. When offered a choice of treatment setting for uterine polypectomy, patients have a preference for office over inpatient treatment. Ambulatory gynaecology services should be available within healthcare systems to meet patient demand.

Polypropylene mesh as an alternative option for uterine preservation in pelvic reconstruction in patients with uterine prolapse.

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Huang, Kuan-Hui; Chuang, Fei-Chi; Fu, Hung-Chun; Kung, Fu-Tsai

2012-01-01

  The aim of this study was to evaluate the efficacy and safety of polypropylene mesh for uterine preservation during pelvic reconstruction in patients with severe uterine prolapse. The study included 67 women with severe uterine prolapse (pelvic organ prolapse quantification stage III/IV) who received transvaginal mesh reconstruction with uterine preservation. Surgery combined with a transobturator membrane sling procedure (tension-free vaginal tape-transobturator route) was performed in 54 patients. Among them, 18 had urodynamic stress incontinence, 30 had occult stress urinary incontinence, and six had mixed urinary incontinence. Objective assessments were carried out with the pelvic organ prolapse quantification staging system, urodynamic examination, and 1-h pad test. Evaluation of urinary and prolapse symptoms comprised the subjective assessment. The mean follow-up interval was 19.6 months (12-40 months). The objective cure rate for the treatment of uterine prolapse was 89.5%, and the objective cure rate for the treatment of urinary incontinence was more than 90%. Uterine preservation in pelvic reconstruction is technically feasible and the subjective and objective assessments imply that uterine preservation in pelvic reconstruction is an alternative option for indicated patients. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts.

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Liu, Ying; Geng, Yue-Hang; Yang, Hui; Yang, Han; Zhou, Yan-Ting; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

2018-05-04

Our previous work has demonstrated that extracellular ATP is an important pro-invasive factor, and in this study, we tapped into a possible mechanism involved. We discovered that ATP could upregulate both the intracellular expression and secretion of S100A4 in breast cancer cells and fibroblasts. Apart from stimulating breast cancer cell motility via intracellular S100A4, ATP enhanced the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblast (CAF)-like cells, which in turn secreted S100A4 to further promote cancer cell motility. Both apyrase and niclosamide treatments could inhibit metastasis of inoculated tumors to lung, liver and kidney in mice model, and CAFs from these treated tumors exhibited weakened migration-stimulating capacity for breast cancer cells. Collectively, our data indicate that extracellular ATP promotes the interactions between breast cancer cells and fibroblasts, which work collaboratively via production of S100A4 to exacerbate breast cancer metastasis. Copyright © 2018. Published by Elsevier B.V.

Uterine arterial embolization with PVA particles as a the treatment of uterine leiomyomas (with the analysis of 16 cases)

International Nuclear Information System (INIS)

Zhou Ruming; Liu Minhua; Qiu Shuibo; Zhuang Shaoyu; Yang Huijun

2003-01-01

Objective: To investigate the technic and the clinical effect of uterine arterial embolization as the treatment of uterine leiomyoma. Methods: Bilateral uterine arterial embolization was performed in 16 patients with uterine leiomyomas. The embolic agents were polyvinyl alcohol (PVA) particles sided 350 μm-500 μm in diameter and gelfoam. The clinical manifestations and the size of tumors were investigated in a 6-month post-procedure follow-up. Results: In all patients with hypermenorrhea was relieved, in average the uterine size was reduced by 48.9% and the size of tumor was reduced by 49.2% after the intervention. No serious complication occurred. Conclusion: Uterine arterial embolization is effective in relieving the clinical symptoms and debulking the leiomyoma. it is a valuable technique, and easily accepted by patients

Carp head kidney leukocytes display different patterns of oxygen radical production after stimulation with PAMPs and DAMPs

DEFF Research Database (Denmark)

Jiménez, Natalia Ivonne Vera; Nielsen, Michael Engelbrecht

2013-01-01

. Consistent with a pathogen eradication strategy, ROS responses to PAMP stimulation (β-glucan) was fast, vigorous and highly dominated by production of superoxide anion. In contrast, stimulation with DAMPs led to a slow, subtle but long-lasting production of oxygen radicals dominated by hydrogen peroxide....... Using an in vitro model of scratch-wounded CCB fibroblast cell cultures and a novel PhotoID proliferation assay, stimulation with low and continuous levels of hydrogen peroxide (5μM) led to a slight increase in the percentage of wound recovery and thus promoted wound closure. In contrast, high doses...... and thereby potential tissue damage. Direct in vitro stimulation with β-glucans did not impact fibroblast scratch-wound recovery, which further suggests that interaction with tissue-resident leukocytes or other components of the fish immune system are required to induce fibroblast proliferation and thus...

Technique and methods in uterine leiomyoma embolization

International Nuclear Information System (INIS)

Helmberger, T.K.; Jakobs, T.F.; Reiser, M.F.

2003-01-01

Uterine leiomyomas are the most common benign tumors of the female urogenital tract. Beside the classic surgical treatment options the minimal-invasive embolization therapy of the leiomyomas increasingly gains importance world-wide. Technique, complications, and results of uterine leiomyoma embolization will be presented. After careful evaluation of indications for embolization the procedure is mostly performed under conscious sedation. A single-sided femoral access route together with cross-over technique generally allows for a flow-directed embolization via both uterine arteries. After embolizing the vessels supplying the tumor, the uterine arteries should be still patent. The success rate of embolization of uterine leiomyomas ranges between 85 and 100%, whereas a reduction in size of the tumors in 42 to 83% and a relief of symptoms in up to 96% can be achieved. The total complication rate is about 10% with mainly ''minor complications''. Worldwide only three deaths following embolization of uterine leiomyomas were reported. The high technical and clinical success rate together with a low complication rate make the embolization of uterine leiomyomas a minimally-invasive alternative to the classic treatment. As long term results are not available indication to embolization of uterine leiomyomas must be carefully established in consensus with gynecologists. (orig.) [de

Uterine transplantation: a promising surrogate to surrogacy?

Science.gov (United States)

Grynberg, Michael; Ayoubi, Jean-Marc; Bulletti, Carlo; Frydman, Rene; Fanchin, Renato

2011-03-01

Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility. © 2011 New York Academy of Sciences.

Fibroblast-matrix interplay: Nintedanib and pirfenidone modulate the effect of IPF fibroblast-conditioned matrix on normal fibroblast phenotype.

Science.gov (United States)

Epstein Shochet, Gali; Wollin, Lutz; Shitrit, David

2018-03-12

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM). Normal fibroblast CM served as control. Normal fibroblasts were cultured on both types of CM, and cell count, cell distribution and markers of myofibroblast differentiation; transforming growth factor beta (TGFβ) signalling; and ECM expression were assessed. The effects of the anti-fibrotic drugs nintedanib and pirfenidone at physiologically relevant concentrations were also explored. Normal fibroblasts cultured on IPF-CM arranged in large aggregates as a result of increased proliferation and migration. Moreover, increased levels of pSmad3, pSTAT3 (phospho signal transducer and activator of transcription 3), alpha smooth muscle actin (αSMA) and Collagen1a were found, suggesting a differentiation towards a myofibroblast-like phenotype. SB505124 (10 μmol/L) partially reversed these alterations, suggesting a TGFβ contribution. Furthermore, nintedanib at 100 nmol/L and, to a lesser extent, pirfenidone at 100 μmol/L prevented the IPF-CM-induced fibroblast phenotype alterations, suggesting an attenuation of the ECM-fibroblast interplay. IPF fibroblasts alter the ECM, thus creating a CM that further propagates an IPF-like phenotype in normal fibroblasts. This assay demonstrated differences in drug activities for approved IPF drugs at clinically relevant concentrations. Thus, the matrix-fibroblast phenotype interplay might be a relevant assay to explore drug candidates for IPF treatment. © 2018 Asian Pacific Society of Respirology.

Uterine artery embolisation for uterine leiomyomas

African Journals Online (AJOL)

The presenting symptoms were menorrhagia, dysmenorrhoea, pressure symptoms and intermenstrual bleeding. Three women were treated for primary infertility. Uterine artery sub-selection and embolisation was successful in all patients. Complications included low-grade pyrexia (3/36, 8.3%) and readmission (1/36, 2.8%).

Transvaginal color Doppler imaging of uterine contractions in early pregnancies: Significance of uterine contractions in early pregnancy failure

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun Ju; Han, Chang Jin; Suh, Jung Ho; Kwon, Hyuck Chan [Aju University SChool of Medicine, Suwon (Korea, Republic of)

1999-06-15

To assess uterine contractions in early pregnancies using transvaginal color Doppler sonography (TVCDS) and to determine the role of uterine contractions in the diagnosis of early pregnancy failure. 76 patients with abnormal pregnancy diagnosed by sonography or histopathology up to 10 weeks of gestation and 38 normal pregnant women as the control group were examines with TVCDS. The presence of uterine contractions was determined by complete or partial disappearance of the color flow signals of vessels within myometrium, and the direction, amplitude (grade 1-3), and interval of uterine contractions were also evaluated. Uterine contractions were identified in 42 (55.3%) of 76 patients with abnormal pregnancy, whereas they were detected only in 2 (5.3%) of 38 normal pregnant women who had initial grade 1 contraction but disappeared in the follow-up study. In 26 patients with blighted ovum or missed abortion, 15 patients (57.7%),showed uterine contraction of grade 1 in 3 cases, grade 2 in 8 cases, and grade 3 in 4 cases and interval from 45 seconds to 5 minutes. In 30 patients with inevitable or incomplete abortion, 23 patients (76.6%) showed uterine contraction of grade 1 in 2 cases, grade 2 in 9 cases, and grade 3 in 12 cases and interval from 1 to 5 minutes. 4 (20%) of 20 patients with threatened abortion had uterine contraction of grade 2 and interval from 2 to 4 minutes. The presence of uterine contractions was significantly different in abnormal pregnancies compared with that of normal and also among the tree different groups of abnormal pregnancies, but the amplitude did not differ.

Transvaginal color Doppler imaging of uterine contractions in early pregnancies: Significance of uterine contractions in early pregnancy failure

International Nuclear Information System (INIS)

Lee, Eun Ju; Han, Chang Jin; Suh, Jung Ho; Kwon, Hyuck Chan

1999-01-01

To assess uterine contractions in early pregnancies using transvaginal color Doppler sonography (TVCDS) and to determine the role of uterine contractions in the diagnosis of early pregnancy failure. 76 patients with abnormal pregnancy diagnosed by sonography or histopathology up to 10 weeks of gestation and 38 normal pregnant women as the control group were examines with TVCDS. The presence of uterine contractions was determined by complete or partial disappearance of the color flow signals of vessels within myometrium, and the direction, amplitude (grade 1-3), and interval of uterine contractions were also evaluated. Uterine contractions were identified in 42 (55.3%) of 76 patients with abnormal pregnancy, whereas they were detected only in 2 (5.3%) of 38 normal pregnant women who had initial grade 1 contraction but disappeared in the follow-up study. In 26 patients with blighted ovum or missed abortion, 15 patients (57.7%),showed uterine contraction of grade 1 in 3 cases, grade 2 in 8 cases, and grade 3 in 4 cases and interval from 45 seconds to 5 minutes. In 30 patients with inevitable or incomplete abortion, 23 patients (76.6%) showed uterine contraction of grade 1 in 2 cases, grade 2 in 9 cases, and grade 3 in 12 cases and interval from 1 to 5 minutes. 4 (20%) of 20 patients with threatened abortion had uterine contraction of grade 2 and interval from 2 to 4 minutes. The presence of uterine contractions was significantly different in abnormal pregnancies compared with that of normal and also among the tree different groups of abnormal pregnancies, but the amplitude did not differ.

LXA{sub 4} actions direct fibroblast function and wound closure

Energy Technology Data Exchange (ETDEWEB)

Herrera, Bruno S. [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Leung, Kai P., E-mail: kai.p.leung.civ@mail.mil [Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Van Dyke, Thomas E., E-mail: tvandyke@forsyth.org [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States)

2015-09-04

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

New techniques using transcervical uterine cannulation for the diagnosis of uterine disorders in bitches.

Science.gov (United States)

Watts, J R; Wright, P J; Lee, C S; Whithear, K G

1997-01-01

A technique for collecting uterine samples from bitches without the need for surgery was developed. This technique involved visualizing the cervix with a rigid endoscope and passing a catheter through the cervix into the uterus. Samples for microbiology and cytology were obtained by the infusion and aspiration of sterile normal saline. This technique allowed uterine microbiology and cytology of the normal bitch throughout the reproductive cycle. Microorganisms were frequently recovered from the uterus during pro-oestrus and oestrus, but rarely at other stages of the reproductive cycle. The uterine microflora often reflected the vaginal microflora during pro-oestrus and oestrus. The cells found in uterine cytology samples from normal bitches included endometrial epithelial cells, leukocytes, erythrocytes, cervical cells, spermatozoa and bacteria. The types, proportions, morphology and numbers of cells varied throughout the reproductive cycle. The endoscope could be passed into the uterus and the endometrium examined from parturition until day 23 post partum. These procedures and contrast hysterography were used to investigate the reproductive tract of bitches. The above techniques have facilitated the diagnosis of postpartum metritis (n = 3), pyometra (n = 2), endometritis (n = 1), abortion (n = 1), retained placenta (n = 1), postpartum uterine rupture (n = 1), endometrial subinvolution (n = 1) and misalliance (n = 1) in 21 bitches investigated.

Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser

Science.gov (United States)

Illescas-Montes, Rebeca; Melguizo-Rodríguez, Lucía; Manzano-Moreno, Francisco Javier; García-Martínez, Olga; Ruiz, Concepción

2017-01-01

Background: Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. Methods: The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2–1 W and energy density: 1–7 J/cm2) using different transmission modes (continuous or pulsed). The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. Results: fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm2; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. Conclusion: The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing. PMID:28773152

Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser

Directory of Open Access Journals (Sweden)

Rebeca Illescas-Montes

2017-07-01

Full Text Available Background: Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. Methods: The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2–1 W and energy density: 1–7 J/cm2 using different transmission modes (continuous or pulsed. The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. Results: fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm2; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. Conclusion: The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing.

Biochemical mechanisms of skin radiation burns inhibition and healing by the volumetric autotransplantation of fibroblasts and of keratinocytes with fibroblasts composition

Directory of Open Access Journals (Sweden)

L. V. Altukhova

2015-09-01

the burn area, and mutual stimulation of auto-fibroblasts and auto-keratinocytes to proliferate and to synthesize biologically active substances, i.e. cytokines and growth factors.

Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

LENUS (Irish Health Repository)

Burke, J P

2012-02-01

BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

UTERINE ARTERIOVENOUS MALFORMATION: A CASE REPORT

OpenAIRE

Chandrashekar Murthy; Kiran

2014-01-01

Uterine arteriovenous malformation (AVM) is a rare condition, with less than 100 cases reported in the literature. Despite it being rare, it is a potentially life threatening disease. This case report describes 31- year-old women who presented with abnormal uterine bleeding. Trans abdominal sonography, colour and spectral Doppler imaging was performed, diagnosis was confirmed by non- invasive MRI scan. Laparoscopic bilateral uterine artery ligation was done successfully.

Carcinoma-Associated Fibroblasts Are a Promising Therapeutic Target

International Nuclear Information System (INIS)

Togo, Shinsaku; Polanska, Urszula M.; Horimoto, Yoshiya; Orimo, Akira

2013-01-01

Human carcinomas frequently exhibit significant stromal reactions such as the so-called “desmoplastic stroma” or “reactive stroma”, which is characterised by the existence of large numbers of stromal cells and extracellular matrix proteins. Carcinoma-associated fibroblasts (CAFs), which are rich in activated fibroblast populations exemplified by myofibroblasts, are among the predominant cell types present within the tumour-associated stroma. Increased numbers of stromal myofibroblasts are often associated with high-grade malignancies with poor prognoses in humans. CAF myofibroblasts possess abilities to promote primary tumour development, growth and progression by stimulating the processes of neoangiogenesis as well as tumour cell proliferation, survival, migration and invasion. Moreover, it has been demonstrated that CAFs serve as a niche supporting the metastatic colonisation of disseminated carcinoma cells in distant organs. Their contribution to primary and secondary malignancies makes these fibroblasts a potential therapeutic target and they also appear to be relevant to the development of drug resistance and tumour recurrence. This review summarises our current knowledge of tumour-promoting CAFs and discusses the therapeutic feasibility of targeting these cells as well as disrupting heterotypic interactions with other cell types in tumours that may improve the efficacy of current anti-tumour therapies

Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent skin dermal fibroblast.

Science.gov (United States)

Hou, Jingang; Kim, Sunchang

2018-05-05

Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H 2 O 2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP). The induction of SASP was regulated by p38MAPK/MSK2/NF-κB pathway. Interestingly, inhibition of p38MAPK activation only partially suppressed SASP. However, SASP was significantly inhibited by SB747651A, a specific MSK inhibitor. Additionally, we demonstrate that SASP stimulates migration of keratinocytes and myofibroblast transition of fibroblast, through fold-increased secretion of growth factors, platelet-derived growth factor AA (PDGF-AA) and AB (PDGF-AB), transforming growth factor beta 1 (TGF-β1) and beta 2 (TGF-β2), vascular endothelial growth factor A (VEGF-A) and D (VEGF-D), vascular endothelial growth factor receptor 2 (VEGFR2) and 3 (VEGFR3). Importantly, we also confirmed ginsenoside Rb1 promoted SASP-mediated healing process via p38MAPK/MSK2/NF-κB pathway. The results pointed to senescent fibroblast as a potential mechanism of wound healing control in human skin. Further, it provided a candidate targeted for wound therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

Directory of Open Access Journals (Sweden)

Cornelia Tolg

Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

Protein, RNA, and DNA synthesis in cultures of skin fibroblasts from healthy subjects and patients with rheumatic diseases

International Nuclear Information System (INIS)

Abakumova, O.Y.; Kutsenko, N.G.; Panasyuk, A.F.

1985-01-01

To study the mechanism of the lasting disturbance of fibroblast function, protein, RNA and DNA synthesis was investigated in skin fibroblasts from patients with rheumatoid arthritis (RA) and systemic scleroderma (SS). The labeled precursors used to analyze synthesis of protein, RNA, and DNA were 14 C-protein hydrolysate, ( 14 C)uridine, and ( 14 C) thymidine. Stimulation was determined by measuring incorporation of ( 14 C)proline into fibroblast proteins. During analysis of stability of fast-labeled RNA tests were carried out to discover whether all measurable radioactivity belonged to RNA molecules

Role of MRI in detecting involvement of the uterine internal os in uterine cervical cancer: Systematic review of diagnostic test accuracy

Energy Technology Data Exchange (ETDEWEB)

Boer, Peter de, E-mail: p.deboer@amc.uva.nl [Department of Radiation Oncology, Academic Medical Centre (AMC), University of Amsterdam (UvA), Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Adam, Judit A. [Department of Radiology, AMC, UvA (Netherlands); Department of Nuclear Medicine, AMC, UvA (Netherlands); Buist, Marrije R. [Department of Gynaecology and Obstetrics, AMC, UvA (Netherlands); Vijver, Marc J. van de [Department of Pathology, AMC, UvA (Netherlands); Rasch, Coen R. [Department of Radiation Oncology, Academic Medical Centre (AMC), University of Amsterdam (UvA), Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Stoker, Jaap; Bipat, Shandra [Department of Radiology, AMC, UvA (Netherlands); Stalpers, Lukas J.A. [Department of Radiation Oncology, Academic Medical Centre (AMC), University of Amsterdam (UvA), Meibergdreef 9, 1105 AZ Amsterdam (Netherlands)

2013-09-15

Purpose: In patients with uterine cervical cancer, pretreatment recognition of uterine extension is crucial in treatment decision-making for fertility-sparing surgery and for target delineation in radiotherapy. Although MRI is generally considered the most reliable method, its value for detecting involvement of the uterine internal os is unclear. Methods: Medline, Embase and Cochrane databases were systematically searched (January 1997–December 2012) for MRI studies that measured the accuracy of involvement of the uterine internal os compared to histopathology as reference standard in patients with uterine cervical cancer. Data were assessed using the QUADAS tool. Accuracy concerned either involvement (yes/no) of the uterine internal os, or measuring invasion distance toward the uterine corpus. Results: Two retrospective and two prospective studies described 366 patients diagnosed with uterine cervical cancer FIGO stage IIB or below, in whom 64 (17%) had uterine internal os involvement. For three studies the summary estimates of specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were 91%, 97%, 99%, 79% and 95%, respectively; one study had an area under the curve (AUC) of 0.8. Conclusion: MRI has a high level of accuracy; however, data are limited and for validation a large prospective study is needed that compares actual measurements on MRI with histopathological examination.

Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts

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Chung-Hsun Chang

2014-11-01

Full Text Available BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon.

Medical Treatment of Uterine Leiomyoma

Science.gov (United States)

Sabry, Mohamed; Al-Hendy, Ayman

2012-01-01

Uterine leiomyomas (also called myomata or fibroids) are the most common gynecologic tumors in the United States. The prevalence of leiomyomas is at least 3 to 4 times higher among African American women than in white women. Pathologically, uterine leiomyomas are benign tumors that arise in any part of the uterus under the influence of local growth factors and sex hormones, such as estrogen and progesterone. These common tumors cause significant morbidity for women and they are considered to be the most common indication for hysterectomy in the world; they are also associated with a substantial economic impact on health care systems that amounts to approximately $2.2 billion/year in the United States alone. Uterine myomas cause several reproductive problems such as heavy or abnormal uterine bleeding, pelvic pressure, infertility, and several obstetrical complications including miscarriage and preterm labor. Surgery has traditionally been the gold standard for the treatment of uterine leiomyomas and has typically consisted of either hysterectomy or myomectomy. In recent years, a few clinical trials have evaluated the efficacy of orally administered medications for the management of leiomyoma-related symptoms. In the present review, we will discuss these promising medical treatments in further detail. PMID:22378865

[Development of an Analgesia Therapy System for Delivery Based on Bio-feedback Transcuataneous Electrical Nerve Stimulation].

Science.gov (United States)

Deng Songbo; Lu Yaosheng; Fang, Kun; Qin, Ruyi; Lin, Zhan

2015-06-01

Transcuataneous electrical nerve stimulation (TENS) analgesia as a non-drug method has received people's more and more attention recently. Considering problems of existing products, such as unstable performance and unsatisfied effectiveness, we developed a new analgesia therapy system for delivery based on bio-feedback TENS in our laboratory. We proposed a new idea for stimulation signal design, that is, we modulated a middle frequency signal by a traditional low frequency TENS wave in the new system. We designed different prescription waves for pain relief during a uterine contraction or massage between contractions. In the end, a bio-feedback TENS method was proposed, in which the waveforms of stimulation signals were selected and their parameters were modified automatically based on feedback from uterine pressure, etc. It was proved through quality tests and clinical trials that the system had good performance and satisfied analgesia effectiveness.

Medical Treatment for Uterine Myomas

Directory of Open Access Journals (Sweden)

Ming-Hui Cheng

2008-03-01

Full Text Available Uterine myomas are the most common benign tumors in the female reproductive tract. Most women with myomas are asymptomatic. Therefore, expectant observation and follow-up are often recommended for these myoma patients. However, myomas may cause menstrual symptoms, pelvic pain, pressure complaints, subfer-tility or pregnancy-related complications, with resultant requests for a definitive treatment. The management of myomas has become multidisciplinary in the past 20 years. Basically, the choice of treatment depends on the patient's age, the reason for treatment, the issue of fertility preservation, and the patient's preference. The treatment spectrum includes an expectant management, medical therapy, surgical intervention, uterine artery embolization or ablative techniques. Medical therapy is an option for women with symptomatic myomas who prefer non-surgical treatment, consider fertility preservation, or expect a less aggressive operation after shrinkage of the uterine volume. This review will summarize the recent well-documented drugs for the management of uterine myomas.

Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

Directory of Open Access Journals (Sweden)

Tea eLanisnik Rizner

2012-03-01

Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

Comparative studies on the increase of uterine weight and related mechanisms of cadmium and p-nonylphenol

International Nuclear Information System (INIS)

Zhang Wenchang; Yang Jinsong; Wang Jiali; Xia Pincang; Xu Youqiong; Jia Haimei; Chen Yongshan

2007-01-01

The research was designed to compare the effect of cadmium and p-nonylphenol on the increase of uterine weight and to study the related mechanisms. It provided basic evidence for us to understand the possible different mechanisms among different EEDs. In this study, both ovaries of 60 Wistar rats (28 days age) were ectomized, and after 21 days recovery, the rats were randomly assigned into six groups and exposed to cadmium (0.12, 1.20 mg/kg), NP (100, 200 mg/kg), control (sterile PBS), and positive control (17β-estradiol) per day for 3 days, respectively, then related indexes were detected. The results showed that the increase of uterine weight induced by cadmium was accompanied by the increase of the thickness of luminal epithelium cell and endometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium, while the increase of uterine weight induced by p-nonylphenol was accompanied by the increase of the thickness of luminal epithelium cell, endometrium, and myometrium but the decrease of nuclear/cytoplasm of luminal epithelium cell and endometrium. Cadmium could inhibit the positive expression of PCNA while p-nonylphenol prompted it. Exposure to cadmium and NP both could also stimulate phosphorylation of ERK mitogen-activated protein kinases, implying that this signal pathway had an effect on the increase of the uterine weight induced by cadmium and p-nonylphenol. The results indicate that cadmium may induce the increase of uterine weight, which is accompanied with toxic effect on endometrium, while NP's effect of the increase of uterine weight is due to cell proliferation of endometrium, the mechanisms of which are the same as estrogen, but they may both activate ERK signal pathway

Evaluation on the safety of transcatheter uterine artery embolization for uterine myoma

International Nuclear Information System (INIS)

Li Yong; Chen Xiaoming; Du Juan; Zuo Yuewei; Hu Xiaoping; Luo Pengfei

2005-01-01

Objective: To observe complications of transcatheter uterine artery embolization (TUAE) for uterine fibroids and to evaluate its long-term safety. Methods: One hundred and ninety-eight women with uterine fibroids were treated by TUAE. The bilateral TUAE were performed using lipiodol-pingyangmycineemulsion (LPE) and gelatin sponge particles in 186 women. Among them, 138 patients were followed up for 1 to 3 year and complications were observed. Results: Complications included ecchymosis and ulceration on buttock (n=1); ulcer of labia minora (n=1); urinary retention (n=12); urinary tract infection (n=1); expelling of necrotic fibroids via vagina (n=5); secondary infection of chocolate cyst of ovary (n=1); increasing in endometrial thickness and calcification (n=1) and amenorrhea (n=2). Conclusion: TUAE is a treatment with long-term safety, while severe complications or sequelae may occur to a few patients, so strict indication should be insisted in patient selection. (authors)

Current status, questions and challenges of transcatheter uterine artery embolization for the treatment of uterine fibroids

International Nuclear Information System (INIS)

Chen Xiaoming; Luo Pengfei

2006-01-01

Current status, questions and challenges of transcatheter uterine artery embolization (UAE) in the treatment of uterine fibroids were summarized and analysed. It has been proved that UAE presents a good effectiveness in controlling the symptoms and shrinkage of fibroid and uterine volumes during follow-up of 4 to 6.9 years domestically and abroad, but relapse of the fibroid may however occur in 2 years or longer after UAE. Generally speaking, UAE is safe in the treatment of uterine fibroids but has a possibility of serious complications. UAE has no damage on normal uterine tissues but may affect pregnancy and delivery of patients significantly later on the cause of hypoxia and inertia of uterus. UAE may cause amenorrhea in the minority of women with ovarian failure and endometrium atrophy. The current questions are how to improve long-term efficiency to reduce relapse of tumor and to insure the safety of UAE. It is our further task to exploit more new effective and safe embolic agents by using animal and clinical study on the basic knowledge of pathology, pharmacology, biochemistry, endocrinology and molecular biology. (authors)

Effect of macrophage and matrix metalloproteinase-9 on proliferation of pulmonary fibroblast and synthesis of collagen IV

International Nuclear Information System (INIS)

Song Liangwen; Sun Li; Diao Ruiying; Li Yang; Zhang Yong; Yin Jiye

2006-01-01

Objective: To explore pathogenetic mechanism in initiation of radiation-induced pulmonary fibrosis. Methods: Alveolar macrophages in Wistar rats irradiated by 60 Co γ-ray were collected by alveolar lavage; condition medium was prepared for stimulating human lung fibroblast (HLF) proliferation; HLF proliferation activity was determined by MTT method; collagen IV (Col IV) in HLF was determined by Western blot; the activity of matrix metalloproteinase-9 (MMP-9) was determined by zymography. Results: HLF proliferation activity was significantly increased after stimulation of condition medium, and the increase was most evident within 48-72 hs. Col IV synthesis in HLF was increased and reached a peak at 12 h after stimulation and then began to decrease. MMP-9 activity began to increase at 12 h and reached a peak at 48 h and then decreased after 72 h. Conclusions: Cobalt-60 gamma ray irradiation of 20 Gy can stimulate secretion of some cytokines in alveolar macrophage to promote pulmonary interstitial fibroblast proliferation and synthesis of Col IV . Col IV can stimulate MMP-9 increase; MMP-9 can degrade excess Col IV. Such changes are involved in remodeling process of early pulmonary injury. (authors)

Transformation of human mesenchymal cells and skin fibroblasts into hematopoietic cells.

Directory of Open Access Journals (Sweden)

David M Harris

Full Text Available Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza and the growth factors (GF granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy.

Use of ICD-10 codes to monitor uterine rupture

DEFF Research Database (Denmark)

Thisted, Dorthe L A; Mortensen, Laust Hvas; Hvidman, Lone

2014-01-01

OBJECTIVES: Uterine rupture is a rare but severe complication in pregnancies after a previous cesarean section. In Denmark, the monitoring of uterine rupture is based on reporting of relevant diagnostic codes to the Danish Medical Birth Registry (MBR). The aim of our study was to examine the vali......OBJECTIVES: Uterine rupture is a rare but severe complication in pregnancies after a previous cesarean section. In Denmark, the monitoring of uterine rupture is based on reporting of relevant diagnostic codes to the Danish Medical Birth Registry (MBR). The aim of our study was to examine...... uterine ruptures, the sensitivity and specificity of the codes for uterine rupture were 83.8% and 99.1%, respectively. CONCLUSION: During the study period the monitoring of uterine rupture in the MBR was inadequate....

The management of uterine leiomyomas.

Science.gov (United States)

Vilos, George A; Allaire, Catherine; Laberge, Philippe-Yves; Leyland, Nicholas

2015-02-01

The aim of this guideline is to provide clinicians with an understanding of the pathophysiology, prevalence, and clinical significance of myomata and the best evidence available on treatment modalities. The areas of clinical practice considered in formulating this guideline were assessment, medical treatments, conservative treatments of myolysis, selective uterine artery occlusion, and surgical alternatives including myomectomy and hysterectomy. The risk-to-benefit ratio must be examined individually by the woman and her health care provider. Implementation of this guideline should optimize the decision-making process of women and their health care providers in proceeding with further investigation or therapy for uterine leiomyomas, having considered the disease process and available treatment options, and reviewed the risks and anticipated benefits. Published literature was retrieved through searches of PubMed, CINAHL, and Cochrane Systematic Reviews in February 2013, using appropriate controlled vocabulary (uterine fibroids, myoma, leiomyoma, myomectomy, myolysis, heavy menstrual bleeding, and menorrhagia) and key words (myoma, leiomyoma, fibroid, myomectomy, uterine artery embolization, hysterectomy, heavy menstrual bleeding, menorrhagia). The reference lists of articles identified were also searched for other relevant publications. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to January 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The majority of fibroids are asymptomatic and require no intervention or further

Does Size Really Matter? Analysis of the Effect of Large Fibroids and Uterine Volumes on Complication Rates of Uterine Artery Embolisation

International Nuclear Information System (INIS)

Parthipun, A. A.; Taylor, J.; Manyonda, I.; Belli, A. M.

2010-01-01

The purpose of this study was to determine whether there is a correlation between large uterine fibroid diameter, uterine volume, number of vials of embolic agent used and risk of complications from uterine artery embolisation (UAE). This was a prospective study involving 121 patients undergoing UAE embolisation for symptomatic uterine fibroids at a single institution. Patients were grouped according to diameter of largest fibroid and uterine volume. Results were also stratified according to the number of vials of embolic agent used and rate of complications. No statistical difference in complication rate was demonstrated between the two groups according to diameter of the largest fibroid (large fibroids were classified as ≥10 cm; Fisher's exact test P = 1.00), and no statistical difference in complication rate was demonstrated according to uterine volume (large uterine volume was defined as ≥750 cm 3 ; Fisher's exact test P = 0.70). 84 of the 121 patients had documentation of the number of vials used during the procedure. Patients were divided into two groups, with ≥4 used defined as a large number of embolic agent. There was no statistical difference between these two groups and no associated increased risk of developing complications. This study showed no increased incidence of complications in women with large-diameter fibroids or uterine volumes as defined. In addition, there was no evidence of increased complications according to quantity of embolic material used. Therefore, UAE should be offered to women with large fibroids and uterine volumes.

Uterine massage for preventing postpartum haemorrhage.

