1.Effect of growth hormone on endometrium growth of intrauterine adhesion and the underlying mechanism.
Qing FENG ; Aiqian ZHANG ; Dabao XU ; Fei ZENG
Journal of Central South University(Medical Sciences) 2022;47(11):1522-1531
OBJECTIVES:
The main treatment for intrauterine adhesion (IUA) is hysteroscopic adhesiolysis (HA), which most of treatment frequently employs estrogen and progesterone cycle therapy. The growth and coverage of endometrium after operation is a difficult problem, and several hospitals in China have performed growth hormone (GH) in empirically treating IUA, which has achieved excellent curative effects. Unfortunately, the mechanism of action has not yet been clearly elucidated. In previous study, an IUA animal model after surgical abortion and curettage in pregnant rats has been successfully established. In this experiment, the IUA animal model after surgical abortion and curettage in pregnant rats, which is more in line with the mechanism of human intrauterine adhesion, was used for the first time to investigate the therapeutic effect of GH on IUA in the pregnant rat curettage model. The expression of signal transducers and activators of transcription 3(STAT3), phosphorylated STAT3 (p-STAT3), STAT5 and p-STAT5 content were detected by immunohistochemistry to preliminarily explore the possible mechanism of GH involving in promoting endometrial growth of IUA, and to provide a theoretical basis for clinical medication and treatment.
METHODS:
Pregnant rats were anesthetized, and the bilateral embryos were removed completely. Then the rat endometrium was scraped with a curette in 4 different directions (front, back, left, and right). After the IUA animal model was established, the rats were randomly divided into 3 groups (n=5): a control group, a GH group, and a GH + AG490 group. Normal saline (0.4 mL/100 g) was injected subcutaneously at the 7th day after curettage in the control group;0.15 U/100 g of GH was injected subcutaneously at the 7th day after curettage in the GH group; 0.15 U/100 g of GH was injected subcutaneously and 1 mg/100 g AG490 was injected intraperitoneally at the 7th day after curettage in the GH+ AG490 group. All the rats were injected continuously for 5 days. The rats in each group were sacrificed at the 14th day. The uterus of rats in each group was stained with HE staining to explore the endometrial morphology and the number of endometrial glands in each group, and Masson staining was utilized to observe the degree of endometrial fibrosis. The levels of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by immunohistochemistry.
RESULTS:
1) The number of glands in the GH group was more than that in the control group on the 14th day, with statistical difference (P<0.05). However, the number of endometrial glands in the AG490+GH group was decreased compared with the GH group on the 14th day (P<0.05). 2) The fibrosis ratio in the GH group was less than that in the control group at the 14th day after operation (P<0.05). However, the area of endometrial interstitial fibrosis in the AG490+GH group was much higher than that in the GH group 14 days after operation (P<0.05). 3) Compared with the control group, there was not significant difference in the levels of STAT3 and STAT5 in GH group (both P>0.05), while the levels of protein p-STAT3 and p-STAT5 were increased in the GH group (both P<0.05). Compared with the GH group, there was not significant difference in the levels of STAT3 and STAT5 in the AG490+GH group (both P>0.05), while the levels of p-STAT3 and p-STAT5 were decreased in the AG490+GH group (both P<0.05).
CONCLUSIONS
GH can not only promote the growth of endometrial glands in the IUA model, but also reduce the degree of fibrosis and play a role in the treatment of IUA, which may be related to the activation of the Janus kinase (JAK), JAK/STAT3 and STAT5 signaling pathways.
Animals
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Rats
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China
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Growth Hormone
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Endometrium/pathology*
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Tissue Adhesions/drug therapy*
2.Biomechanical and Macroscopic Evaluations of the Effects of 5-Fluorouracil on Partially Divided Flexor Tendon Injuries in Rabbits.
Shkelzen B DUCI ; Hysni M ARIFI ; Hasan R AHMETI ; Suzana MANXHUKA-KERLIU ; Burim NEZIRI ; Agon Y MEKAJ ; Shpetim LAJQI ; Labinot SHAHINI
Chinese Medical Journal 2015;128(12):1655-1661
BACKGROUNDThe main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding. Our purpose was to investigate the effects of 5-fluorouracil (5-FU) on tendon adhesions in partially divided profundus flexor tendons (flexor digitorum profundus [FDPs]) following surgical repair and in partially divided FDPs without surgical repair, and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions.
METHODSWe used 32 adult male European rabbits (Oryctolagus cunniculus) weighing from 2.5 to 3.5 kg. The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits; thus, a total of 64 tendons were examined in this study.
RESULTSBased on the results achieved in our experimental study, the load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU.
CONCLUSIONSThe load (N) significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU. Therefore, these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath, which in this case required greater traction force.
