Comparison of the effect of Everolimus, Prednisolone, and a combination of both on experimentally induced peritoneal adhesions in rats.

Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair.

OBJECTIVES: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15th (early period) or 30th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15th and 30th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. RESULTS: Histopathologically, there were no significant differences among the groups on the 15th day. However, on the 30th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). CONCLUSION: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

Photobiomodulation therapy at 632 nm wavelength ameliorates intrauterine adhesion via activation of cAMP/PKA/CREB pathway.

Intrauterine adhesion (IUA), a major cause of uterine infertility, is pathologically characterized by endometrial fibrosis. Current treatments for IUA have poor efficacy with high recurrence rate, and restoring uterine functions is difficult. We aimed to determine the therapeutic efficacy of photobiomodulation (PBM) therapy on IUA and elucidate its underlying mechanisms. A rat IUA model was established via mechanical injury, and PBM was applied intrauterinely. The uterine structure and function were evaluated using ultrasonography, histology, and fertility tests. PBM therapy induced a thicker, more intact, and less fibrotic endometrium. PBM also partly recovered endometrial receptivity and fertility in IUA rats. A cellular fibrosis model was then established with human endometrial stromal cells (ESCs) cultured in the presence of TGF-ß1. PBM alleviated TGF-ß1-induced fibrosis and triggered cAMP/PKA/CREB signaling in ESCs. Pretreatment with the inhibitors targeting this pathway weakened PBM's protective efficacy in the IUA rats and ESCs. Therefore, we conclude that PBM improved endometrial fibrosis and fertility via activating cAMP/PKA/CREB signaling in IUA uterus. This study sheds more lights on the efficacy of PBM as a potential treatment for IUA.

Review the Role of Metabolism Reprogramming in the Pathogenesis of Post-surgical Adhesion: A New Therapeutic Strategy.

Metabolic reprogramming is defined as the skill of cells to change their metabolism to support the induced energy demand due to continuous growth. Metabolic reprogramming is a well- known occurrence in the progression of neoplastic cells, although, evidence has shown that it is present in fibrotic disorders. Post-surgical adhesion as a fibrotic disorder is a medical challenge and is defined by fibrotic bands connected between organs with the abdominal wall. Despite many investigations carried out about the pathogenesis of the disorder but there are many unknowns, therefore, targeting special pathways may have the potential to prevent the formation of fibrotic bands post-operative. Glycolysis is a necessary metabolic pathway in living cells. In hypoxic conditions, it is the dominant pathway in the production of energy for different types of cells such as fibroblasts, immune cells, and endothelial cells. Also, glycolysis is a main downstream target for transforming growth factor ß (TGF-ß) and upregulates during fibrotic conditions. Furthermore, this is noteworthy that hypoxia induces factor 1 alpha (HIF-1α) as a transcription factor, elevated during the hypoxia condition stimulates different signaling pathways such as TGF-ß/SMAD, nuclear factor kappa B (NF-kB), and mTOR pathway to control glycolytic metabolism and T-cell trafficking for immune cell migration. Different evidence has indicated that the administration of glycolytic inhibitors has the potential to prevent the development of fibrotic markers. In this review, we pointed out the role of the glycolysis pathway and its connection to profibrotic cytokines to promote inflammatory and fibrotic pathways. Based on the results of studies related to fibrotic disorders we hypothesized that targeting glycolysis may have therapeutic potential in the prevention of postoperative adhesions.

Yangmo decoction versus hyaluronic acid gel in women with intrauterine re-adhesion after hysteroscopic adhesiolysis: a retrospective efficacy and safety analysis.