Science.gov (United States)

Hofmeyr, G Justus; Abdel-Aleem, Hany; Abdel-Aleem, Mahmoud A

2013-07-01

Postpartum haemorrhage (PPH) (bleeding from the genital tract after childbirth) is a major cause of maternal mortality and disability, particularly in under-resourced areas. In these settings, uterotonics are often not accessible. There is a need for simple, inexpensive techniques which can be applied in low-resourced settings to prevent and treat PPH. Uterine massage is recommended as part of the routine active management of the third stage of labour. However, it is not known whether it is effective. If shown to be effective, uterine massage would represent a simple intervention with the potential to have a major effect on PPH and maternal mortality in under-resourced settings. To determine the effectiveness of uterine massage after birth and before or after delivery of the placenta, or both, to reduce postpartum blood loss and associated morbidity and mortality. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). All published, unpublished and ongoing randomised controlled trials comparing uterine massage alone or in addition to uterotonics before or after delivery of the placenta, or both, with non-massage. Two researchers independently considered trials for eligibility, assessed risk of bias and extracted the data using the agreed form. Data were checked for accuracy. The effect of uterine massage commenced before or after placental delivery were first assessed separately, and then the combined for an overall result. This review included two randomised controlled trials. The first trial included 200 women who were randomised to receive uterine massage or no massage following delivery of the placenta, after active management of the third stage of labour including use of oxytocin. The numbers of women with blood loss more than 500 mL was small, with no statistically significant difference (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.16 to 1.67). There were no cases of retained placenta in either group. The mean

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

Science.gov (United States)

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

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Berndt, Alexander, E-mail: alexander.berndt@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Büttner, Robert, E-mail: Robert-Buettner@gmx.net [Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, 07740 Jena (Germany); Gühne, Stefanie, E-mail: stefanie_guehne@gmx.net [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Gleinig, Anna, E-mail: annagleinig@yahoo.com [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Richter, Petra, E-mail: P.Richter@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Chen, Yuan, E-mail: Yuan.Chen@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Franz, Marcus, E-mail: Marcus.Franz@med.uni-jena.de [Clinic of Internal Medicine I, Jena University Hospital, 07740 Jena (Germany); Liebmann, Claus, E-mail: Claus.Liebmann@uni-jena.de [Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, 07740 Jena (Germany)

2014-04-01

Crosstalk between carcinoma associated fibroblasts (CAFs) and oral squamous cell carcinoma (OSCC) cells is suggested to mediate phenotype transition of cancer cells as a prerequisite for tumour progression, to predict patients’ outcome, and to influence the efficacy of EGFR inhibitor therapies. Here we investigate the influence of activated fibroblasts as a model for CAFs on phenotype and EGFR signalling in OSCC cells in vitro. For this, immortalised hTERT-BJ1 fibroblasts were activated with TGFβ1 and PDGFAB to generate a myofibroblast or proliferative phenotype, respectively. Conditioned media (FCM{sub TGF}, FCM{sub PDGF}) were used to stimulate PE/CA-PJ15 OSCC cells. Results were compared to the effect of conditioned media of non-stimulated fibroblasts (FCM{sub B}). FCM{sub TGF} stimulation leads to an up-regulation of vimentin in the OSCC cells and an enhancement of invasive behaviour, indicating EMT-like effects. Similarly, FCM{sub TGF}≫FCM{sub PDGF} induced up-regulation of EGFR, but not of ErbB2/ErbB3. In addition, we detected an increase in basal activities of ERK, PI3K/Akt and Stat3 (FCM{sub TGF}>FCM{sub PDGF}) accompanied by protein interaction of vimentin with pERK. These effects are correlated with an increased proliferation. In summary, our results suggest that the activated myofibroblast phenotype provides soluble factors which are able to induce EMT-like phenomena and to increase EGFR signalling as well as cell proliferation in OSCC cells. Our results indicate a possible influence of activated myofibroblasts on EGFR-inhibitor therapy. Therefore, CAFs may serve as promising novel targets for combined therapy strategies. - Highlights: • A cell culture model for cancer associated fibroblasts is described. • The mutual interaction with OSCC cells leads to up-regulation of EGFR in tumour cells. • mCAF induces EGFR downstream signalling with increased proliferation in OSCC. • Erk activation is associated with protein interaction with vimentin

Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

International Nuclear Information System (INIS)

Berndt, Alexander; Büttner, Robert; Gühne, Stefanie; Gleinig, Anna; Richter, Petra; Chen, Yuan; Franz, Marcus; Liebmann, Claus

2014-01-01

Crosstalk between carcinoma associated fibroblasts (CAFs) and oral squamous cell carcinoma (OSCC) cells is suggested to mediate phenotype transition of cancer cells as a prerequisite for tumour progression, to predict patients’ outcome, and to influence the efficacy of EGFR inhibitor therapies. Here we investigate the influence of activated fibroblasts as a model for CAFs on phenotype and EGFR signalling in OSCC cells in vitro. For this, immortalised hTERT-BJ1 fibroblasts were activated with TGFβ1 and PDGFAB to generate a myofibroblast or proliferative phenotype, respectively. Conditioned media (FCM TGF , FCM PDGF ) were used to stimulate PE/CA-PJ15 OSCC cells. Results were compared to the effect of conditioned media of non-stimulated fibroblasts (FCM B ). FCM TGF stimulation leads to an up-regulation of vimentin in the OSCC cells and an enhancement of invasive behaviour, indicating EMT-like effects. Similarly, FCM TGF ≫FCM PDGF induced up-regulation of EGFR, but not of ErbB2/ErbB3. In addition, we detected an increase in basal activities of ERK, PI3K/Akt and Stat3 (FCM TGF >FCM PDGF ) accompanied by protein interaction of vimentin with pERK. These effects are correlated with an increased proliferation. In summary, our results suggest that the activated myofibroblast phenotype provides soluble factors which are able to induce EMT-like phenomena and to increase EGFR signalling as well as cell proliferation in OSCC cells. Our results indicate a possible influence of activated myofibroblasts on EGFR-inhibitor therapy. Therefore, CAFs may serve as promising novel targets for combined therapy strategies. - Highlights: • A cell culture model for cancer associated fibroblasts is described. • The mutual interaction with OSCC cells leads to up-regulation of EGFR in tumour cells. • mCAF induces EGFR downstream signalling with increased proliferation in OSCC. • Erk activation is associated with protein interaction with vimentin as sign of EMT. • Results qualify

Area detection of uterine peristalsis using cine-MR images

International Nuclear Information System (INIS)

Sato, Tetsuo; Fujita, Nao; Nakai, Asako; Togashi, Kaori; Kuhara, Shigehide; Okada, Tomohisa

2011-01-01

In this paper, a technique for evaluating uterine peristalsis obtained by magnetic resonance images is proposed. Uterine peristalsis is the wavelike movement of uterine muscle contractions with rhythm and direction. Correlation between direction of uterine peristalsis and menstrual cycle has been reported, which is supposed to help sperm transpotation and implantation. While evaluation of uterine peristalsis has been done, they are very subjective and no quantitative evaluation has been established. In the proposed method the peristalsis area and their contraction intensity were calculated. The points of uterine peristalsis was estimated by the spatio-temporal map, which reflect the time series behavior of the intensities around points set on uterine endometrial boundaries. Then peristalsis area was decided as the estimated points. The contraction intensity was defined as the ratio of the signal intensity change in the peristalsis area. (author)

Uterine sacculation.

Science.gov (United States)

Spearing, G J

1978-01-01

A case of uterine sacculation is reported in which a classic cesarean section was required for safe delivery. The definition and diagnosis of the condition and some difficulties in management are discussed.

Evaluation and management of abnormal uterine bleeding in premenopausal women.

Science.gov (United States)

Sweet, Mary Gayle; Schmidt-Dalton, Tarin A; Weiss, Patrice M; Madsen, Keith P

2012-01-01

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

Directory of Open Access Journals (Sweden)

Yi-Nong Niu

2016-01-01

Full Text Available In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3 cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3 mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun−/− fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride′s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

[Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].

Science.gov (United States)

de Los Rios, P José F; López, R Claudia; Cifuentes, P Carolina; Angulo, C Mónica; Palacios-Barahona, Arlex U

2015-07-01

To evaluate the effectiveness of the hysteroscopic polypectomy in terms of the decrease of the abnormal uterine bleeding. A cross-sectional and analytical study was done with patients to whom a hysteroscopic polypectomy was done for treating the abnormal uterine bleeding, between January 2009 and December 2013. The response to the treatment was evaluated via a survey given to the patients about the behavior of the abnormal uterine bleeding after the procedure and about overall satisfaction. The results were obtained after a hysteroscopic polypectomy done to 128 patients and were as follows. The average time from the polypectomy applied until the survey was 30.5 months, with a standard deviation of 18 months. 67.2% of the patients reported decreased abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On average 82.8% of the. patients were satisfied with the treatment. Bivariate and multivariate analysis showed no association between the variables studied and no improvement of abnormal uterine bleeding after surgery (polypectomy). There were no complications. Hysteroscopic polypectomy is a safe surgical treatment, which decreases on two of three patients the abnormal uterine bleeding in the presence of endometrial polyps, with an acceptable level of satisfaction.

Lajjalu treatment of uterine prolapse

Directory of Open Access Journals (Sweden)

T M Shivanandaiah

2010-01-01

Full Text Available Mimosa pudica was found useful in cases of uterine prolapse with bleeding, consistent with my experience of working with the condition for more than 45 years, and treating hundreds of such cases of uterine prolapse. Hysterectomy has been avoided up to this date, and is not now expected to be recommended.

Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

International Nuclear Information System (INIS)

Wang, Xianwei; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L.

2012-01-01

Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22 phox , p47 phox , p67 phox , NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H 2 O 2 . Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen

Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

Energy Technology Data Exchange (ETDEWEB)

Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

2012-03-15

Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

MR imaging features of the congenital uterine anomalies

International Nuclear Information System (INIS)

Hamcan, S.; Akgun, V.; Battal, B.; Kocaoglu, M.

2012-01-01

Full text: Introduction: Congenital uterine anomalies are common and usually asymptomatic. The agenesis, malfusion or deficient resorption of the Mullerian canals during embryogenesis may lead to these anomalies. Although ultrasonography (US) is the first step imaging technique in assessment of the uterine pathologies, it can be insufficient in differentiation of them. Magnetic resonance (MR) imaging is an adequate imaging technique in depicting pelvic anatomy and different types of uterine anomalies. Objectives and tasks: In this article, we aimed to present imaging features of the uterine anomalies. Material and methods: Pelvic MR scans of the cases who were referred to our radiology department for suspicious uterine anomaly were evaluated retrospectively. Results: We determined uniconuate uterus (type II), uterus didelphys (type III), bicornuate uterus (type IV), uterine septum (type V) and arcuate uterus (type VI) anomalies according to ASRM (American Society of Reproductive Medicine) classification. Conclusion: In cases with such pathologies leading to obstruction, dysmenorrhea or palpable pelvic mass in the puberty are the main clinical presentations. In cases without obstruction, infertility or multiple abortions can be encountered in reproductive ages. The identification of the subtype of the uterine anomalies is important for the preoperative planning of the management. MR that has multiplanar imaging capability and high soft tissue resolution is a non-invasive and the most important imaging modality for the detection and classification of the uterine anomalies

Uterine sarcoma

Science.gov (United States)

... Livingstone; 2014:chap 88. Crum CP, Laury AR, Hirsch MS, Quick CM, Peters WA. Undifferentiated uterine sarcoma. ... Crum CP, Quick CM, Laury AR, Peters WA, Hirsch MS, eds. Gynecologic and Obstetric Pathology . Philadelphia, PA: ...

Diffuse uterine leiomyomatosis in a child

International Nuclear Information System (INIS)

Pai, Deepa; Coletti, Monette C.; Ladino-Torres, Maria; Caoili, Elaine; Elkins, Matthew

2012-01-01

Leiomyomas are the most common benign uterine tumor; however, this entity is relatively uncommon in the pediatric population. Although leiomyomas most commonly present as solitary uterine masses, unusual patterns of growth have been described including diffuse leiomyomatosis. In this condition, the myometrium of the uterus is symmetrically expanded by innumerable confluent leiomyomas; this pattern of growth is quite uncommon and has never been reported in a pediatric patient. This case report illustrates the imaging appearance of diffuse uterine leiomyomatosis in an otherwise healthy 16-year-old girl. (orig.)

Diffuse uterine leiomyomatosis in a child

Energy Technology Data Exchange (ETDEWEB)

Pai, Deepa; Coletti, Monette C.; Ladino-Torres, Maria; Caoili, Elaine [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Elkins, Matthew [University of Michigan Health System, Department of Pathology, Ann Arbor, MI (United States)

2012-01-15

Leiomyomas are the most common benign uterine tumor; however, this entity is relatively uncommon in the pediatric population. Although leiomyomas most commonly present as solitary uterine masses, unusual patterns of growth have been described including diffuse leiomyomatosis. In this condition, the myometrium of the uterus is symmetrically expanded by innumerable confluent leiomyomas; this pattern of growth is quite uncommon and has never been reported in a pediatric patient. This case report illustrates the imaging appearance of diffuse uterine leiomyomatosis in an otherwise healthy 16-year-old girl. (orig.)

A two dimension model of the uterine electrical wave propagation.

Science.gov (United States)

Rihana, S; Lefrançois, E; Marque, C

2007-01-01

The uterus, usually quiescent during pregnancy, exhibits forceful contractions at term leading to delivery. These contractions are caused by the synchronized propagation of electrical waves from the pacemaker cells to its neighbors inducing the whole coordinated contraction of the uterus wall leading to labor. In a previous work, we simulate the electrical activity of a single uterine cell by a set of ordinary differential equations. Then, this model has been used to simulate the electrical activity propagation. In the present work, the uterine cell tissue is assumed to have uniform and isotropic propagation, and constant electrical membrane properties. The stability of the numerical solution imposes the choice of a critical temporal step. A wave starts at a pacemaker cell; this electrical activity is initiated by the injection of an external stimulation current to the cell membrane. We observe synchronous wave propagation for axial resistance values around 0.5 GOmega or less and propoagation blocking for values greater than 0.7 GOmega. We compute the conduction velocity of the excitation, for different axial resistance values, and obtain a velocity about 10 cm/sec, approaching the one described by the literature for the rat at end of term.

SAOS-2 osteosarcoma cells bind fibroblasts via ICAM-1 and this is increased by tumour necrosis factor-α.

Science.gov (United States)

David, Manu S; Kelly, Elizabeth; Cheung, Ivan; Xaymardan, Munira; Moore, Malcolm A S; Zoellner, Hans

2014-01-01

We recently reported exchange of membrane and cytoplasmic markers between SAOS-2 osteosarcoma cells and human gingival fibroblasts (h-GF) without comparable exchange of nuclear markers, while similar h-GF exchange was seen for melanoma and ovarian carcinoma cells. This process of "cellular sipping" changes phenotype such that cells sharing markers of both SAOS-2 and h-GF have morphology intermediate to that of either cell population cultured alone, evidencing increased tumour cell diversity without genetic change. TNF-α increases cellular sipping between h-GF and SAOS-2, and we here study binding of SAOS-2 to TNF-α treated h-GF to determine if increased cellular sipping can be accounted for by cytokine stimulated SAOS-2 binding. More SAOS-2 bound h-GF pe-seeded wells than culture plastic alone (pcells migrating across different microenvironments can influence subsequent interactions with fibroblasts. Since cytokine stimulated binding was comparable in magnitude to earlier reported TNF-α stimulated cellular sipping, we conclude that TNF-α stimulated cellular sipping likely reflects increased SAOS-2 binding as opposed to enhanced exchange mechanisms.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

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Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-06-15

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

International Nuclear Information System (INIS)

Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

2017-01-01

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Chorionic gonadotropin and uterine dialogue in the primate

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Strakova Zuzana

2004-07-01

Full Text Available Abstract Implantation is a complex spatio-temporal interaction between the growing embryo and the mother, where both players need to be highly synchronized to be able to establish an effective communication to ensure a successful pregnancy. Using our in vivo baboon model we have shown that Chorionic Gonadotropin (CG, as the major trophoblast derived signal, not only rescues the corpus luteum but also modulates the uterine environment in preparation for implantation. This response is characterized by an alteration in both the morphological and biochemical activity in the three major cell types: luminal and glandular epithelium and stromal fibroblasts. Furthermore, CG and factors from the ovary have a synergistic effect on the receptive endometrium. Novel local effects of CG which influence the immune system to permit the survival of the fetal allograft and prevent endometrial cell death are also discussed in this review. An alternate extracellular signal-regulated kinase (ERK activation pathway observed in epithelial endometrial cells and the possibility of differential expression of the CG/LH-R isoforms during gestation, open many questions regarding the mechanism of action of CG and its signal transduction pathway within the primate endometrium.

System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.

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Megha Rajaram

Full Text Available Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose five representative fibroblast-secreted factors for in vivo analysis. We found that the majority (three out of five played equally major roles in promoting tumorigenicity, and intriguingly, each one had distinct effects on the tumor microenvironment. Specifically, fibroblast-secreted amphiregulin promoted breast cancer cell survival, whereas the chemokine CCL7 stimulated tumor cell proliferation while CCL2 promoted innate immune cell infiltration and angiogenesis. The other two factors tested had minor (CCL8 or minimally (STC1 significant effects on the ability of fibroblasts to promote tumor growth. The importance of parallel interactions between fibroblasts and cancer cells was tested by simultaneously targeting fibroblast-secreted amphiregulin and the CCL7 receptor on cancer cells, and this was significantly more efficacious than blocking either pathway alone. We further explored the concept of parallel interactions by testing the extent to which induction of critical fibroblast-secreted proteins could be achieved by single, previously identified, factors produced by breast cancer cells. We found that although single factors could induce a subset of genes, even combinations of factors failed to induce the full repertoire of functionally important fibroblast-secreted proteins. Together, these results delineate a complex network of tumor-fibroblast interactions that act in parallel to promote tumorigenicity and suggest that effective anti

Ergosterol peroxide from Cordyceps cicadae ameliorates TGF-β1-induced activation of kidney fibroblasts.

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Zhu, Rong; Zheng, Rong; Deng, Yueyi; Chen, Yiping; Zhang, Shuwei

2014-02-15

Chronic kidney disease is a growing public health problem with an urgent need for new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese medicine. C. cicadae has been used to treat many kinds of diseases and has a potential benefit on renoprotection. This study aimed to investigate the anti-fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by transforming growth factor-β1 (TGF-β1) and EP treatment was applied to explore its potential anti-fibrotic effects. Cell proliferation was investigated using MTT analysis. Fibrosis-associated protein expression was analyzed using immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-β1-induced renal fibroblast proliferation, expression of cytoskeleton protein and CTGF, as well as ECM production. Additionally, EP blocked TGF-β1-stimulated phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-β1-induced expression of fibronectin was attenuated by either inhibition of MAPKs or by EP treatment. In conclusion, our findings demonstrate that EP is able to suppress TGF-β1-induced fibroblasts activation in NRK-49F. This new information provides a line of theoretical evidence supporting the use of C. cicadae in the intervention of kidney disease and suggests that EP has the potential to be developed as a therapeutic agent to prevent renal fibrosis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Uterine rupture without previous caesarean delivery

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Thisted, Dorthe L. A.; H. Mortensen, Laust; Krebs, Lone

2015-01-01

to uterine rupture when adjusted for parity, epidural analgesia and augmentation by oxytocin. CONCLUSION: Although uterine rupture is rare, its association with epidural analgesia and augmentation of labour with oxytocin in multipara should be considered. Thus, vigilance should be exercised when labour...

Uterine mesenchymal tumors

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Nikhil A Sangle

2011-01-01

Full Text Available Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can frequently be diagnostically challenging. Differentiation between the benign and malignant counterparts of mesenchymal tumors is significant due to differences in clinical outcome, and the role of the surgical pathologist in making this distinction (especially in the difficult cases cannot be underestimated. Although immunohistochemical stains are supportive toward establishing a final diagnosis, the morphologic features trump all the other ancillary techniques for this group of neoplasms. This review therefore emphasizes the key morphologic features required to diagnose and distinguish uterine mesenchymal tumors from their mimics, with a brief description of the relevant immunohistochemical features.

Physiological Uptake of 18F-Fluorodeoxyglucose in Uterine Endometrium and Myometrium: Correlation with Uterine Motility Evaluated by Cine Magnetic Resonance Imaging

International Nuclear Information System (INIS)

Kido, A.; Nishizawa, S.; Okada, H.; Nakamoto, Y.; Yamamoto, A.; Fujimoto, K.; Togashi, K.

2009-01-01

Background: Accumulation of 18 F-fluorodeoxyglucose ( 18 F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. Purpose: To investigate the relationship between radiometabolic activity of 18 F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). Material and Methods: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. Results: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32±1.47) than in those without contractions (2.45±0.66). Conclusion: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium

Physiological Uptake of 18F-Fluorodeoxyglucose in Uterine Endometrium and Myometrium: Correlation with Uterine Motility Evaluated by Cine Magnetic Resonance Imaging

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Kido, A.; Nishizawa, S.; Okada, H. (Hamamatsu Medical Imaging Center, Hamamatsu Medical Photonics Foundation, Hamakita City, Shizuoka (Japan)); Nakamoto, Y.; Yamamoto, A.; Fujimoto, K.; Togashi, K. Dept. of Diagnostic Radiology, Kyoto Univ. Hospital, Kyoto City, Kyoto (Japan))

2009-05-15

Background: Accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the uterine endometrium and uterine motility are dependent on menstrual cycle. However, the relationship between them remains unknown. Purpose: To investigate the relationship between radiometabolic activity of 18F-FDG in the uterus and uterine motility observed by cine magnetic resonance imaging (MRI). Material and Methods: The study population consisted of 65 healthy, fertile women, selected from 229 women who underwent positron emission tomography (PET), computed tomography (CT), and MRI for cancer screening at our facility. They were divided into three groups according to their menstrual cycle phases: menstrual, follicular-periovulatory, and luteal. Regions of interest (ROIs) were placed over the endometrium and myometrium to calculate the standardized uptake value (SUV). Uterine peristalsis and contraction shown by cine MR imaging were evaluated visually, and the correlation between FDG uptake and uterine movements was assessed. Results: After excluding nine patients due to inadequate images, 56 patients (19 follicular-periovulatory, 27 luteal, and 10 menstrual) were analyzed. FDG uptake of the endometrium, frequency of peristalsis, and the presence of sustained contraction varied according to the menstruation cycle, with a tendency toward greater uptake in the menstrual phase, but there was little relationship between the frequency of uterine peristalsis and FDG accumulation in the uterus. Significantly higher FDG accumulation in the endometrium was observed in patients with sustained contractions (3.32+-1.47) than in those without contractions (2.45+-0.66). Conclusion: Our preliminary data suggest that FDG accumulation in the endometrium tends to be higher in patients with uterine contraction, although there was no significant correlation between uterine peristalsis and FDG uptake in the uterine myometrium or endometrium

Quantification of epithelial cells in coculture with fibroblasts by fluorescence image analysis.

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Krtolica, Ana; Ortiz de Solorzano, Carlos; Lockett, Stephen; Campisi, Judith

2002-10-01

To demonstrate that senescent fibroblasts stimulate the proliferation and neoplastic transformation of premalignant epithelial cells (Krtolica et al.: Proc Natl Acad Sci USA 98:12072-12077, 2001), we developed methods to quantify the proliferation of epithelial cells cocultured with fibroblasts. We stained epithelial-fibroblast cocultures with the fluorescent DNA-intercalating dye 4,6-diamidino-2-phenylindole (DAPI), or expressed green fluorescent protein (GFP) in the epithelial cells, and then cultured them with fibroblasts. The cocultures were photographed under an inverted microscope with appropriate filters, and the fluorescent images were captured with a digital camera. We modified an image analysis program to selectively recognize the smaller, more intensely fluorescent epithelial cell nuclei in DAPI-stained cultures and used the program to quantify areas with DAPI fluorescence generated by epithelial nuclei or GFP fluorescence generated by epithelial cells in each field. Analysis of the image areas with DAPI and GFP fluorescences produced nearly identical quantification of epithelial cells in coculture with fibroblasts. We confirmed these results by manual counting. In addition, GFP labeling permitted kinetic studies of the same coculture over multiple time points. The image analysis-based quantification method we describe here is an easy and reliable way to monitor cells in coculture and should be useful for a variety of cell biological studies. Copyright 2002 Wiley-Liss, Inc.

Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.

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Amer, Radgonde; Rabinowich, Liane; Maftsir, Genia; Puxeddu, Ilaria; Levi-Schaffer, Francesca; Solomon, Abraham

2010-10-01

To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB). TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry. MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB. MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.

Endovascular uterine artery interventions

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Chandan J Das

2017-01-01

Full Text Available Percutaneous vascular embolization plays an important role in the management of various gynecologic and obstetric abnormalities. Transcatheter embolization is a minimally invasive alternative procedure to surgery with reduced morbidity and mortality, and preserves the patient's future fertility potential. The clinical indications for transcatheter embolization are much broader and include many benign gynecologic conditions, such as fibroid, adenomyosis, and arteriovenous malformations (AVMs, as well as intractable bleeding due to inoperable advanced-stage malignancies. The most well-known and well-studied indication is uterine fibroid embolization. Uterine artery embolization (UAE may be performed to prevent or treat bleeding associated with various obstetric conditions, including postpartum hemorrhage (PPH, placental implantation abnormality, and ectopic pregnancy. Embolization of the uterine artery or the internal iliac artery also may be performed to control pelvic bleeding due to coagulopathy or iatrogenic injury. This article discusses these gynecologic and obstetric indications for transcatheter embolization and reviews procedural techniques and outcomes.

Uterine sarcoma - current perspectives.

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Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases.

S100A4 amplifies TGF-β-induced fibroblast activation in systemic sclerosis

DEFF Research Database (Denmark)

Tomcik, Michal; Palumbo-Zerr, Katrin; Zerr, Pawel

2015-01-01

(SSc). METHODS: The expression of S100A4 was analysed in human samples, murine models of SSc and in cultured fibroblasts by real-time PCR, immunohistochemistry and western blot. The functional role of S100A4 was evaluated using siRNA, overexpression, recombinant protein and S100A4 knockout (S100A4...... or stimulation with recombinant S100A4 induced an activated phenotype in resting normal fibroblasts. In contrast, knockdown of S100A4 reduced the pro-fibrotic effects of TGF-β and decreased the release of collagen. S100A4(-/-) mice were protected from bleomycin-induced skin fibrosis with reduced dermal...

Aberrations in uterine contractile patterns in mares with delayed uterine clearance after administration of detomidine and oxytocin.

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von Reitzenstein, Marcela; Callahan, Megan A; Hansen, Peter J; LeBlanc, Michelle M

2002-09-01

An experiment was conducted to determine whether the uterotonic effects of oxytocin, a drug used to treat mares that have a delay in uterine clearance were affected by the sedative detomidine (an alpha2-agonist), a drug used to treat fractious mares. An additional objective was to identify propagation patterns of uterine contractions and determine whether these patterns differed between normal mares and mares with delayed uterine clearance (DUC). Intrauterine pressure was measured in five reproductively normal mares and four mares with DUC during estrus using an 8-F Milar catheter with two discrete pressure sensors. Mares received one of three treatments in random order: detomidine (0.001 mg/kg; i.v.); detomidine followed in 10 min by oxytocin (10 IU; i.v.); and saline (0.9% NaCl 0.5 ml; i.v.) followed in 10 min by oxytocin. All treatments induced waves of contractions; however, only three mares with DUC exhibited contractions after administration of detomidine. Normal mares experienced more uterine contractions (P detomidine before oxytocin increased the number of contractions (P Detomidine had no effect in mares with delayed clearance. All mares had more propagating than non-propagating uterine contractions (74 +/- 8 versus 25 +/- 8%, respectively). Normal mares exhibited a normal propagation pattern more frequently (P detomidine increased the number (P detomidine augmented the uterotonic effect of oxytocin in normal mares but not in mares with DUC. Data suggest that mares with DUC have a defect in myoelectrical signaling and a decrease in the contractile strength of the uterine muscle.

CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

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Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

1999-06-01

On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

Monophasic Pulsed 200-μA Current Promotes Galvanotaxis With Polarization of Actin Filament and Integrin α2β1 in Human Dermal Fibroblasts.

Science.gov (United States)

Uemura, Mikiko; Maeshige, Noriaki; Koga, Yuka; Ishikawa-Aoyama, Michiko; Miyoshi, Makoto; Sugimoto, Masaharu; Terashi, Hiroto; Usami, Makoto

2016-01-01

The monophasic pulsed microcurrent is used to promote wound healing, and galvanotaxis regulation has been reported as one of the active mechanisms in the promotion of tissue repair with monophasic pulsed microcurrent. However, the optimum monophasic pulsed microcurrent parameters and intracellular changes caused by the monophasic pulsed microcurrent have not been elucidated in human dermal fibroblasts. The purpose of this study was to investigate the optimum intensity for promoting galvanotaxis and the effects of electrical stimulation on integrin α2β1 and actin filaments in human dermal fibroblasts. Human dermal fibroblasts were treated with the monophasic pulsed microcurrent of 0, 100, 200, or 300 μA for 8 hours, and cell migration and cell viability were measured 24 hours after starting monophasic pulsed microcurrent stimulation. Polarization of integrin α2β1 and lamellipodia formation were detected by immunofluorescent staining 10 minutes after starting monophasic pulsed microcurrent stimulation. The migration toward the cathode was significantly higher in the cells treated with the 200-μA monophasic pulsed microcurrent than in the controls (P microcurrent did not alter the migration ratio. The electrostimulus of 200 μA also promoted integrin α2β1 polarization and lamellipodia formation at the cathode edge (P microcurrent intensity to promote migration toward the cathode, and this intensity could regulate polarization of migration-related intracellular factors in human dermal fibroblasts.

In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts

DEFF Research Database (Denmark)

Perentes, Jean Y; McKee, Trevor D; Ley, Carsten D

2009-01-01

Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased...... tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases....

Fibroblastic rheumatism

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Jyoti Ranjan Parida

2017-01-01

Full Text Available Fibroblastic rheumatism (FR is a rare dermoarthopathy reported from different parts of the world since 1980. Although the exact cause is unknown, few reports implicate infection may be a triggering event. Patients usually present with multiple skin nodules and polyarthropathy with progressive skin contractures. Laboratory parameters including acute phase reactants are usually normal. The confirmatory diagnosis is based on histopathologic study of skin nodules, which demonstrate fibroblastic proliferation, thickened collagen fibers, dermal fibrosis, and decreased number of elastic fibers. Immunoreactivity for b-catenin, smooth muscle actin, and the monoclonal antibody HHF35 show myofibroblastic differentiation. Treatments with oral prednisolone and other disease-modifying drugs such as methotrexate, infliximab, and interferon have been tried with variable success. In general, skin lesions respond more aptly than joint symptoms indicating that skin fibroblast is more amenable to treatment than synovial fibroblasts. Awareness regarding this orphan disease among clinicians and pathologists will help in more reporting of such cases and finding out optimal treatment regimen.

Uterine artery chemoembolization: its application in treating cervical pregnancy

International Nuclear Information System (INIS)

Zhang Guofu; Shang Mingyi; Tian Xiaomei; Han Zhigang; Wang Xuezhen; Wang Dongyan; Huang Zirong; Xu Congjian

2009-01-01

Objective: To discuss the feasibility and safety of uterine artery chemoembolization in the treatment of cervical pregnancy. Methods: During the period of Sep. 2005-Dec. 2007, uterine artery chemoemboliztion was performed in 12 patients with cervical pregnancy in the authors' hospital. Via bilateral uterine arteries 100 mg MTX and 80,000 U Gentamycin were infused separately, after that the bilateral uterine arteries were embolized with gelfoam. Cleaning of the uterus and the cervix uteri was carried out in 24 -72 h after the procedure. Results: The technical success rate of bilateral uterine artery chemoembolization was 100%. The blood loss was 50-100 ml (mean 65 ml) during the procedure of cleaning the uterus and the cervix uteri. No serious complications occurred. Conclusion: Uterine artery chemoembolization is an effective and safe treatment for cervical pregnancy, which can greatly avoid unnecessary uterectomy and preserve fertility function. (authors)

Imaging of uterine cervix carcinoma

International Nuclear Information System (INIS)

Viala, J.

2000-01-01

Imaging of uterine cervix carcinoma has evolved during the last decade. Recent developments in magnetic resonance imaging have expanded the role of MRI in evaluating the pathology of uterine cervix carcinoma. MRI is now the modality of choice for tumor staging, evaluating tumor response to treatment, diagnosing recurrences and for evaluating pregnant patients. MRI images will soon be used to calculate dosimetry for brachytherapy with matching and fusion software. (author)

Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

International Nuclear Information System (INIS)

Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

1991-01-01

Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

Transvaginal sonography combined with saline contrast sonohysterography in evaluating the uterine cavity in premenopausal patients with abnormal uterine bleeding

DEFF Research Database (Denmark)

Dueholm, M; Forman, A; Jensen, ML

2001-01-01

OBJECTIVES: To evaluate whether saline contrast sonohysterography (SCSH) adds additional information to that obtained by transvaginal sonography (TVS) for predicting endometrial abnormality in premenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS: This was a two......-center prospective study at a university clinic and a central hospital in Denmark. The uterine cavity was evaluated with TVS and SCSH in 470 premenopausal patients with abnormal uterine bleeding. One hundred and eighty-nine of the patients had operative hysteroscopy or hysterectomy within 4 months which provided...... uterine bleeding. All abnormalities except one were found at SCSH, while TVS alone missed polyps and had almost one in four equivocal findings. The use of TVS, without saline contrast, left one in five of the polyps undiagnosed in referred patients with abnormal bleeding....

Uterine sarcoma – current perspectives

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Benson C

2017-08-01

Full Text Available Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade, undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. Keywords: sarcoma, leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyoma

Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

International Nuclear Information System (INIS)

An, Caiyan; Sato, Koichi; Wu, Taoya; Bao, Muqiri; Bao, Liang; Tobo, Masayuki; Damirin, Alatangaole

2015-01-01

The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

Energy Technology Data Exchange (ETDEWEB)

An, Caiyan [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia (China); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Wu, Taoya; Bao, Muqiri; Bao, Liang [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Damirin, Alatangaole, E-mail: bigaole@imu.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China)

2015-05-01

The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis.

