The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-surgical Adhesions.

BACKGROUND: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, few improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered a blood pressure regulator. However, recent studies have indicated that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and wound healing. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion. METHODS: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion. RESULTS: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are used for targeting the RAS system, and some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including telmisartan, valsartan, and enalapril. CONCLUSION: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting the Renin-Angiotensin System may help to prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.

Intrauterine Adhesions After Chlamydia Infection With a Levonorgestrel-Releasing Intrauterine Device in Place.

BACKGROUND: Little is known about the long-term reproductive effects of pelvic infection when a levonorgestrel-releasing intrauterine device (LNG-IUD) is in situ. Society guidelines do not recommend removing an LNG-IUD during pelvic infection. CASE: A 37-year-old woman presented with primary infertility, and the only contributing factor was intrauterine adhesions in the shape of an IUD. She was known to previously have an LNG-IUD and was treated for asymptomatic chlamydia infection while the IUD was in place. After lysis of adhesions, she successfully conceived spontaneously. CONCLUSION: Data on long-term reproductive effects of pelvic infection with an LNG-IUD in situ are not available, and there may be consequences affecting the intrauterine milieu requiring further studies and potential counseling.

The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections.

PURPOSE: To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment. DESIGN: Retrospective cross-sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres. METHODS: A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group. RESULTS: At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p = 0.455). Mean follow-up (FU) was 35.98 months (min 6 - max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p < 0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA- eyes. No significant difference was found between VMA+ and VMA- eyes regarding their mean best-corrected visual acuity (BCVA) at baseline and at each annual time point (p = 0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p = 0.0303). CONCLUSIONS: Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.

WJ­MSCs intervention may relieve intrauterine adhesions in female rats via TGF­β1­mediated Rho/ROCK signaling inhibition.

Estrogen is a commonly used hormone in the adjuvant treatment of intrauterine adhesion (IUA), which can promote endometrial growth. Stem cell transplantation has also been reported to promote endometrial regeneration in IUA due to its potential differentiative capacity. Human Wharton's jelly mesenchymal stem cells (WJ­MSCs) are isolated from the umbilical cord, possess strong self­renewal and proliferative abilities, and are hypo­immunogenic and non­tumorigenic. Therefore, the present study aimed to investigate the therapeutic effects and underlying mechanism of WJ­MSCs transplantation with estrogen treatment, separately or as a combined therapy, on IUA. The IUA model was established using the ethanol damage method. A total of 50 Sprague­Dawley female rats were randomly divided into the control, IUA model, WJ­MSCs treatment, estrogen treatment and WJ­MSCs+ estrogen treatment groups (n=10/group). WJ­MSCs were injected three times at 5­day intervals. IUA rats in the estrogen group received 0.2 mg/kg estrogen through intragastric administration, once every 2 days for 8 weeks. Morphological changes were evaluated by hematoxylin­eosin staining. Immunohistochemical evaluations of pan­keratin, vimentin, transforming growth factor (TGF)­ß1, RhoA, RhoB, RhoC, Rho­associated coiled­coil­containing protein kinase (ROCK)I, and ROCKII expression were performed in uterine tissue. After treatment, the uterine specimens were observed to have increased uterine thickness and gland numbers in all treatment groups compared with the IUA group; however, the degree of restoration in the independent WJ­MSCs and estrogen treatment groups was better than in the combined treatment group. Immunohistochemical analysis demonstrated that pan­keratin expression was increased, and RhoA, ROCKI and TGF­ß1 expression was significantly inhibited in the WJ­MSCs and WJ­MSCs + estrogen treatment groups compared with the IUA group; however, the expression levels of these proteins were similar among all treatment groups. No change in vimentin expression was detected in any treatment group. The expression levels of RhoB, RhoC and ROCKII were clearly not affected by WJ­MSCs intervention alone. In conclusion, transplantation of WJ­MSCs may repair endometrial damage in IUA rats via TGF­ß1­mediated inhibition of RhoA/ROCKI signaling.

The efficacy of hydrogel foams in talc Pleurodesis.