BACKGROUND: Hysteroscopic adhesiolysis is the preferred primary method for intrauterine adhesion. However, there is about a 60% of chance of re-adhesion after surgery. The objectives of the study were to evaluate the efficacy and safety of Yangmo decoction as a secondary treatment in preventing intrauterine re-adhesion against those of hyaluronic acid gel. METHODS: Women received oral Yangmo decoction (YD cohort, n = 105) or intrauterine hyaluronic acid gel (HA cohort, n = 125) or did not receive secondary re-adhesion prevention treatments (EP cohort, n = 165) after hysteroscopic adhesiolysis for 6 months. In addition, all women have received 3 mg of oral estrogen and 20 mg oral progesterone combination after hysteroscopic adhesiolysis for 3 months. Intrauterine re-adhesion after hysteroscopic adhesiolysis after 6 months with or without secondary treatment(s) was detected using hysteroscopy. The extent of the cavity, type of adhesion, and the menstrual pattern were included to define the American Fertility Society classification of intrauterine re-adhesions (AFS) score. RESULTS: Fewer numbers of women suffered from intrauterine re-adhesion after hysteroscopic adhesiolysis in the YD cohort than those of the HA (15(14%) vs. 40(32%), p = 0.0019) and the EP (15(14%) vs. 58(35%). p = 0.0001) cohorts. Among women who developed intrauterine re-adhesion, AFS score was fewer for women of the YD cohort than those of HA (2(2-1) vs. 4(4-3), p < 0.001) and the EP (2(2-1) vs. 4(4-4), p < 0.001) cohorts. AFS score after surgery was fewer for women of the HA cohort than those of the EP cohort (p < 0.05). Higher numbers of women of the YD cohort retained pregnancies after 6-months of treatment than those of the HA (55(52%) vs. 45(36%), p = 0.0161) and EP (55(52%) vs. 35(21%), p < 0.0001) cohorts. Among women who develop re-adhesion, 10(10%) women of the YD cohort only had successful pregnancies. CONCLUSIONS: Yangmo decoction for 6 months after hysteroscopic adhesiolysis can reduce AFS score, prevent intrauterine re-adhesion, and increases the chances of successful pregnancies of women. LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.

Effect of topical estrogen cream compared with observation in prepubertal girls with labial adhesions.

BACKGROUND: Topical estrogen treatment has been considered the first-line treatment of labial adhesions in prepubertal girls. However, the effect of topical estrogen cream is different according to studies, and no study compared estrogen cream to observation. OBJECTIVE: This study aims to investigate the efficacy of topical estrogen cream treatment compared with observation in prepubertal girls with labial adhesions. STUDY DESIGN: The medical records of prepubertal girls diagnosed with labial adhesions from April 2005 to June 2019 were retrospectively analyzed. Baseline characteristics such as age at diagnosis and initial symptoms were collected. The primary outcome was the resolution of labial adhesion. Secondary outcomes were recurrence and side effects. RESULTS: A total of 114 patients were enrolled and divided into two groups, topical estrogen cream (n = 94), and observation (n = 20). Girls who were treated with estrogen cream had older age (24.6 ± 19.0 vs. 16.7 ± 15.3 months, p = 0.037) and higher resolution rate than the observation group (100.0% vs. 85.0%, respectively, p = 0.005). Girls younger than 23.3 months showed a significantly higher resolution rate to topical estrogen treatment (100% vs. 86.7%, p = 0.043). Side effects and recurrences occurred exclusively in children treated with topical estrogen therapy without significant differences compared to the observation group. CONCLUSION: Topical estrogen therapy showed a higher resolution rate than observation for the treatment of prepubertal girls with labial adhesions, especially in younger girls.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Sustained Release of Dicumarol via Novel Grafted Polymer in Electrospun Nanofiber Membrane for Treatment of Peritendinous Adhesion.

The prevention and treatment of post-traumatic peritendinous adhesion (PA) have always been a great difficulty for orthopedic surgeons. Current treatments include resecting surgery, non-steroidal anti-inflammatory drugs (NSAIDs) usage and implantable membranes, often target single disease pathogenic processes, resulting in unfavorable therapeutic outcomes. Here a polylactic acid (PLA)-dicumarol conjugates-electrospun nanofiber membrane (ENM) (PCD) is generated, which can achieve spatial accuracy and temporal sustainability in drug release. It is further demonstrated that PCD possesses a significantly higher and more sustainable drug release profile than traditional drug-loading ENM. By providing a physical barrier and continuous releasing of dicumarol, PCD implantation significantly reduces tissue adhesion by 25%, decreases fibroblasts activity and inhibits key fibrogenic cytokine transforming growth factor beta (TGFß) production by 30%, and improves the biomechanical tendon property by 14.69%. Mechanistically, PCD potently inhibits the connexin43 (Cx43) and thereby tunes down the fibroblastic TGFß/Smad3 signaling pathway. Thus, this approach leverages the anti-adhesion effect of dicumarol and drug release properties of grafted copolymer ENM by esters to provide a promising therapeutic strategy for patients who suffer from PA.