Science.gov (United States)

Ding, Hao; Jiang, Lei; Xu, Jing; Bai, Feng; Zhou, Yang; Yuan, Qi; Luo, Jing; Zen, Ke; Yang, Junwei

2017-09-01

Chronic kidney diseases generally lead to renal fibrosis. Despite great progress having been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear, and so far no effective therapeutic antifibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis. Both gene and protein assay showed that the expression of glycolysis enzymes was upregulated in mouse kidneys with unilateral ureter obstruction (UUO) surgery or in transforming growth factor-β1 (TGF-β1)-treated renal interstitial fibroblasts. Aerobic glycolysis flux, indicated by glucose uptake and lactate production, was increased in mouse kidney with UUO nephropathy or TGF-β1-treated renal interstitial fibroblasts and positively correlated with fibrosis process. In line with this, we found that increasing aerobic glycolysis can remarkably induce myofibroblast activation while aerobic glycolysis inhibitors shikonin and 2-deoxyglucose attenuate UUO-induced mouse renal fibrosis and TGF-β1-stimulated myofibroblast activation. Furthermore, mechanistic study indicated that shikonin inhibits renal aerobic glycolysis via reducing phosphorylation of pyruvate kinase type M2, a rate-limiting glycolytic enzyme associated with cell reliance on aerobic glycolysis. In conclusion, our findings demonstrate the critical role of aerobic glycolysis in renal fibrosis and support treatment with aerobic glycolysis inhibitors as a potential antifibrotic strategy. Copyright © 2017 the American Physiological Society.

Bisphenol A, Dichlorodiphenyltrichloroethane (DDT) and Vinclozolin Affect ex-vivo Uterine Contraction in Rats via Uterotonin (Prostaglandin F2α, Acetylcholine and Oxytocin) Related Pathways.

Science.gov (United States)

Salleh, Naguib; Giribabu, Nelli; Feng, Angeline Oh Mei; Myint, Kyaimon

2015-01-01

Bisphenol-A (BPA), dichrolodiphenyltrichloroethane (DDT) and vinclozolin were found able to induce abnormal uterine contraction. The mechanisms involved remains unclear. We hypothesized that the effect of these compounds were mediated via the uterotonin pathways. Therefore, in this study, effects of BPA, vinclozolin and DDT-only and in combination with uterotonins (PGF-2α, acetylcholine and oxytocin) on the force and pattern of uterine contraction were observed. Uteri were harvested from intact adult female rats 24 hours after a single injection (1 mg/kg/b.w) of estrogen to synchronize their oestrous cycle. The uterine horns were subjected for ex-vivo contraction studies in an organ bath connected to Powerlab data acquisition system. Different doses of BPA, vinclozolin and DDT were added into the bathing solution and changes in the pattern and strength of uterine contraction were recorded. Further, increasing doses of uterotonins were concomitantly administered with these compounds and changes in the force and pattern of contraction were observed. In the absence of uterotonins, uterine contractile force decreased with increasing doses of BPA and DDT. However, vinclozolin induced sharp increase in the contractile forces which then gradually decrease. Administration of BPA, DDT and vinclozolin alone reduced the force of uterine contraction following stimulation of contraction by uterotonins. However, BPA, vinclozolin or DDT effects were relieved upon co-administration with uterotonins at increasing doses. The antagonizing effect of uterotonins on BPA, vinclozolin and DDT actions could explain the mechanism underlying the adverse effect of these compounds on uterine contraction.

Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

International Nuclear Information System (INIS)

Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

1990-01-01

Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

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Clancy, Robert M; Markham, Androo J; Jackson, Tanisha; Rasmussen, Sara E; Blumenberg, Miroslav; Buyon, Jill P

2017-09-01

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA. The top 10 upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response [e.g., IFN-induced protein 44-like (IFI44L), of MX dynamin-like GTPase (MX)1, MX2, and radical S -adenosyl methionine domain containing 2 (Rsad2)]. Within the fibrotic pathway, transcript levels of endothelin-1 (EDN1), phosphodiesterase (PDE)4D, chemokine (C-X-C motif) ligand (CXCL)2, and CXCL3 were upregulated, while others, including adenomedullin, RAP guanine nucleotide exchange factor 3 (RAPGEF3), tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, and dual specificity phosphatase 1, were downregulated. Agnostic Database for Annotation, Visualization and Integrated Discovery analysis revealed a significant increase in inflammatory genes, including complement C3A receptor 1 (C3AR1), F2R-like thrombin/trypsin receptor 3, and neutrophil cytosolic factor 2. In addition, stimulated fibroblasts expressed high levels of phospho-MADS box transcription enhancer factor 2 [a substrate of MAPK5 (ERK5)], which was inhibited by BIX-02189, a specific inhibitor of ERK5. Translation to human disease leveraged an unprecedented opportunity to interrogate the transcriptome of fibroblasts freshly isolated and cell sorted without stimulation from a fetal heart with CHB and a matched healthy heart. Consistent with the in vitro data, five IFN response genes were among the top 10 most highly expressed transcripts in CHB fibroblasts. In addition, the expression of matrix-related genes

Phosphatidylinositol 3,4,5-trisphosphate modulation in SHIP2-deficient mouse embryonic fibroblasts.

Science.gov (United States)

Blero, Daniel; Zhang, Jing; Pesesse, Xavier; Payrastre, Bernard; Dumont, Jacques E; Schurmans, Stéphane; Erneux, Christophe

2005-05-01

SHIP2, the ubiquitous SH2 domain containing inositol 5-phosphatase, includes a series of protein interacting domains and has the ability to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)]in vitro. The present study, which was undertaken to evaluate the impact of SHIP2 on PtdIns(3,4,5)P(3) levels, was performed in a mouse embryonic fibroblast (MEF) model using SHIP2 deficient (-/-) MEF cells derived from knockout mice. PtdIns(3,4,5)P(3) was upregulated in serum stimulated -/- MEF cells as compared to +/+ MEF cells. Although the absence of SHIP2 had no effect on basal PtdIns(3,4,5)P(3) levels, we show here that this lipid was significantly upregulated in SHIP2 -/- cells but only after short-term (i.e. 5-10 min) incubation with serum. The difference in PtdIns(3,4,5)P(3) levels in heterozygous fibroblast cells was intermediate between the +/+ and the -/- cells. In our model, insulin-like growth factor-1 stimulation did not show this upregulation. Serum stimulated phosphoinositide 3-kinase (PI 3-kinase) activity appeared to be comparable between +/+ and -/- cells. Moreover, protein kinase B, but not mitogen activated protein kinase activity, was also potentiated in SHIP2 deficient cells stimulated by serum. The upregulation of protein kinase B activity in serum stimulated cells was totally reversed in the presence of the PI 3-kinase inhibitor LY-294002, in both +/+ and -/- cells. Altogether, these data establish a link between SHIP2 and the acute control of PtdIns(3,4,5)P(3) levels in intact cells.

Endometriosis and uterine malformations: infertility may increase severity of endometriosis.

Science.gov (United States)

Boujenah, Jeremy; Salakos, Eleonora; Pinto, Mélodie; Shore, Joanna; Sifer, Christophe; Poncelet, Christophe; Bricou, Alexandre

2017-06-01

The aim of our study was to compare the stage and severity of endometriosis in fertile and infertile women with congenital uterine malformations. We performed an observational study from September 2007 to December 2015 in a tertiary care university hospital and assisted reproductive technology center. A total of 52 patients with surgically proven uterine malformations were included. We compared 41 infertile patients with uterine malformations with 11 fertile patients with uterine malformation. The main outcome was the stage, score and type of endometriosis in regard to infertility and class of uterine malformation. The rate of endometriosis did not differ between the two groups (43.9 vs. 36.4%). The mean revised American Fertility Society score was higher in infertile patients with uterine malformations (19.02 vs. 6, p endometriosis (43.9 vs. 37.5%). Endometrioma and deep infiltrating endometriosis were associated with uterine malformations in infertile women, respectively 14.6 and 0%. No difference in the characteristics of endometriosis was found regarding the class of malformation. The association of uterine malformations and infertility may increase the severity of endometriosis and raise the issue of their diagnosis and management. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

NARCIS (Netherlands)

García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

2008-01-01

To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc

International Nuclear Information System (INIS)

Nikolova, Ekaterina; Mitev, Vanio; Zhelev, Nikolai; Deroanne, Christophe F.; Poumay, Yves

2007-01-01

Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity

Clinical application of arterial embolization for the treatment of uterine leiomyoma

International Nuclear Information System (INIS)

Wu Wei; Cheng Zhigang; Liu Yongsheng; Xia Huihuan; Luo Fuying; Peng Fang

2003-01-01

Objective: To explore the curative effects, side effects and complications of arterial embolization for the treatment of uterine leiomyoma. Methods: Bilateral uterine arterial embolization with silk particles of 350-500 μm was performed in 16 cases of uterine leiomyomas with uterine hemorrhage as the main complaint. Results: 15 patients underwent technically successful embolization. No serious complications occurred. The patients were followed up for 3-12 months. Menses returned to regular cycle. In the patients with anemia, the hemoglobin concentration rose up to normal level. The sizes of uterine leiomyoma decreased by 52% after 6 months of the treatment. Conclusions: Uterine arterial embolization is an effective and less invasive therapy with no serious complications for patients with uterine leiomyoma, especially for presentation of the uterus

Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment

Directory of Open Access Journals (Sweden)

Martin eAugsten

2014-03-01

Full Text Available Tumor- or cancer-associated fibroblasts (CAFs are one of the most abundant stromal cell types in different carcinomas and comprise a heterogeneous cell population. Classically, CAFs are assigned with pro-tumorigenic effects stimulating tumor growth and progression. More recent studies demonstrated also tumor-inhibitory effects of CAFs suggesting that tumor-residing fibroblasts exhibit a similar degree of plasticity as other stromal cell types. Reciprocal interactions with the tumor milieu and different sources of origin are emerging as two important factors underlying CAF heterogeneity. This review highlights recent advances in our understanding of CAF biology and proposes to expand the term of cellular ´polarization´, previously introduced to describe different activation states of various immune cells, onto CAFs to reflect their phenotypic diversity.

Uterine inflammation affects the reproductive performance of dairy cows: A review

Directory of Open Access Journals (Sweden)

Roger Eduardo Molina-Coto

2018-05-01

Full Text Available Incidence of post- partum uterine disease is an important concern in dairy cattle, because it affects its reproduction. Therefore, the objective of this review of literature was to generate a multifactorial overview about uterine diseases, and the reproductive performance of dairy cows, from a zootechnical approach. Dairy cows face multiple challenges around parturition. Immune suppression around calving, exposition to trauma and uterine bacterial contamination, metabolic diseases, lactation, and changes in management make dairy cows susceptible to uterine diseases. Most cows are able to eliminate uterine infection after calving, however, some cows keep uterine disease. Uterine disease may show clinical signs, but also silent signs that affect fertility as well. Poor reproductive performance is not caused by those signs by themselves, but due to alterations in ovarian and uterine function. Also, the problem of this silent signs is that farmers become aware of the disease when it has already caused negative effects on the reproductiveperformance. Sometimes, uterine disease is still present at the moment of the first service after calving. Uterine diseasemake it harder for cows to get pregnant because it affects the establishment and maintenance of pregnancy, being another cause for infertility, increasing the cull rate and decreasing incomes from the dairy industry.

TRANSVAGINAL SONOGRAPHY COMBINED WITH SALINE CONTRAST SONOHYSTEROGRAPHY IN EVALUATING THE UTERINE CAVITY IN PREMENOPAUSAL PATIENTS WITH ABNORMAL UTERINE BLEEDING

Directory of Open Access Journals (Sweden)

K. G. M. Premleel

2016-06-01

Full Text Available OBJECTIVES To evaluate whether saline contrast sonohysterography (SCSH improved the diagnostic accuracy of transvaginal sonography (TVS for predicting endometrial abnormality in premenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS The uterine cavity was evaluated with TVS and SCSH in 60 premenopausal patients with abnormal uterine bleeding. All 58 patients underwent operative hysteroscopy or hysterectomy within 4 months which provided a detailed description of the uterine cavity and was used as the true value for exclusion of polyps and submucous myomas. RESULT Out of 60 patients, 45 had uterine abnormalities on TVS and SCSH and rest of the patients who appeared normal but had other abnormalities such as ovarian haemorrhagic cyst. Out of the 45 patients, 9 patients had submucous myomas and 9 were diagnosed as endometrial polyp. The findings were confirmed using hysterectomy/hysteroscopy/endometrial sampling. CONCLUSION The use of TVS without saline contrast left nine submucosal fibroids and five in nine of the polyps undiagnosed in referred patients with complaints of abnormal bleeding. It also helps in reducing the rate of more invasive procedures such as hysteroscopy. However, studies carried out for longer duration and large study population are required to validate our findings

Enhanced myometrial autophagy in postpartum uterine involution

Directory of Open Access Journals (Sweden)

Keng-Fu Hsu

2014-09-01

Conclusion: Autophagy of myocytes may play an important role in uterine involution. These results have implications for our understanding of myometrial functional adaptations during pregnancy and the physiological role of autophagy in the uterine remodeling events in the postpartum period.

Uterin Lipoleiomyoma: MR Findings

International Nuclear Information System (INIS)

Batur, Abdussamet; Alpaslan, Muhammed; Dundar, Ilyas; Ozgokce, Mesut; Yavuz, Alpaslan

2015-01-01

Uterine lipoleiomyoma is a rare and specific type of leiomyoma. A 60-year-old postmenopausal woman presented with abdominal pain. Her pelvic ultrasound demonstrated a normal- sized uterus with a well- circumscribed, heterogeneous mass located in the anterior corpus. A pelvic MRI revealed a mass including hyperintense areas on T1-weighted images and hypointense on fat-suppressed T1-weighted images, compatible with lipoleiomyoma. Uterine lipoleiomyomas are often misdiagnosed pre-operatively and it is important to distinguish leiomyomas from other tumors for prevention from supererogatory surgery. Imaging plays an important role for the exact differentiation

Increased expression of electron transport chain genes in uterine leiomyoma.

Science.gov (United States)

Tuncal, Akile; Aydin, Hikmet Hakan; Askar, Niyazi; Ozkaya, Ali Burak; Ergenoglu, Ahmet Mete; Yeniel, Ahmet Ozgur; Akdemir, Ali; Ak, Handan

2014-01-01

The etiology and pathophysiology of uterine leiomyomas, benign smooth muscle tumors of the uterus, are not well understood. To evaluate the role of mitochondria in uterine leiomyoma, we compared electron transport gene expressions of uterine leiomyoma tissue with myometrium tissue in six uterine leiomyoma patients by RT-PCR array. Our results showed an average of 1.562 (±0.445) fold increase in nuclear-encoded electron transport genes. These results might suggest an increase in size, number, or activity of mitochondria in uterine leiomyoma that, to our knowledge, has not been previously reported. © 2014 by the Association of Clinical Scientists, Inc.

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

International Nuclear Information System (INIS)

Fuchigami, Takao; Kibe, Toshiro; Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio; Nishizawa, Yoshiaki; Hijioka, Hiroshi; Fujii, Tomomi; Ueda, Masahiro; Nakamura, Norifumi; Kiyono, Tohru; Kishida, Michiko

2014-01-01

Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

Regulation of IL-6 and IL-8 production by reciprocal cell-to-cell interactions between tumor cells and stromal fibroblasts through IL-1α in ameloblastoma

Energy Technology Data Exchange (ETDEWEB)

Fuchigami, Takao [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kibe, Toshiro [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Koyama, Hirofumi; Kishida, Shosei; Iijima, Mikio [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Nishizawa, Yoshiaki [Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Hijioka, Hiroshi; Fujii, Tomomi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ueda, Masahiro [Natural Science Centre for Research and Education, Kagoshima University, 1-21-24 Koorimoto, Kagoshima 890-8580 (Japan); Nakamura, Norifumi [Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Kiyono, Tohru [Department of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuouku, Tokyo 104-0045 (Japan); Kishida, Michiko, E-mail: kmichiko@m2.kufm.kagoshima-u.ac.jp [Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

2014-09-05

Highlights: • We studied the interaction between tumor cells and fibroblasts in ameloblastoma. • AM-3 ameloblastoma cells secreted significantly high IL-1α levels. • IL-1α derived from AM-3 cells promoted IL-6 and IL-8 secretion of fibroblasts. • IL-6 and IL-8 activated the cellular motility and proliferation of AM-3 cells. - Abstract: Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave

The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

International Nuclear Information System (INIS)

Ndukwe Erlingsson, Uzochi Chimdinma; Iacobazzi, Francesco; Liu, Aiping; Ardon, Orly; Pasquali, Marzia; Longo, Nicola

2013-01-01

Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP + ) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP + accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [ 14 C]-palmitate oxidation (measured as [ 14 C]O 2 release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency

Uterine biology in pigs and sheep

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Bazer Fuller W

2012-07-01

Full Text Available Abstract There is a dialogue between the developing conceptus (embryo-fetus and associated placental membranes and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling, implantation, regulation of gene expression by uterine epithelial and stromal cells, placentation and exchange of nutrients and gases. The uterus provide a microenvironment in which molecules secreted by uterine epithelia or transported into the uterine lumen represent histotroph required for growth and development of the conceptus and receptivity of the uterus to implantation. Pregnancy recognition signaling mechanisms sustain the functional lifespan of the corpora lutea (CL which produce progesterone, the hormone of pregnancy essential for uterine functions that support implantation and placentation required for a successful outcome of pregnancy. It is within the peri-implantation period that most embryonic deaths occur due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. With proper placentation, the fetal fluids and fetal membranes each have unique functions to ensure hematotrophic and histotrophic nutrition in support of growth and development of the fetus. The endocrine status of the pregnant female and her nutritional status are critical for successful establishment and maintenance of pregnancy. This review addresses the complexity of key mechanisms that are characteristic of successful reproduction in sheep and pigs and gaps in knowledge that must be the subject of research in order to enhance fertility and reproductive health of livestock species.

State and development of uterine myoma embolization in Germany

International Nuclear Information System (INIS)

Jakobs, T.F.; Helmberger, T.K.; Reiser, M.F.

2003-01-01

To evaluate the current situation and implementation of embolization of uterine leiomyomas into the treatment concept in women with symptomatic uterine leiomyomas in Germany. A questionnaire addressing the clinical background of uterine myomas, recommended treatment concepts, preclinical evaluation, technical approach and complications was sent to 164 departments of gynecology and radiology in Germany. 33 radiological departments and 19 gynecological departments submitted a completed questionnaire. Only 7 departments of radiology reported to have own experience with embolization of uterine leiomyomas, while only 2 departments of gynecology considered embolization as an alternative treatment option in patients with symptomatic leiomyomas. 18/33 radiological departments offer this treatment option but get no patient referrals. Agreement was found concerning the indications for treatment, preclinical evaluation by ultrasound and MRI, preferable location of treatable fibroids, technical approach and pain management. The embolization of uterine leiomyomas in patients with symptomatic myomas is regardless of the well documented high efficacy and low complication rate not yet an established treatment option in Germany. Interventional radiologists and gynecologists have to evaluate the indications for the embolization of uterine leiomyomas together before the procedure is advised to the patient, because it seems mandatory to add this procedure to the standard armamentarium of treatment options in uterine myomas. (orig.) [de

The application of uterine artery embolization for the treatment of uterine scar pregnancy after cesarean section

International Nuclear Information System (INIS)

Chen Yi; Xie Chunming; Yang Minling; Feng Duiping; Pang Ningdong; Cui Liping; Cui Jinxi; Liu Wenying

2012-01-01

Objective: To assess the clinical value of uterine arterial embolization (UAE) in treating uterine scar pregnancy after cesarean section. Methods: A total of' 35 cases with cesarean scar pregnancy, admitted to authors' hospital during the period from Jan. 2007 to June 2011, were divided into two groups: embolization group (n=21) and non-embolization group (n=14). By using Seldinger technique, UAE was performed via the right femoral access and gelatin sponge particle was used as embolization agent to occlude the uterine artery. In embolization group, sixteen patients received uterine cavity curettage one or two days after UAE, while five patients received laparotomy or perineotomy surgery to remove the lesions after UAE. In non-embolization group, uterine cavity curettage was performed directly in 8 patients, local injection of' methotrexate followed by uterine cavity curettage was carried out in 3 patients, and direct laparotomy to remove the lesions was adopted in the remaining 3 patients. The blood loss during the procedure, the hospitalization days and the time for β-HCG levels falling to normal were documented. The results were compared between the two groups. Results: UAE was successfully accomplished in all the 21 patients of embolization group and the uterus was preserved in all patients. For the embolization group, the mean hospitalization time was (11.5±3.6) days, and the time for β-HCG levels falling to normal was (18.6±4.9) days. For the non-embolization group, the mean hospitalization time was(20.4±5.2)days, and the time for β-HCG levels falling to normal was (28.7±5.6)days. Hysterectomy had to be carried out in two patients of non-embolization group due to the massive bleeding occurred in therapeutic procedures. Conclusion: For the treatment of cesarean scar pregnancy, UAE is very effective and mini-invasive with high success rate. UAE can preserve the patient's reproductive function, and it also plays a significant role in preventing hemorrhage

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

Science.gov (United States)

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Increasing age influences uterine integrity, but not ovarian function or oocyte quality, in the cheetah (Acinonyx jubatus).

Science.gov (United States)

Crosier, Adrienne E; Comizzoli, Pierre; Baker, Tom; Davidson, Autumn; Munson, Linda; Howard, JoGayle; Marker, Laurie L; Wildt, David E

2011-08-01

Although the cheetah (Acinonyx jubatus) routinely lives for more than 12 yr in ex situ collections, females older than 8 yr reproduce infrequently. We tested the hypothesis that reproduction is compromised in older female cheetahs due to a combination of disrupted gonadal, oocyte, and uterine function/integrity. Specifically, we assessed 1) ovarian response to gonadotropins; 2) oocyte meiotic, fertilization, and developmental competence; and 3) uterine morphology in three age classes of cheetahs (young, 2-5 yr, n = 17; prime, 6-8 yr, n = 8; older, 9-15 yr, n = 9). Ovarian activity was stimulated with a combination of equine chorionic gonadotropin and human chorionic gonadotropin (hCG), and fecal samples were collected for 45 days before gonadotropin treatment and for 30 days after oocyte recovery by laparoscopy. Twenty-six to thirty hours post-hCG, uterine morphology was examined by ultrasound, ovarian follicular size determined by laparoscopy, and aspirated oocytes assessed for nuclear status or inseminated in vitro. Although no influence of age on fecal hormone concentrations or gross uterine morphology was found (P > 0.05), older females produced fewer (P 0.05) nuclear status and ability to reach metaphase II and fertilize in vitro. A histological assessment of voucher specimens revealed an age-related influence on uterine tissue integrity, with more than 87% and more than 56% of older females experiencing endometrial hyperplasia and severe pathologies, respectively. Our collective findings reveal that lower reproductive success in older cheetahs appears to be minimally influenced by ovarian and gamete aging and subsequent dysfunction. Rather, ovaries from older females are responsive to gonadotropins, produce normative estradiol/progestogen concentrations, and develop follicles containing oocytes with the capacity to mature and be fertilized. A more likely cause of reduced fertility may be the high prevalence of uterine endometrial hyperplasia and related

Perfusion-weighted MR imaging of uterine leiomyoma

Energy Technology Data Exchange (ETDEWEB)

Takase, Hiroyasu; Munechika, Hirotsugu [Showa Univ., Tokyo (Japan). School of Medicine

2001-06-01

Serial images of uterine leiomyoma in gradient-echo, echo-planar, magnetic resonance imaging were taken to draw a {delta}R2{sup *} curve after intravenous bolus injection of Gd-DTPA. The {delta}R2{sup *} integral was calculated from a {delta}R2{sup *} curve to have relative perfusion of uterine leiomyoma. We then, evaluated the amount of perfusion correlated with MR findings, size and number of leiomyoma or the clinical symptoms and established that perfusion was correlated positively with the findings of T2 weighted images and clinical symptoms but not with other MR findings or size and number of leiomyoma. In conclusion, we presumed that the clinical symptoms could be reduced by decreasing of an amount of perfusion of uterine leiomyoma in some means. However, it remained uncertain why severe clinical symptoms were associated with a high amount of perfusion in uterine leiomyomas. (author)

Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration

DEFF Research Database (Denmark)

Angebault, Claire; Gueguen, Naig; Desquiret-Dumas, Valerie

2011-01-01

to impairment in some cases and stimulation in others. Conclusion: These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment....... of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements. Results: Complex I activity was 42% greater in treated fibroblasts compared to controls (p = 0.002). Despite this complex I activity improvement, the effects on mitochondrial respiration were contradictory, leading...

Insulin binding and stimulation of hexose and amino acid transport by normal and receptor-defective human fibroblasts

International Nuclear Information System (INIS)

Longo, N.; Nagata, N.; Danner, D.; Priest, J.; Elsas, L.

1986-01-01

The authors analyzed insulin receptors in cells cultured from a sibship of related parents who had two offspring with severe insulin resistance (Leprechaunism). 124 I-Insulin (1 ng/ml) binding to skin fibroblasts from the proband, mother, and father was 9, 60 and 62% of control cells, respectively, at equilibrium, Non-linear regression analysis, utilizing a two receptors model, of curvilinear Scatchard plots indicated a reduced number of high-affinity binding sites in both parents. Influx of L-Proline (System A), L-Serine (ASC) and L-Leucine (L) was similar in control and mutant cells. Similarly, during the depletion of intracellular amino acid pools, there was a release from transinhibition for System A and a decrease of transstimulation of Systems ASC and L in both cell lines. Surprisingly, insulin augmented, normally, A system influx with an ED 50 = 70 ng/ml at 24 0 C and 7 ng/ml at 37 0 C. By contrast insulin failed to simulated 3-0-methyl-D-glucose influx into the proband's cells, while normal cells were stimulated 30% with an ED 50 of 6 ng/ml. These results indicate that defective high-affinity insulin binding is inherited as an autosomal recessive trait; that general membrane functions are intact; that insulin regulates A system amino acid and hexose transport by two different mechanisms; and, that the latter mechanism is impaired by this family's receptor mutation

Uterine artery embolisation for uterine fibroids using a 4F Rosch inferior mesenteric catheter

International Nuclear Information System (INIS)

Ho, Simon S.M.; Cowan, Nigel C.

2005-01-01

Purpose:To evaluate in a prospective study the use of a 4F Rosch inferior mesenteric (RIM) catheter for uterine artery embolisation (UAE). UAE was performed in 72 women over a 37-month period. A 4F RIM braided J-curve 65-cm catheter was used in combination with an angled hydrophilic 150 cm, 0.035'' flexible tip guide-wire to catheterise the horizontal portion of both uterine arteries (UA) from a right common femoral artery (CFA) approach. Technical success was defined as successful catheterisation and embolisation of both uterine arteries. Fluoroscopic and procedure times were recorded. Mean subject age=43.7 years (range=25-57 years). Technical success was 98.6% (n=71/72). A single approach via the right CFA was used in 88.9% (n=64/72) and a bilateral CFA approach in 11.1% (n=8/72). Bilateral uterine artery catheterisation using a single 4F RIM catheter via the right CFA approach was successful in 79.2% (n=57/72). Microcatheters were used in 2.8% of patients (n=2/72). Mean fluoroscopic time=13.6±5.3 min (mean±SD). Mean procedure time=44.2±16.5 min. High technical success rate for UAE is possible using a single 4F RIM catheter via a unilateral right CFA approach, which obviates the need for Waltman loop formation, reversed curve catheters and complex suture-catheter arrangements. (orig.)

Uterine fibroid embolization

International Nuclear Information System (INIS)

Totev, M.

2013-01-01

Full text: Introduction: Today, after numerous lengthy randomized trials embolization of uterine fibroids has become a standard treatment. Percutaneous embolization of myomas is a micro - invasive surgery, which can be regarded as an alternative to traditional surgery. Although these data 2/3 of the patients were not informed about this treatment option. What you will learn: The uterine embolization is minimal invasive non-surgical procedure. It is an alternative treatment to surgery. Under local anesthesia in the femoral artery puncture reaches the internal iliac artery and uterine arteries. Reached selectively by the catheter and chemicals, which causes clogging, are injected into them. In the vessels that feed fibroids occur a process like an attack, the feeding stops, it starts to shrink and it is replaced by fibrous tissue. The blood vessels of the healthy tissue are different in size and have a plurality of collateral connections as opposed to those of the myoma and thus the blood supply to the normal tissue of the uterus is not distorted. Discussion: Nowadays there are more well- calibrated materials for embolization and those with a particle size of about 700µ are proven as the most successful. The procedure is well tolerated, but after a pain occurs, which has to be covered with anesthetics. Usually pain and metrorrhagia disappear immediately. The fibroids themselves shrink to varying degrees. Hospital stay was significantly shorter than that after surgery, and remained fertile power. Complications are few and rare require further treatment. Multiple nodes are problematic and it is difficult to detect the primary one. A three and six months tracking by MRI is desirable. Conclusion: Embolization of uterine myoma is an established method of treatment primarily on clinical symptoms resulting therefrom. In all patients rapidly disappear metrorrhagia symptoms and morbidity, the volume of the assembly decrease, which together with shorter hospital stays and

Effect of magnetic resonance imaging characteristics on uterine fibroid treatment

Directory of Open Access Journals (Sweden)

Duc NM

2018-04-01

Full Text Available Nguyen Minh Duc, Huynh Quang HuyDepartment of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, VietnamAbstract: Uterine fibroids are the most common gynecological benign tumors adversely affecting the quality of life of women of a reproductive age. Magnetic resonance imaging (MRI is efficient at localizing the site of lesions and characterizing uterine fibroids before treatment. Understanding the different characteristics of uterine fibroids on MRI is essential, because it not only enables prompt diagnosis, but also guides the development of suitable therapeutic methods. This pictorial review demonstrates the effect of MRI features on uterine fibroid treatment. Keywords: uterine fibroids, characteristics, magnetic resonance imaging, treatments

Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

Energy Technology Data Exchange (ETDEWEB)

Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

2017-07-15

Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

Clinical evaluation of high dose rate intra-cavitary irradiation for treatment of uterine cervical cancer, combined with pepleomycin suppository in uterine cavity

International Nuclear Information System (INIS)

Yamanashi, Shunji; Abe, Tatsuyuki; Mochizuki, Sachio; Murakami, Yoshitaka; Iida, Nobuhisa.

1990-01-01

By means of re-irradiation using pepleomycin suppository in uterine cavity, we attained local control for one patient who had local recurrence in uterine cavity and suffered from uterine fluor in which viable cancer cells were confirmed. We were enlightened by this therapeutic experience, so we attempted combination therapy using pepleomycin suppositories to supplement intra-cavitary irradiation, for the 11 selected patients who were suffering from uterine fluor. We investigated the treatment results in 7 patients of stage III out of 11 patients (of all stages), in comparison with 13 patients of stage III who were treated by irradiation alone. Consequently, these treatment results were approximately equivalent, and the incidence of sigmoid complications could be decreased. Side effects which were followed by the combination therapy were not serious, and so we believe that pepleomycin suppository is a simple method and valuable to supplement radiation therapy of uterine cervical cancer. (author)

Clinical evaluation of high dose rate intra-cavitary irradiation for treatment of uterine cervical cancer, combined with pepleomycin suppository in uterine cavity

Energy Technology Data Exchange (ETDEWEB)

Yamanashi, Shunji; Abe, Tatsuyuki; Mochizuki, Sachio (Jikei Univ., Tokyo (Japan). School of Medicine); Murakami, Yoshitaka; Iida, Nobuhisa

1990-02-01

By means of re-irradiation using pepleomycin suppository in uterine cavity, we attained local control for one patient who had local recurrence in uterine cavity and suffered from uterine fluor in which viable cancer cells were confirmed. We were enlightened by this therapeutic experience, so we attempted combination therapy using pepleomycin suppositories to supplement intra-cavitary irradiation, for the 11 selected patients who were suffering from uterine fluor. We investigated the treatment results in 7 patients of stage III out of 11 patients (of all stages), in comparison with 13 patients of stage III who were treated by irradiation alone. Consequently, these treatment results were approximately equivalent, and the incidence of sigmoid complications could be decreased. Side effects which were followed by the combination therapy were not serious, and so we believe that pepleomycin suppository is a simple method and valuable to supplement radiation therapy of uterine cervical cancer. (author).

Uterine artery embolization for adenomyosis without fibroids

Energy Technology Data Exchange (ETDEWEB)

Kim, M.D. E-mail: mdkim@cha.ac.kr; Won, J.W.; Lee, D.Y.; Ahn, C.-S

2004-06-01

AIM: To evaluate the potential usefulness of transcatheter uterine artery embolization as a treatment for symptomatic adenomyosis in patients without uterine fibroids. MATERIALS AND METHODS: Uterine artery embolization using polyvinyl alcohol particles sized 250-710 mm was performed in 43 patients (mean; 40.3 years, range; 31-52 years) with dysmenorrhoea, menorrhagia, or bulk-related symptoms (pelvic heaviness, urinary frequency) due to adenomyosis without fibroids. All patients underwent pre-procedural and 3.5 months (range 1-8 months) follow-up magnetic resonance imaging (MRI) with contrast enhancement. Clinical symptoms were also assessed at the time of MRI before and after embolization. RESULTS: Significant improvement of dysmenorrhoea (95.2%) and menorrhagia (95.0%) was reported in most patients. Contrast-enhanced MRI revealed non-enhancing areas suggesting coagulation necrosis of adenomyosis in 31 patients (72.1%), decreased size without necrosis in 11 patients (25.6%), and no change in one patient (2.3%). The mean volume reduction of the uteri after uterine artery embolization was 32.5% (from 321.7{+-}142.9 to 216.7{+-}130.1 cm{sup 3}). CONCLUSION: Transcatheter uterine artery embolization is an effective therapy for the treatment of symptomatic pure adenomyosis, and may be a valuable alternative to hysterectomy.

Uterine artery embolization for adenomyosis without fibroids

International Nuclear Information System (INIS)

Kim, M.D.; Won, J.W.; Lee, D.Y.; Ahn, C.-S.