Animals ; Fluorouracil ; therapeutic use ; Male ; Rabbits ; Tendon Injuries ; drug therapy ; physiopathology ; Tendons ; drug effects ; pathology ; Tissue Adhesions ; drug therapy ; physiopathology ; Wound Healing ; drug effects
3.The Effects of Melatonin on Postoperative Intraabdominal Adhesion Formation.
Ahmet HATIPOGLU ; Zeliha TURKYILMAZ ; Selva MERT
Yonsei Medical Journal 2007;48(4):659-664
PURPOSE: Postoperative intraabdominal adhesion formation is a major clinical problem. No previous study was found, reporting the relationship between adhesion formation and melatonin administration, but melatonin, a strong antioxidant, is recognized to have certain effects on the progression of adhesion formation mechanism. It was therefore decided to investigate the effects of melatonin on postoperative adhesion formation. MATERIALS AMD METHODS: A total number of 24 Spraque-Dawley rats were utilized. Three groups, described as: Group A, sham laparatomy (n=8), Group B, rats that underwent only ischemia-reperfusion (n=8) and Group C, rats that underwent ischemia- reperfusion and were given 10 mg/kg melatonin solution i.v. (n=8). For Groups B and C, the ileocolic vessels were clamped. Blood glutathione peroxidase levels of all study groups were assessed, then microscopic and macroscopic adhesion scores were evaluated. RESULTS: Glutathione peroxidase levels of the melatonin-treated group were significantly higher and fibroblast proliferation and macroscopic adhesion scores were significantly lower, than in the melatonin-free group. CONCLUSION: The results of this study supported the hypothesis, that melatonin administration may prevent intraabdominal adhesions resulting from surgery.
Abdomen/pathology/*surgery
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Animals
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Antioxidants/*therapeutic use
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Melatonin/*therapeutic use
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Postoperative Complications/*prevention & control
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Rats
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Rats, Sprague-Dawley
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Tissue Adhesions/drug therapy/pathology
4.Clinical study of the effect of methylene blue combined with aprotinin on intraperitoneal adhesion.
Tian-sheng CAO ; Rui-hua LIU ; Xiao-ming SUN
Chinese Journal of Gastrointestinal Surgery 2005;8(1):24-25
OBJECTIVETo study the effect of methylene blue combined with aprotinin on intraperitoneal adhesion.
METHODSFrom May 2000 to February 2004, there were 83 patients receiving total or partial colectomy and temporary ileostomy or colostomy, and second anastomosis was performed within 8-12 weeks after the first operation. These patients were divided into four groups and followed by intraperitoneal administration of saline,methylene blue,aprotinin,combined methylene blue and aprotinin respectively during the second operation, then adhesion formation was quantitatively graded.
RESULTSThe adhesion rate was 15% in combination group, 83% in saline group, 40% in methylene blue group, and 45% in aprotinin group, respectively. The adhesion rate was significantly lower in combination group(P< 0.05).
CONCLUSIONSMethylene blue and aprotinin can decrease the incidence of intraperitoneal adhesion significantly. The combination of these two drugs has significant effectiveness in the treatment of intraperitoneal adhesion.
Aprotinin ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Methylene Blue ; therapeutic use ; Peritoneal Diseases ; pathology ; prevention & control ; Postoperative Complications ; prevention & control ; Tissue Adhesions ; prevention & control
5.Effects of mitomycin C on delayed adjustment in experimental strabismus surgery.
Se Oh OH ; Bong Leen CHANG ; Jaeheung LEE
Korean Journal of Ophthalmology 1995;9(1):51-58
In adjustable strabismus surgery, a satisfactory final result would be achieved with delayed adjustment. However, the postoperative adhesions following strabismus surgery make delayed adjustment impossible. We evaluated the efficacy of mitomycin C in reducing the severity of postoperative adhesions following strabismus surgery and in delaying the time adjustment after surgery. Experimental rabbits underwent a hang-back recession procedure in the superior rectus muscle. A topical application of mitomycin C was made between the conjunctiva and the sclera for 5 minutes during the operation. We then studied the possible time of delayed adjustment and estimated the minimal forces required for the adjustment. The topical application of 0.1 mg/ml mitomycin C between the conjunctiva and sclera allowed for a 2-week delayed adjustment after surgery, and 0.2 mg/ml mitomycin C prevented the adhesions between these tissues and the muscle 5 weeks after surgery. These results suggest that topical mitomycin C may enhance the success rate of strabismus surgery with delayed adjustment and reduce postoperative adhesions.
Administration, Topical
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Animals
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Chemotherapy, Adjuvant
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Conjunctiva/drug effects
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Mitomycin/administration & dosage/*pharmacology
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Oculomotor Muscles/drug effects/pathology/*surgery
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Ophthalmic Solutions
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Postoperative Complications/prevention & control
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Rabbits
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Sclera/drug effects
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Strabismus/drug therapy/pathology/*surgery
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Suture Techniques
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Tissue Adhesions/prevention & control
6.Effect of platelet-derived growth factor-BB on the healing and adhesion of rat tendon.