Exosome-Based Regimen Rescues Endometrial Fibrosis in Intrauterine Adhesions Via Targeting Clinical Fibrosis Biomarkers.

Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell-derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome-based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients.

Exploring new therapeutic potentials of curcumin against post-surgical adhesion bands.

BACKGROUND: Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. METHODS: Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. RESULTS: Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. CONCLUSION: These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Effect of growth hormone on endometrium growth of intrauterine adhesion and the underlying mechanism. / ç”Ÿé•¿æ¿€ç´ ä¿ƒè¿›å®«è ”ç²˜è¿žå­å®«å† è†œç”Ÿé•¿çš„ä½œç”¨åŠå ¶æ½œåœ¨æœºåˆ¶.

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.

Amniotic membrane extract-enriched hydrogel augments the therapeutic effect of menstrual blood-derived stromal cells in a rat model of intrauterine adhesion.

We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) is a safe and effective therapy for treating intrauterine adhesions (IUA). However, improving the colonization and therapeutic efficiency of MenSCs is still needed before full clinical application. Here, we established an amniotic membrane extract (AME)-enriched RGD hydrogel, and evaluated the therapeutic effect of this adjuvant combined with MenSCs transplantation in an IUA rat model. Our results indicated that AME promoted the proliferation and secretion of MenSCs in vitro, up-regulated the expression of apoptosis-suppressing gene BCL2 and down-regulated the expression of apoptosis-related genes Caspase-3 and Caspase-8. The AME-enriched hydrogel was biocompatible, and improved the survival of MenSCs in vitro and in vivo. It also promoted the retention of MenSCs in IUA uterus and augmented the effects of MenSCs on improving uterus morphology, endometrial proliferation, endometrial receptivity and fibrosis suppression. In addition, co-transplantation of MenSCs with AME-enriched hydrogel markedly down-regulated the expressions of inflammation-related genes IL10 and TGFß while up-regulated the IL4/IFN-γ ratio in the IUA endometrium, and improved the expressions of cell proliferation-related antigen, gland-regeneration-related marker leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), angiogenesis-related marker platelet and endothelial cell adhesion molecule 1 (PECAM1), endometrial receptivity related genes ITGα5 and ITGß3. Our study suggested that AME and MenSCs had a synergistic effect. Co-transplantation of MenSCs with AME-enriched hydrogel provided a promising approach for stem cell-based IUA treatment.

A mechanically robust and stable estradiol-loaded PHEMA-based hydrogel barrier for intrauterine adhesion treatment.

Estrogen combined with physical barrier therapy may be a prospective method to repair a damaged endometrium and prevent postsurgical re-adhesion in the treatment of intrauterine adhesions (IUAs), but there lacks a suitable scaffold with good biocompatibility, appropriate mechanical properties, and drug-releasing kinetics. Herein, a mechanically robust and stable barrier based on the poly(hydroxyethyl methacrylate) (PHEMA) hydrogel combined with estradiol-loaded mesoporous silica is designed. The network is formed by covalent bonds and noncovalent coordination bonds, which endow the hydrogel with superior mechanical properties to most reported PHEMA-based hydrogels. Meanwhile, the covalent bonds impart excellent stability to the hydrogel, which maintains its structure and mechanical properties in a simulated uterine fluid for 30 days. The excellent mechanical properties and stability are comparable to those of a typical barrier material intrauterine device (IUD), enabling the hydrogel to be retained in the uterus and removed intact like an IUD. In vitro and in vivo experiments show that the hydrogel possesses good biocompatibility similar to pure PHEMA hydrogels. In addition, the hydrogel releases estradiol continuously and stably, and exhibits a good therapeutic effect in promoting the proliferation of endometrial cells and inhibiting the progression of fibrosis. Therefore, the combinational advantages make the present hydrogel very promising in IUA treatment.