2004-01-01

AIM: To evaluate the potential usefulness of transcatheter uterine artery embolization as a treatment for symptomatic adenomyosis in patients without uterine fibroids. MATERIALS AND METHODS: Uterine artery embolization using polyvinyl alcohol particles sized 250-710 mm was performed in 43 patients (mean; 40.3 years, range; 31-52 years) with dysmenorrhoea, menorrhagia, or bulk-related symptoms (pelvic heaviness, urinary frequency) due to adenomyosis without fibroids. All patients underwent pre-procedural and 3.5 months (range 1-8 months) follow-up magnetic resonance imaging (MRI) with contrast enhancement. Clinical symptoms were also assessed at the time of MRI before and after embolization. RESULTS: Significant improvement of dysmenorrhoea (95.2%) and menorrhagia (95.0%) was reported in most patients. Contrast-enhanced MRI revealed non-enhancing areas suggesting coagulation necrosis of adenomyosis in 31 patients (72.1%), decreased size without necrosis in 11 patients (25.6%), and no change in one patient (2.3%). The mean volume reduction of the uteri after uterine artery embolization was 32.5% (from 321.7±142.9 to 216.7±130.1 cm 3 ). CONCLUSION: Transcatheter uterine artery embolization is an effective therapy for the treatment of symptomatic pure adenomyosis, and may be a valuable alternative to hysterectomy

Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

Energy Technology Data Exchange (ETDEWEB)

Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Karhemo, Piia-Riitta [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Räsänen, Kati [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Laakkonen, Pirjo [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Vaheri, Antti [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland)

2016-07-01

Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.

Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients.

Science.gov (United States)

Zamarrón, Alicia; García, Marta; Río, Marcela Del; Larcher, Fernando; Juarranz, Ángeles

2017-09-29

PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.

Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

Science.gov (United States)

Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

2015-10-01

Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

Surgical findings at laparatomy for uterine fibroid in University of ...

African Journals Online (AJOL)

A three year review of the surgical findings at Laparotomy for uterine fibroids at the ... that uterine fibroid plays a role in the process of spontaneous conception. ... Other factors found to be associated with uterine fibroid are the numbers, size, ...

Diffusion-weighted MR imaging of uterine leiomyomas following uterine artery embolization

International Nuclear Information System (INIS)

Sutter, Olivier; Shotar, Eimad; Guerrache, Youcef; Place, Vinciane; Oprea, Raluca; Le Dref, Olivier; Boudiaf, Mourad; Soyer, Philippe; Dohan, Anthony; Dautry, Raphael; Sirol, Marc; Ricbourg, Aude

2016-01-01

To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI). Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE. By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 x 10"-"3 mm"2/s vs. 0.712 x 10"-"3 mm"2/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization. Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect. (orig.)

Diffusion-weighted MR imaging of uterine leiomyomas following uterine artery embolization

Energy Technology Data Exchange (ETDEWEB)

Sutter, Olivier; Shotar, Eimad; Guerrache, Youcef; Place, Vinciane; Oprea, Raluca; Le Dref, Olivier; Boudiaf, Mourad [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Soyer, Philippe; Dohan, Anthony [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Universite Paris-Diderot, Sorbonne Paris Cite, Paris (France); UMR INSERM 965, Hopital Lariboisiere, Paris (France); Dautry, Raphael; Sirol, Marc [Hopital Lariboisiere, AP-HP, Department of Body and Interventional Imaging, Paris (France); Universite Paris-Diderot, Sorbonne Paris Cite, Paris (France); Ricbourg, Aude [Hopital Lariboisiere-AP-HP, Department of Obstetrics and Gynecology, Paris (France)

2016-10-15

To test whether variations in apparent diffusion coefficient (ADC) values of uterine leiomyomas after uterine artery embolization (UAE) may correlate with outcome and assess the effects of UAE on leiomyomas and normal myometrium with magnetic resonance imaging (MRI). Data of 49 women who underwent pelvic MRI before and after UAE were retrospectively reviewed. Uterine and leiomyoma volumes, ADC values of leiomyomas, and normal myometrium were calculated before and after UAE. By comparison with baseline ADC values, a significant drop in leiomyoma ADC was found at 6-month post-UAE (1.096 x 10{sup -3} mm{sup 2}/s vs. 0.712 x 10{sup -3} mm{sup 2}/s, respectively; p < 0.0001), but not at 48-h post-UAE. Leiomyoma devascularization was complete in 40/49 women (82 %) at 48 h and in 37/49 women (76 %) at 6 months. Volume reduction and leiomyoma ADC values at 6 months correlated with the degree of devascularization. There was a significant drop in myometrium ADC after UAE. Perfusion defect of the myometrium was observed at 48 h in 14/49 women (28.5 %) in association with higher degrees of leiomyoma devascularization. Six months after UAE, drop in leiomyoma ADC values and volume reduction correlate with the degree of leiomyoma devascularization. UAE affects the myometrium as evidenced by a drop in ADC values and initial myometrial perfusion defect. (orig.)

Effects of mechanical strain on human mesenchymal stem cells and ligament fibroblasts in a textured poly(L-lactide) scaffold for ligament tissue engineering.

Science.gov (United States)

Kreja, Ludwika; Liedert, Astrid; Schlenker, Heiter; Brenner, Rolf E; Fiedler, Jörg; Friemert, Benedikt; Dürselen, Lutz; Ignatius, Anita

2012-10-01

The purpose of this study was to prove the effect of cyclic uniaxial intermittent strain on the mRNA expression of ligament-specific marker genes in human mesenchymal stem cells (MSC) and anterior cruciate ligament-derived fibroblasts (ACL-fibroblasts) seeded onto a novel textured poly(L-lactide) scaffold (PLA scaffold). Cell-seeded scaffolds were mechanically stimulated by cyclic uniaxial stretching. The expression of ligament matrix gene markers: collagen types I and III, fibronectin, tenascin C and decorin, as well as the proteolytic enzymes matrix metalloproteinase MMP-1 and MMP-2 and their tissue specific inhibitors TIMP-1 and TIMP-2 was investigated by analysing the mRNA expression using reverse transcriptase polymerase chain reaction and related to the static control. In ACL-fibroblasts seeded on PLA, mechanical load induced up-regulation of collagen types I and III, fibronectin and tenascin C. No effect of mechanical stimulation on the expression of ligament marker genes was found in undifferentiated MSC seeded on PLA. The results indicated that the new textured PLA scaffold could transfer the mechanical load to the ACL-fibroblasts and improved their ligament phenotype. This scaffold might be suitable as a cell-carrying component of ACL prostheses.

Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

International Nuclear Information System (INIS)

Schweikert, H.U.; Hein, H.J.; Romijn, J.C.; Schroeder, F.H.

1982-01-01

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC

Preterm labor--modeling the uterine electrical activity from cellular level to surface recording.

Science.gov (United States)

Rihana, S; Marque, C

2008-01-01

Uterine electrical activity is correlated to the appearance of uterine contractions. forceful contractions appear at the end of term. Therefore, understanding the genesis and the propagation of uterine electrical activity may provide an efficient tool to diagnose preterm labor. Moreover, the control of uterine excitability seems to have important consequences in the control of preterm labor. Modeling the electrical activity in uterine tissue is thus an important step in understanding physiological uterine contractile mechanisms and to permit uterine EMG simulation. Our model presented in this paper, incorporates ion channel models at the cell level, the reaction diffusion equations at the tissue level and the spatiotemporal integration at the uterine EMG reconstructed level. This model validates some key physiological observation hypotheses concerning uterine excitability and propagation.

Uterine sarcoma – current perspectives

Science.gov (United States)

Benson, Charlotte; Miah, Aisha B

2017-01-01

Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade), undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. PMID:28919822

ERα inhibited myocardin-induced differentiation in uterine fibroids

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Liao, Xing-Hua, E-mail: xinghualiao@hotmail.com [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Li, Jun-Yan [Henan Vocational College of Applied Technology, Zhengzhou 450042 (China); Dong, Xiu-Mei [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Yuncheng County People' s Hospital, Shandong 274700 (China); Wang, Xiuhong [Xianning Central Hospital, Department of Obstetrics and Gynecology, Xianning, Hubei 437100 (China); Xiang, Yuan; Li, Hui; Yu, Cheng-Xi; Li, Jia-Peng; Yuan, Bai-Yin [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Zhou, Jun, E-mail: zhoujun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); School of Medicine, Wuhan University of Science and Technology, Wuhan 430065 (China); Zhang, Tong-Cun, E-mail: zhangtongcun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

2017-01-01

Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibroids have barely been addressed. We noticed that the expression of myocardin was markedly reduced in human uterine fibroid tissue compared with corresponding normal or adjacent myometrium tissue. Here we reported that myocardin induced the transcription and expression of differentiation markers SM22α and alpha smooth muscle actin (α-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ERα. Notably, we showed that, ERα induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ERα interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22α promoter activity. Furthermore, ERα inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22α, a SMC differentiation marker. Our data thus provided important and novel insights into how ERα and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.

Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression.

Science.gov (United States)

Shannon, Diane B; McKeown, Scott T W; Lundy, Fionnuala T; Irwin, Chris R

2006-01-01

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha-SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor -beta1 and -beta3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7-day period. alpha-SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme-linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor-beta1 and -beta3, over the concentration range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel contraction and alpha-SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.

Use of abdominal binder as anti-shock garment; an adjunct to uterine tamponade in uterine atony

International Nuclear Information System (INIS)

Kallue, U.R.; Chughtai, F.; Chaudry, A.; Shamin, Z.

2017-01-01

Objective: Aim of the study was to control life threatening post partum haemorrhage (PPH) in women till blood and blood products were made available or the women transferred to a better equipped centre. Study Design: A prospective interventional consecutive case series. Place and Duration of Study: It was conducted in three hospitals; Heavy Industries Taxila (HIT) hospital Apr 2005 to Sep 2010, Pakistan Ordinance Factories (POF) hospital Wah cantt Oct 2011 to Dec 2014 and Combined Military Hospital (CMH) Tarbela Dec 2014 to Dec 2015. Material and Methods: Abdominal binder was used in 22 consecutive women, having moderate to severe primary PPH due to uterine atony, where despite uterotonics (i.v oxytocin, rectal misoprostol) and bimanual compression, uterine tamponade was performed but complete control of haemorrhage was not achieved. Protocols for the treatment of obstetric haemorrhage and hypotensive shock were observed, including administration of intravenous crystalloid fluids and blood transfusion. If required, surgery was performed in the form of uterine arteries ligation or B-Lynch sutures. Obstetric hysterectomy was performed to save the woman's life if conservative procedures failed. Results: Bleeding and hypotension were controlled successfully in 19 (86.4%) of these women. In 03 (14.6%) women, bleeding persisted and so hysterectomy had to be resorted to. There was no maternal mortality. At 06 weeks postnatal follow up, none of the patients were found to suffer from long term debility; physical or psychological. Conclusion: Abdominal binder was found to be very effective in controlling bleeding and hypotensive crisis due to significant PPH due to uterine atony, as an adjunct to uterine tamponade. (author)

Role of bevacizumab in uterine leiomyosarcoma.

Science.gov (United States)

Bogani, Giorgio; Ditto, Antonino; Martineli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Fonatella, Caterina; Sanfilippo, Roberta; Leone Roberti Maggiore, Umberto; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

2018-06-01

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of chlorhexidine, essential oils and herbal medicines (Salvia, Chamomile, Calendula) on human fibroblast in vitro.

Science.gov (United States)

Wyganowska-Swiatkowska, Marzena; Urbaniak, Paulina; Szkaradkiewicz, Anna; Jankun, Jerzy; Kotwicka, Malgorzata

2016-01-01

Antiseptic rinses have been successfully used in inflammatory states of the gums and oral cavity mucosa. Antibacterial effects of chlorhexidine, essential oils and some herbs are well documented. Reaction of host tissue to these substances has much poorer documentation. The aim of the study was to analyse the influence of chlorhexidine (CHX), essential oil (EO: thymol, 0.064%; eucalyptol, 0.092%; methyl salicylate, 0.060%; menthol, 0.042%) mouth rinses and salvia, chamomile and calendula brews on fibroblast biology in vitro. The human fibroblast CCD16 line cells were cultured in incubation media which contained the examined substances. After 24 and 48 hours, the cell morphology, relative growth and apoptosis were evaluated. Exposure of fibroblasts to CHX, EO or salvia caused various changes in cell morphology. Cells cultured for 48 hours with CHX revealed a noticeably elongated shape of while cells cultured in high EO concentration or with salvia were considerably smaller and contracted with fewer projections. Chlorhexidine, EO and salvia reduced the fibroblast proliferation rate and stimulated cell death. Both reactions to EO were dose dependent. Cells exposure to chamomile or calendula brews did not change morphology or proliferation of fibroblasts. The results of this in vitro study showed that in contrast to chamomile and calendula, the brews of EO, CHX or salvia had a negative influence on fibroblast biology.

Uterine Cancer Statistics

Science.gov (United States)

... Doing AMIGAS Stay Informed Cancer Home Uterine Cancer Statistics Language: English (US) Español (Spanish) Recommend on Facebook ... the most commonly diagnosed gynecologic cancer. U.S. Cancer Statistics Data Visualizations Tool The Data Visualizations tool makes ...

Dynamical analysis of uterine cell electrical activity model.

Science.gov (United States)

Rihana, S; Santos, J; Mondie, S; Marque, C

2006-01-01

The uterus is a physiological system consisting of a large number of interacting smooth muscle cells. The uterine excitability changes remarkably with time, generally quiescent during pregnancy, the uterus exhibits forceful synchronized contractions at term leading to fetus expulsion. These changes characterize thus a dynamical system susceptible of being studied through formal mathematical tools. Multiple physiological factors are involved in the regulation process of this complex system. Our aim is to relate the physiological factors to the uterine cell dynamic behaviors. Taking into account a previous work presented, in which the electrical activity of a uterine cell is described by a set of ordinary differential equations, we analyze the impact of physiological parameters on the response of the model, and identify the main subsystems generating the complex uterine electrical activity, with respect to physiological data.

A large uterine leiomyoma leading to non-puerperal uterine inversion: A case report

Directory of Open Access Journals (Sweden)

Batool Teimoori

2017-08-01

Full Text Available Background: Although leiomyomas are the most common gynecologic disorders, non-puerperal uterine inversion due to leiomyoma is considered as a rare clinical problem. This condition can occur as a complication of a large sub-mucous leiomyoma that leads to dilate cervix and protrude into vagina. The patient may have several symptoms such as heavy vaginal bleeding, pelvic pain and intermittent acute urinary retention. Case: We presented a 32-year-old nulliparous woman with 17 years of unexplained infertility and diagnosis of a large vaginal prolapsed non-pedunculated leiomyoma. Conclusion: Haultain’s procedure was used to reposition uterine inversion and remove leiomyoma through a posterior incision, using laparotomy

The effect of valinomycin in fibroblasts from patients with fatty acid oxidation disorders

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Ndukwe Erlingsson, Uzochi Chimdinma [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Iacobazzi, Francesco [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); Department of Basic Medical Sciences, University of Bari, Piazza Giulio Cesare 11, Policlinico, I-70124 Bari (Italy); Liu, Aiping [ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Ardon, Orly; Pasquali, Marzia [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States); Longo, Nicola, E-mail: Nicola.Longo@hsc.utah.edu [Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Mario Capecchi Drive, Salt Lake City, UT 84132 (United States); ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108 (United States); Department of Pathology, University of Utah, Salt Lake City, UT 84132 (United States)

2013-08-09

Highlights: •Valinomycin can cause mitochondrial stress and stimulate fatty acid oxidation. •Cells with VLCAD deficiency fail to increase fatty acid oxidation in response to valinomycin. •Response to valinomycin can help in the diagnosis of VLCAD deficiency. -- Abstract: Disorders of the carnitine cycle and of the beta oxidation spiral impair the ability to obtain energy from fats at time of fasting and stress. This can result in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic medical problems. The in vitro study of fibroblasts from patients with these conditions is impaired by their limited oxidative capacity. Here we evaluate the capacity of valinomycin, a potassium ionophore that increases mitochondrial respiration, to increase the oxidation of fatty acids in cells from patients with inherited fatty acid oxidation defects. The addition of valinomycin to fibroblasts decreased the accumulation of the lipophilic cation tetraphenylphosphonium (TPP{sup +}) at low concentrations due to the dissipation of the mitochondrial membrane potential. At higher doses, valinomycin increased TPP{sup +} accumulation due to the increased potassium permeability of the plasma membrane and subsequent cellular hyperpolarization. The incubation of normal fibroblasts with valinomycin increased [{sup 14}C]-palmitate oxidation (measured as [{sup 14}C]O{sub 2} release) in a dose-dependent manner. By contrast, valinomycin failed to increase palmitate oxidation in fibroblasts from patients with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts from patients heterozygous for this condition. These results indicate that valinomycin can increase fatty acid oxidation in normal fibroblasts and could be useful to differentiate heterozygotes from patients affected with VLCAD deficiency.

Uterine cancer in the writings of ancient Greek physicians.

Science.gov (United States)

Tsoucalas, Gregory; Karamanou, Marianna; Sgantzos, Markos; Deligeoroglou, Efthimios; Androutsos, George

2015-01-01

In this article, we present the views on uterine cancer of the ancient Greek physicians. We emphasize on uterine's cancer aetiology according to the dominant in antiquity humoural theory, on its surgical treatment suggested by Soranus of Ephesus, and in the vivid description provided by Aretaeus of Cappadocia. During that period, uterine cancer was considered as an incurable and painful malignancy and its approach was mainly palliative.

Incidence and clinical characteristics of unexpected uterine sarcoma after hysterectomy and myomectomy for uterine fibroids: a retrospective study of 10,248 cases

Directory of Open Access Journals (Sweden)

Zhao WC

2015-10-01

Full Text Available Wan-Cheng Zhao,1 Fang-Fang Bi,1 Da Li,2 Qing Yang11Department of Obstetrics and Gynecology, 2Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaBackground: Uterine fibroids often require a hysterectomy or myomectomy via laparotomy or laparoscopy. Morcellation is often necessary to perform a laparoscopic surgery. The objective of this study is to determine the incidence of unexpected uterine sarcomas (UUSs after hysterectomy and myomectomy for uterine fibroids and to reduce the occurrence and avoid the morcellation of UUSs by analyzing their characteristics.Methods: Women who had a hysterectomy or myomectomy for uterine fibroids in Shengjing Hospital of China Medical University between November 2008 and November 2014 were selected for the study, and their clinical characteristics were analyzed.Results: During the period, 48 UUSs were found in 10,248 cases, and the overall incidence was 0.47%. There was no statistical difference (P=0.449 regarding the incidence (0.50% vs 0.33% between 42 UUSs in 8,456 cases undergoing laparotomy and six UUSs in 1,792 cases undergoing laparoscopy. Most of the UUSs were stage I (89.58%, which occurred more commonly (56.25% in women aged 40–49. Abnormal uterine bleeding (39.58% was the main clinical manifestation. Rapidly growing pelvic masses (12.5%, rich blood flow signals (18.75%, and degeneration of uterine fibroids (18.75% prompted by ultrasonography may suggest the possibility of UUSs. The margins of most UUSs (93.75% were regular, which may cause UUSs to be misdiagnosed as uterine fibroids. Fifteen cases underwent magnetic resonance imaging examinations. Approximately 73.33% showed heterogeneous and hypointense signal intensity on T1-weighted images, and 80% showed intermediate-to-high signal intensity on T2-weighted images, with necrosis and hemorrhage in 40% of cases. After contrast administration, 80% presented early heterogeneous

Serial ultrasonographic appearance of postpartum uterine involution in beagle dogs.

Science.gov (United States)

Yeager, A E; Concannon, P W

1990-09-01

Postpartum changes in uterine shape, architecture, echogenicity and diameter were determined during the serial examinations of five beagle bitches. During postpartum Week 1, the uterine horns were tubular structures composed of multiple layers of various echogenicity and had multiple, discrete enlargements with hypoechoic centers at placental sites. Diameters ranged from 1.1 to 3.8 cm at placental site enlargements, and 0.5 to 1.4 cm between enlargements. Uterine involution appeared to be completed by 15 wk post partum. At 15 weeks the uterine horns of each dog were uniform hypoechoic, tubular structures without enlargements and had a reduced diameter of 0.3 to 0.6 cm. These ultrasonographic findings are similar to previously reported gross and light microscopic descriptions of canine uterine involution.

Embolization of Uterine Arteriovenous Malformations Associated with Cyanotic Congenital Heart Disease

International Nuclear Information System (INIS)

Wijesekera, N. T.; Padley, S. P.; Kazmi, F.; Davies, C. L.; McCall, J. M.

2009-01-01

Uterine arteriovenous malformation (AVM) is a rare cause of vaginal bleeding and miscarriage. We report two cases of uterine AVMs in patients with a history of complex congenital heart disease, an association that has not been previously described. Both patients were treated by selective uterine artery embolization, a minimally invasive therapy that has revolutionized the management of uterine AVMs, thus offering an alternative to conventional hysterectomy.

Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

Science.gov (United States)

Marinković, Aleksandar; Mih, Justin D.; Park, Jin-Ah; Liu, Fei

2012-01-01

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation. PMID:22659883

Abnormal Uterine Bleeding: American College of Nurse-Midwives.

Science.gov (United States)

2016-07-01

Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach. © 2016 by the American College of Nurse-Midwives.

Uterine fibroid management: from the present to the future

Science.gov (United States)

Donnez, Jacques; Dolmans, Marie-Madeleine

2016-01-01

Abstract Uterine fibroids (also known as leiomyomas or myomas) are the most common form of benign uterine tumors. Clinical presentations include abnormal bleeding, pelvic masses, pelvic pain, infertility, bulk symptoms and obstetric complications. Almost a third of women with leiomyomas will request treatment due to symptoms. Current management strategies mainly involve surgical interventions, but the choice of treatment is guided by patient's age and desire to preserve fertility or avoid ‘radical’ surgery such as hysterectomy. The management of uterine fibroids also depends on the number, size and location of the fibroids. Other surgical and non-surgical approaches include myomectomy by hysteroscopy, myomectomy by laparotomy or laparoscopy, uterine artery embolization and interventions performed under radiologic or ultrasound guidance to induce thermal ablation of the uterine fibroids. There are only a few randomized trials comparing various therapies for fibroids. Further investigations are required as there is a lack of concrete evidence of effectiveness and areas of uncertainty surrounding correct management according to symptoms. The economic impact of uterine fibroid management is significant and it is imperative that new treatments be developed to provide alternatives to surgical intervention. There is growing evidence of the crucial role of progesterone pathways in the pathophysiology of uterine fibroids due to the use of selective progesterone receptor modulators (SPRMs) such as ulipristal acetate (UPA). The efficacy of long-term intermittent use of UPA was recently demonstrated by randomized controlled studies. The need for alternatives to surgical intervention is very real, especially for women seeking to preserve their fertility. These options now exist, with SPRMs which are proven to treat fibroid symptoms effectively. Gynecologists now have new tools in their armamentarium, opening up novel strategies for the management of uterine fibroids. PMID

Neomycin inhibits PDGF-induced IP3 formation and DNA synthesis but not PDGF-stimulated uptake of inorganic phosphate in C3H/10T1/2 fibroblasts.

Science.gov (United States)

Vassbotn, F S; Langeland, N; Holmsen, H

1990-09-01

Porcine PDGF was found to increase [3H]inositol trisphosphate, [3H]thymidine incorporation and 32P-labelling of polyphosphoinositides in C3H/10T1/2 Cl 8 fibroblasts. These responses to PDGF stimulation were all inhibited by 5 mM neomycin, a polycationic aminoglycoside formerly known to inhibit polyphosphoinositide turnover. PDGF also markedly increased the cellular uptake of inorganic [32P]Pi. This response of PDGF was not inhibited by neomycin (5 mM). Thus, neomycin inhibited PDGF-induced IP3 formation, 32P-labelling of polyphosphoinositides and DNA synthesis, but not cellular uptake of inorganic phosphate. These effects of neomycin suggest a bifurcation of the initial part of the PDGF-induced signal transduction, separating at the receptor level or before phospholipase C activation.

Non-Puerperal Uterine Inversion: A Case Report

OpenAIRE

Fofie, C O; Baffoe, P

2010-01-01

Non-puerperal uterine inversion is rare. A 42-year old woman presented with lower abdominal pain, offensive vaginal discharge and a huge protruding mass per vaginum. A clinical diagnosis of non-puerperal uterine inversion was made and she successfully underwent vaginal hysterectomy. A high index of suspicion is required to make a prompt diagnosis.

Uterine bacterial flora in postpartum Danish Holstein dairy cows determined using DNA-based fingerprinting: Correlation to uterine condition and calving management

DEFF Research Database (Denmark)

Elkjær, K.; Ancker, M.-L.; Gustafsson, H.

2013-01-01

The overall aim of this study was to describe uterine bacterial flora during the postpartum period in Danish Holstein cows using the Terminal Restriction Fragment Length Polymorphism (T-RFLP) method. This method produces a pattern of nucleic acid fragments from the microorganisms present, reflect......The overall aim of this study was to describe uterine bacterial flora during the postpartum period in Danish Holstein cows using the Terminal Restriction Fragment Length Polymorphism (T-RFLP) method. This method produces a pattern of nucleic acid fragments from the microorganisms present......, reflecting the “fingerprint” of the actual microbial flora. As well as characterizing changes in flora with time from calving and between herds, data were examined for strong relations between uterine bacterial flora, calving management and uterine condition. In total 125 Holstein cows from five herds were...... included, and for each cow calving management was recorded. Cows were clinically examined on average 8 (range 0–19) and 28 (range 22–38) days after calving, and a uterine sample was taken for bacterial identification using T-RFLP. Milk samples were taken weekly for progesterone analysis. Bacteria were...

Uterine fibroid embolisation: Initial experience in our local population

International Nuclear Information System (INIS)

Jawad, R.A.; Rehman, I.; Rana, A.I.; Tariq, N.; Tariq, N.

2013-01-01

Objective: To evaluate the results of uterine fibroid embolisation as a treatment option for symptomatic uterine fibroids in the local population. Methods: The retrospective study was done at the Department of Diagnostic and Interventional Radiology, Shifa International Hospital, Islamabad, and comprised records of 12 patients with symptomatic uterine fibroids who had undergone uterine fibroid embolisation with the use of polyvinyl alcohol between May 2008 and July 2012. All of these patients had been assessed by a gynaecologist. Pre-embolisation workup was done by pelvic Magnetic Resonance Imaging. A detailed questionnaire was prepared to assess clinical improvement and interval change in fibroid size on follow-up imaging. Results: A technically successful embolisation was done in all patients. All patients experienced immediate post-procedure pain, but responded to conservative treatment. Clinical follow-up showed a significant reduction in symptoms within six months of the procedure, with 88% improvement in menorrhagia and 100% improvement in pain. Follow-up imaging showed reduction in fibroid sizes ranging from 17-63%. Two patients developed infection, which is a known complication of this procedure. Conclusion: Uterine fibroid embolisation is a well-recognised treatment option for symptomatic uterine fibroids. Ascertaining its long-term results in our local population will, however, require additional studies with larger patient populations. (author)

3D DSA findings of uterine artery and its optimal projection position

International Nuclear Information System (INIS)

Lu Weifu; Zhang Aiwu; Zhou Chunze; Lu Dong; Xiao Jingkun; Wang Weiyu; Zhang Xingming; Zhang Zhengfeng; Hou Changlong

2011-01-01

Objective: to observe the origin site, anatomic features of uterine artery with 3D DSA and to discuss the optimal projection position in order to improve the success rate of super-selective catheterization of uterine artery. Methods: Prospective pelvic angiography was performed in 42 adult females (a total of 84 uterine arteries). 3D DSA was carried out with 206 ° rotation. 3D reconstruction of the obtained images was performed and the angiographic manifestations of the uterine artery were analyzed. The optimal projection position for the displaying of uterine artery was discussed. The quality of images obtained with the projection angle of 15 °-25 °, 25 °-35 ° and 35 °-45 ° was determined and the results were compared with each other. Results: The orifices of all 84 uterine arteries could be well demonstrated on 3D DSA images. The uterine artery was originated from the anterior trunk of internal iliac artery (n=58, 69%), from main stem of internal iliac artery (n=16, 19.1%), from internal pudenda artery (n=8, 9.5%) and from inferior gluteal artery (n=2, 2.4%). The best projection position to show the opening and route of the uterine artery was contralateral oblique view of 25-35 degrees (P<0.05). Conclusion: 3D DSA can clearly display the anatomy of the uterine artery, which is very helpful for the management of super-selective catheterization of uterine artery. The optimal projection position for uterine artery is contralateral oblique view of 25-35 degrees. (authors)

Obstructive Small Bowel Metastasis from Uterine Leiomyosarcoma: A Case Report

Directory of Open Access Journals (Sweden)

Mutahir A. Tunio

2014-01-01

Full Text Available Background. Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy with an overall poor prognosis. Lungs, bones, and brain are common sites of metastases of uterine leiomyosarcoma. Metastases of uterine leiomyosarcoma to the small bowel are extremely rare, and only four case reports have been published to date. Case presentation. A 55-year-old Saudi woman diagnosed with a case of uterine leiomyosarcoma treated with total abdominal hysterectomy (TAH and bilateral salpingooophorectomy (BSO presented in emergency room after sixteen months with acute abdomen. Subsequent work-up showed a jejunal mass for which resection and end-to-end anastomosis were performed. Biopsy confirmed the diagnosis of small bowel metastasis from uterine leiomyosarcoma. Further staging work-up showed wide spread metastasis in lungs and brain. After palliative cranial irradiation, systemic chemotherapy based on single agent doxorubicin was started. Conclusion. Metastatic leiomyosarcoma of small bowel from uterine leiomyosarcoma is a rare entity and is sign of advanced disease. It should be differentiated from primary leiomyosarcoma of small bowel as both are treated with different systemic chemotherapeutic agents.

Regulation and inhibition of collagenase expression by long-wavelength ultraviolet radiation in cultured human skin fibroblasts

International Nuclear Information System (INIS)

Petersen, Marta; Hamilton, Tiffani; Haili Li

1995-01-01

The cellular mechanisms responsible for the connective tissue changes produced by chronic exposure to UV light are poorly understood. collagenase, a metalloproteinase, initiates degradation of types I and III collagen and thus plays a key role in the remodeling of dermal collagen. Collagenase synthesis by fibroblasts and keratinocytes involves the protein kinase C (PKC) second messenger system, and corticosteroids have been shown to suppress its synthesis at the level of gene transcription. Long-wavelength UV light (UVA, 320-400 nm) stimulates the synthesis of interstitial collagenase, as well as increasing PKC activity, in human skin fibroblasts in vitro. This study explores the regulation of collagenase expression by UVA in cultured human skin fibroblasts. Specifically, the time course, the effect of actinomycin D, an inhibitor of RNA synthesis, as well as the effect of PKC inhibitors and dexamethansone on expression of collagenase following UVA irradiation were examined. (Author)

Apparatus for treating carcinoma of the uterine cervix

International Nuclear Information System (INIS)

Kumar, P.P.

1984-01-01

Disclosed is an apparatus for treating carcinoma of the uterine cervix by judiciously applying radioactive material immediately adjacent the uterine cervix for an extended period of time empirically determined by the radiologist. The novel apparatus comprises three radioactively chargeable components including a central tubular tandem vaginally insertable longitudinally into the uterine cervix and two non-lineal tubular ovoidal assemblies longitudinally locatable at the cervix and positioned laterally between the respective vaginal walls and the uterine cervix. The ovoidal assemblies are conveniently removably and pivotably connected to the central tandem component externally of the vaginal along the sagittal plane through a novel adapter member whereby the radioactively chargeable ovoidal assemblies tend to remain within a laterally extending plane located substantially midway the transversely separated vasicovaginal and rectovaginal septa, even though the patient periodically shifts her reclining posture during the extended treatment by said vaginally protruding apparatus

Importance of histopathological examination of endometrium in Dysfunctional Uterine Bleeding.

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Dr. Yaminee Rana

2017-12-01

Full Text Available Introduction: Abnormal uterine bleeding is a common condition affecting women of reproductive age that has significant social and economic impact. Dysfunctional uterine bleeding (DUB is defined as abnormal uterine bleeding in the absence of organic disease. Dysfunctional uterine bleeding is one of the most commonly encountered gynaecological problems. Objectives: This study is done to evaluate the histopathological pattern of the endometrial biopsies of patients with dysfunctional uterine bleeding and its correlation with clinical data. Methods: The present prospective study included evaluation of 208 cases of dysfunctional uterine bleeding in the Department of Pathology, B. J. Medical College, Ahmedabad over a period of 10 months, from January 2017 to October 2017. Women presenting with abnormal uterine bleeding were included in the study. Those women in which bleeding is secondary to systemic causes, organic causes and due to cervical and vaginal causes were excluded. The specimens were processed, embedded and cut into sections of 3-4 microns. The histopathological patterns were studied. Results: Age distribution varied from 18 years to 70 years, majority of the patients were between 21 to 30 years. Among the cases of DUB, proliferative phase accounted for 66.3% and secretory phase accounted for 21.3%. 18 cases (8.6% of atrophic endometrium, four cases (1.9% of irregular shedding and two cases of luteal phase insufficiency were received. Conclusion: Dysfunctional uterine bleeding is a common and debilitating condition in women of reproductive age. Endometrial biopsy could be effectively used as the first diagnostic step in DUB and thus ensures correct management.

Role of magnetic resonance imaging in patient selection for uterine artery embolization

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Cura, M.; Cura, A.; Bugnone, A.

2006-01-01

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is an effective treatment of symptomatic uterine leiomyoma in the appropriate candidates, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. Magnetic resonance imaging (MRI) can be used to assess women with symptoms potentially attributable to uterine leiomyomas, and help to determine who is an appropriate candidate for UAE. Because of soft tissue characterization, multiplanar imaging capabilities, and enhancement, MR imaging not only accurately detects and characterizes uterine leiomyomas but also may predict who will benefit from the embolization. MRI ability to detect coexistent uterine or pelvic pathology may change the diagnosis and treatment management of patients being evaluated for UAE

Role of magnetic resonance imaging in patient selection for uterine artery embolization

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Cura, M.; Cura, A.; Bugnone, A. [Univ. of Texas Health Science Center, San Antonio, TX (United States). Dept. of Radiology

2006-12-15

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is an effective treatment of symptomatic uterine leiomyoma in the appropriate candidates, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. Magnetic resonance imaging (MRI) can be used to assess women with symptoms potentially attributable to uterine leiomyomas, and help to determine who is an appropriate candidate for UAE. Because of soft tissue characterization, multiplanar imaging capabilities, and enhancement, MR imaging not only accurately detects and characterizes uterine leiomyomas but also may predict who will benefit from the embolization. MRI ability to detect coexistent uterine or pelvic pathology may change the diagnosis and treatment management of patients being evaluated for UAE.