BACKGROUND: Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Pleurodesis with talc slurry is a standard treatment option, but clinical failures occur, possible due to poor talc delivery. A novel drug-delivery system was developed that fills the entire thoracic cavity with a liquid foam containing talc. The foam is designed to gel and adhere to the tissue walls at body temperature, to improve talc deposition and efficacy. METHODS: Rheology, foam stability, and ex-vivo coating and bio-adhesion studies were performed on three concentrations of a novel hydrogel talc foam system that was developed to improve delivery of talc to the pleural surfaces. A New Zealand rabbit model of pleurodesis was used to evaluate effectiveness of the foams at inducing adhesion formation and compared to talc slurry. The rabbits were recovered after they had one of the test agents instilled into their pleura, and then sacrificed after 28 days. Pleurodesis was assessed by a blinded pathologist using a standardized pathological scoring system. RESULTS: All talc foam formulations produced foams that gelled at physiological temperatures and were relatively stable for at least two hours. As the concentration of the formulation increased the gelation temperature decreased and the foam adhesiveness increased. Rabbits that received talc foam had significantly greater adhesion formation than talc slurry (mean score of 2.21 vs. 1.18 (p < 0.05)). Rabbits that received the 20% foam developed the most adhesions. CONCLUSIONS: This study demonstrates that our triblock copolymer hydrogel foam delivery system enhances adhesion formation in an experimental model. This novel approach can have important clinical impact, potentially improving efficacy of existing therapies and reducing the need for more invasive treatments.

Breast implant surface texture impacts host tissue response.

BACKGROUND: Surface texture of a breast implant influences tissue response and ultimately device performance. Characterizing differences among available surface textures is important for predicting and optimizing performance. METHODS: Scanning electron microscopy (SEM) and X-ray computed tomography (CT)-imaging were used to characterize the topography and surface area of 12 unique breast implant surface textures from seven different manufacturers. Samples of these surface textures were implanted in rats, and tissue response was analyzed histologically. In separate experiments, the force required to separate host tissue from the implant surface texture was used as a measure of tissue adherence. RESULTS: SEM imaging of the top and cross section of the implant shells showed that the textures differed qualitatively in evenness of the surface, presence of pores, size and openness of the pores, and the depth of texturing. X-ray CT imaging reflected these differences, with the texture surface area of the anterior of the shells ranging from 85 to 551 mm2, which was 8-602% greater than that of a flat surface. General similarities based on the physical structure of the surfaces were noted among groups of textures. In the rat models, with increasing surface texture complexity, there was increased capsule disorganization, tissue ingrowth, and tissue adherence. CONCLUSIONS: Surface area and topography of breast implant textures are important factors contributing to tissue ingrowth and adherence. Based on surface area characteristics and measurements, it is possible to group the textures into four classifications: smooth/nanotexture (80-100 mm2), microtexture (100-200 mm2), macrotexture (200-300 mm2), and macrotexture-plus (> 300 mm2).

A prospective randomized experimental study to investigate the peritoneal adhesion formation after waterjet injection and argon plasma coagulation (HybridAPC) in a rat model.

BACKGROUND: This prospective, randomized, controlled, single-blinded study investigates the peritoneal adhesion formation of HybridAPC (waterjet elevation of the peritoneum with subsequent argon plasma coagulation) versus only waterjet (elevation with the same instrument, but without subsequent argon plasma coagulation) in a rat model (24 female Wistar rats). MATERIALS AND METHODS: Bilateral lesions were created on the abdominal wall with HybridAPC on one sidewall and waterjet elevation on the other sidewall of the peritoneum in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. MAIN OUTCOME MEASURE(S): Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. RESULT(S): Incidence of adhesion formation was 2.3% for HybridAPC; no adhesions occurred for peritoneal elevation with saline (p = 1.00). Histologic evaluation revealed no acute inflammation in both groups. An overall moderate degree of granulation tissue formation and myonecrosis was observed in the HybridAPC group, whereas no chronic inflammation and myonecrosis occurred after elevation without thermal ablation (p < 0.0001). CONCLUSION(S): This study investigates the effect of waterjet elevation of the peritoneum with and without subsequent thermal ablation on adhesion formation in a rat model for the first time. Peritoneal waterjet elevation with saline does not provide any risk of adhesion formation. Thermal coagulation with APC after waterjet elevation of the peritoneum creates advantageous peritoneal conditions due to a permanent moist tissue surface and the cooling effect of the injected solution, resulting in no significant difference in adhesion formation compared to peritoneal elevation without thermal ablation. HybridAPC can thus be regarded as a beneficial coagulation method with only minor adhesion formation due to positive tissue effects of the combined waterjet.