AICAR attenuates postoperative abdominal adhesion formation by inhibiting oxidative stress and promoting mesothelial cell repair.

BACKGROUND: Postoperative abdominal adhesion is one of most common complications after abdominal operations. 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) is an adenosine 5'-monophosphate activated protein kinase (AMPK) pathway agonist that inhibits inflammation, reduces cell fibrosis and cellular reactive oxygen species (ROS) injury, promotes autophagy and mitochondrial function. This study aimed to explore the mechanism of AICAR in inhibiting adhesion formation. MATERIALS AND METHODS: Forty rats were randomly divided into five groups. All of the rats except the sham group received cecal abrasion to establish an adhesion model. The rats in the sodium hyaluronate group were treated with 2 mL sodium hyaluronate before closing the peritoneal cavity. The AICAR 1 and 2 groups were treated with 100 mg/kg and 200 mg/kg AICAR, respectively. Seven days after the operation, all of the rats were euthanized, and the adhesion condition was evaluated by Nair's system. Inflammation was assessed by Eosin-hematoxylin (HE) staining and transforming growth factor-ß (TGF-ß1) detection. Oxidative stress effect was determined by ROS, nitric oxide (NO) level, superoxide dismutase (SOD), catalase, glutathione peroxidase (Gpx) and malondialdehyde (MDA) levels in adhesion tissue. Then, Sirius red picric acid staining was used to detect the fiber thickness. Immunohistochemical staining of cytokeratin-19 (CK-19), alpha-smooth muscle actin (α-SMA) and nuclear factor erythroid 2-related factor 2 (Nrf2) was also performed. Finally, HMrSV5 cells were treated with TGF-ß1 and AICAR, the mRNA expression of E-cadherin, α-SMA and vimentin was assessed by q-PCR and cellular immunofluorescent staining. RESULTS: The rats in the AICAR-treated group had fewer adhesion formation incidences and a reduced Nair's score. The inflammation was determined by HE staining and TGF-ß1 concentration. The ROS, SOD, Catalase, Gpx, MDA levels and fiber thickness were decreased by AICAR treatments compared to the control. However, the NO production, Nrf2 levels and peritoneal mesothelial cell integrity were promoted after AICAR treatments. In vitro work, AICAR treatments reduced E-cadherin, α-SMA and vimentin mRNA level compared to that in the TGF-ß1 group. CONCLUSION: AICAR can inhibit postoperative adhesion formation by reducing inflammation, decreasing oxidative stress response and promoting peritoneal mesothelial cell repair.

Dual-Modal Imaging and Synergistic Spinal Tumor Therapy Enabled by Hierarchical-Structured Nanofibers with Cascade Release and Postoperative Anti-adhesion.

Most treatments for spinal cancer are accompanied by serious side effects including subsequent tumor recurrence, spinal cord compression, and tissue adhesion, thus a highly effective treatment is crucial for preserving spinal and neurological functionalities. Herein, trilayered electrospun doxorubicin@bovine serum albumin/poly(ε-caprolactone)/manganese dioxide (DOX@BSA/PCL/MnO2) nanofibers with excellent antiadhesion ability, dual glutathione/hydrogen peroxide (GSH/H2O2) responsiveness, and cascade release of Mn2+/DOX was fabricated for realizing an efficient spinal tumor therapy. In detail, Fenton-like reactions between MnO2 in the fibers outermost layer and intra-/extracellular glutathione within tumors promoted the first-order release of Mn2+. Then, sustained release of DOX from the fibers' core layer occurred along with the infiltration of degradation fluid. Such release behavior avoided toxic side effects of drugs, regulated inflammatory tumor microenvironment, amplified tumor elimination efficiency through synergistic chemo-/chemodynamic therapies, and inhibited recurrence of spinal tumors. More interestingly, magnetic resonance and photoacoustic dual-modal imaging enabled visualizations of tumor therapy and material degradation in vivo, achieving rapid pathological analysis and diagnosis. On the whole, such versatile hierarchical-structured nanofibers provided a reference for rapid and potent theranostic of spinal cancer in future clinical translations.