The effect of peri-implantation administration of uterine relaxing agents in assisted reproduction treatment cycles: a systematic review and meta-analysis.

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Khairy, Mohammed; Dhillon, Rima K; Chu, Justin; Rajkhowa, Madhurima; Coomarasamy, Arri

2016-04-01

Sub-endometrial junctional zone peristalsis is increased by ovarian stimulation and traumatic embryo transfer, and is linked with decreased implantation and pregnancy rates in assisted reproduction treatments. Various agents have been used to inhibit uterine hyper-peristalsis at the time of embryo transfer with conflicting results. This systematic review aimed to identify if uterine relaxants administered in the peri-implantation period during assisted reproduction treatments could improve pregnancy outcomes through literature search with no language restrictions. The review reports on 3546 patients in 17 randomized controlled trials published between 1993 and 2014. Women undergoing assisted reproduction techniques who either received a uterine relaxant agent in the peri-implantation period versus placebo or no treatment were included. Primary outcome was live birth rate. The meta-analyses did not show statistically significant benefit of any uterine relaxing agents on live birth rate. Other meta-analyses did not show a significant effect on the clinical pregnancy, spontaneous abortion, ectopic pregnancy and multiple pregnancy rate. Most of the included studies were of low quality and lacked significant power to detect minimally important effect. Evidence is insufficient to recommend using these agents in routine practice. Further methodologically robust randomized controlled trials with more refined selection criteria might reveal a beneficial effect. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Analysis of adverse reactions and complications of transcatheter uterine artery embolization (TUAE) for uterine fibroids

International Nuclear Information System (INIS)

Chen Xiaoming; Luo Pengfei; Du Juan; Zuo Yuewei; Hu Xiaoping; Hong Danhua; Lin Huahuan; Li Gaowen; Liu Suyun

2002-01-01

Objective: To investigate the adverse reactions and complications as well as their preventive and therapeutic measures of TUAE for uterine fibroids. Methods: One hundred and eighty-two patients with uterine fibroids were treated by TUAE. Bilateral uterine arteries were embolized using lipiodol-pingyangmycin emulsion (LPE), together with Gelfoam particles. All patients were hospitalized for 3 to 10 days after TUAE and were followed up for 1 to 24 months to observe the adverse reactions and complications. Results: Adverse reactions of TUAE included postembolization syndrome ( n 182); urinary irritation ( n = 24), and hyporrhea of vagina ( n = 25 ) . Complications of TUAE included expelling of necrotic fibroids per vagina ( n = 5 ); urinary retention ( n = 10); urinary tract infection ( n = 1 ); ulcer of labia minora ( n = 1 ); ecchymosis and ulceration on buttock ( n = 1), and secondary infection of chocolate cyst of ovary. ( n = 1 ). All the above-mentioned side effects of TUAE recovered to normal after expectant or especial treatment without any sequels left. Conclusion: The adverse reactions of TUAE are reversible and the complications of TUAE are preventable and curable

Fibroblasts and the extracellular matrix in right ventricular disease.

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Frangogiannis, Nikolaos G

2017-10-01

Right ventricular failure predicts adverse outcome in patients with pulmonary hypertension (PH), and in subjects with left ventricular heart failure and is associated with interstitial fibrosis. This review manuscript discusses the cellular effectors and molecular mechanisms implicated in right ventricular fibrosis. The right ventricular interstitium contains vascular cells, fibroblasts, and immune cells, enmeshed in a collagen-based matrix. Right ventricular pressure overload in PH is associated with the expansion of the fibroblast population, myofibroblast activation, and secretion of extracellular matrix proteins. Mechanosensitive transduction of adrenergic signalling and stimulation of the renin-angiotensin-aldosterone cascade trigger the activation of right ventricular fibroblasts. Inflammatory cytokines and chemokines may contribute to expansion and activation of macrophages that may serve as a source of fibrogenic growth factors, such as transforming growth factor (TGF)-β. Endothelin-1, TGF-βs, and matricellular proteins co-operate to activate cardiac myofibroblasts, and promote synthesis of matrix proteins. In comparison with the left ventricle, the RV tolerates well volume overload and ischemia; whether the right ventricular interstitial cells and matrix are implicated in these favourable responses remains unknown. Expansion of fibroblasts and extracellular matrix protein deposition are prominent features of arrhythmogenic right ventricular cardiomyopathies and may be implicated in the pathogenesis of arrhythmic events. Prevailing conceptual paradigms on right ventricular remodelling are based on extrapolation of findings in models of left ventricular injury. Considering the unique embryologic, morphological, and physiologic properties of the RV and the clinical significance of right ventricular failure, there is a need further to dissect RV-specific mechanisms of fibrosis and interstitial remodelling. Published on behalf of the European Society of

Bicornuate-Septate Uterus: A New Congenital Uterine Anomaly

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Babak Dabir-Ashrafi

2008-08-01

Full Text Available Bicornuate uterus is class IV and septate uterus is class Vin uterine anomaly classification.Bicornuate uterus is almost always treated by laparotomy and metroplasty. But the treatment of choice for septate uterus is hysteroscopic metroplasty. Bicornuate- septate uterus which is described in this paper is a new class of uterine anomaly(between class IV & V. The advantages of hysteroscopic metroplasty to laparotomy and metroplasty have been proven previously.It is important to know if the uterine anomaly is pure bicornuate or bicornuate-septate. In the latter case, we suggest the first line of operation should be hysteroscopic metroplasty.

Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

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Saso, Srdjan; Louis, Louay S; Doctor, Farah; Hamed, Ali Hassan; Chatterjee, Jayanta; Yazbek, Joseph; Bora, Shabana; Abdalla, Hossam; Ghaem-Maghami, Sadaf; Thum, Meen-Yau

2015-12-01

An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies

HMB-45 reactivity in conventional uterine leiomyosarcomas.

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Simpson, Karen W; Albores-Saavedra, Jorge

2007-01-01

We studied the human melanoma black-45 (HMB-45) reactivity in 25 uterine leiomyosarcomas including 23 conventional and 2 myxoid variants. Eleven tumors were poorly differentiated, and 14 were well to moderately differentiated. Nine uterine leiomyosarcomas labeled with HMB-45 in 10% or less of the tumor cells. Six were poorly differentiated and 3 were well differentiated. Our study indicates that 36% of conventional leiomyosarcomas focally express HMB-45. HMB-45 reactivity was more common in the poorly differentiated than in the well-differentiated group of leiomyosarcomas. In light of our findings and of those recently reported in the literature, we believe that the term PEComa should not be used for uterine leiomyosarcomas with clear cells or for conventional leiomyosarcomas that stain positively with HMB-45.

Imaging before and after uterine artery embolization

International Nuclear Information System (INIS)

Kroencke, T.J.

2008-01-01

Percutaneous catheter-based embolization treatment of symptomatic uterine fibroids has evolved into the most widely used alternative therapeutic approach to surgical treatment worldwide. Uterine artery embolization (UAE) induces infarction of leiomyomas, resulting in ischemic necrosis, hyaline degeneration, and size reduction with resolution of associated symptoms. Published experience suggests that UAE is an effective and reliable option for treating uterine fibroids with high patient satisfaction. Magnetic resonance imaging (MRI) is superior to ultrasonography for determining the site, size and number of fibroids, which is important for establishing the indication for UAE. Other potential advantages of MRI include the option of performing MR angiography (MRA) and obtaining contrast-enhanced images for monitoring the outcome of UAE and assessing possible complications after UAE. (orig.) [de

Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

Science.gov (United States)

Stessuk, Talita; Puzzi, Maria Beatriz; Chaim, Elinton Adami; Alves, Paulo César Martins; de Paula, Erich Vinicius; Forte, Andresa; Izumizawa, Juliana Massae; Oliveira, Carolina Caliári; Frei, Fernando; Ribeiro-Paes, João Tadeu

2016-09-01

The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo.

Responses of fibroblasts and glial cells to nanostructured platinum surfaces

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Pennisi, C P; Sevcencu, C; Yoshida, K [Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg (Denmark); Dolatshahi-Pirouz, A; Foss, M; Larsen, A Nylandsted; Besenbacher, F [Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus (Denmark); Hansen, J Lundsgaard [Department of Physics and Astronomy, Aarhus University, Aarhus (Denmark); Zachar, V, E-mail: cpennisi@hst.aau.d [Laboratory for Stem Cell Research, Aalborg University (Denmark)

2009-09-23

The chronic performance of implantable neural prostheses is affected by the growth of encapsulation tissue onto the stimulation electrodes. Encapsulation is associated with activation of connective tissue cells at the electrode's metallic contacts, usually made of platinum. Since surface nanotopography can modulate the cellular responses to materials, the aim of the present work was to evaluate the 'in vitro' responses of connective tissue cells to platinum strictly by modulating its surface nanoroughness. Using molecular beam epitaxy combined with sputtering, we produced platinum nanostructured substrates consisting of irregularly distributed nanopyramids and investigated their effect on the proliferation, cytoskeletal organization and cellular morphology of primary fibroblasts and transformed glial cells. Cells were cultured on these substrates and their responses to surface roughness were studied. After one day in culture, the fibroblasts were more elongated and their cytoskeleton less mature when cultured on rough substrates. This effect increased as the roughness of the surface increased and was associated with reduced cell proliferation throughout the observation period (4 days). Morphological changes also occurred in glial cells, but they were triggered by a different roughness scale and did not affect cellular proliferation. In conclusion, surface nanotopography modulates the responses of fibroblasts and glial cells to platinum, which may be an important factor in optimizing the tissue response to implanted neural electrodes.

Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications.

Science.gov (United States)

Moravek, Molly B; Yin, Ping; Ono, Masanori; Coon, John S; Dyson, Matthew T; Navarro, Antonia; Marsh, Erica E; Chakravarti, Debabrata; Kim, J Julie; Wei, Jian-Jun; Bulun, Serdar E

2015-01-01

Uterine leiomyoma is the most common benign tumor in women and is thought to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a cellular insult. Leiomyomas cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are the most common indication for hysterectomy in the USA. A slow rate of cell proliferation, combined with the production of copious amounts of extracellular matrix, accounts for tumor expansion. A common salient feature of leiomyomas is their responsiveness to steroid hormones, thus providing an opportunity for intervention. A comprehensive search of PUBMED was conducted to identify peer-reviewed literature published since 1980 pertinent to the roles of steroid hormones and somatic stem cells in leiomyoma, including literature on therapeutics that target steroid hormone action in leiomyoma. Reviewed articles were restricted to English language only. Studies in both animals and humans were reviewed for the manuscript. Estrogen stimulates the growth of leiomyomas, which are exposed to this hormone not only through ovarian steroidogenesis, but also through local conversion of androgens by aromatase within the tumors themselves. The primary action of estrogen, together with its receptor estrogen receptor α (ERα), is likely mediated via induction of progesterone receptor (PR) expression, thereby allowing leiomyoma responsiveness to progesterone. Progesterone has been shown to stimulate the growth of leiomyoma through a set of key genes that regulate both apoptosis and proliferation. Given these findings, aromatase inhibitors and antiprogestins have been developed for the treatment of leiomyoma, but neither treatment results in complete regression of leiomyoma, and tumors recur after treatment is stopped. Recently, distinct cell populations were discovered in leiomyomas; a small population showed stem-progenitor cell properties, and

Obstetric outcome of women with uterine anomalies in China.

Science.gov (United States)

Zhang, Yan; Zhao, Yang-yu; Qiao, Jie

2010-02-20

Congenital uterine anomalies are associated with the highest incidence of reproductive failure and obstetric complications. This study aimed to summarize the clinical characteristics and prenatal outcome of pregnancy in women with congenital uterine malformations. This retrospective study evaluated the fertility and obstetric outcome of 116 inpatients with uterine malformations with pregnancy in Peking University Third Hospital from June 1998 to June 2009. A total of 270 randomly selected pregnant women with a previously confirmed normally shaped uterus as a control group. Student's t test and analysis of variance (ANOVA) were used to compare means for normally distributed variables. The analysis was carried out using the SPSS. Among 21 961 deliveries in Peking University Third Hospital, 116 (0.45%) were in women with uterine anomalies. A septate uterus was present in 43 (37.1%) and the uterus didelphys in 28 (24.2%) of the 116 women identified. Bicornuate uterus, arcuate and unicomate uterus were observed in 12 (10.3%), 18 (15.5%) and 15 (12.9%) patients, respectively. Patients with uterine anomalies had significantly higher rates of malpresentation (38.8%), preterm delivery (19.8%), and cesarean section (78.5%) compared with the group of women with a normal uterus. Patients with uterine anomalies had significantly lower mean birth-weight neonates and a significantly higher incidence of small for gestationalage (SGA) neonates; women with uterus didelphys more frequently required infertility treatment than patients with other uterine anomalies (P unicorns (P < 0.05). Women with congenital uterinemal formation usually have higher incidence of complications during pregnancy and delivery. A septate uterus appears to be associated with poorer obstetric outcomes.

The hallmarks of fibroblast ageing.

Science.gov (United States)

Tigges, Julia; Krutmann, Jean; Fritsche, Ellen; Haendeler, Judith; Schaal, Heiner; Fischer, Jens W; Kalfalah, Faiza; Reinke, Hans; Reifenberger, Guido; Stühler, Kai; Ventura, Natascia; Gundermann, Sabrina; Boukamp, Petra; Boege, Fritz

2014-06-01

Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular matrix and fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage accumulation and (mal-)adaptation, thus constituting a powerful indicator system for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge regarding dermal fibroblast ageing. We discriminate processes inducible in culture from phenomena apparent in skin biopsies or primary cells from old donors, coming to the following conclusions: (i) Fibroblasts aged in culture exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of these hallmarks have been detected or investigated in fibroblasts aged in situ (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit additional features currently not considered ubiquitous hallmarks of ageing. (iv) The ageing process of dermal fibroblasts in their physiological tissue environment has only been partially elucidated, although these cells have been a preferred model of cell ageing in vitro for decades. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

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Ma, Zhen-Yu [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, No.250 Changgang East Road, Guangzhou 510260, Guangdong Province (China); Zhong, Zhi-Gang; Qiu, Meng-Yao; Zhong, Yu-Hua [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China); Zhang, Wei-Xi, E-mail: weixizhang@qq.com [Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong Province (China)

2016-03-18

Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-β1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-β1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-β1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKβ with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-β1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. - Highlights: • TGF-β1 promotes survival and proliferation in dystrophic muscle fibroblasts. • TGF-β1 activated the canonical NF-κB pathway in dystrophic muscle fibroblasts. • Canonical NF-κB pathway mediates these effects of TGF-β1.

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

International Nuclear Information System (INIS)

Ma, Zhen-Yu; Zhong, Zhi-Gang; Qiu, Meng-Yao; Zhong, Yu-Hua; Zhang, Wei-Xi

2016-01-01

Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-β1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-β1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-β1 treatment activated the canonical NF-κB pathway; and we found that pharmacological inhibition of IKKβ with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-β1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. - Highlights: • TGF-β1 promotes survival and proliferation in dystrophic muscle fibroblasts. • TGF-β1 activated the canonical NF-κB pathway in dystrophic muscle fibroblasts. • Canonical NF-κB pathway mediates these effects of TGF-β1.

The effect of tranilast on fibroblast activation protein α (FAP-α expression in normal and keloid fibroblasts in vitro

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Paweł P. Antończak

2017-07-01

Full Text Available Introduction . Tranilast (N-(3’,4’-demethoxycinnamoyl-anthranilic acid is an anti-allergic drug. Its mechanism of action is based on the inhibition of antigen-induced release of chemical mediators from mast cells and basophils. It also reveals antifibroproliferative activities. These properties of tranilast are used in the treatment of hypertrophic scars and keloids. Keloids are characterized by incorrect extracellular matrix components turnover. Fibroblasts derived from keloids reveal overproduction of collagen type I and decreased degradation of extracellular matrix in comparison with normal fibroblasts. Fibroblast activation protein α (FAP-α may play an important role in remodeling of extracellular matrix and the invasive properties of keloids. Objective . In the present study, the effect of tranilast on expression of FAP-α gene and its protein was evaluated in normal human dermal fibroblasts and fibroblasts derived from keloids cultured in vitro . Materials and methods. In the first stage of the study, the influence of tranilast on cell viability was estimated. The second stage of the study included the quantitative evaluation of FAP-α mRNA expression in normal and keloid fibroblasts treated with tranilast. The third stage of the study comprised fibroblast activation protein α expression analysis in the examined cells treated with tranilast. Results and conclusions . The expression of FAP-α gene and fibroblast activation protein α is higher in keloid fibroblasts. Tranilast at concentrations of 3 μM and 30 μM up-regulated mRNA FAP-α expression in normal fibroblasts but did not influence keloid fibroblasts. The drug, at concentrations of 30 μM and 300 μM up-regulated fibroblast activation protein α expression in normal fibroblasts and did not influence keloid fibroblasts. Tranilast antiproliferative effect is not associated with FAP-α expression in keloid fibroblasts.

Fibroblast growth factor receptors in breast cancer.

Science.gov (United States)

Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

Malignant mixed mullerian tumor arising from the uterine cervix: A case report

International Nuclear Information System (INIS)

Shim, Jong Joon; Shim, Jae Chan; Lee, Kyoung Eun; Lee, Ghi Jai; Kim, Ho Kyun; Suh, Jung Ho; Lee, Hye Kyung

2012-01-01

Malignant mixed mullerian tumors (MMMTs) are a rare uterine tumor and contribute to approximately 1-3% of all corpus malignant tumors. MMMTs are usually in the uterine corpus, but can also arise from the uterine cervix, vagina, ovaries and fallofian tubes. MMMTs of the uterine cervix are extremely rare. MMMTs are highly malignant and tend to maintain a rapid growth and exhibit a high rate of recurrence. Therefore, the prognosis of patients diagnosed with these types of tumors is extremely poor. We report a rare case of a malignant mixed mullerian tumor arising from the uterine cervix and introduce CT and MRI findings. CT and magnetic resonance findings of the uterine cervical MMMT in our case show highly aggressive features, such as parametrial involvement, pelvic and paraaortic lymphadenopathy, and distant metastasis and high enhancement

Effective salvage of acute massive uterine bleeding using intrauterine balloon tamponade in a uterine adenomyosis patient on dienogest.

Science.gov (United States)

Nishino, Kimihiro; Hayashi, Kazumasa; Chaya, Jyunya; Kato, Noriko; Yamamuro, Osamu

2013-03-01

We present the case of a 37-year-old nulliparous woman in whom acute massive uterine bleeding during dienogest therapy was successfully treated using intrauterine balloon tamponade. Abnormal uterine bleeding and several cases of profuse bleeding causing severe anemia in association with dienogest therapy have been reported, but this is the first reported case involving hypovolemic shock. While successful control of postpartum hemorrhage with intrauterine balloon tamponade has been well described, applications for non-obstetric bleeding, particularly in the presence of underlying diseases, such as adenomyosis, have only rarely been reported. This procedure can be easily, promptly, and safely implemented without analgesia, anesthesia, or laparotomy; it can be used with a minimally dilated external cervical os or narrow uterine cavity; and it can preserve fertility. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

Directory of Open Access Journals (Sweden)

Jyh-Horng Wang

Full Text Available Fibroblast-like synoviocytes (FLS play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs. The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol, the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2, and matrix metalloproteinases (MMPs by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL. In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.

Effects of cholera toxin and isobutylmethylxanthine on growth of human fibroblasts

International Nuclear Information System (INIS)

Espinoza, B.; Wharton, W.

1986-01-01

Cholera toxin produced a dose-dependent decrease in the restimulation of G 0 /G 1 traverse in density-arrested human fibroblasts but did not inhibit the stimulation of cells arrested in G 0 after serum starvation at low density. In addition, cholera toxin did not inhibit the proliferation of sparse logarithmically growing human fibroblasts, even when low concentrations of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) were also present. However, the final density to which sparse cells grew was limited by cholera toxin, when added either alone or together with low concentrations of IBMX. In contrast, high concentrations of the phosphodiesterase inhibitor alone produced a profound inhibition in the growth of sparse human fibrobasts. IBMX produced an inhibition both in the G 1 and in the G 2 phases of the cell cycle by a mechanism(s) that was not related to the magnitude of the increases in adenosine 3,5-cyclic monophosphate concentrations

Radiological appearances of degenerative uterine leiomyomas

International Nuclear Information System (INIS)

Tzvetankov, K.; Hadjidekov, G.; Plachkov, I.; Yankova, M.

2013-01-01

Uterine fibroids, also known as leiomyomas, are the most common uterine neoplasms. Although benign, they can be associated with significant morbidity and are the commonest indication for hysterectomy. They are often discovered incidentally when performing imaging for other reasons. Usually first identified with US, they can be further characterized with MRI. They are usually easily recognizable, but degenerate fibroids can have unusual appearances. Knowledge of the different appearances of fibroids on imaging is important as it enables prompt diagnosis and thereby guides treatment. (authors)

Psychological assessment tool for patients diagnosed with absolute uterine factor infertility and planning to undergo uterine transplantation.

Science.gov (United States)

Saso, S; Bracewell-Milnes, T; Ismail, L; Hamed, A H; Thum, M-Y; Ghaem-Maghami, S; Del Priore, G; Smith, J R

2014-08-01

Uterine transplantation (UTn) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI) and who are willing to bear their own child. AUFI renders a woman 'unconditionally infertile'. For AUFI women in general, UTn may offer a way to re-discover their own femininity through the restoration of fertility. Thus, when faced with a patient who may undergo UTn, the 'holistic approach' takes on an extra meaning. This is because the psychological element is two-sided for these patients. On one side lies the psychology of infertility, and on the other and equally important, is the substantially higher prevalence of psychiatric disorders in transplant candidates and recipients than in the general population. However, the psychology of a potential recipient of a uterine graft in order to bring about fertility has not been adequately explored or reviewed scientifically. We have presented here an outline of the areas which should be included in a psychological assessment for patients wishing to undergo UTn.

Opposite cytokine synthesis by fibroblasts in contact co-culture with osteosarcoma cells compared with transwell co-cultures.

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David, Manu S; Kelly, Elizabeth; Zoellner, Hans

2013-04-01

We recently reported exchange of membrane and cytoplasm during contact co-culture between human Gingival Fibroblasts (h-GF) and SAOS-2 osteosarcoma cells, a process we termed 'cellular sipping' to reflect the manner in which cells become morphologically diverse through uptake of material from the opposing cell type, independent of genetic change. Cellular sipping is increased by Tumor Necrosis Factor-α (TNF-α), and we here show for the first time altered cytokine synthesis in contact co-culture supporting cellular sipping compared with co-culture where h-GF and SAOS-2 were separated in transwells. SAOS-2 had often undetectably low cytokine levels, while Interleukin-6 (IL-6), Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) were secreted primarily by TNF-α stimulated h-GF and basic Fibroblast Growth Factor (FGF) was prominent in h-GF lysates (p cultures permitting cellular sipping had lower IL-6, G-CSF and GM-CSF levels, as well as higher lysate FGF levels compared with TNF-α treated h-GF alone (p cultures in transwells, with increased IL-6, G-CSF and GM-CSF levels (p cultures where cellular sipping occurs, potentially contributing to tumor inflammatory responses. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

The utility of diffusion-weighted MR imaging in differentiation of uterine adenomyosis and leiomyoma

International Nuclear Information System (INIS)

Yang Qiong; Zhang Lihua; Su Jing; Liu Jianyu

2011-01-01

Purpose: To investigate the value of diffusion-weighted MR imaging (DWI), especially apparent diffusion coefficient (ADC) in the differentiation of uterine adenomyosis and leiomyoma. Materials and methods: 17 patients with uterine leiomyoma and 22 patients with uterine adenomyosis underwent diffusion-weighted imaging (DWI) in addition to routine MR imaging. The ADC values, as well as ADC D-value (defined as the ADC value of high signal intensive foci minus the ADC value of lesion tissues the difference in value), were measured and compared to investigate whether they could help in the differentiation of uterine adenomyosis and leiomyoma. Histopathologic examination was conducted as the golden standard. Results: For high signal intensive foci within the lesions, uterine adenomyosis demonstrated significantly lower mean ADC value than uterine leiomyoma (1.582 vs. 2.122 x 10 -3 mm 2 /s, P = 0.001). For lesion tissues, uterine adenomyosis demonstrated significantly higher mean ADC value than uterine leiomyoma (1.214 vs. 0.967 x 10 -3 mm 2 /s, P = 0.001). However, there was overlap between uterine adenomyosis and leiomyoma in both measurements. Mean ADC D-value was significantly lower in uterine adenomyosis than in uterine leiomyoma (0.369 vs. 1.096 x 10 -3 mm 2 /s, P = 0.000). ADC D-value had no overlap between uterine adenomyosis and leiomyoma. Conclusion: DWI can be applied for the further differentiation of uterine adenomyosis and leiomyoma, in addition to routine MR imaging. ADC D-value may be a more useful tool than ADC value in the differentiation.

The utility of diffusion-weighted MR imaging in differentiation of uterine adenomyosis and leiomyoma

Energy Technology Data Exchange (ETDEWEB)

Yang Qiong, E-mail: yangq1112@126.com [Department of Radiology, Peking University Third Hospital, Beijing 100191 (China); Zhang Lihua, E-mail: zhanglh04036@yahoo.com.cn [Department of Radiology, Peking University Third Hospital, Beijing 100191 (China); Su Jing, E-mail: bjmusujing@gmail.com [Department of Pathology, Peking University Health Science Center, Beijing 100191 (China); Liu Jianyu, E-mail: jyliu5791@sina.com [Department of Radiology, Peking University Third Hospital, Beijing 100191 (China)

2011-08-15

Purpose: To investigate the value of diffusion-weighted MR imaging (DWI), especially apparent diffusion coefficient (ADC) in the differentiation of uterine adenomyosis and leiomyoma. Materials and methods: 17 patients with uterine leiomyoma and 22 patients with uterine adenomyosis underwent diffusion-weighted imaging (DWI) in addition to routine MR imaging. The ADC values, as well as ADC D-value (defined as the ADC value of high signal intensive foci minus the ADC value of lesion tissues the difference in value), were measured and compared to investigate whether they could help in the differentiation of uterine adenomyosis and leiomyoma. Histopathologic examination was conducted as the golden standard. Results: For high signal intensive foci within the lesions, uterine adenomyosis demonstrated significantly lower mean ADC value than uterine leiomyoma (1.582 vs. 2.122 x 10{sup -3} mm{sup 2}/s, P = 0.001). For lesion tissues, uterine adenomyosis demonstrated significantly higher mean ADC value than uterine leiomyoma (1.214 vs. 0.967 x 10{sup -3} mm{sup 2}/s, P = 0.001). However, there was overlap between uterine adenomyosis and leiomyoma in both measurements. Mean ADC D-value was significantly lower in uterine adenomyosis than in uterine leiomyoma (0.369 vs. 1.096 x 10{sup -3} mm{sup 2}/s, P = 0.000). ADC D-value had no overlap between uterine adenomyosis and leiomyoma. Conclusion: DWI can be applied for the further differentiation of uterine adenomyosis and leiomyoma, in addition to routine MR imaging. ADC D-value may be a more useful tool than ADC value in the differentiation.

Three-dimensional transvaginal ultrasound: clinical implementation in assessing uterine cavity

OpenAIRE

Abdelaziz E. Tammam; Mostafa M. Khodry; Shymaa M. A. Elnagar; Ahmed H. Abdella; Sayed A. M. Taha

2015-01-01

Background: Three-dimensional transvaginal ultrasonography (3D TVS) represents a new technique of imaging and provides a unique diagnostic tool for non-invasive examination of the uterine morphology and diagnosis of congenital uterine anomalies. In this study the clinical value of 3D TVS in diagnosis of uterine cavity abnormalities were evaluated. Methods: A prospective of diagnostic accuracy study included 226 patients with various clinical presentations; infertility, recurrent pregnancy ...

A new method used in laparoscopic hysterectomy for uterine manipulation: uterine rein technique.

Science.gov (United States)

Boztosun, Abdullah; Atılgan, Remzi; Pala, Şehmus; Olgan, Şafak

2018-03-22

The aim of this study is to define a new method of manipulating the uterus during laparoscopic hysterectomy. A total laparoscopic hysterectomy (TLH) with the newly defined technique was performed in 29 patients between July 2016 and July 2017. In this new technique, the uterus was bound from uterine corpus and fundus like a bridle with polyester tape, to allow abdominal manipulation. The technique was successfully performed at the first attempt in 93.1% of cases. It was repeated in two cases (6.9%) since the polyester tape departed away from the uterus at the first attempt. The mean application time was 11.2 min. The vaginal manipulator was not required in any of the cases. There were no intraoperative complications. In conclusion, this method has the advantages of not requiring any vaginal manipulator, reducing the number of people required during operation, permitting a near maximum manipulation of the uterus in all three dimensions, and giving the control of these manipulations directly to the surgeon. On the other hand, the technique also has some inadequacies which should be discussed and improved on in the future. Impact of statement What is already known on this subject? In a laparoscopic hysterectomy, manipulation of the uterus is essential for anatomical dissection of the regions and completion of the operation without complications. An ideal uterine manipulator is defined as inexpensive, as convenient, fast and suitable for injecting solutions, removing the need for an assistant and most importantly offering the most suitable range of motion. In this study, we describe a new and different technique (rein technique) allowing the abdominal manipulation of the uterus in a laparoscopic hysterectomy and discuss the advantages and disadvantages of this method. What do the results of this study add? The procedure was easily accomplished in most patients. We did not need to use an extra uterine manipulator in any of the cases. What are the implications of these

Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

Science.gov (United States)

Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

2013-03-01

Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

Therapy for fibrocystic breast disease in patients with uterine myoma

Directory of Open Access Journals (Sweden)

N. V. Kulagina

2010-01-01

Full Text Available Examination of 112 patients with uterine myoma revealed the high rate of concomitance of uterine and breast hyperplastic processes due to the commonness of the pathogenesis of these processes. Different forms of fibrocystic disease (FCD were identified in 76.8% of the patients with uterine myoma; diffuse FCD with a predominance of a fibrous component was more common (54.7%. The efficacy of Indinol in the treatment of FCD was evaluated in the patients with uterine myoma. The clinical symptoms of mastodynia were relieved in 63.4% of the patients; 33.7% of the women had positive X-ray changes a year after start of therapy, as evidenced by mammography.

Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models.

Directory of Open Access Journals (Sweden)

Erna G Santoso

Full Text Available Infertility caused by ovarian or tubal problems can be treated using In Vitro Fertilization and Embryo Transfer (IVF-ET; however, this is not possible for women with uterine loss and malformations that require uterine reconstruction for the treatment of their infertility. In this study, we are the first to report the usefulness of decellularized matrices as a scaffold for uterine reconstruction. Uterine tissues were extracted from Sprague Dawley (SD rats and decellularized using either sodium dodecyl sulfate (SDS or high hydrostatic pressure (HHP at optimized conditions. Histological staining and quantitative analysis showed that both SDS and HHP methods effectively removed cells from the tissues with, specifically, a significant reduction of DNA contents for HHP constructs. HHP constructs highly retained the collagen content, the main component of extracellular matrices in uterine tissue, compared to SDS constructs and had similar content levels of collagen to the native tissue. The mechanical strength of the HHP constructs was similar to that of the native tissue, while that of the SDS constructs was significantly elevated. Transmission electron microscopy (TEM revealed no apparent denaturation of collagen fibers in the HHP constructs compared to the SDS constructs. Transplantation of the decellularized tissues into rat uteri revealed the successful regeneration of the uterine tissues with a 3-layer structure 30 days after the transplantation. Moreover, a lot of epithelial gland tissue and Ki67 positive cells were detected. Immunohistochemical analyses showed that the regenerated tissues have a normal response to ovarian hormone for pregnancy. The subsequent pregnancy test after 30 days transplantation revealed successful pregnancy for both the SDS and HHP groups. These findings indicate that the decellularized matrix from the uterine tissue can be a potential scaffold for uterine regeneration.

Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts.

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Fronza, M; Heinzmann, B; Hamburger, M; Laufer, S; Merfort, I

2009-12-10

PHARMACOLOGICAL RELEVANCE: Presentation of the scratch assay as a convenient and inexpensive in vitro tool to gain first insights in the wound healing potential of plant extracts and natural compounds. The present study deals with the optimization of the scratch assay which can be used as an in vitro model for quantification of fibroblast migration to and proliferation into the wounded area. It is suitable for the first evaluation of the wound re-epithelialization potential of crude herbal extracts, isolated compounds and pharmaceutical preparations. As a proof of concept three preparations from traditional medicinal plants were investigated. Swiss 3T3 albino mouse fibroblasts were used in monolayers and platelet derived growth factor as positive control. Hexane and ethanolic extracts from Calendula officinalis and Matricaria recutita, Hypericum oil as well as the triterpenoids faradiol myristate and palmitate were studied. To differentiate between proliferation and migration antimitotic mitomycin C was added. Both extracts of Calendula officinalis stimulated proliferation and migration of fibroblasts at low concentrations, e.g. 10 microg/ml enhanced cell numbers by 64.35% and 70.53%, respectively. Inhibition of proliferation showed that this effect is mainly due to stimulation of migration. Faradiol myristate and palmitate gave comparable stimulation rates at an almost 50 microg/ml concentration, indicating that they contribute partially, but not most significantly to the wound healing effects of Calendula preparations. Extracts from Matricaria recutita were only moderately active. Hypericum oil was cytotoxic at concentrations higher than 0.5 microg/ml. The scratch assay in the present form can be used as a promising scientific approach and platform to differentiate between plant extracts known for their wound healing and their anti-inflammatory properties.

Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing.