Targeting lysyl oxidase reduces peritoneal fibrosis.

BACKGROUND: Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions. METHODS: Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro. RESULTS: NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro. CONCLUSION: Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development.

Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions.

BACKGROUND: Activation of inflammation-mediated endometrial injury is suggested to play a decisive role in pathogenesis of intrauterine adhesion (IUA). The stem cell theory of endometrial diseases has been given a hotspot, in that human endometrial stem cells have been isolated from the endometrium. Three transcription factors that play key roles in maintaining pluripotency and self-renewal in stem cells are sex-determining region Y-box2 (SOX2), Nanog homebox (NANOG), and octamer-binding protein (OCT4), which may be responsible for the damage or repair process of uterine endometrium. We aim to investigate the expression of SOX2, NANOG and OCT4 in a mouse model of acute uterine injury induced by peritoneal injection of lipopolysaccharide (LPS) and also analyze their changes in endometrium of women with IUA. METHODS: The mouse uterine horns were collected at 0 h, 6 h, 12 h, 18 h or 24 h after a single dose of LPS or PBS injection. Meanwhile, we recruited 19 women with IUA diagnosed by hysteroscopy and 16 disease-free women as control group. Endometrial tissue samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with Quantitative Real-time Polymerase Chain Reaction and Western blotting assay. RESULTS: In a mouse model of acute uterine injury, there was significant upregulation of NANOG at 6 h, SOX2 and OCT4 at 12 h compared with the values before injection or PBS injection. NANOG expression reached a peak at 6 h, while SOX2 and OCT4 peaked later at 12 h after LPS treatment. NANOG mRNA and protein expressions were significantly higher in endometrium of IUA patients compared to those of the control group. CONCLUSIONS: Expression of pluripotency factors SOX2, NANOG and OCT4 increased in a mouse model of LPS-induced acute uterine injury. NANOG peaked earlier followed by the other two factors before returning to baseline levels. NANOG but not SOX2 and OCT4 expression was overexpressed in the endometrium of women with IUA. They may be involved in the formation or restoration of IUA, and their roles in pathogenesis of IUA need to be further studied.

The Effect of Ankaferd Blood Stopper? on Epidural Fibrosis After Laminectomy in Rats: An Experimental Study.

AIM: Lumbar epidural fibrosis is increasingly recognized as a cause of persistent back pain. The aim of this study was to examine the effect Ankaferd Blood Stopper on epidural fibrosis following laminectomy in rat models. MATERIAL AND METHODS: Twenty Sprague-Dawley male rats were randomly allocated to 2 groups of 10 each. The dura mater and nerve root were exposed after L1 unilateral laminectomy. Close attention was paid not to traumatize the dura, the nerve roots, or the dissected muscles. Immediate muscle and skin closure was made in sham group. In the Ankaferd Blood Stopper group, cotton wool soaked with 1 mL Ankaferd Blood Stopper was applied to the exposure site for 5 minutes, and muscle and skin closure was then made. Histological analysis was performed at four weeks postoperatively. RESULTS: Epidural fibrosis formation evaluation and fibroblastic activity evaluation revealed that there was a significant difference between the sham and the Ankaferd Blood Stopper treated groups (p = 0.011, p = 0.009). Severe epidural adhesions were observed in the Ankaferd Blood Stopper group. Dissection of these epidural adhesions was difficult and accompanied by bleeding and disruption of the dura mater. CONCLUSION: The results of this study showed that there was no positive effect of Ankaferd Blood Stopper on the prevention of epidural fibrosis, which is one of the most significant problems following spinal surgery, and the epidural fibrosis actually increased.

Effects of Topical Cova™, Tisseel® and Adcon® Gel Application on the Development of Spinal Peridural Fibrosis: An Experimental Study in Rats.