Tamoxifen Prevents Peritendinous Adhesions: A Preliminary Report.

Background: Scarless healing comprises the ultimate goal after an injury. Since tendon healing results in a fibrotic scar, an injured tendon can never regain the mechanical potential and strength of its uninjured form. A wide variety of studies focus on the tendon healing with an absent or minimal peritendinous adhesions. However, no simple method has managed it at all. Possible complex actions and peritendinous environmental events take place during the tendon healing process. Tamoxifen (TAM), besides its breast cancer-related usage, is a potent antifibrotic drug. Here, we aimed to reduce the peritendinous adhesion with TAM administration. Methods: Achilles tendons of 44 Wistar albino rats were randomly distributed in 4 groups. In group 1, bilateral lower extremities were used as control and sham. Groups 2 and 3 were comprised of low-dose (1 mg/kg) and high-dose (40 mg/kg) systemic administration of TAM, respectively. Group 4 included local administration (1 mg/kg) of TAM. Biomechanical, macroscopical, and histopathological analyses were done and compared statistically. Biomechanically, the maximum force that led to tendon rupture was determined, and tensile force data were recorded via tensile testing device. Macroscopical and histopathological analysis were composed of the quantity, quality, and grade of peritendinous adhesions. Results: Macroscopic and histopathologic findings revealed that groups 2 and 3 had a variety of values ranging between slight to severe adhesions. In group 2, almost half of the animals had moderate adhesions, whereas in group 3, the majority of the animals had moderate adhesions. There were no animals with moderate or severe adhesions in group 4. Statistically significant values were calculated between sham and control groups. Biomechanically, group 2 showed the most significant result. The tendons in group 2 had the highest stiffness when maximal force was applied to rupture the tendons. Henceforth, all these consequences were proven statistically. Conclusion: We achieved less peritendinous adhesion with the local administration of TAM when compared to systemic administration of TAM. A better understanding of the peritendinous environmental process will reveal to develop new therapies in the prevention of peritendinous adhesions.

Effect of angiotensin II pathway inhibitors on post-surgical adhesion band formation: a potential repurposing of old drugs.

BACKGROUND: In this study we investigated the therapeutic potential of angiotensin II pathway inhibitors in attenuating post-surgical adhesion band formation in tendon injury. METHOD: We assigned 30 Wistar albino rats to 5 groups, including negative control, positive control, sham, Telmisartan- and Enalapril-treated groups (n=6). Telmisartan and Enalapril at a dose of 10 mg/kg were administered intraperitoneally for 21 days. Hematoxylin-Eosin, and Masson's trichrome staining were used to measure the inflammatory cell accumulation and collagen deposition in the Achilles tendon tissue sections. Oxidative stress markers were analyzed in tissue samples by spectrophotometric methods. Properties of Achilles tendon adhesions were compared based on Tang and Ishiyama scoring systems in the presence and absence of angiotensin II pathway inhibitors. RESULTS: Telmisartan and Enalapril reduced severity, length, and density of surgical-induced tendon adhesion at site of injury (***p < 0.001). Our results showed that administration of angiotensin II pathway inhibitors decreased infiltration of inflammatory cells to the injured area (*p < 0.05) and suppressed inflammation by regulating oxidative stress markers including MDA (***p < 0.001), total thiol (***p < 0.001), CAT (***p < 0.001), and SOD (***p < 0.001), in post-operative Achilles tendon tissues. Significant lower collagen deposition and formation of fibrotic tissues was seen in Telmisartan- and Enalapril-treated groups as detected by Masson's trichrome staining which correlated with a decrease in quantity (**p < 0.01) and grading of fibrosis score (***p < 0.001), in adhesive tissues. Moreover, inhibition of angiotensin II pathway could also ameliorate mechanical properties including ultimate load (***p < 0.001), and ultimate stress (*p < 0.05) in injured Tendons. CONCLUSION: Our results showed that ssuppression of inflammation and fibrosis are two mechanisms by which Telmisartan and Enalapril elicit potent protective responses post Achilles tendon injuries.

Polypropylene mesh combined with electrospun poly (L-lactic acid) membrane in situ releasing sirolimus and its anti-adhesion efficiency in rat hernia repair.