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Xian, Law Jia; Chowdhury, Shiplu Roy; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

2015-03-01

Platelet-rich plasma (PRP) has been found to contain a high concentration of growth factors that are present during the process of healing. Studies conducted found that application of PRP accelerates wound healing. In this study, we characterized the skin cell suspension harvested using the co-isolation technique and evaluated the effects of PRP (10% and 20%, v/v) on co-cultured keratinocytes and fibroblasts in terms of wound healing. Human keratinocytes and fibroblasts were harvested via co-isolation technique and separated via differential trypsinization. These cells were then indirectly co-cultured in medium supplemented with 10% or 20% PRP for 3 days without medium change for analysis of wound-healing potential. The wound-healing potential of keratinocytes and fibroblasts was evaluated in terms of growth property, migratory property, extracellular matrix gene expression and soluble factor secretion. The co-isolation technique yielded a skin cell population dominated by fibroblasts and keratinocytes, with a small amount of melanocytes. Comparison between the 10% and 20% PRP cultures showed that the 10% PRP culture exhibited higher keratinocyte apparent specific growth rate, and secretion of hepatocyte growth factor, monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein 78 and vascular endothelial growth factor A, whereas the 20% PRP culture has significantly higher collagen type 1 and collagen type 3 expressions and produced more granulocyte-macrophage colony-stimulating factor. PRP concentration modulates keratinocyte and fibroblast wound healing potential, whereby the 10% PRP promotes wound remodeling, whereas the 20% PRP enhances inflammation and collagen deposition. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Successful Magnetic Resonance Imaging-Guided Focused Ultrasound Surgery for Recurrent Uterine Fibroid Previously Treated with Uterine Artery Embolization

Directory of Open Access Journals (Sweden)

Sang-Wook Yoon

2010-01-01

Full Text Available A 45-year-old premenopausal woman was referred to our clinic due to recurring symptoms of uterine fibroids, nine years after a uterine artery embolization (UAE. At the time of screening, the patient presented with bilateral impairment and narrowing of the uterine arteries, which increased the risk of arterial perforation during repeated UAE procedures. The patient was subsequently referred for magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS treatment. Following the treatment, the patient experienced a significant improvement in symptoms (symptom severity score was reduced from 47 to 12 by 1 year post-treatment. MR images at 3 months showed a 49% decrease in fibroid volume. There were no adverse events during the treatment or the follow-up period. This case suggests that MRgFUS can be an effective treatment option for patients with recurrent fibroids following previous UAE treatment.

Uterine Fibroid Embolization (UFE)

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... or gynecologist. top of page What are the benefits vs. risks? Benefits Uterine fibroid embolization, done under local anesthesia , is ... risk of infection. The chance of infection requiring antibiotic treatment appears to be less than one in ...

Uterine prolapse prevention in Eastern Nepal

DEFF Research Database (Denmark)

Radl, Christina Mathilde; Rajwar, Ranjita; Aro, Arja R.

2012-01-01

are working well or the attitudes toward them. This paper presents the findings of a qualitative study on primary and secondary prevention of uterine prolapse in Eastern Nepal. Method: The study involved eight focus group discussions with 71 women in six villages of the eastern districts of Siraha and Saptari......: It was found that patriarchy, gender discrimination, and cultural traditions such as early marriage and pregnancy make it difficult for people to discontinue uterine prolapse risk behaviors. Women are aware of risk factors, prevention, and treatment, but are powerless to change their situations. Health...

Long-term efficiency and safety of trans-catheter uterine artery embolization by lipiodol-pingyingmycin emulsion for uterine fibroids

International Nuclear Information System (INIS)

Du Juan; Zuo Yuewei; Hong Nanhua; Chen Xiaoming; Li Yong

2009-01-01

Objective: To investigate the long-term efficiency and safety of trans-catheter uterine artery embolization using lipiodol-pingyingmycin emulsion (LPE-TUAE) for uterine fibroids. Methods: Two hundred and forty-three patients with uterine fibroids were treated by LPE-TUAE. Fourteen of them underwent hysterectomy or myomectomy 3 days to 6 months after LPE-TUAE. The specimens were studied pathologically. Another 229 patients were followed up for 1 to 4 years to observe the long-term outcomes. Results: Menorrhagia became normal or improved markedly in 96.0% (193/201). Lumbago and lower abdominal pain disappeared or relieved markedly in 949% (94/99). Bulk-related symptoms disappeared or lessened markedly in 96.0% (48/50). Ultrasound revealed that the average decreased rate in the largest fibroid volume were 60.7% at 1 year, 63.3% at 2 year, 65.6% at 3 year and 67.4% at 4 year after embolization, and the average decreased rate in the largest uterine volume were 49.6% at 1 year, 54.3% at 2 year, 55.2% at 3 year and 57.1% at 4 year after embolization. Reoccurrence rate of myoma was 10.8% 3-4 year after embolization. No significant difference was found in hormone level between pre- and post-embolization. Pathological studies of specimens showed that lipiodol was only accumulated in fibroids and was not seen in myometrium. Spotty necrosis 2 weeks after embolization and extensive patchy necrosis 3 weeks after embolization were occurred in fibroids. Necrosis was not showed in myometrium. No serious complications occurred. Conclusion: LPE-TUAE possesses a good long-term effectiveness for uterine fibroids, which doesn't cause the damage on ovarian function and normal myometrium or serious complications. (authors)

Evaluation of obstetricians' surgical decision making in the management of uterine rupture.

Science.gov (United States)

Eze, Justus Ndulue; Anozie, Okechukwu Bonaventure; Lawani, Osaheni Lucky; Ndukwe, Emmanuel Okechukwu; Agwu, Uzoma Maryrose; Obuna, Johnson Akuma

2017-06-08

Uterine rupture is an obstetric calamity with surgery as its management mainstay. Uterine repair without tubal ligation leaves a uterus that is more prone to repeat rupture while uterine repair with bilateral tubal ligation (BTL) or (sub)total hysterectomy predispose survivors to psychosocial problems like marital disharmony. This study aims to evaluate obstetricians' perspectives on surgical decision making in managing uterine rupture. A questionnaire-based cross-sectional study of obstetricians at the 46th annual scientific conference of Society of Gynaecology and Obstetrics of Nigeria in 2012. Data was analysed by descriptive and inferential statistics. Seventy-nine out of 110 obstetricians (71.8%) responded to the survey, of which 42 (53.2%) were consultants, 60 (75.9%) practised in government hospitals and 67 (84.8%) in urban hospitals, and all respondents managed women with uterine rupture. Previous cesarean scars and injudicious use of oxytocic are the commonest predisposing causes, and uterine rupture carries very high incidences of maternal and perinatal mortality and morbidity. Uterine repair only was commonly performed by 38 (48.1%) and uterine repair with BTL or (sub) total hysterectomy by 41 (51.9%) respondents. Surgical management is guided mainly by patients' conditions and obstetricians' surgical skills. Obstetricians' distribution in Nigeria leaves rural settings starved of specialist for obstetric emergencies. Caesarean scars are now a rising cause of ruptures. The surgical management of uterine rupture and obstetricians' surgical preferences vary and are case scenario-dependent. Equitable redistribution of obstetricians and deployment of medical doctors to secondary hospitals in rural settings will make obstetric care more readily available and may reduce the prevalence and improve the outcome of uterine rupture. Obstetrician's surgical decision-making should be guided by the prevailing case scenario and the ultimate aim should be to avert

Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-β responsiveness

International Nuclear Information System (INIS)

Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew; Lyons, Karen M.; Varga, John

2008-01-01

Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-β (TGF-β) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-β, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-β. To explore this notion, we characterized TGF-β-induced activation of fibroblasts from CCN2-null (CCN2 -/- ) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-β signal transduction and regulation of collagen gene expression were examined in CCN2 -/- MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2 -/- MEFs was markedly reduced compared to wild type MEFs, TGF-β-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2 -/- MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-β-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts

Estrogen action in the mouse uterus: differential nuclear localization of estradiol in uterine cell types

International Nuclear Information System (INIS)

Korach, K.S.; Lamb, J.C.

1981-01-01

Autoradiographic studies of labeled steroid uptake in mouse uterine tissue indicated that labeled estradiol was predominantly sequestered in the nuclei of stromal and glandular epithelial cells at 1 h. Luminal epithelial cells did not show appreciable nuclear accumulation of labeled estradiol until 7-8 h after hormone injection. Studies using non-target tissues and unlabeled steroids indicated that the nuclear uptake events were tissue and estrogen steroid specific. The temporal pattern of steroid hormone uptake in the uterus would suggest that an initial interaction in stromal and glandular epithelial cells may be required prior to nuclear stimulation in the luminal epithelial target cell

Mathematical modeling of electrical activity of uterine muscle cells.

Science.gov (United States)

Rihana, Sandy; Terrien, Jeremy; Germain, Guy; Marque, Catherine

2009-06-01

The uterine electrical activity is an efficient parameter to study the uterine contractility. In order to understand the ionic mechanisms responsible for its generation, we aimed at building a mathematical model of the uterine cell electrical activity based upon the physiological mechanisms. First, based on the voltage clamp experiments found in the literature, we focus on the principal ionic channels and their cognate currents involved in the generation of this electrical activity. Second, we provide the methodology of formulations of uterine ionic currents derived from a wide range of electrophysiological data. The model is validated step by step by comparing simulated voltage-clamp results with the experimental ones. The model reproduces successfully the generation of single spikes or trains of action potentials that fit with the experimental data. It allows analyzing ionic channels implications. Likewise, the calcium-dependent conductance influences significantly the cellular oscillatory behavior.

Lack of co-ordinate expression of the alpha1(I) and alpha1(III) procollagen genes in fibroblast clonal cultures.

Science.gov (United States)

Yamaguchi, Y; Crane, S; Zhou, L; Ochoa, S M; Falanga, V

2000-12-01

Several extracellular matrix genes, most notably alpha1(I) and alpha1(III) procollagen, are reported to be co-ordinately expressed in cultures of dermal fibroblasts. However, it remains unclear whether the expression of these genes is truly co-ordinate or whether it may be the result of averaging the phenotypic expression of different fibroblast subpopulations present within each culture. Objectives To determine by Northern analysis the correlation between alpha1(I) and alpha1(III) procollagen mRNA levels in clonal populations of human dermal fibroblasts. As previously described, clonal cultures were derived from parent strains of human dermal fibroblasts by a microscopically controlled dilution technique and by stimulation of single cells with low oxygen tension in the early phases of clonal growth. In agreement with previous reports, we found that baseline steady-state levels of alpha1(I) procollagen mRNA were co-ordinately regulated with the alpha1(III) procollagen mRNA in 26 parent strains (r = 0. 9003; P ordinate regulation observed in non-clonal cultures, suggesting that these two genes operate under different sets of regulatory controls. This clonal heterogeneity may provide additional flexibility to the process of tissue repair and fibroblast clonal expansion.

Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts.

Science.gov (United States)

Anitua, Eduardo; de la Fuente, María; Ferrando, Marcos; Quintana, Fernando; Larreategui, Zaloa; Matorras, Roberto; Orive, Gorka

2016-11-01

To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation (T-test or Mann-Whitney U-test). We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro, enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in "in vivo" endometrial development and especially in human embryo implantation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

International Nuclear Information System (INIS)

Malpass, Gloria E.; Arimilli, Subhashini; Prasad, G.L.; Howlett, Allyn C.

2014-01-01

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes

Regulation of gene expression by tobacco product preparations in cultured human dermal fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Malpass, Gloria E., E-mail: gloria.malpass@gmail.com [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Arimilli, Subhashini, E-mail: sarimill@wakehealth.edu [Department of Microbiology and Immunology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States); Prasad, G.L., E-mail: prasadg@rjrt.com [R and D Department, R.J. Reynolds Tobacco Company, Winston-Salem, NC 27102 (United States); Howlett, Allyn C., E-mail: ahowlett@wakehealth.edu [Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157 (United States)

2014-09-01

Skin fibroblasts comprise the first barrier of defense against wounds, and tobacco products directly contact the oral cavity. Cultured human dermal fibroblasts were exposed to smokeless tobacco extract (STE), total particulate matter (TPM) from tobacco smoke, or nicotine at concentrations comparable to those found in these extracts for 1 h or 5 h. Differences were identified in pathway-specific genes between treatments and vehicle using qRT-PCR. At 1 h, IL1α was suppressed significantly by TPM and less significantly by STE. Neither FOS nor JUN was suppressed at 1 h by tobacco products. IL8, TNFα, VCAM1, and NFκB1 were suppressed after 5 h with STE, whereas only TNFα and NFκB1 were suppressed by TPM. At 1 h with TPM, secreted levels of IL10 and TNFα were increased. Potentially confounding effects of nicotine were exemplified by genes such as ATF3 (5 h), which was increased by nicotine but suppressed by other components of STE. Within 2 h, TPM stimulated nitric oxide production, and both STE and TPM increased reactive oxygen species. The biological significance of these findings and utilization of the gene expression changes reported herein regarding effects of the tobacco product preparations on dermal fibroblasts will require additional research. - Highlights: • Tobacco product preparations (TPPs) alter gene expression in dermal fibroblasts. • Some immediate early genes critical to the inflammatory process are affected. • Different TPPs produce differential responses in certain pro-inflammatory genes.

Evaluation of life quality after arterial uterine embolization for leiomyoma

International Nuclear Information System (INIS)

Liu Zhaoyu; Shan Ming; Lu Zaiming; Zheng Jiahe; Zhang Jun; Sun Wei

2007-01-01

Objective: To evaluate the quality of life in women with uterine leiomyoma after treatment by uterine arterial embolization. Methodes: 118 patients of uterine leiomyoma were treated by uterine arterial embolization (UAE) from January 2003 to March 2005. The quality of life was measured by a fibroid specific symptom and HRQOL questionnaire pre-and post-embolization. Patients satisfaction was surveyed together with decrease of fibroids' mass measurement. Results: The decrease of fibroid size and uterine volume were 49.6% and 45.2% at 6 months after embolization with simultaneously obvious improvement of clinical symptoms. The scores of quality of life obviously improved in all follow-up subscales (P<0.001). No amenorrhea occurred during the period of observation with more than 60% of respondents acknowledging the positive improvement in fibroid-related symptoms though UAE; and 80% would probably or definitely take UAE as the first choice of treatment again. Conclusion: The treatment of symptomatic leiomyomas by UAE can improve the quality of life dramatically with a promising satisfaction. (authors)

Renal transplantation-related risk factors for the development of uterine adenomatoid tumors.

Science.gov (United States)

Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

2016-08-01

•We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.•Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.•The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors.

Silencing Histone Deacetylase 7 Alleviates Transforming Growth Factor-β1-Induced Profibrotic Responses in Fibroblasts Derived from Peyronie’s Plaque

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Dong Hyuk Kang

2018-05-01

Full Text Available Purpose: Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs in fibroblasts isolated from plaque tissue of Peyronie’s disease (PD or normal tunica albuginea (TA and to examine the anti-fibrotic effect of small interfering RNA (siRNA-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque. Materials and Methods: For differential gene expression study, we performed reverse-transcriptase polymerase chain reaction for HDAC isoforms (1–11 in fibroblasts isolated from PD plaque or normal TA. Fibroblasts isolated from PD plaque were pretreated with HDAC7 siRNA (100 pmol and then stimulated with transforming growth factor-β1 (TGF-β1, 10 ng/mL. Protein was extracted from treated fibroblasts for Western blotting. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-β1-induced nuclear translocation of Smad2/3 and myofibroblastic differentiation. Results: The mRNA expression of HDAC2, 3, 4, 5, 7, 8, 10, and 11 was higher in fibroblasts isolated from PD plaque than in fibroblasts isolated from normal TA tissue. Knockdown of HDAC7 in PD fibroblasts inhibited TGF-β1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-β1-induced production of extracellular matrix protein. Conclusions: These findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.

Uterine Leiomyomas: An ENIGMA

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Kempula Geethamala

2016-01-01

Conclusion: Though hysterectomy is a routine procedure in the management of uterine leiomyomas, occasional cases of tumor or infective pathology may be missed. Therefore, histopathology is mandatory and conscientious quest must be done for confirmed diagnosis and ensuring optimal management.

The application of uterine artery chemoembolization in treating cesarean section scar pregnancy

International Nuclear Information System (INIS)

Zhang Guofu; Wang Tianping; Gu Shouxin; Han Zhigang; Zhang Di; Tian Xiaomei; Wang Xuezhen; Yu Fei; Huang Zirong

2010-01-01

Objective: To discuss the feasibility and safety of uterine artery chemoembolization in treating cesarean section scar pregnancy. Methods: During the period of Jun. 2005-Jun. 2010, uterine artery chemoembolization was performed in 130 patients with cesarean section scar pregnancy in authors' hospital. Via bilateral uterine arteries 100-150 mg MTX and 80 000 u Gentamycin were infused separately, which was followed by the embolization of bilateral uterine arteries with Gelfoam. Of the total 130 patients,coexisted leiomyoma was found in 23 and embolization therapy with PVA microspheres was employed. Curettage of uterus was carried out within 24-72 hours after the procedure. Results: The success rate of bilateral uterine artery chemoembolization was 100%. The blood loss during curettage procedure was 12-110 ml (mean 28.5 ml). No serious complications occurred. Conclusion: The uterine artery chemoembolization is an effective and safe treatment for cesarean section scar pregnancy. This technique can greatly avoid unnecessary uterectomy and, thus, preserve the fertility of the female patients. (authors)

A Case of Lymphoepithelioma-like Carcinoma in the Uterine Cervix.

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Takebayashi, Kanetoshi; Nishida, Masakazu; Matsumoto, Harunobu; Nasu, Kaei; Narahara, Hisashi

2015-02-11

Lymphoepithelioma-like carcinoma occurring in the reproductive organs is a rare variant of squamous cell carcinoma, and this tumor of the uterine cervix accounts for 0.7% of all primary cervical uterine neoplasms. Associations with Epstein-Barr virus (EBV) and human papilloma virus (HPV) have been demonstrated in some studies. Some investigators suggested that EBV has an important role in the initiation of lymphoepitheliomalike carcinoma in Asian women. Here we report the case of a 45-year-old Japanese woman, gravida 2 and parity 2. She was admitted due to severe atypical genital bleeding caused by uterine cervical cancer. A >60-mm tumor was detected at the uterine cervix, and no distal metastasis or swallowing of lymph nodes was revealed by magnetic resonance imaging and a computed tomography scan. The cervical cancer stage FIGO Ib2 was diagnosed, and a radical hysterectomy was performed for this malignant tumor. The in situ hybridization for EBV was negative. HVP infection was strongly suspected because the squamous cell carcinoma was observed macroscopically in the uterine cervix. The prognosis of uterine lymphoepithelioma-like carcinoma is thought to be better than those of other cervical cancer types, but careful follow-up at fixed intervals is recommended. The patient has been followed up for 4 months since her surgery, and no evidence of recurrence has been detected.

A case of lymphoepithelioma-like carcinoma in the uterine cervix

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Kanetoshi Takebayashi

2015-03-01

Full Text Available Lymphoepithelioma-like carcinoma occurring in the reproductive organs is a rare variant of squamous cell carcinoma, and this tumor of the uterine cervix accounts for 0.7% of all primary cervical uterine neoplasms. Associations with Epstein-Barr virus (EBV and human papilloma virus (HPV have been demonstrated in some studies. Some investigators suggested that EBV has an important role in the initiation of lymphoepithelioma-like carcinoma in Asian women. Here we report the case of a 45-year-old Japanese woman, gravida 2 and parity 2. She was admitted due to severe atypical genital bleeding caused by uterine cervical cancer. A >60-mm tumor was detected at the uterine cervix, and no distal metastasis or swallowing of lymph nodes was revealed by magnetic resonance imaging and a computed tomography scan. The cervical cancer stage FIGO Ib2 was diagnosed, and a radical hysterectomy was performed for this malignant tumor. The in situ hybridization for EBV was negative. HVP infection was strongly suspected because the squamous cell carcinoma was observed macroscopically in the uterine cervix. The prognosis of uterine lymphoepithelioma-like carcinoma is thought to be better than those of other cervical cancer types, but careful follow-up at fixed intervals is recommended. The patient has been followed up for 4 months since her surgery, and no evidence of recurrence has been detected.

Analysis of the long and middle term effect of uterine artery embolization for uterine leiomyomas

International Nuclear Information System (INIS)

Shi Limin; Luo Pengfei; Chen Xiaoming

2006-01-01

Uterine artery embolization (UAE) is a safe and effective method for uterine leiomyomas but its long and middle term effects are definite. Furthermore it bears some exquisite comparison with the conventional therapy but not as a radical one, with a tendency. However, to develop new leiomyomas and recurrence after UAE, there for all patients should be monitored with clinical and imaging examinations for more than 2 years after the procedure. At present, a few literatures involving the factors that could influence the effects of UAE have been issued. It is necessary to carry on large-scale clinical research of the related factors influencing the results of UAE in order to guide clinical practice correctly and swiftly. (authors)

Hibiscus syriacus Extract from an Established Cell Culture Stimulates Skin Wound Healing.

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di Martino, O; Tito, A; De Lucia, A; Cimmino, A; Cicotti, F; Apone, F; Colucci, G; Calabrò, V

2017-01-01

Higher plants are the source of a wide array of bioactive compounds that support skin integrity and health. Hibiscus syriacus , family Malvaceae, is a plant of Chinese origin known for its antipyretic, anthelmintic, and antifungal properties. The aim of this study was to assess the healing and hydration properties of H. syriacus ethanolic extract (HSEE). We established a cell culture from Hibiscus syriacus leaves and obtained an ethanol soluble extract from cultured cells. The properties of the extract were tested by gene expression and functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE treatment increased the healing potential of fibroblasts and keratinocytes. Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by 16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%. These results were confirmed on skin explants, where HSEE accelerated the wound healing activity in terms of epithelium formation and fibronectin production. Moreover, HSEE increased the expression of genes involved in skin hydration and homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20 and 58%, respectively. Our data show that HSEE contains compounds capable of stimulating expression of biomarkers relevant to skin regeneration and hydration thereby counteracting molecular pathways leading to skin damage and aging.

Hibiscus syriacus Extract from an Established Cell Culture Stimulates Skin Wound Healing

Directory of Open Access Journals (Sweden)

O. di Martino

2017-01-01

Full Text Available Higher plants are the source of a wide array of bioactive compounds that support skin integrity and health. Hibiscus syriacus, family Malvaceae, is a plant of Chinese origin known for its antipyretic, anthelmintic, and antifungal properties. The aim of this study was to assess the healing and hydration properties of H. syriacus ethanolic extract (HSEE. We established a cell culture from Hibiscus syriacus leaves and obtained an ethanol soluble extract from cultured cells. The properties of the extract were tested by gene expression and functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE treatment increased the healing potential of fibroblasts and keratinocytes. Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by 16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%. These results were confirmed on skin explants, where HSEE accelerated the wound healing activity in terms of epithelium formation and fibronectin production. Moreover, HSEE increased the expression of genes involved in skin hydration and homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20 and 58%, respectively. Our data show that HSEE contains compounds capable of stimulating expression of biomarkers relevant to skin regeneration and hydration thereby counteracting molecular pathways leading to skin damage and aging.

Vaginal or uterine bleeding - overview

Science.gov (United States)

... and other menstrual conditions; Abnormal menstrual periods; Abnormal vaginal bleeding ... There are many causes of abnormal vaginal bleeding. HORMONES ... Doctors call the problem abnormal uterine bleeding (AUB) . AUB ...

Acquired uterine vascular malformations: radiological and clinical outcome after transcatheter embolotherapy

Energy Technology Data Exchange (ETDEWEB)

Maleux, Geert; Heye, Sam; Wilms, Guy [University Hospitals Gasthuisberg, Department of Radiology, Leuven (Belgium); Timmerman, Dirk [University Hospitals Gasthuisberg, Department of Obstetrics and Gynecology, Leuven (Belgium)

2006-02-01

The purpose of this retrospective study is to assess the radiological and clinical outcome of transcatheter embolization of acquired uterine vascular malformations in patients presenting with secondary postpartum or postabortion vaginal hemorrhage. In a cohort of 17 patients (mean age: 29.7 years; standard deviation: 4.23; range: 25-38 years) 18 embolization procedures were performed. Angiography demonstrated a uterine parenchymal hyperemia with normal drainage into the large pelvic veins (''low-flow uterine vascular malformation'') in 83% (n=15) or a direct arteriovenous fistula (''high-flow uterine vascular malformation'') in 17% (n=3). Clinically, in all patients the bleeding stopped after embolization but in 1 patient early recurrence of hemorrhage occurred and was treated by hysterectomy. Pathological analysis revealed a choriocarcinoma. During follow-up (mean time period: 18.8 months; range: 1-36 months) 6 patients became pregnant and delivered a healthy child. Transcatheter embolization of the uterine arteries, using microparticles, is safe and highly effective in the treatment of a bleeding acquired uterine vascular malformation. In case of clinical failure, an underlying neoplastic disease should be considered. Future pregnancy is still possible after embolization. (orig.)

Scleroderma fibroblasts: Some aspects of in vitro assessment of collagen synthesis

International Nuclear Information System (INIS)

Krieg, T.; Max-Planck-Institut fuer Biochemie, Muenchen; Luderschmidt, C.; Braun-Falco, O.; Weber, L.; Mueller, P.K.

1981-01-01

Fibroblasts were cultured from skin biopsies of patients with systemic sclerosis in different stages of the disease. In vitro synthesis of collagen was checked after a pulse with tritiated proline. The ratio between type I and type III collagen was normal in all patients. Six of seven cultures derived from patients in the active state showed an increased synthesis of collagen relative to other proteins. Addition of serum (normal and diseased) to the culture medium did not stimulate synthesis of collagen in any culture with normal collagen synthesis. (orig.) [de

Scleroderma fibroblasts: some aspects of in vitro assessment of collagen synthesis

Energy Technology Data Exchange (ETDEWEB)

Krieg, T.; Luderschmidt, C.; Braun-Falco, O.; Weber, L.; Mueller, P.K.

1981-01-01

Fibroblasts were cultured from skin biopsies of patients with systemic sclerosis in different stages of the disease. In vitro synthesis of collagen was checked after a pulse with tritiated proline. The ratio between type I and type III collagen was normal in all patients. Six of seven cultures derived from patients in the active state showed an increased synthesis of collagen relative to other proteins. Addition of serum (normal and diseased) to the culture medium did not stimulate synthesis of collagen in any culture with normal collagen synthesis.

PALM-COEIN Nomenclature for Abnormal Uterine Bleeding.

Science.gov (United States)

Deneris, Angela

2016-05-01

Approximately 30% of women will experience abnormal uterine bleeding (AUB) during their life time. Previous terms defining AUB have been confusing and imprecisely applied. As a consequence, both clinical management and research on this common problem have been negatively impacted. In 2011, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Group (FMDG) published PALM-COEIN, a new classification system for abnormal bleeding in the reproductive years. Terms such as menorrhagia, menometrorrhagia, metrorrhagia, dysfunctional uterine bleeding, polymenorrhea, oligomenorrhea, and uterine hemorrhage are no longer recommended. The PALM-COEIN system was developed to standardize nomenclature to describe the etiology and severity of AUB. A brief description of the PALM-COEIN nomenclature is presented as well as treatment options for each etiology. Clinicians will frequently encounter women with AUB and should report findings utilizing the PALM-COEIN system. © 2016 by the American College of Nurse-Midwives.

Successful Pregnancy after Treatment with Ulipristal Acetate for Uterine Fibroids

OpenAIRE

Monleón, Javier; Martínez-Varea, Alicia; Galliano, Daniela; Pellicer, Antonio

2014-01-01

This case report presents a clinical pregnancy after ulipristal acetate (UA) to decrease uterine fibroid size. A 37-year-old patient, gravida 1, abortus 1, with uterine fibroids was treated with 5 mg of UA daily for 13 weeks starting eight months after a multiple laparotomic myomectomy. Fibroid shrinkage and restoration of the morphology of endometrial cavity were evaluated in order to allow a subsequent pregnancy. A decrease of the uterine fibroids and a normal morphology of the endometrial ...

Synergistic Induction of Eotaxin and VCAM-1 Expression in Human Corneal Fibroblasts by Staphylococcal Peptidoglycan and Either IL-4 or IL-13

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Ken Fukuda

2011-01-01

Conclusions: Interaction of innate and adaptive immunity, as manifested by synergistic stimulation of eotaxin and VCAM-1 expression in corneal fibroblasts by peptidoglycan and Th2 cytokines, may play an important role in tissue eosinophilia associated with ocular allergy.

Live fate-mapping of joint-associated fibroblasts visualizes expansion of cell contributions during zebrafish fin regeneration.

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Tornini, Valerie A; Thompson, John D; Allen, Raymond L; Poss, Kenneth D

2017-08-15

The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tissue. However, these studies have labeled general cell types rather than granular cell subpopulations, and they do not explain the developmental transitions that must occur for distal structures to arise from cells with proximal identities in the appendage stump. Here, we find that regulatory sequences of tph1b , which encodes an enzyme that synthesizes serotonin, mark a subpopulation of fibroblast-like cells restricted to the joints of uninjured adult zebrafish fins. Amputation stimulates serotonin production in regenerating fin fibroblasts, yet targeted tph1b mutations abrogating this response do not disrupt fin regeneration. In uninjured animals, tph1b -expressing cells contribute fibroblast progeny that remain restricted to joints throughout life. By contrast, upon amputation, tph1b + joint cells give rise to fibroblasts that distribute across the entire lengths of regenerating fin rays. Our experiments visualize and quantify how incorporation into an appendage blastema broadens the progeny contributions of a cellular subpopulation that normally has proximodistal restrictions. © 2017. Published by The Company of Biologists Ltd.

A homeopathic remedy from arnica, marigold, St. John's wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts.

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Hostanska, Katarina; Rostock, Matthias; Melzer, Joerg; Baumgartner, Stephan; Saller, Reinhard

2012-07-18

Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712-2), its succussed hydroalcoholic solvent (0712-1) and unsuccussed solvent (0712-3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined "wound field". All assays were performed in three independent controlled experiments. None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712-2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712-1) at 1:100 dilutions (p 0.05). Preparation (0712-2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712-1), which caused 22.1% wound closure. Results of this study showed that the low potency homeopathic remedy (0712-2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis.

The value of uterine artery embolization in treatment of hysteromyoma

International Nuclear Information System (INIS)

Chen Ying

2009-01-01

Objective: To investigate the value of UAE in treatment of Hysteromyoma. Methods: Select 20 cases of patients with symptomatic uterine fibroids, intubate with Uterine artery, then inject Polyvinyl alcohol particles transcatheter Embolizae Uterine artery. After the operation, observe the patient follow-up for 6-18 months, to find the situation of symptom improvement and the change of the size of uterus and myoma. Results: After the operation of UAE 2-6 months, the symptoms of the patients improve significantly or disappear. After 6-18 months, B-mode ultrasonography shows that Myoma volume narrow 30%-85%, average to narrow 60%. Uterine volume narrow 25%-70%, average to narrow 50%. No Serious complications. Conclusion: UAE is a safe and effective method to cure Hysteromyoma. It worth promoting in clinical sicience. (authors)

Effect of SMAD7 gene overexpression on TGF-β1-induced profibrotic responses in fibroblasts derived from Peyronie's plaque

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Min Ji Choi

2015-06-01

Full Text Available Transforming growth factor-β1 (TGF-β1 has been identified as one of the most important fibrogenic cytokines associated with Peyronie's disease (PD. The mothers against decapentaplegic homolog 7 (SMAD7 is an inhibitory Smad protein that blocks TGF-β signaling pathway. The aim of this study was to examine the anti-fibrotic effect of the SMAD7 gene in primary fibroblasts derived from human PD plaques. PD fibroblasts were pretreated with the SMAD7 gene and then stimulated with TGF-β1. Treated fibroblasts were used for Western blotting, fluorescent immunocytochemistry, hydroxyproline determination, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. Overexpression of the SMAD7 gene inhibited TGF-β1-induced phosphorylation and nuclear translocation of SMAD2 and SMAD3, transdifferentiation of fibroblasts into myofibroblasts, and quashed TGF-β1-induced production of extracellular matrix protein and hydroxyproline. Overexpression of the SMAD7 gene decreased the expression of cyclin D1 (a positive cell cycle regulator and induced the expression of poly (ADP-ribose polymerase 1, which is known to terminate Smad-mediated transcription, in PD fibroblasts. These findings suggest that the blocking of the TGF-β pathway by use of SMAD7 may be a promising therapeutic strategy for the treatment of PD.

Equibiaxial cyclic stretch stimulates fibroblasts to rapidly remodel fibrin.

Science.gov (United States)

Balestrini, Jenna Leigh; Billiar, Kristen Lawrence

2006-01-01

Understanding the effects of the mechanical environment on wound healing is critical for developing more effective treatments to reduce scar formation and contracture. The aim of this study was to investigate the effects of dynamic mechanical stretch on cell-mediated early wound remodeling independent of matrix alignment which obscures more subtle remodeling mechanisms. Cyclic equibiaxial stretch (16% stretch at 0.2 Hz) was applied to fibroblast-populated fibrin gel in vitro wound models for eight days. Compaction, density, tensile strength, and collagen content were quantified as functional measures of remodeling. Stretched samples were approximately ten times stronger, eight-fold more dense, and eight times thinner than statically cultured samples. These changes were accompanied by a 15% increase in net collagen but no significant differences in cell number or viability. When collagen crosslinking was inhibited in stretched samples, the extensibility increased and the strength decreased. The apparent weakening was due to a reduction in compaction rather than a decrease in ability of the tissue to withstand tensile forces. Interestingly, inhibiting collagen crosslinking had no measurable effects on the statically cultured samples. These results indicate that amplified cell-mediated compaction and even a slight addition in collagen content play substantial roles in mechanically induced wound strengthening. These findings increase our understanding of how mechanical forces guide the healing response in skin, and the methods employed in this study may also prove valuable tools for investigating stretch-induced remodeling of other planar connective tissues and for creating mechanically robust engineered tissues.

Non-puerperal uterine inversion: A case report | Fofie | Ghana ...

African Journals Online (AJOL)

Non-puerperal uterine inversion is rare. A 42-year old woman presented with lower abdominal pain, offensive vaginal discharge and a huge protruding mass per vaginum. A clinical diagnosis of non-puerperal uterine inversion was made and she successfully underwent vaginal hysterectomy. A high index of suspicion is ...