AIM: Leptomeningeal adhesions and fibrosis in the spinal peridural space are the most common causes of post-laminectomy syndrome. Fibrin sealant agents and membrane barriers are commonly used for hemostasis and sealing purposes in spinal surgery. Peridural fibrosis may be a risk of the usage of these topical agents. In this study, we aimed to compare the effects of Cova ™, Tisseel® and Adcon ® Gel on the development of spinal peridural fibrosis in the experimental rat model. MATERIAL AND METHODS: Thirty-two Sprague Dawley female rats were randomly divided into 4 groups. Groups were constituted as group 1; Cova™ group (laminectomy+Cova™), group 2; Tisseel® group (laminectomy+Tisseel®), group 3; Adcon®Gel group (laminectomy + Adcon®Gel), group 4; control group (laminectomy only). Six weeks after laminectomy, spinal columns were removed en bloc between L1 and L4 vertebrae. Peridural fibrosis was evaluated histologically and the results were compared statistically. RESULTS: Statistically significant reduction of peridural fibrosis was achieved in groups 1, 2, and 3 when compared with the control group (p < 0.05). Our data revealed a statistically significant difference between group 1 and group 3 (p < 0.05). When we compared with group 2 and 3, the fibrosis grades were not different between these two groups (p > 0.05). CONCLUSION: Fibrin sealant agent Tisseel® and membrane barrier Cova™ do not enhance peridural fibrosis following laminectomy. Cova™ and Tisseel® may be appropriate for hemostasis and leakage prevention during the spinal surgery and it is safe to leave these materials on the operation surface.

Bowel strangulation caused by massive intraperitoneal adhesion due to effective chemotherapy for multiple peritoneal metastases originating from descending colon cancer.

We describe a case of bowel strangulation caused by massive peritoneal adhesion as a result of effective chemotherapy. A 71-year-old man, who had obstructive descending colon cancer with massive peritoneal metastases and, therefore, received palliative surgery consisting of diverting colostomy and sampling of peritoneal nodules, developed bowel strangulation on day 4 of the 2nd course of chemotherapy, including irinotecan, l-leucovorin, and 5-fluorouracil. Emergent celiotomy showed a massive intraperitoneal adhesion formed around several intestinal loops, which were not observed at the prior surgery. One loop was strangled, but recovered by adhesiotomy alone. Intestinal loops were formed around aggregates of peritoneal nodules as the centers, several of which were then sampled. We closed the abdomen after all intestinal loops were eradicated by total enterolysis. Fortunately, the patient has been doing well and received chemotherapy without recurrent bowel obstruction 10 months after the present episode. Histological findings of the aggregates causing intestinal loops demonstrated extensive necrosis of cancerous tissue surrounded by fibrosis with abundant lymphocyte infiltration. These findings were not observed in the specimen sampled before chemotherapy, suggesting that intestinal loops were caused by inflammatory adhesion occurring around the peritoneal metastases as a result of effectiveness of chemotherapy.

The effect of enoxaparin on seroma and mesh-tissue adhesion in a hernia model.

The aim of this study was to investigate whether enoxaparin (ENX) administration would increase seroma risk and worsen mesh tissue recovery in an experimental rat hernia repair model. Fifty-six adult male Wistar-Albino rats were included in the study. Rats were equally and randomly separated into seven groups: Group 1, Control, only subcutaneous dissection was performed; group 2, Sham, Hernia defect was primary sutured; Group 3, Prolene mesh; Group 4, Dual mesh; Group 5, ENX + Sham; Group 6, ENX + Prolene mesh; Group 7, ENX + Dual mesh. ENX was subcutaneously injected at a dose of 180 U/kg per day for 7 days. Rats were killed after the amount of subcutaneous seroma was determined by ultrasound on day 7 following the surgical procedure. Mesh-tissue healing was evaluated using histopathological and immunohistochemical (CD31) staining methods. The mean seroma amount significantly increased in Groups 5-7 compared to Groups 2-4. CD31 immunostaining showed a reduction in neovascularization in Groups 6 and 7, compared to Groups 3 and 4. Neovascularization decreased and hemorrhage, necrosis and oedema findings remarkably increased in Groups 6 and 7, when compared to Groups 3 and 4. Fibroblastic activity and inflammation were more prominent in Groups 3 and 4. It should be kept in mind that ENX interferes with inflammation, which is desired in the early period of healing and leads to an increase in overall seroma amount with anti-coagulant effects, which in turn may disrupt wound healing and mesh-tissue adhesions, as was indicated in our study.

Minimal effective dose of povidone-iodine in abdominal surgery Our clinical experience.