This study developed, a novel polypropylene (PP) mesh combined with poly (L-lactic acid) (PLA) electrospun nanofibers loaded sirolimus (SRL). The PP mesh was combined with PLA/SRL (1/0, 1/0.01, 1/0.02; mass ratios) composed electrospun membrane characterized by FTIR spectroscopy, XPS and SEM, and evaluated for cytocompatibility in vitro. In an in vivo study, a total of 84 Sprague-Dawley rats were employed to evaluate the efficacy of the novel composite PP mesh anti-adhesion, mechanical properties and inflammation. As a results, the PLA/SRL membrane could compound with PP mesh stably and load SRL. Although tensile testing showed that the mechanical properties of composite mesh decreased in vivo, the integration strength between the tissue and mesh was still able to counteract intra-abdominal pressure. Compared with the native PP mesh group, the novel PP mesh group showed a lower score for abdominal adhesion and inflammation. More importantly, the novel PP mesh completely integrated with the abdominal wall and had sufficient mechanical strength to repair abdominal wall defects.

THE IMPACT OF THE VITREOMACULAR INTERFACE ON FUNCTIONAL AND ANATOMICAL OUTCOMES IN DIABETIC MACULAR EDEMA TREATED WITH THREE DIFFERENT ANTI-VEGF AGENTS: Post Hoc Analysis of The Protocol T Study.

PURPOSE: To investigate the impact of baseline vitreomacular interface status on treatment outcomes in patients treated with three different anti-vascular endothelial growth factors for diabetic macular edema. METHODS: Post hoc analysis from patients enrolled in the DRCR.net Protocol T study. Optical coherence tomography images were analyzed at baseline and at the end of follow-up to identify the presence of complete vitreomacular adhesion, partial vitreomacular adhesion, vitreomacular traction syndrome, and complete posterior vitreous detachment. RESULTS: Six hundred and twenty-nine eyes were eligible for the study based on the study criteria. Complete adhesion eyes gained on average +3.7 more ETDRS letters compared with the complete posterior vitreous detachment group at the end of the 12 months follow-up ( P < 0.001). Baseline vitreomacular interface status had no significant influence on central subfield thickness at 12 months ( P = 0.144). There was no difference between the treatment arms based on effect of baseline vitreomacular interface status on best-corrected visual acuity gain. CONCLUSION: This study provides evidence that vitreomacular interface status affects functional outcomes in diabetic macular edema patients treated with anti-vascular endothelial growth factor injections. The presence of complete or partial vitreomacular adhesion at baseline may be associated with a larger treatment benefit than those with complete posterior vitreous detachment.

Complex assessment of immunosuppression effects in prevention and treatment of adhesive disease, an experiment.

The cause of all small bowel obstruction in 60-75% of cases is adhesive development. The first and main method for adhesion prevention is undoubtedly the surgical technique, but the prevention of adhesive development is still actual. We aimed to study macroscopic and microscopic peculiarities of the intestine, peritoneum, and scars of the anterolateral abdominal wall. Also, immunological blood changes were observed in rats with the experimental created adhesive disease on the background of azathioprine introduction. The experiment was conducted on 40 rats divided into 2 subgroups: 20 animals as an experimental group (EG1) and 20 as a control group (CG1). Animals from EG received azathioprine (Moshimerampreparaty named by N.A. Semashko, Russia) in a dosage of 1 mg/100g of weight once a day for the first 3 days (starting from the day of surgery). The control group did not receive any drugs. All 40 rats survived the postoperative period. Rats were removed from the experiment on the 7th day after the operation. There were significant statistical differences in most indicators between the experimental and control groups. Phagocytic index (PI) was reduced by 4.55 due to the natural reaction of the rat organism to the surgery. Indicators of EG were a slight decrease in leukocytes and lymphocytes by 0.3 and 0.9, respectively, a moderate decrease in T-lymphocytes by no more than 2.0, and a decrease in phagocytic activity by 5.8. Immunosuppression with azathioprine significantly reduced the frequency and severity of the adhesive process of the abdominal cavity. Used in the recommended dose does not significantly inhibit important indicators of immunity and does not affect wound healing processes.