Cadmium stimulates myofibroblast differentiation and mouse lung fibrosis

International Nuclear Information System (INIS)

Hu, Xin; Fernandes, Jolyn; Jones, Dean P.; Go, Young-Mi

2017-01-01

Highlights: • Low-dose Cd stimulates differentiation of human lung fibroblast to myofibroblast. • Cd-stimulated fibrosis signaling involves activation of SMAD transcription factor. • Low-dose Cd intake in mice activates myofibroblast differentiation. - Abstract: Increasing evidence suggests that Cd at levels found in the human diet can cause oxidative stress and activate redox-sensitive transcription factors in inflammatory signaling. Following inflammation, tissue repair often involves activation of redox-sensitive transcription factors in fibroblasts. In lungs, epithelial barrier remodeling is required to restore gas exchange and barrier function, and aberrant myofibroblast differentiation leads to pulmonary fibrosis. Contributions of exogenous exposures, such as dietary Cd, to pulmonary fibrosis remain inCompletely defined. In the current study, we tested whether Cd activates fibrotic signaling in human fetal lung fibroblasts (HFLF) at micromolar and submicromolar Cd concentrations that do not cause cell death. Exposure of HFLF to low-dose Cd (≤1.0 μM) caused an increase in stress fibers and increased protein levels of myofibroblast differentiation markers, including α-smooth muscle actin (α-SMA) and extra-domain-A-containing fibronectin (ED-A-FN). Assay of transcription factor (TF) activity using a 45-TF array showed that Cd increased activity of 12 TF, including SMAD2/3/4 (mothers against decapentaplegic homolog) signaling differentiation and fibrosis. Results were confirmed by real-time PCR and supported by increased expression of target genes of SMAD2/3/4. Immunocytochemistry of lungs of mice exposed to low-dose Cd (0.3 and 1.0 mg/L in drinking water) showed increased α-SMA protein level with lung Cd accumulation similar to lung Cd in non-smoking humans. Together, the results show that relatively low Cd exposures stimulate pulmonary fibrotic signaling and myofibroblast differentiation by activating SMAD2/3/4-dependent signaling. The results

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells.

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Liu, Zhiyong; Hartman, Yolanda E; Warram, Jason M; Knowles, Joseph A; Sweeny, Larissa; Zhou, Tong; Rosenthal, Eben L

2011-08-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN depleted head and neck cancer tumor cells

Science.gov (United States)

Liu, Zhiyong; Hartman, Yolanda E.; Warram, Jason M.; Knowles, Joseph A.; Sweeny, Larrisa; Zhou, Tong; Rosenthal, Eben L.

2011-01-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were co-cultured with fibroblasts or inoculated with fibroblasts into SCID mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Co-culture experiments demonstrated fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN silenced cells compared to control vector transfected cells, while inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast co-culture, suggesting the importance of FGFR2 signaling in fibroblast mediated tumor growth. Analysis of xenografted tumors revealed EMMPRIN silenced tumors had a larger stromal compartment compared to control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast independent tumor growth. PMID:21665938

Opposing roles of C/EBPbeta and AP-1 in the control of fibroblast proliferation and growth arrest-specific gene expression

DEFF Research Database (Denmark)

Gagliardi, Mark; Maynard, Scott; Miyake, Tetsuaki

2003-01-01

in the levels of AP-1 proteins. Therefore, C/EBPbeta is a negative regulator of AP-1 expression and activity in CEF. The expression of cyclin D1 and cell proliferation were stimulated by the dominant negative mutant of C/EBPbeta but not in the presence of TAM67, a dominant negative mutant of c-Jun and AP-1. CEF......Chicken embryo fibroblasts (CEF) express several growth arrest-specific (GAS) gene products in G0. In contact-inhibited cells, the expression of the most abundant of these proteins, the p20K lipocalin, is activated at the transcriptional level by C/EBPbeta. In this report, we describe the role of C....../EBPbeta in CEF proliferation. We show that the expression of a dominant negative mutant of C/EBPbeta (designated Delta184-C/EBPbeta) completely inhibited p20K expression at confluence and stimulated the proliferation of CEF without inducing transformation. Mouse embryo fibroblasts nullizygous for C/EBPbeta had...

Second primary tumor and radiation induced neoplasma in the uterine cancer

International Nuclear Information System (INIS)

Sakurai, Tomoyasu; Nishio, Masamichi; Kagami, Yoshikazu; Murakami, Yoshitaka; Narimatsu, Naoto; Kanemoto, Toshitaka

1984-01-01

This report is concerned with multiple primary cancers developing in invasive uterine cancer. Second primary tumors were recorded 27 women with a total of 30 non-uterine cancer (exception of radiation-induced cancer). 17 patients of radiation-induced neoplasm were observed (Rectal cancer 4, soft part sarcoma 4, cancer of urinary bladder 3, bone tumor 3, uterin cancer 2 and cancer of Vulva 1). One case is 4 legions (corpus, sigma, thymoma and stomach), 2 cases are 3 lesions (uterine cervix, stomach and maxillay siuis: uterine cervix, thyroidal gland and radiation-induced soft part sarcoma). Only 5 of these 17 patients were known irradiated dose (50 Gy--55 Gy), however others unknown. The mean latent periods of 17 cases of radiation induced neoplasms are 19.4 years. 16 patients of late second cancers of the cervix appearing from 11 to 36 years (average 19.5 years) after initial radiotherapy were recorded. (author)

Role of MR in diagnosis of uterine leiomyoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Sung Moon; Lee, Hee Jung; Kim, Jung Sik; Joo, Yang Gu; Kim, Hong; Suh, Soo Jhi [Keimyung University School of Medicine, Daegu (Korea, Republic of)

1994-04-15

Uterine myoma is the most common benign uterine neoplasm, and associated with numerous gynecologic and obsteric complication. Preoperative acurrate analysis of the number, location and type of the myoma is important, especially in reproductive women. We analyze the MR findings of uterine myoma for evaluation of the role of MR in diagnosis of uterine myoma. We analyze MR findings of 76 myomas in 40 patients, and 34 myomas in 17 patients of them were confirmed by surgery. With 2.0T Spectro-20000(Gold-star, Korea), T1WI axial images and T2WI axial and sagittal images were obtained. Locations were classified into fundus, anterior body, posterior body, right body, left body, and cervix. Types were classified into submucosal, intramural, and subserosal. Associated findings were analyzed also. The most common location and type were posterior body and intramural type, respectively. Ten myomas were confirmed on surgery only, and the causes were as follows: first, all 10 myomas were less than 2 cm in size; second, 1 subserosal myoma was abutted to a large ovarian mass; third, small myomas were abutted to each other, or small one was adjacent to larger one and considered as one large myoma. Degenerative change was noted in 50% of histologically confirmed cases. High signal halo on T2WI was noted in 14%. MR is excellent in detection and localization of uterine leiomyoma larger than 2cm, and may be a preoperative diagnostic method of choice in patient who need myomectomy for preservation of childbearing function.

Abnormal uterine bleeding in reproductive-aged women.

Science.gov (United States)

Matthews, Michelle L

2015-03-01

Abnormal uterine bleeding is a common medical condition with several causes. The International Federation of Gynecology and Obstetrics published guidelines in 2011 to develop universally accepted nomenclature and a classification system. In addition, the American College of Obstetrics and Gynecology recently updated recommendations on evaluation of abnormal uterine bleeding and indications for endometrial biopsies. This article reviews both medical and surgical treatments, including meta-analysis reviews of the most effective treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

OpenAIRE

Bianchessi, Marta; Chen, Yuwen; Durgam, Sushmitha; Pondenis, Holly; Stewart, Matthew

2015-01-01

Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assa...

Inter-operator Variability in Defining Uterine Position Using Three-dimensional Ultrasound Imaging

DEFF Research Database (Denmark)

Baker, Mariwan; Jensen, Jørgen Arendt; Behrens, Claus F.

2013-01-01

significantly larger inter-fractional uterine positional displacement, in some cases up to 20 mm, which outweighs the magnitude of current inter-operator variations. Thus, the current US-phantom-study suggests that the inter-operator variability in addressing uterine position is clinically irrelevant.......In radiotherapy the treatment outcome of gynecological (GYN) cancer patients is crucially related to reproducibility of the actual uterine position. The purpose of this study is to evaluate the inter-operator variability in addressing uterine position using a novel 3-D ultrasound (US) system....... The study is initiated by US-scanning of a uterine phantom (CIRS 404, Universal Medical, Norwood, USA) by seven experienced US operators. The phantom represents a female pelvic region, containing a uterus, bladder and rectal landmarks readily definable in the acquired US-scans. The organs are subjected...

Superselective uterine artery embolization for the control and prevention of obstetric hemorrhage

International Nuclear Information System (INIS)

Song Li; Tong Xiaoqiang; Wang Jian; Yang Min; Lv Yongxing; Zou Yinghua

2008-01-01

Objectives: To evaluate the efficacy of superselective uterine artery embolization for treatment and prevention of obstetric hemorrhage. Methods: Between April 2004 and December 2007, 47 consecutive patients underwent uterine artery embolization to control or prevent hemorrhage, including 20 patients for preventing hemorrhage before abortion and 27 for controlling obstetric hemorrhage. Results: Bilateral uterine artery embolization was performed in all cases except one for abnormal vascular anatomy receiving unilateral approach. Within 10 days after embolization, curettage abortion or uterine-incision delivery was done without hysterectomy, and hemorrhage during abortion was less with average of 54 ml. Conclusions: The high success rate, effectiveness and possibility of preserving reproductive function have made uterine artery embolization the technique of choice to control obstetric hemorrhage, and prophylactic embolization, can prevent hemorrhage before abortion. (authors)

Fertility after uterine artery embolization of fibroids

DEFF Research Database (Denmark)

Karlsen, K; Hrobjartsson, A; Korsholm, M

2018-01-01

PURPOSE: The impact of uterine artery embolization (UAE) for the purpose of diminishing the effect of uterine fibroids on fertility is unclear. We have investigated the reported rates of pregnancy and miscarriage after treatment of uterine fibroids with UAE. MATERIALS AND METHODS: We searched...... intervention was included. The PRISMA guideline was used to do a systematic review using the main outcomes pregnancy rate and miscarriage rate. Risk of bias was assessed by the Cochrane risk of bias tool or by ROBINS-I. The quality of evidence was assessed by the GRADE approach. RESULTS: We included 17 studies...... (989 patients): 1 RCT, 2 cohort studies, and 14 case series. Pregnancy rates after UAE were 50% in the RCT and 51 and 69% in the cohort studies. Among the case series median pregnancy rate was 29%. Miscarriage rates were 64% in the RCT. Miscarriage rates at 56 and 34% were found in the cohort studies...

Uterine bacterial flora in postpartum Danish Holstein dairy cows determined using DNA-based fingerprinting: correlation to uterine condition and calving management.

Science.gov (United States)

Elkjær, K; Ancker, M-L; Gustafsson, H; Friggens, N C; Waldmann, A; Mølbak, L; Callesen, H

2013-04-01

The overall aim of this study was to describe uterine bacterial flora during the postpartum period in Danish Holstein cows using the Terminal Restriction Fragment Length Polymorphism (T-RFLP) method. This method produces a pattern of nucleic acid fragments from the microorganisms present, reflecting the "fingerprint" of the actual microbial flora. As well as characterizing changes in flora with time from calving and between herds, data were examined for strong relations between uterine bacterial flora, calving management and uterine condition. In total 125 Holstein cows from five herds were included, and for each cow calving management was recorded. Cows were clinically examined on average 8 (range 0-19) and 28 (range 22-38) days after calving, and a uterine sample was taken for bacterial identification using T-RFLP. Milk samples were taken weekly for progesterone analysis. Bacteria were found in all cows at both examinations, and the flora was composed of many species, including species not traditionally reported to be present in the bovine uterus. The bacterial composition differed according to days from calving and herd. In all five herds Fusobacterium necrophorum, Pseudomonas/Acinetobacter and Bacteroides/Sphingobacterium/Prevotellaceae were among the most common at both examinations. In four herds there was a percentage decrease of F. necrophorum from first to second examination, and in all herds there was a percentage increase of Pseudomonas/Acinetobacter from first to second examination. No differences in bacterial flora were found between cows with different uterine scores, which were influenced by herd, calving difficulty and retained placenta. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics.

Science.gov (United States)

Alberola-Rubio, J; Prats-Boluda, G; Ye-Lin, Y; Valero, J; Perales, A; Garcia-Casado, J

2013-12-01

Non-invasive recording of uterine myoelectric activity (electrohysterogram, EHG) could provide an alternative to monitoring uterine dynamics by systems based on tocodynamometers (TOCO). Laplacian recording of bioelectric signals has been shown to give better spatial resolution and less interference than mono- and bipolar surface recordings. The aim of this work was to study the signal quality obtained from monopolar, bipolar and Laplacian techniques in EHG recordings, as well as to assess their ability to detect uterine contractions. Twenty-two recording sessions were carried out on singleton pregnant women during the active phase of labour. In each session the following simultaneous recordings were obtained: internal uterine pressure (IUP), external tension of abdominal wall (TOCO) and EHG signals (5 monopolar and 4 bipolar recordings, 1 discrete approximation to the Laplacian of the potential and 2 estimates of the Laplacian from two active annular electrodes). The results obtained show that EHG is able to detect a higher number of uterine contractions than TOCO. Laplacian recordings give improved signal quality over monopolar and bipolar techniques, reduce maternal cardiac interference and improve the signal-to-noise ratio. The optimal position for recording EHG was found to be the uterine median axis and the lower centre-right umbilical zone. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts.

Science.gov (United States)

Oztürk, Nilgün; Korkmaz, Seval; Oztürk, Yusuf; Başer, K Hüsnü Can

2006-03-01

Wound healing properties of Gentian (Gentiana lutea ssp. symphyandra) extract and its main constituents, gentiopicroside, sweroside and swertiamarine (compounds 1-3, respectively) were evaluated by comparison with dexpanthenol on cultured chicken embryonic fibroblasts. The extract was also analyzed by HPLC to quantify its constituents. Chicken embryonic fibroblasts from fertilized eggs were incubated with the plant extract and its constituents, compounds 1-3. Using microscopy, mitotic ability, morphological changes and collagen production in the cultured fibroblasts were evaluated as parameters. Wound healing activity of Gentian seems to be mainly due to the increase in the stimulation of collagen production and the mitotic activity by compounds 2 and 3, respectively (p < 0.005 in all cases). All three compounds also exhibited cytoprotective effects, which may cause a synergism in terms of wound healing activity of Gentian. The findings demonstrated the wound healing activity of Gentian, which has previously been based only on ethnomedical data.

Review literature on uterine carcinosarcoma

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Rajendra Singh

2014-01-01

Full Text Available Carcinosarcoma of the uterus is a rare gynaecological neoplasm, which is also known as malignant mixed mesodermal tumor. Traditionally this tumour has been regarded as a subtype of uterine sarcoma, and its origin remains controversial. The exact nature and prognosis was not clear in the past. It is believed that uterine carcinosarcoma have a Mullerian duct origin and have a capacity to differentiate into various mesenchymal and epithelial components. Regarding the histogensis, various theories have been given; of which ′conversion theory′ was broadly accepted. Carcinosarcoma are mostly of monoclonal origin with the carcinomatous component being the driving force. This type of tumor is broadly divided into two groups, homologous and heterologous, depending on the characteristics of the stroma or mesenchymal components of endometrial tissue. It is more frequent in black women and postmenopausal women. Radiation is a possible etiological factor but the exact etiology is not known yet. However, tamoxifen may induce carcinogenesis in some patients. Its clinical feature is very similar to endometrial carcinoma i.e. postmenopausal vaginal bleeding, have a very aggressive behavior and a poor prognosis. This pelvic malignancy is treated by multimodality therapy including surgery, chemotherapy and radiotherapy. Here we are reviewing old concepts about the disease and modern understandings of the origin, classification, pathogenesis and recent advances in the treatment of the uterine carcinosarcoma.

Abnormal uterine bleeding in perimenopause.

Science.gov (United States)

Goldstein, S R; Lumsden, M A

2017-10-01

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Cerrahi sonrası hızlı tekrarlayan andiferansiye uterin sarkom

OpenAIRE

Aşkar, N; Bayrak, Z; Demirtaş, G S; Terek, M C; Dikmen, Y; Zekioğlu, O

2012-01-01

Uterine sarcoma is a tumor accounting for only 1% of female genital tract malignancies and between 3% and 7% of uterine tumors. Although a high percentage of patients are diagnosed in the early stages, the survival rates are low. The patients usually present with abnormal vaginal bleeding, abdominal discomfort and pelvic masses. Uterine sarcomas are rapidly progressive tumors. Regional recurrence and distant metastasis are high. About 34-64% patients were reported with relapses. The majority...

A homeopathic remedy from arnica, marigold, St. John’s wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts

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Hostanska Katarina

2012-07-01

Full Text Available Abstract Background Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. Methods We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712–2, its succussed hydroalcoholic solvent (0712–1 and unsuccussed solvent (0712–3 on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined “wound field”. All assays were performed in three independent controlled experiments. Results None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712–2 exerted a stimulating effect on fibroblast migration (31.9% vs 14.7% with succussed solvent (0712–1 at 1:100 dilutions (p  0.05. Preparation (0712–2 at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p  Conclusion Results of this study showed that the low potency homeopathic remedy (0712–2 exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis.

A homeopathic remedy from arnica, marigold, St. John’s wort and comfrey accelerates in vitro wound scratch closure of NIH 3T3 fibroblasts

Science.gov (United States)

2012-01-01

Background Drugs of plant origin such as Arnica montana, Calendula officinalis or Hypericum perforatum have been frequently used to promote wound healing. While their effect on wound healing using preparations at pharmacological concentrations was supported by several in vitro and clinical studies, investigations of herbal homeopathic remedies on wound healing process are rare. The objective of this study was to investigate the effect of a commercial low potency homeopathic remedy Similasan® Arnica plus Spray on wound closure in a controlled, blind trial in vitro. Methods We investigated the effect of an ethanolic preparation composed of equal parts of Arnica montana 4x, Calendula officinalis 4x, Hypericum perforatum 4x and Symphytum officinale 6x (0712–2), its succussed hydroalcoholic solvent (0712–1) and unsuccussed solvent (0712–3) on NIH 3T3 fibroblasts. Cell viability was determined by WST-1 assay, cell growth using BrdU uptake, cell migration by chemotaxis assay and wound closure by CytoSelect ™Wound Healing Assay Kit which generated a defined “wound field”. All assays were performed in three independent controlled experiments. Results None of the three substances affected cell viability and none showed a stimulating effect on cell proliferation. Preparation (0712–2) exerted a stimulating effect on fibroblast migration (31.9%) vs 14.7% with succussed solvent (0712–1) at 1:100 dilutions (p  0.05). Preparation (0712–2) at a dilution of 1:100 promoted in vitro wound closure by 59.5% and differed significantly (p < 0.001) from succussed solvent (0712–1), which caused 22.1% wound closure. Conclusion Results of this study showed that the low potency homeopathic remedy (0712–2) exerted in vitro wound closure potential in NIH 3T3 fibroblasts. This effect resulted from stimulation of fibroblasts motility rather than of their mitosis. PMID:22809174

Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

International Nuclear Information System (INIS)

Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B.; Altran, Silvana C.; Isaac, Cesar

2011-01-01

Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Altran, Silvana C.; Isaac, Cesar [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Lab. de Microcirurgia Plastica; Esteves-Pedro, Natalia M. [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Ciencias Farmaceuticas. Lab. de Controle Biologico; Herson, Marisa R. [DonorTissue Bank of Victoria (Australia)

2011-07-01

Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

Epicatechin stimulates mitochondrial activity and selectively sensitizes cancer cells to radiation.

Directory of Open Access Journals (Sweden)

Hosam A Elbaz

Full Text Available Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (--epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (--epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and Western blot analyses. (--Epicatechin stimulated mitochondrial respiration and oxygen consumption in Panc-1 cells. Human normal fibroblasts were not affected. (--Epicatechin sensitized Panc-1, U87, and MIA PaCa-2 cells with an average radiation enhancement factor (REF of 1.7, 1.5, and 1.2, respectively. (--Epicatechin did not sensitize normal fibroblast cells to ionizing radiation with a REF of 0.9, suggesting cancer cell selectivity. (--Epicatechin enhanced Chk2 phosphorylation and p21 induction when combined with radiation in cancer, but not normal, cells. Taken together, (--epicatechin radiosensitized cancer cells, but not normal cells, and may be a promising candidate for pancreatic cancer treatment when combined with radiation.

Use of Ulipristal Acetate for the Management of Fibroid-Related Acute Abnormal Uterine Bleeding.

Science.gov (United States)

Arendas, Kristina; Leyland, Nicholas A

2016-01-01

Episodes of acute abnormal uterine bleeding related to uterine fibroids can cause significant morbidity. Traditional management with high-dose hormonal regimens may not be as effective when used in women with fibroids. A 32-year-old woman with a 12 cm uterine fibroid presented with an episode of acute abnormal uterine bleeding requiring blood transfusion. In lieu of using a hormonal maintenance regimen after the bleeding had stabilized, the patient was treated with ulipristal acetate 5 mg daily for three months. Amenorrhea was induced rapidly and the patient had no further episodes of acute excessive uterine bleeding. She subsequently underwent a laparoscopic myomectomy with a satisfactory outcome. Ulipristal acetate has been shown to induce amenorrhea rapidly in women with uterine fibroids, and it can be a useful treatment in the emergency management of fibroid-related acute abnormal uterine bleeding. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

Science.gov (United States)

Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

2015-01-01

It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

Science.gov (United States)

Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

2015-01-01

It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca.

Directory of Open Access Journals (Sweden)

Jun-Jie Wang

Full Text Available It has been widely known that the giant panda (Ailuropoda melanoleuca is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF, a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro.

Uterine sarcoma part III—Targeted therapy: The Taiwan Association of Gynecology (TAG systematic review

Directory of Open Access Journals (Sweden)

Ming-Shyen Yen

2016-10-01

Full Text Available Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy, many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Hysteroscopic view of uterine cavity after normal and PPROM pregnancies

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Roshan Nikbakht

2015-01-01

Full Text Available Background: Preterm premature rupture of membranes (PPROM occurs in 17% of pregnancies, which leads to 20% of perinatal death. According to previous studies uterine anomalies are one of the risk factors for preterm birth, PPROM and pregnancies complications. The aim of this study was to evaluate the relationship between PPROM and rupture of membrane (ROM with uterine cavity anomalies based on hysteroscopic findings. Methods: This cross-sectional study was conducted in Imam Khomeini Hospital, Ahvaz, Iran, from May 2011 to May 2012. After conducting a pilot study, 66 nulliparous pregnant women at 14-37 weeks of pregnancy with PPROM and ROM were selected randomly. Then the women were evaluated by hysteroscopy at least six weeks after delivery or miscarriage. The control group includes 66 women with at least one normal pregnancy (without history of PPROM, secondary infertility or recurrent abortion, who underwent diagnostic or therapeutic hysteroscopy for other reasons than PPROM. The hysteroscope instrument specifications were KARL STORZ model (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany, inner sheet 26153 BI, outer sheet 26153 BO, and BA lens with 30 degree. Normal saline solution (Sodium Chloride 0.9% also was applied as distention medium. The study was approved by Ethic Committee of Ahvaz Jundihspur University of Medical Sciences. Informed consent was obtained for all participants. Results: Overall, the frequency of uterine anomalies in case and control groups was 12.12% and 3%, respectively (P<0.05 based on Chi-square test. Possibility of uterine cavity anomalies in the women with preterm premature rupture of membranes (PPROM was significantly higher than the women with normal pregnancy (OR=4.41, CI 95%: 0.9-21/63. About 3% of patients in the case group had undefined uterine anomalies. This anomaly was not in mentioned uterine anomalies classification of American fertility association. We did not observe such anomaly in control group

Conservative Treatment of a Gossypiboma Causing Uterine Wound Dehiscence

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Taner A. Usta

2013-01-01

Full Text Available We present a rare case with gossypiboma following cesarean section which led to uterine wound dehiscence. A 30-year-old woman had been submitted to an emergency cesarean section 4 months previously at another hospital. Clinical and ultrasound findings revealed a large intra-abdominal mass and diffuse peritonitis. At laparotomy, a gossypiboma causing an abscess and uterine wound dehiscence with necrosis of the margins was detected. We performed repetitive wound debridements under broad-spectrum antibiotic cover and eventually resutured the incision. Although hysterectomy has so far been the choice of treatment in the literature once a uterine wound dehiscence had occurred, it was possible in this case to preserve the uterus.

Conservative Treatment of a Gossypiboma Causing Uterine Wound Dehiscence

Science.gov (United States)

Usta, Taner A.; Ozyurek, Sefik E.; Gundogdu, Elif C.

2013-01-01

We present a rare case with gossypiboma following cesarean section which led to uterine wound dehiscence. A 30-year-old woman had been submitted to an emergency cesarean section 4 months previously at another hospital. Clinical and ultrasound findings revealed a large intra-abdominal mass and diffuse peritonitis. At laparotomy, a gossypiboma causing an abscess and uterine wound dehiscence with necrosis of the margins was detected. We performed repetitive wound debridements under broad-spectrum antibiotic cover and eventually resutured the incision. Although hysterectomy has so far been the choice of treatment in the literature once a uterine wound dehiscence had occurred, it was possible in this case to preserve the uterus. PMID:24106624

A novel role of EMMPRIN/CD147 in transformation of quiescent fibroblasts to cancer-associated fibroblasts by breast cancer cells

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Xu, Jing; Lu, Yang; Qiu, Songbo; Chen, Zhi-Nan; Fan, Zhen

2013-01-01

We tested the novel hypothesis that EMMPRIN/CD147, a transmembrane glycoprotein overexpressed in breast cancer cells, has a previously unknown role in transforming fibroblasts to cancer-associated fibroblasts, and that cancer-associated fibroblasts in turn induce epithelial-to-mesenchymal transition of breast cancer cells. Co-culture of fibroblasts with breast cancer cells or treatment of fibroblasts with breast cancer cell conditioned culture medium or recombinant EMMPRIN/CD147 induced expression of α-SMA in the fibroblasts in an EMMPRIN/CD147-dependent manner and promoted epithelial-to-mesenchymal transition of breast cancer cells and enhanced cell migration potential. These findings support a novel role of EMMPRIN/CD147 in regulating the interaction between cancer and stroma. PMID:23474495

Morcellation of undiagnosed uterine sarcoma: A critical review.

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Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Martinelli, Fabio; Donfrancesco, Cristina; Indini, Alice; Lorusso, Domenica; Raspagliesi, Francesco

2016-02-01

In the recent decades, laparoscopy has replaced open abdominal procedures in the setting of gynecologic surgery. Extraction of large specimens (e.g., large uteri or myomas) following operative laparoscopy is technically challenging. Technological attempts allow the removal of large and solid pelvic masses via small abdominal incisions (using instruments called morcellators), thus reducing unnecessary laparotomies and improving short-term patients' outcomes. However, morcellation of undiagnosed uterine malignancies may lead to worse survival outcomes. Therefore, the Food and Drug Administration (FDA) warns about the use of power morcellators, thus causing ongoing concerns on the applicability of minimally invasive approaches for myomectomy and the removal of large uteri. In the present review, we sought to assess pro and cons regarding minimally invasive morcellation. This review will discuss the effects of morcellation of undiagnosed uterine malignancies, focusing on possible techniques for preoperative detection of uterine sarcoma and for avoiding intra-abdominal dissemination of potentially malignant tissues. Further efforts are necessary in order to identify tools to make a more accurate and reliable preoperative diagnosis of uterine masses. However, on the light of the current evidence, intra-abdominal morcellation should be banned from clinical practice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Investigating uterine disease in the bitch: uterine cannulation for cytology, microbiology and hysteroscopy.

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Watts, J R; Wright, P J

1995-05-01

A technique for transcervical cannulation of the uterus of the bitch for the collection of samples for cytology and microbiology was developed. This technique involved passing a cannula into the uterus with the aid of an endoscope. The uterus was cannulated successfully in mature bitches (over 10 kg) 110 times in 144 attempts. Success of cannulation was influenced by the experience of the operator and ease of cannulation by the stage of the reproductive cycle, the size of the bitch and the type of cannula. Complications associated with the procedure were endometritis, vaginitis and vaginal tears. Uterine cannulation was generally possible in all bitches studied at all stages of the reproductive cycle. Techniques for the collection of samples from the uterus for cytology and microbiology and for the processing of samples for uterine cytology are outlined. Hysteroscopy was performed on seven occasions in post partum bitches and was found to be possible at least until day 17 after whelping.

The association between uterine leiomyoma and placenta abruption: A meta-analysis.

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Jenabi, Ensiyeh; Ebrahimzadeh Zagami, Samira

2017-11-01

Some epidemiological studies have found that uterine leiomyoma can increase the risk of placenta abruption. To date, the meta-analysis has not been performed for assessing the relationship between uterine leiomyoma and placenta abruption. This meta-analysis was conducted to estimate the association between uterine leiomyoma and the risk of placenta abruption. A literature search was conducted out in major databases PubMed, Web of Science, and Scopus from the earliest possible year to October 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed by Begg's and Egger's tests. The results were showed using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random-effects model. The literature search included 953 articles until October 2016 with 232,024 participants. Based on OR estimates obtained from case-control and cohort studies, there was significant association between uterine leiomyoma and placenta abruption (2.63; 95% CI: 1.38, 3.88). We showed based on reports in observational studies that uterine leiomyoma is a risk factor for placenta abruption.

Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas

International Nuclear Information System (INIS)

Nishino, Mizuki; Togashi, Kaori; Nakai, Asako; Hayakawa, Katsumi; Kanao, Shotarou; Iwasaku, Kazuhiro; Fujii, Shingo

2005-01-01

Purpose: Submucosal leiomyoma is one of the most recognized causes of infertility and habitual abortion. The purpose of this study is to evaluate uterine peristalsis, a cycle-related inherent contractility of uterus probably responsible for sperm transport and conservation of pregnancy, in patients with uterine leiomyomas using cine magnetic resonance (MR) imaging. Materials and methods: Study population consisted of 26 female patients (age range: 19-51 years, mean: 41 years), in which 16 patients had submucosal leiomyomas and 10 patients had intramural or subserosal leiomyomas. We prospectively performed MR imaging of the midsagittal plane of uterus using 1.5 T magnet (Symphony, Siemens Medical Systems) with a body array coil, and obtained 60 half-Fourier acquisition single shot turbo spin echo (HASTE) images (Echo time=80 ms, FOV=300 mm, slice thickness 5 mm, matrix 256x256) within 2 min, and displayed them on cine mode at 12x faster than real speed. Evaluated were peristaltic movements at the endometral-myometrial junction and focal myometrial movements, adjacent to leiomyomas, regarding presence, direction, frequency, and conduction. Results: The peristaltic movements were identified in 12/16 patients with submucosal lesions and 10/10 with other leiomyomas. The frequency and direction were cycle-related. Loss of peristalsis was noted adjacent to submucosal myomas in 4/12 patients, but was not in others. Focal myometrial movements were noted in 9/16 patients with submucosal myomas, but not in others. Conclusions: Uterine peristaltic movements were partly interrupted by submucosal leiomoymas, but not by myometrial or subserosal leiomyomas. Loss of peristalsis and focal myometrial movements was noted only adjacent to submucosal leiomyomas. These findings are considered to represent dysfunctional contractility, and may be related with pregnancy loss

Uterine contractions evaluated on cine MR imaging in patients with uterine leiomyomas

Energy Technology Data Exchange (ETDEWEB)

Nishino, Mizuki E-mail: mizuki@mbox.kyoto-inet.or.jpnishinomizuki@hotmail.com; Togashi, Kaori; Nakai, Asako; Hayakawa, Katsumi; Kanao, Shotarou; Iwasaku, Kazuhiro; Fujii, Shingo

2005-01-01

Purpose: Submucosal leiomyoma is one of the most recognized causes of infertility and habitual abortion. The purpose of this study is to evaluate uterine peristalsis, a cycle-related inherent contractility of uterus probably responsible for sperm transport and conservation of pregnancy, in patients with uterine leiomyomas using cine magnetic resonance (MR) imaging. Materials and methods: Study population consisted of 26 female patients (age range: 19-51 years, mean: 41 years), in which 16 patients had submucosal leiomyomas and 10 patients had intramural or subserosal leiomyomas. We prospectively performed MR imaging of the midsagittal plane of uterus using 1.5 T magnet (Symphony, Siemens Medical Systems) with a body array coil, and obtained 60 half-Fourier acquisition single shot turbo spin echo (HASTE) images (Echo time=80 ms, FOV=300 mm, slice thickness 5 mm, matrix 256x256) within 2 min, and displayed them on cine mode at 12x faster than real speed. Evaluated were peristaltic movements at the endometral-myometrial junction and focal myometrial movements, adjacent to leiomyomas, regarding presence, direction, frequency, and conduction. Results: The peristaltic movements were identified in 12/16 patients with submucosal lesions and 10/10 with other leiomyomas. The frequency and direction were cycle-related. Loss of peristalsis was noted adjacent to submucosal myomas in 4/12 patients, but was not in others. Focal myometrial movements were noted in 9/16 patients with submucosal myomas, but not in others. Conclusions: Uterine peristaltic movements were partly interrupted by submucosal leiomoymas, but not by myometrial or subserosal leiomyomas. Loss of peristalsis and focal myometrial movements was noted only adjacent to submucosal leiomyomas. These findings are considered to represent dysfunctional contractility, and may be related with pregnancy loss.

AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

Energy Technology Data Exchange (ETDEWEB)

Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

2015-06-15

Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

Misdiagnosed Uterine Rupture of an Advanced Cornual Pregnancy

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Christian Linus Hastrup Sant

2012-01-01

Full Text Available Cornual pregnancy is a diagnostic and therapeutic challenge with potential severe consequences if uterine rupture occurs with following massive intraabdominal bleeding. We report a case of a misdiagnosed ruptured cornual pregnancy occurring at 21 weeks of gestation. Ultrasound examination and computer tomography revealed no sign of abnormal pregnancy. The correct diagnosis was first made at emergency laparotomy. Uterine rupture should be considered in pregnant women presenting with abdominal pain and haemodynamic instability.