UNLABELLED: The aim of this study is to evaluate the thyroid function tests in order to examine whether 10 % of Povidone-Iodine(PI), the medication we applied in 1/5 ratio diluted with 0.9 %NaCl, joins the systemic circulation during clean contaminated, contaminated and dirty operations for solid organ hydatid cysts in abdominal area to avoid abscess formation and spreading. 7 men and 6 women were included to the present study, prospectively. The mean age was 33.69(± 13.49). TSH, free T3 (fT3) and free T4 (fT4) hormone levels were measured before the operation and at the third day of postoperative period. Amount of used povidone-iodine for patients was recorded. As a result of statistical analysis applied, the preoperative and post operative values were not significantly different regarding with the measured hormone levels (preTSH vs postTSH: p= 0.984; prefT3 vs postfT3: p= 0.101; prefT4 vs postfT4: p=0.146). Thus, it has been shown that the dose we used is effective, and it does not enters at all or at quite low levels into the systemic circulation. Patients whom this application performed, abscess and intestinal adhesions have not been observed in our clinical experience. We recommend the use of suggested doses of Povidone-Iodine in the presence of intraabdominal perforation and abscess or in cases such as carrying a risk of cyst spreading to intraabdominal area in hydatid cysts. KEY WORDS: Povidone-iodine, Surgical adhesions, Surgical wound infections, Thyroid function tests.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS / EFEITOS DO TRATAMENTO TÓPICO COM O LÁTEX DA EUPHORBIA TIRUCALLI NA SOBREVIDA E NAS ADERÊNCIAS INTESTINAIS DE RATOS COM PERITONITE EXPERIMENTAL

Background: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. Aim: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. Methods: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. Results: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. Conclusions: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Racional: O uso de plantas da família Euphorbiaceae, principalmente a Euphorbia tirucalli (avelós), tem sido popularmente difundido para o tratamento de uma variedade de doenças de natureza infecciosa, tumoral e inflamatória. Objetivo: Avaliar o efeito do tratamento tópico com a solução aquosa do látex do avelós na sobrevida e nas aderências intestinas de ratos com peritonite experimental. Métodos: Foi induzido peritonite em 24 ratos Wistar e randomizados em quatro grupos de seis, assim distribuídos: 1) Controle - (n=6), nenhum tratamento; 2) Antibiótico - (n=6), tratamento com dose única intramuscular de antibiótico Unasyn (Pfizer - São Paulo); 3) Salina - (n=6), lavagem da cavidade abdominal com solução fisiológica 0,9%; 4) E.Tirucalli - (n=6), lavagem da cavidade abdominal com E. tirucalli na concentração de 12 mg/ml. Os animais que morreram foram submetidos à necropsia e o horário do óbito anotado. Os sobreviventes foram submetidos à eutanásia no 11odia de pós-operatório e, posteriormente, realizou-se a necropsia para avaliação da formação de aderências. Resultados: Os grupos controle e antibiótico obtiveram diferença significativa (p<0,01) com relação às horas de vida entre os grupos salina e E. tirucalli. Não houve diferença significativa (p>0,05) na sobrevida dos animais dos grupos salina e E. tirucalli, no entanto, houve um óbito no grupo salina. A necropsia dos animais dos grupos salina e E. tirucalli mostrou aderências firmes e resistentes à manipulação entre alças intestinais e parede abdominal. Os demais grupos não tiveram formação de aderências. Conclusão: O tratamento tópico com o látex da E. tirucalli estimulou maior formação de aderências intestinais e evitou o óbito de todos animais com peritonite até o período avaliado.

The time course of resolution of adhesions during fibrinolytic therapy in tetracycline-induced pleural injury in rabbits.

The time required for the effective clearance of pleural adhesions/organization after intrapleural fibrinolytic therapy (IPFT) is unknown. Chest ultrasonography and computed tomography (CT) were used to assess the efficacy of IPFT in a rabbit model of tetracycline-induced pleural injury, treated with single-chain (sc) urokinase plasminogen activators (scuPAs) or tissue PAs (sctPA). IPFT with sctPA (0.145 mg/kg; n = 10) and scuPA (0.5 mg/kg; n = 12) was monitored by serial ultrasonography alone (n = 12) or alongside CT scanning (n = 10). IPFT efficacy was assessed with gross lung injury scores (GLIS) and ultrasonography scores (USS). Pleural fluids withdrawn at 0-240 min and 24 h after IPFT were assayed for PA and fibrinolytic activities, α-macroglobulin/fibrinolysin complexes, and active PA inhibitor 1 (PAI-1). scuPA and sctPA generated comparable steady-state fibrinolytic activities by 20 min. PA activity in the scuPA group decreased slower than the sctPA group (kobs = 0.016 and 0.042 min(-1)). Significant amounts of bioactive uPA/α-macroglobulin (but not tPA; P < 0.05) complexes accumulated at 0-40 min after IPFT. Despite the differences in intrapleural processing, IPFT with either fibrinolysin was effective (GLIS ≤ 10) in animals imaged with ultrasonography only. USS correlated well with postmortem GLIS (r(2) = 0.85) and confirmed relatively slow intrapleural fibrinolysis after IPFT, which coincided with effective clearance of adhesions/organization at 4-8 h. CT scanning was associated with less effective (GLIS > 10) IPFT and higher levels of active PAI-1 at 24 h following therapy. We concluded that intrapleural fibrinolysis in tetracycline-induced pleural injury in rabbits is relatively slow (4-8 h). In CT-scanned animals, elevated PAI-1 activity (possibly radiation induced) reduced the efficacy of IPFT, buttressing the major impact of active PAI-1 on IPFT outcomes.