Yue LIN ; Hong-wei LIANG ; Yun-jian LI ; Xin YAN ; Qian TAN
Chinese Journal of Burns 2010;26(4):304-308
OBJECTIVETo study the effect of platelet-derived growth factor-BB (PDGF-BB) gene transfected rat tendon cells on the healing and adhesion of rat tendon.
METHODSA model of heel tendon injury was reproduced in 90 rats. They were randomly divided into three groups: experiment group [with injection of 20 µL rat tendon cells (1 × 10(8) cell/mL) transfected with PDGF-BB gene into the injured tendon ends], control group [with injection of 20 µL non-transfected rat tendon cells (1 × 10(8) cell/mL) into the injured tendon ends], and blank control group (without treatment), with 30 rats in each group. Heel tendon ends were sutured with 6-0 thread by modified Kessler method and immobilized with tube-type plaster of Paris cast for one week. Rat tendon cells transfected with PDGF-BB gene were identified with gene sequencing and RT-PCR. Tendon tissue sample was harvested 3 days or 1, 2, 4, 8 week(s) after operation (POD or POW) for morphology and histology observation, and bio-mechanical test. The degree of tendon adhesion, the number of Fb and collagen fiber content in tissue, maximum tensile strength and sliding distance of tendon, and concentration of PDGF-BB in tendon tissue among groups were compared. Data were processed with t test.
RESULTS(1) PDGF-BB mRNA expressed stably in PDGF-BB gene transfected tendon cells as testified by RT-PCR and gene sequencing. (2) Obvious edema and inflammatory cells infiltration were observed in each group on POD 3, but they were less pronounced in experiment group. And the changes in all groups were ameliorated gradually. The difference in grading of tendon adhesion was not obvious among groups in POW 4 and 8. (3) Fb number in experiment group in POW 2, 4, 8 was respectively fewer than that of control group and blank control group (with t value respectively 2.94, 4.26, 5.76 and 4.00, 3.83, 6.12, P < 0.05 or P < 0.01). (4) Collagen fiber content in rat tendon of experimental group in POW 4 was (43 ± 6)%, which was significantly lower as compared with that of control group [(55 ± 8)%] and blank control group [(61 ± 8)%] (with t value respectively 2.94 and 4.41, P < 0.05 or P < 0.01). (5) The largest sliding distance of tendon in experiment group in POW 4 and 8 were (3.25 ± 0.33) and (3.65 ± 0.21) mm, which were significantly longer than those in control group [(2.29 ± 0.40), (2.21 ± 0.37) mm] and blank control group [(2.01 ± 0.23), (1.89 ± 0.24) mm] (with t value respectively 4.53, 8.29 and 7.55, 13.52, P values all below 0.01). There was no statistical significant difference among the three groups in the maximum tensile strength of tendon (with t value respectively 0.41, 0.41, 0.77, 0.72, P values all above 0.05). (6) Content of PDGF-BB in tendon tissue of experimental group on POD 3 and in POW 2, 4 were (12.95 ± 1.36), (8.32 ± 0.94), (9.10 ± 1.06) ng/mL, all significantly higher than those in control group [(1.13 ± 0.21), (2.07 ± 0.48), (3.85 ± 0.39) ng/mL] (with t value respectively 21.04, 14.50, 11.39, P values all below 0.01).
CONCLUSIONSPDGF-BB gene transfected rat tendon cells can promote endogenous healing of tendon and prevent tendon adhesion.
Animals ; Platelet-Derived Growth Factor ; genetics ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Sprague-Dawley ; Tendon Injuries ; pathology ; therapy ; Tendons ; drug effects ; pathology ; Tensile Strength ; Tissue Adhesions ; Transfection ; Wound Healing
7.Effects of Vitreomacular Traction on Ranibizumab Treatment Response in Eyes with Neovascular Age-related Macular Degeneration.
Kang Hoon LEE ; Hee Seung CHIN ; Na Rae KIM ; Yeon Sung MOON
Korean Journal of Ophthalmology 2015;29(6):396-403
PURPOSE: To investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD). METHODS: A retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection. RESULTS: One month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 microm and 121.68 microm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up. CONCLUSIONS: VA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.
Aged
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Aged, 80 and over
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Angiogenesis Inhibitors/*therapeutic use
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Female
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Follow-Up Studies
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Humans
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Intravitreal Injections
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Male
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Middle Aged
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Ranibizumab/*therapeutic use
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Retina/pathology
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Retinal Diseases/*physiopathology
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Retrospective Studies
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Tissue Adhesions
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Tomography, Optical Coherence
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Vascular Endothelial Growth Factor A/antagonists & inhibitors
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Visual Acuity/drug effects
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Vitreous Body/*pathology
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Wet Macular Degeneration/*drug therapy/physiopathology