Misdiagnosed uterine rupture of an advanced cornual pregnancy

DEFF Research Database (Denmark)

Sant, Christian Linus Hastrup; Andersen, Poul Erik

2012-01-01

Cornual pregnancy is a diagnostic and therapeutic challenge with potential severe consequences if uterine rupture occurs with following massive intraabdominal bleeding. We report a case of a misdiagnosed ruptured cornual pregnancy occurring at 21 weeks of gestation. Ultrasound examination...... and computer tomography revealed no sign of abnormal pregnancy. The correct diagnosis was first made at emergency laparotomy. Uterine rupture should be considered in pregnant women presenting with abdominal pain and haemodynamic instability....

Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide

International Nuclear Information System (INIS)

Chandrasekhar, Y.; Armstrong, D.T.

1991-01-01

The authors have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with [3H]-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing [3H]-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen-induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus

Frequency, predisposing factors and fetomaternal outcome in uterine rupture

International Nuclear Information System (INIS)

Malik, H.S.

2006-01-01

To determine the frequency and to analyze the predisposing factors, maternal and fetal outcome of uterine rupture. All cases of ruptured uterus, who were either admitted with or who developed this complication in the hospital, were included in the study. Demographic data, details regarding the most probable predisposing factor, type of rupture, the management and maternal and fetal outcome were taken into consideration for analysis.During three years, total number of deliveries was 18668, and there were 103 cases of uterine rupture (0.55%).Out of these, only 13 (12.62%) patients were booked. Most of the patients presented between the ages of 26-30 years (42.71%). Majority of ruptures occurred in para 2-4 (44.66%). Fifty five cases (53.39%) had a previous caesarean section scar. In 68 (66.01%) cases, the tear was located in lower uterine segment. In 93 (90.29%) cases, anterior uterine wall was involved. Rupture was complete in 79 (76.69%)cases. Repair of uterus was done in 79 (76.69%) cases. Hysterectomy was performed in 24 (23.30%) cases. There were 8 (7.76% or 77.66/1000) maternal deaths and 85 (81.73% or 825 / 1000) perinatal deaths.This study confirms high frequency of such serious preventable obstetrical problem which can lead to high fetomaternal mortality. Rupture of caesarean section scar was the most common cause of uterine rupture found in this series. (author)

Modified uterine allotransplantation and immunosuppression procedure in the sheep model.

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Li Wei

Full Text Available OBJECTIVE: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. METHODS: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. RESULTS: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. CONCLUSION: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model

OpenAIRE

Saso, Srdjan; Petts, Gemma; David, Anna L.; Thum, Meen-Yau; Chatterjee, Jayanta; Vicente Antón, José Salvador; Marco Jiménez, Francisco; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priorei, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J. Richard

2015-01-01

[EN] Objective: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. Study desig...

Effects of combined pulse electromagnetic field stimulation plus glutamine on the healing of colonic anastomosis in rats.

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Girgin, Sadullah; Gedik, Ercan; Ozturk, Hayrettin; Akpolat, Veysi; Akbulut, Veysi; Kale, Ebru; Buyukbayram, Huseyin; Celik, Salih

2009-04-01

An experimental study was designed to investigate the effect of combined pulse electromagnetic field (PEMF) stimulation plus glutamine administration on colonic anastomosis. Anastomosis of the left colon was performed in 28 rats, which were divided into four groups; Group 1: normal resection anastomosis plus oral 50 mg/kg/day glutamine; Group 2: normal resection anastomosis plus PEMF stimulation plus oral 50 mg/kg/day glutamine; Group 3: normal resection anastomosis plus PEMF stimulation; Group 4: normal resection anastomosis. On the seventh postoperative day, the animals were killed and the bursting pressure and tissue hydroxyproline concentration of the anastomosis were analyzed and compared. The mean anastomotic bursting pressure in Group 2 was significantly higher than in Groups 1 and 4. On the other hand, the mean anastomotic bursting pressure in Group 1 was significantly higher than in Group 4. The collagen deposition and the fibroblast infiltration were significantly increased on the seventh day in Group 3 compared the other groups. On the other hand, Groups 1 and 2 had higher scores for collagen deposition and fibroblast infiltration than Group 4. In conclusion, burst pressures, hydroxyproline, and histologic features (fibroblast infiltration and collagen deposition) were improved in the PEMF group, and both PEMF and glutamine-enriched nutrition provide a significant gain in the strength of colonic anastomoses in rats.

Electrical stimulation of schwann cells promotes sustained increases in neurite outgrowth.

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Koppes, Abigail N; Nordberg, Andrea L; Paolillo, Gina M; Goodsell, Nicole M; Darwish, Haley A; Zhang, Linxia; Thompson, Deanna M

2014-02-01

Endogenous electric fields are instructive during embryogenesis by acting to direct cell migration, and postnatally, they can promote axonal growth after injury (McCaig 1991, Al-Majed 2000). However, the mechanisms for these changes are not well understood. Application of an appropriate electrical stimulus may increase the rate and success of nerve repair by directly promoting axonal growth. Previously, DC electrical stimulation at 50 mV/mm (1 mA, 8 h duration) was shown to promote neurite outgrowth and a more pronounced effect was observed if both peripheral glia (Schwann cells) and neurons were co-stimulated. If electrical stimulation is delivered to an injury site, both the neurons and all resident non-neuronal cells [e.g., Schwann cells, endothelial cells, fibroblasts] will be treated and this biophysical stimuli can influence axonal growth directly or indirectly via changes to the resident, non-neuronal cells. In this work, non-neuronal cells were electrically stimulated, and changes in morphology and neuro-supportive cells were evaluated. Schwann cell response (morphology and orientation) was examined after an 8 h stimulation over a range of DC fields (0-200 mV/mm, DC 1 mA), and changes in orientation were observed. Electrically prestimulating Schwann cells (50 mV/mm) promoted 30% more neurite outgrowth relative to co-stimulating both Schwann cells with neurons, suggesting that electrical stimulation modifies Schwann cell phenotype. Conditioned medium from the electrically prestimulated Schwann cells promoted a 20% increase in total neurite outgrowth and was sustained for 72 h poststimulation. An 11-fold increase in nerve growth factor but not brain-derived neurotrophic factor or glial-derived growth factor was found in the electrically prestimulated Schwann cell-conditioned medium. No significant changes in fibroblast or endothelial morphology and neuro-supportive behavior were observed poststimulation. Electrical stimulation is widely used in

Effects of Mechanical Stretch on Cell Proliferation and Matrix Formation of Mesenchymal Stem Cell and Anterior Cruciate Ligament Fibroblast

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Liguo Sun

2016-01-01

Full Text Available Mesenchymal stem cells (MSCs and fibroblasts are two major seed cells for ligament tissue engineering. To understand the effects of mechanical stimulation on these cells and to develop effective approaches for cell therapy, it is necessary to investigate the biological effects of various mechanical loading conditions on cells. In this study, fibroblasts and MSCs were tested and compared under a novel Uniflex/Bioflex culture system that might mimic mechanical strain in ligament tissue. The cells were uniaxially or radially stretched with different strains (5%, 10%, and 15% at 0.1, 0.5, and 1.0 Hz. The cell proliferation and collagen production were compared to find the optimal parameters. The results indicated that uniaxial stretch (15% at 0.5 Hz; 10% at 1.0 Hz showed positive effects on fibroblast. The uniaxial strains (5%, 10%, and 15% at 0.5 Hz and 10% strain at 1.0 Hz were favorable for MSCs. Radial strain did not have significant effect on fibroblast. On the contrary, the radial strains (5%, 10%, and 15% at 0.1 Hz had positive effects on MSCs. This study suggested that fibroblasts and MSCs had their own appropriate mechanical stimulatory parameters. These specific parameters potentially provide fundamental knowledge for future cell-based ligament regeneration.

Atypical olfactory groove meningioma associated with uterine fibromatosis; case report

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Toma I. Papacocea

2016-11-01

Full Text Available The concomitant presence of the olfactory groove meningioma with uterine fibrosis is very rare. Our report presents the case of a giant olfactory groove meningioma revealed after a uterine fibroma resection in a 44 years-old female, due to a generalized seizure 10 days after operation. Cranial CT-scan identified the tumor as an olfactory groove meningioma. The tumor was operated with a macroscopically complete resection; the endothermal coagulation of the dura attachment was performed (Simpson II with a good postoperative evolution. Laboratory results showed the presence of receptors for steroid hormones both in meningioma and uterine tumor, and the histopathological examination revealed an atypical meningioma with 17% proliferation markers. Our findings suggest that even though meningiomas are benign tumors and a complete resection usually indicates a good prognosis, the association with uterine fibromatosis and the presence of high percentage of steroid receptors creates a higher risk to relapse, imposing therefore a good monitoring.

Intra-uterine insemination: pregnancy rate in relation to number, size of pre-ovulatory follicles and day of insemination.

Science.gov (United States)

Karuppaswamy, J; Smedley, Mamin; Carter, Lindsay

2009-03-01

The objective of the study was to analyse the pregnancy rate in intra-uterine insemination (IUI) in relation to pre-ovulatory follicular number, size and day of insemination. A retrospective analysis of 216 completed IUI cycles was used in an attempt to identify significant variables predictive of treatment success. Couples with unexplained infertility and male factor infertility underwent IUI with or without ovarian stimulation. The mean number of IUI cycles per patient was 4.1, the overall pregnancy rate was 27.3% per patient, and the pregnancy rate per cycle was 6.9%. The pregnancy rate was 4.4% when one follicle was produced, whereas with more than two follicles, the rate increased to 21.2%. Hormonal stimulation using clomiphene citrate and/or human menopausal gonadotrophin/follicle stimulating hormone yielded a significant higher pregnancy rate compared to IUI in natural cycles (10.3% versus 3.3%). Although not statistically significant, the pregnancy rate decreased with advancing age of woman. The results suggest that IUI is a useful method of assisted conception in unexplained infertility and higher pregnancy rates can be achieved with good patient selection and ovarian stimulation.

Dealing with uterine fibroids in reproductive medicine.

Science.gov (United States)

Gambadauro, P

2012-04-01

Women who wish to conceive are nowadays more likely to present with uterine fibroids, mainly because of the delay in childbearing in our society. The relationship between uterine fibroids and human reproduction is still controversial and counselling patients might sometimes be challenging. This paper is to assist those involved in the management of patients of reproductive age presenting with uterine fibroids. The interference of fibroids on fertility largely depends on their location. Submucous fibroids interfere with fertility and should be removed in infertile patients, regardless of the size or the presence of symptoms. Intramural fibroids distorting the cavity reduce the chances of conception, while investigations on intramural fibroids not distorting the cavity have so far given controversial results. No evidence supports the systematic removal of subserosal fibroids in asymptomatic, infertile patients. Myomectomy is still the 'gold standard' in fibroid treatment for fertility-wishing patients. In experienced hands, hysteroscopic myomectomy is minimally invasive, safe, and effective. Abdominal and laparoscopic myomectomy might be challenging, but potential risks could be reduced by new strategies and techniques.

A mutein of human basic fibroblast growth factor TGP-580 accelerates colonic ulcer healing by stimulating angiogenesis in the ulcer bed in rats.

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Satoh, H; Szabo, S

2015-10-01

Previously, we reported that TGP-580, a mutein of human basic fibroblast growth factor (bFGF), accelerated the healing of gastric and duodenal ulcers in rats. In the present study, we examined the effect of TGP-580 on the healing of colonic ulcers. In male Sprague Dawley rats, ulcers were induced in the colon 6 cm from the anus by enema of 50 μl of 3% N-ethylmaleimide, a sulfhydryl alkylator. The lesions were examined under a dissecting microscope (x10). The concentration of bFGF in the ulcerated colon was measured by enzyme immunoassay, and both the distribution of bFGF and the density of microvessels in the ulcer bed were examined by immunohistochemical staining. The content of bFGF in the ulcerated colon was markedly increased associated with ulcer healing, and ulcer healing was significantly delayed by intravenous administration of a monoclonal antibody for bFGF (MAb 3H3) once daily for 10 days. In the ulcer bed, many cells such as fibroblasts, vascular endothelial cells and macrophages were positively stained with bFGF antiserum. TGP-580, human bFGF or dexamethasone was given intracolonally twice daily for 10 days, starting the day after ulcer induction. TGP-580 (0.2 - 20 μg/ml, 200 μl/rat) dose-dependently accelerated ulcer healing, and its effect was more than 10 times stronger than that of human bFGF. Density (μm/0.01 mm(2)) of microvessels in the ulcer bed was significantly increased by treatment with TGP-580, and there was a good correlation between the density of microvessels and the decrease of ulcerated area (R(2) = 0.633). On the other hand dexamethasone (20 μg/ml) inhibited angiogenesis in the ulcer bed and delayed ulcer healing. These results suggest that angiogenesis in the ulcer bed plays an important role in ulcer healing, and that bFGF mutein TGP-580 accelerated colonic ulcer healing, at least in part, by stimulating angiogenesis, whereas glucocorticoids may delay the healing by inhibiting angiogenesis.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

Science.gov (United States)

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Fibroblast cultures in duchenne muscular dystrophy

International Nuclear Information System (INIS)

Ionasescu, V.; Lara-Braud, C.; Zellweger, H.; Ionasescu, R.; Burmeister, L.

1977-01-01

Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-( 3 H)-proline for 24 hours. Intracellular collagen incoption was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts. (author)

Comparing focused ultrasound and uterine artery embolization for uterine fibroids – Rationale and Design of the Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT) trial

Science.gov (United States)

Bouwsma, Esther V.A.; Hesley, Gina K.; Woodrum, David A.; Weaver, Amy L.; Leppert, Phyllis C.; Peterson, Lisa G.; Stewart, Elizabeth A.

2011-01-01

Objective To present the rational, design and methodology of the FIRSTT study (Fibroid Interventions: Reducing Symptoms Today and Tomorrow, NCT00995878, clinicaltrials.gov). Design Randomized Clinical Trial (RCT) Setting Two Academic Medical Centers Patient(s) Premenopausal women with symptomatic uterine fibroids. Intervention(s) Participants are randomized to two FDA-approved minimally invasive treatments for uterine leiomyomas: uterine artery embolization (UAE) and MRI guided focused ultrasound (MRgFUS). Main Outcome Measure(s) The primary endpoint is defined as the need for an additional intervention for fibroid symptoms following treatment. Secondary outcomes consist of group differences in symptom alleviation, recovery trajectory, health related quality of life, impairment of ovarian reserve, treatment complications and the economic impact of these issues. Results The trial is currently in the phase of active recruitment. Conclusions This RCT will provide important evidence-based information for patients and health care providers regarding optimal minimally invasive treatment approach for women with symptomatic uterine leiomyomas. PMID:21794858

Effect of postpartum suppression of ovulation on uterine involution in dairy cows.

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Heppelmann, M; Brömmling, A; Weinert, M; Piechotta, M; Wrenzycki, C; Bollwein, H

2013-09-15

The objective of this study was to investigate the effect of time of first postpartum ovulation after calving on uterine involution in dairy cows with and without uterine puerperal disease. Transvaginal follicular puncture (FP) of follicles >6 mm suppressed ovulation and development of a CL until Day 42 after calving. Fifty-three lactating Holstein Friesian cows (3.4 ± 1.2 years old, parity 2.5 ± 1.0 [median ± mean absolute deviation]) were divided into groups on the basis of the presence (UD+) or absence (UD-) of uterine disease and whether FP was carried out (FP+) or not (FP-). Uterine disease was defined as the occurrence of retained fetal membranes and/or metritis. This resulted in the following groups: UD-FP- (n = 15), UD-FP+ (n = 13), UD+FP- (n = 13), and UD+FP+ (n = 12). A general examination, vaginoscopy, transrectal palpation, and transrectal B-mode sonography of the reproductive organs were conducted on Days 8, 11, 18, and 25 and then every 10 days until Day 65 after calving. After hormonal synchronization of ovulation (cloprostenol between Days 55 and 60 postpartum and GnRH 2 days later), cows were inseminated in the next spontaneous estrus. On average, the cows ovulated on Day 21.0 ± 6.0 (UD-FP-), 50.0 ± 4.0 (UD-FP+), 16.0 ± 3.0 (UD+FP-), and 48.0 ± 2.0 (UD+FP+) postpartum. Calving-to-conception interval and first-service conception rates were not affected by FP (P > 0.05). Healthy cows with FP had smaller (P uterine horn and cervical diameters assessed sonographically than cows without FP. FP reduced the prevalence of purulent vaginal discharge and uterine size assessed transrectally in UD+ cows (P uterine involution in cows with and without uterine disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Primary histiocytic sarcoma of the uterine cervix: an extremely rare entity

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Binesh Fariba

2017-03-01

Full Text Available Objective. Histiocytic sarcoma (HS is an extraordinary rare tumor and it has an offensive clinical course. HS of the uterine cervix is a far uncommon tumor with just a few cases described so far. Here we presented a case of primary HS of the uterine cervix in a 62-year-old female initially misdiagnosed as large cell non-keratinizing squamous cell carcinoma. To the best of our knowledge, this is the first reported case of HS of the uterine cervix from Iran.

Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms.

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Michael A Seidman

Full Text Available BACKGROUND: Power morcellation has become a common technique for the minimally invasive resection of uterine leiomyomas. This technique is associated with dissemination of cellular material throughout the peritoneum. When morcellated uterine tumors are unexpectedly found to be leiomyosarcomas or tumors with atypical features (atypical leiomyoma, smooth muscle tumor of uncertain malignant potential, there may be significant clinical consequences. This study was undertaken to determine the frequency and clinical consequence of intraperitoneal dissemination of these neoplasms. METHODOLOGY/PRINCIPAL FINDINGS: From 2005-2010, 1091 instances of uterine morcellation were identified at BWH. Unexpected diagnoses of leiomyoma variants or atypical and malignant smooth muscle tumors occurred in 1.2% of cases using power morcellation for uterine masses clinically presumed to be "fibroids" over this period, including one endometrial stromal sarcoma (ESS, one cellular leiomyoma (CL, six atypical leiomyomas (AL, three smooth muscle tumor of uncertain malignant potential (STUMPs, and one leiomyosarcoma (LMS. The rate of unexpected sarcoma after the laparoscopic morcellation procedure was 0.09%, 9-fold higher than the rate currently quoted to patients during pre-procedure briefing, and this rate may increase over time as diagnostically challenging or under-sampled tumors manifest their biological potential. Furthermore, when examining follow-up laparoscopies, both from in-house and consultation cases, disseminated disease occurred in 64.3% of all tumors (zero of one ESS, one of one CL, zero of one AL, four of four STUMPs, and four of seven LMS. Only disseminated leiomyosarcoma, however, was associated with mortality. Procedures are proposed for pathologic evaluation of morcellation specimens and associated follow-up specimens. CONCLUSIONS/SIGNIFICANCE: While additional study is warranted, these data suggest uterine morcellation carries a risk of disseminating

Radiologic diagnosis and treatment of iatrogenic acquired uterine arteriovenous malformation

International Nuclear Information System (INIS)

Kwon, Jung Hyeok

2002-01-01

To analyze gray-scale US, color and duplex Doppler US, and angiographic findings in patients with acquired uterine arteriovenous malformations (AVMs), and to evaluate the usefulness of these modalities in the diagnosis of this disease and the effect of transcatheter arterial embolization in its treatment. During a recent seven-year period, we diagnosed 21 cases of acquired uterine AVM. Nineteen of these patients had a history of causative D and C (between one and seven D and C procedures per patient), one had a history of causative cesarean section, and one had cervical conization. All patients underwent transabdominal and endovaginal gray-scale, color Doppler, and duplex Doppler US and angiography, with therapeutic embolization of bilateral uterine arteries. The majority underwent follow-up Doppler US after embolization. The gray-scale US morphology of uterine AVMs included subtle myometrial inhomogeneity and multiple distinct, small anechoic spaces in the thickened myometrium or endometrium. Color Doppler US showed a tangle of tortuous vessels with multidirectional, high-velocity arterial flow, which was focally or asymmetrically distributed. Duplex Doppler US depicted a waveform of fast arterial flow with low resistance, while angiography demonstrated a complex tangle of vessels supplied by enlarged uterine arteries, in association with early venous drainage during the arterial phase, and staiss of contrast medium within abnormal vasculature. Where AVMs were combined with a pseudoaneurysm, this finding was observed. Transcatheter arterial embolization provided a complete cure, without recurrence. Color and duplex Doppler US in an appropriate modality for the detection and diagnosis of uterine AVMs and for follow-up after embolization. Transcatheter arterial embolization is a safe and effective method of treating this disease

Radiologic diagnosis and treatment of iatrogenic acquired uterine arteriovenous malformation

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jung Hyeok [College of Medicine, Keimyung Univ., Taegu (Korea, Republic of)

2002-05-01

To analyze gray-scale US, color and duplex Doppler US, and angiographic findings in patients with acquired uterine arteriovenous malformations (AVMs), and to evaluate the usefulness of these modalities in the diagnosis of this disease and the effect of transcatheter arterial embolization in its treatment. During a recent seven-year period, we diagnosed 21 cases of acquired uterine AVM. Nineteen of these patients had a history of causative D and C (between one and seven D and C procedures per patient), one had a history of causative cesarean section, and one had cervical conization. All patients underwent transabdominal and endovaginal gray-scale, color Doppler, and duplex Doppler US and angiography, with therapeutic embolization of bilateral uterine arteries. The majority underwent follow-up Doppler US after embolization. The gray-scale US morphology of uterine AVMs included subtle myometrial inhomogeneity and multiple distinct, small anechoic spaces in the thickened myometrium or endometrium. Color Doppler US showed a tangle of tortuous vessels with multidirectional, high-velocity arterial flow, which was focally or asymmetrically distributed. Duplex Doppler US depicted a waveform of fast arterial flow with low resistance, while angiography demonstrated a complex tangle of vessels supplied by enlarged uterine arteries, in association with early venous drainage during the arterial phase, and staiss of contrast medium within abnormal vasculature. Where AVMs were combined with a pseudoaneurysm, this finding was observed. Transcatheter arterial embolization provided a complete cure, without recurrence. Color and duplex Doppler US in an appropriate modality for the detection and diagnosis of uterine AVMs and for follow-up after embolization. Transcatheter arterial embolization is a safe and effective method of treating this disease.

Labor Dystocia and the Risk of Uterine Rupture in Women with Prior Cesarean.

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Vachon-Marceau, Chantale; Demers, Suzanne; Goyet, Martine; Gauthier, Robert; Roberge, Stéphanie; Chaillet, Nils; Laroche, Jasmin; Bujold, Emmanuel

2016-05-01

Objective The objective of this study was to evaluate the association between labor dystocia and uterine rupture. Methods We performed a secondary analysis of a multicenter case-control study that included women with single, prior, low-transverse cesarean section who experienced complete uterine rupture during a trial of labor (TOL). For each case, three women who underwent a TOL without uterine rupture were selected as controls. Data were collected on cervical dilatations from admission to delivery. We evaluated the relationship between uterine rupture and labor dystocia according to several criteria, including the World Health Organization's (WHO's) partogram. Results Data were available for 90 cases and 260 controls. Compared with the controls, uterine rupture was associated with less cervical dilatation on admission, slower cervical dilatation in the first stage of labor and longer second stage of labor (all with p dystocia is a significant risk factor for uterine rupture. Labor progression should be assessed regularly in women with prior cesarean. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Uterine Tissue Engineering and the Future of Uterus Transplantation.

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Hellström, Mats; Bandstein, Sara; Brännström, Mats

2017-07-01

The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

In vitro study of RRS HA injectable mesotherapy/biorevitalization product on human skin fibroblasts and its clinical utilization.

Science.gov (United States)

Deglesne, Pierre-Antoine; Arroyo, Rodrigo; Ranneva, Evgeniya; Deprez, Philippe

2016-01-01

Mesotherapy/biorevitalization with hyaluronic acid (HA) is a treatment approach currently used for skin rejuvenation. Various products with a wide range of polycomponent formulations are available on the market. Most of these formulations contain noncross-linked HA in combination with a biorevitalization cocktail, formed by various amounts of vitamins, minerals, amino acids, nucleotides, coenzymes, and antioxidants. Although ingredients are very similar among the different products, in vitro and clinical effects may vary substantially. There is a real need for better characterization of these products in terms of their action on human skin or in vitro skin models. In this study, we analyzed the effect of the RRS(®) (Repairs, Refills, Stimulates) HA injectable medical device on human skin fibroblasts in vitro. Skin fibroblast viability and its capacity to induce the production of key extracellular matrix were evaluated in the presence of different concentrations of RRS HA injectable. Viability was evaluated through colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and key extracellular matrix genes, type I collagen and elastin, were quantified by quantitative polymerase chain reaction. Results demonstrated that RRS HA injectable could promote human skin fibroblast viability (+15%) and increase fibroblast gene expression of type I collagen and elastin by 9.7-fold and 14-fold in vitro, respectively. These results demonstrate that mesotherapy/biorevitalization products can, at least in vitro, effectively modulate human skin fibroblasts.

Midterm Results after Uterine Artery Embolization Versus MR-Guided High-Intensity Focused Ultrasound Treatment for Symptomatic Uterine Fibroids

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Froeling, V., E-mail: vera.froeling@charite.de; Meckelburg, K., E-mail: katrin.meckelburg@charite.de; Scheurig-Muenkler, C., E-mail: christian.scheurig-muenkler@charite.de; Schreiter, N. F., E-mail: nils.schreiter@charite.de; Kamp, J., E-mail: julia.kamp@charite.de; Maurer, M. H., E-mail: martin.maurer@charite.de; Beck, A., E-mail: alexander.beck@charite.de; Hamm, B., E-mail: bernd.hamm@charite.de; Kroencke, T. J., E-mail: Thomas.kroencke@charite.de [Charite-Universitaetsmedizin Berlin, Department of Radiology (Germany)

2013-12-15

Purpose: To compare the rate of reintervention and midterm changes in symptom severity (SS) and Total health-related quality of life (HRQoL) scores after uterine artery embolization (UAE) and magnetic resonance-guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. Methods: Eighty women (median age 38.3 years), equally eligible for MR-g HIFU and UAE who underwent one of both treatments between 2002 and 2009 at our institution, were included. The primary end point of the study was defined as the rate of reintervention after both therapies. The secondary outcome was defined as changes in SS and Total HRQoL scores after treatment. SS and Total HRQoL scores before treatment and at midterm follow-up (median 13.3 months) were assessed by the uterine fibroid symptom and quality-of-life questionnaire (UFS-QoL) and compared. Results: The rate of reintervention was significantly lower after UAE than after MR-g HIFU (p = 0.002). After both treatments, SS and Total HRQoL scores improved significantly from baseline to follow-up (UAE: p < 0.001, p < 0.001; MR-g HIFU: p = 0.002, p < 0.001). Total HRQoL scores were significantly higher after UAE than after MR-g HIFU (p = 0.032). Changes in the SS scores did not differ significantly for both treatments (p = 0.061). Conclusion: UAE and MR-g HIFU significantly improved the health-related quality of life of women with symptomatic uterine fibroids. After UAE, the change in Total HRQoL score improvement was significantly better, and a significantly lower rate of reintervention was observed.

Midterm Results after Uterine Artery Embolization Versus MR-Guided High-Intensity Focused Ultrasound Treatment for Symptomatic Uterine Fibroids

International Nuclear Information System (INIS)

Froeling, V.; Meckelburg, K.; Scheurig-Muenkler, C.; Schreiter, N. F.; Kamp, J.; Maurer, M. H.; Beck, A.; Hamm, B.; Kroencke, T. J.

2013-01-01

Purpose: To compare the rate of reintervention and midterm changes in symptom severity (SS) and Total health-related quality of life (HRQoL) scores after uterine artery embolization (UAE) and magnetic resonance–guided high-intensity focused ultrasound (MR-g HIFU) for symptomatic uterine fibroids. Methods: Eighty women (median age 38.3 years), equally eligible for MR-g HIFU and UAE who underwent one of both treatments between 2002 and 2009 at our institution, were included. The primary end point of the study was defined as the rate of reintervention after both therapies. The secondary outcome was defined as changes in SS and Total HRQoL scores after treatment. SS and Total HRQoL scores before treatment and at midterm follow-up (median 13.3 months) were assessed by the uterine fibroid symptom and quality-of-life questionnaire (UFS-QoL) and compared. Results: The rate of reintervention was significantly lower after UAE than after MR-g HIFU (p = 0.002). After both treatments, SS and Total HRQoL scores improved significantly from baseline to follow-up (UAE: p < 0.001, p < 0.001; MR-g HIFU: p = 0.002, p < 0.001). Total HRQoL scores were significantly higher after UAE than after MR-g HIFU (p = 0.032). Changes in the SS scores did not differ significantly for both treatments (p = 0.061). Conclusion: UAE and MR-g HIFU significantly improved the health-related quality of life of women with symptomatic uterine fibroids. After UAE, the change in Total HRQoL score improvement was significantly better, and a significantly lower rate of reintervention was observed

The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.

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Kahounová, Zuzana; Kurfürstová, Daniela; Bouchal, Jan; Kharaishvili, Gvantsa; Navrátil, Jiří; Remšík, Ján; Šimečková, Šárka; Študent, Vladimír; Kozubík, Alois; Souček, Karel

2017-04-06

The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (Ep

Risk Factors for Uterine Atony/Postpartum Hemorrhage Requiring Treatment after Vaginal Delivery

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Wetta, Luisa A; Szychowski, Jeff M; Seals, Ms. Samantha; Mancuso, Melissa S; Biggio, Joseph R; Tita, Alan TN

2013-01-01

Objective To identify risk factors for uterine atony or hemorrhage. Study Design Secondary analysis of a 3-arm double-blind randomized trial of different dose-regimens of oxytocin to prevent uterine atony after vaginal delivery. The primary outcome was uterine atony or hemorrhage requiring treatment. Twenty-one potential risk factors were evaluated. Logistic regression was used to identify independent risk factors using 2 complementary pre-defined model selection strategies. Results Among 1798 women randomized to 10, 40 or 80U prophylactic oxytocin after vaginal delivery, treated uterine atony occurred in 7%. Hispanic (OR 2.1; 95% CI 1.3–3.4) and non-Hispanic whites (OR 1.6; 95% CI 1.0–2.5), preeclampsia (OR 3.2; 95% CI 2.0–4.9) and chorioamnionitis (OR 2.8; 95% CI 1.6–5.0) were consistent independent risk factors. Other risk factors based on the specified selection strategies were obesity, induction/augmentation of labor, twins, hydramnios, anemia, and arrest of descent. Amnioinfusion appeared to be protective against uterine atony (OR 0.53; 95% CI 0.29–0.98). Conclusion Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity, preeclampsia and chorioamnionitis. PMID:23507549

Evaluation of the Uterine Causes of Female Infertility by Ultrasound: A Literature Review

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Shohreh Irani

2017-04-01

Full Text Available Background & aim: Various uterine disorders lead to infertility in women of reproductive ages. This study was performed to describe the common uterine causes of infertility and sonographic evaluation of these causes for midwives. Methods: This literature review was conducted on the manuscripts published at such databases as Elsevier, PubMed, Google Scholar, and SID as well as the original text books between 1985 and 2015. The search was performed using the following keywords: infertility, uterus, ultrasound scan, transvaginal sonography, endometrial polyp, fibroma, leiomyoma, endometrial hyperplasia, intrauterine adhesion, Asherman’s syndrome, uterine synechiae, adenomyosis, congenital uterine anomalies, and congenital uterine malformations. Results: Atotal of approximately 180 publications were retrieved from the respective databases out of which 44 articles were more related to our topic and studied as suitable references. In addition, 11 published books on ultrasonography and infertility were evaluated to provide more precise knowledge on the mentioned areas. According to the literature, ultrasonography has a crucial role in the investigation and differentiation of uterine disorders in females with infertility. However, the diagnosis depends on the day of menstruation, clinical prese-ntations, and the suspected uterine disorder. In this review, we provided the key notes about proper timing of the ultrasound examination. Conclusion: Ultrasonography is the first step imaging tool in the investigation of female infertility, which provides information for the diagnosis of uterine disorders. However, the accurate diagnosis depends on the “time of evaluation”. Therefore, every midwife needs to learn about the “optimum timing” for ultrasound evaluation based on each patient.

A fibroblast-associated antigen: Characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells

DEFF Research Database (Denmark)

Rønnov-Jessen, Lone; Celis, Julio E.; van Deurs, Bo

1992-01-01

major brands migrating at apparent Mr of 38,000, 45,000, and 80,000, in addition to many minor bands between Mr 45,000 and 97,000, including Mr 52,000. The Mr 45,000 and 38,000 were associated with the cell membrane and Mr 52,000 as well as Mr 38,000 were associated with the lysosomes. The 1B10......Fibroblasts with smooth muscle differentiation are frequently derived from human breast tissue. Immunofluorescence cytochemistry of a fibroblast-associated antigen recognized by a monoclonal antibody (MAb), 1B10, was analyzed with a view to discriminating smooth muscle differentiated fibroblasts...

Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

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Ganesh Kolumam

2015-07-01

Full Text Available Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.

Microallelotyping defines novel regions of loss of heterozygosity in uterine leiomyomas

DEFF Research Database (Denmark)

Canevari, Renata de Azevedo; Pontes, Anaglória; Rogatto, Silvia Regina

2005-01-01

Uterine leiomyomas are extremely common, benign, smooth muscle tumors that represent a significant public health problem. Although there have been few molecular studies of uterine leiomyomas, most of them have reported a very low frequency of loss of heterozygosity (LOH) in different regions...... of the genome. The detection of LOH has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types. We have used a set of 15 microsatellite polymorphism markers to examine the frequency of allele loss in a panel of 64 human uterine leiomyomas matched...... to normal DNAs. The markers were chosen from regions involved in losses identified by comparative genomic hybridization in a subset of uterine leiomyomas described in a previous report. DNA from tumors and normal tissue was amplified by the polymerase chain reaction and subsequently analyzed using an ABI...