EFFECTS OF TOPICAL TREATMENT WITH EUPHORBIA TIRUCALLI LATEX ON THE SURVIVAL AND INTESTINAL ADHESIONS IN RATS WITH EXPERIMENTAL PERITONITIS.

BACKGROUND: The use of plants of the family Euphorbiaceae, particularly Euphorbia tirucalli (avelós) has been popularly widespread for treating a variety of diseases of infectious, tumoral, and inflammatory. AIM: To demonstrated antimicrobial and immunomodulatory effects of these extracts, evaluating the effect of a topical treatment with an aqueous solution of avelós latex on the survival and on intestinal adhesions in rats with experimental peritonitis. METHODS: Peritonitis was induced in 24 Wistar rats, that were randomized into four groups of six as follows: (1) Control group (n=6), no treatment; (2) Antibiotic group (n=6), treatment with a single intramuscular dose of antibiotic Unasyn; (3) Saline group (n=6), the abdominal cavity was washed with 0.9% saline; and (4) E.tirucalli group (n=6), the abdominal cavity was washed with E. tirucalli at a concentration of 12 mg/ml. The animals that died were necropsied, and the time of death was recorded. The survivors were killed on postoperative day 11, and necropsy was subsequently performed for evaluation of the intestinal adhesions. RESULTS: Significant differences were observed in the control and antibiotic groups (p<0.01) with respect to the survival hours when compared with the saline and E. tirucalli groups. There was no significant difference (p>0.05) in the survival of animals in the saline andE. tirucalli groups; however, one animal died in the saline group. Necropsy of the animals in the saline and E. tirucalligroups showed strong adhesions resistant to manipulation, between the intestinal loops and abdominal wall. The remaining groups did not show any adhesions. CONCLUSIONS: Topical treatment with E. tirucalli latex stimulated an increased formation of intestinal adhesions and prevented the death of all animals with peritonitis.

Inflammatory responses and side effects generated by several adjuvant-containing vaccines in turbot.

Several of the adjuvants used in fish vaccines cause adhesions in internal organs when they are injected intraperitoneally. We describe the damage caused by vaccines containing different adjuvants in the turbot Scophthalmus maximus and show that internal adhesions can be greatly reduced by injecting the fish in a specific way. Injection of fish with the needle directed towards the anterior part of the peritoneal cavity induced formation of a single cell-vaccine mass (CVM) that became attached to the parietal peritoneum. However, injection of the fish with the needle pointing in the opposite direction generated many small CVM that became attached to the visceral and parietal peritoneum and in some cases caused internal adhesions. We describe the structural and cellular changes in the adjuvant-induced CVMs. The CVMs mainly comprised neutrophils and macrophages, although most of the former underwent apoptosis, which was particularly evident from day 3 post-injection. The apoptotic cells were phagocytosed by macrophages, which were the dominant cell type from the first days onwards. All of the vaccines induced angiogenesis in the area of contact between the CVM and the mesothelium. Vaccines containing oil-based adjuvants or microspheres induced the formation of granulomas in the CVM; however, no granulomas were observed in the CVM induced by vaccines containing aluminium hydroxide or Matrix-Q(®) as adjuvants. All of the vaccines induced strong migration of cells to the peritoneal cavity. Although some of these cells remained unattached in the peritoneal cavity, most of them formed part of the CVM. We also observed migration of the cells from the peritoneal cavity to lymphoid organs, indicating bidirectional traffic of cells between the inflamed areas and these organs.