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1.
Arch Gynecol Obstet ; 310(2): 655-672, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38878233

RESUMO

IMPORTANCE: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide. OBJECTIVE: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery. EVIDENCE ACQUISITION: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included. RESULTS: We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0-67%, and 85%, respectively. CONCLUSIONS AND RELEVANCE: Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.


Assuntos
Procedimentos Cirúrgicos em Ginecologia , Complicações Pós-Operatórias , Humanos , Aderências Teciduais/prevenção & controle , Aderências Teciduais/etiologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Cirurgia de Second-Look , Doenças Peritoneais/prevenção & controle , Doenças Peritoneais/etiologia
2.
Inflammopharmacology ; 32(2): 1077-1089, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308792

RESUMO

The aim of this research was to investigate the effects of D-limonene on decreasing post-operative adhesion in rats and to understand the mechanisms involved. Peritoneal adhesions were induced by creating different incisions and excising a 1 × 1 cm section of the peritoneum. The experimental groups included a sham group, a control group in which peritoneal adhesions were induced without any treatment, and two treatment groups in which animals received D-limonene with dosages of 25 and 50 mg/kg after inducing peritoneal adhesions. Macroscopic examination of adhesions showed that both treatment groups had reduced adhesion bands in comparison to the control group. Immunohistochemical assessment of TGF-ß1, TNF-α, and VEGF on day 14 revealed a significant increment in the level of immunopositive cells for the mentioned markers in the control group, whereas administration of limonene in both doses significantly reduced levels of TGF-ß1, TNF-α, and VEGF (P < 0.05). Induction of peritoneal adhesions in the control group significantly increased TGF-ß1, TNF-α, and VEGF on days 3 and 14 in western blot evaluation, while treatment with limonene significantly reduced TNF-α level on day 14 (P < 0.05). Moreover, VEGF levels in both treatment groups significantly reduced on days 3 and 14. In the control group, a significant increment in the levels of MDA and NO and a notable decline in the levels of GPX, CAT was observed (P < 0.05). Limonene 50 group significantly reduced MDA level and increased GPx and CAT levels on day 14 (P < 0.05). In summary, D-limonene reduced adhesion bands, inflammatory cytokines, angiogenesis, and oxidative stress.


Assuntos
Antioxidantes , Fator de Crescimento Transformador beta1 , Ratos , Animais , Limoneno/farmacologia , Antioxidantes/farmacologia , Fator A de Crescimento do Endotélio Vascular , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/farmacologia
3.
Infect Immun ; 91(12): e0038423, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37975682

RESUMO

Candida albicans is a lifelong member of the mycobiome causing mucosal candidiasis and life-threatening, systemic, and intra-abdominal disease in immunocompromised and transplant patients. Despite the clinical importance of intra-abdominal candidiasis with mortality rates between 40% and 70%, the contribution of fungal virulence factors and host immune responses to disease has not been extensively studied. Secretion of the quorum-sensing molecule, farnesol, acts as a virulence factor for C. albicans during systemic infection, while inducing local, protective innate immune responses in oral models of infection. Previously, we reported that farnesol recruits macrophages to the peritoneal cavity in mice, suggesting a role for farnesol in innate immune responses. Here, we expand on our initial findings, showing that farnesol profoundly alters the peritoneal cavity microenvironment promoting innate inflammation. Intra-peritoneal injection of farnesol stimulates rapid local death of resident peritoneal cells followed by recruitment of neutrophils and inflammatory macrophages into the peritoneal cavity and peritoneal mesothelium associated with an early increase in chemokines followed by proinflammatory cytokines. These rapid inflammatory responses to farnesol significantly increase morbidity and mortality of mice with intra-abdominal candidiasis associated with increased formation of peritoneal adhesions, despite similar rates of fungal clearance from the peritoneal cavity and retro-peritoneal organs. C. albicans ddp3Δ/ddp3Δ knockout and reconstituted strains recapitulate these findings. This indicates that farnesol may be detrimental to the host during intra-abdominal infections. Importantly, our results highlight a need to understand how C. albicans virulence factors modulate the host immune response within the peritoneum, an exceedingly common site of Candida infection.


Assuntos
Candidíase , Infecções Intra-Abdominais , Humanos , Animais , Camundongos , Candida albicans , Farneseno Álcool/farmacologia , Cavidade Peritoneal/patologia , Candidíase/microbiologia , Fatores de Virulência
4.
Connect Tissue Res ; 63(3): 200-209, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35321605

RESUMO

This biography of Dr. Joel Rosenbloom is published on the occasion of the 50th anniversary of the journal. Dr. Rosenbloom presents the scientific milestones and achievements throughout his career emphasizing events that have spurred him to launch into a career in biomedical research and education. The biography spans several decades of the life and achievements of a distinguished physician scientist whose dedication to science demonstrates the development of new insights into a variety of connective tissues through technological advances and insightful approaches.


Assuntos
Pesquisa Biomédica , Pesquisa Biomédica/educação , Humanos , Masculino
5.
Eur Surg Res ; 63(3): 145-154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34818645

RESUMO

INTRODUCTION: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with sildenafil, zafirlukast, and pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral zafirlukast, sildenafil, or pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. METHODS: Four groups, each of 10 male Wistar rats weighing 250-300 g, were used. A midline laparotomy was used to excise an area of 1.5 × 1.5 cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of zafirlukast (1.25 mg/kg, group B), sildenafil (15 mg/kg, group C), or pirfenidone (500 mg/kg, group D) were given every day for 8 days. The control group, A, received no treatment. At day 9, animals were reoperated. The implant was resected after ethically approved euthanasia, and specimens were fixed in 10% formaldehyde for histopathology. RESULTS: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (p = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (p = 0.04). Adhesions in group C had less fibrovascular density (p = 0.03) with decreased serosal injuries (p = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (p < 0.01) and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than group B or C (p < 0.01). CONCLUSIONS: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral pirfenidone offered the best performance and could be recommended for human use.


Assuntos
Telas Cirúrgicas , Animais , Humanos , Indóis , Masculino , Fenilcarbamatos , Piridonas , Ratos , Ratos Wistar , Citrato de Sildenafila , Sulfonamidas , Telas Cirúrgicas/efeitos adversos , Aderências Teciduais/prevenção & controle
6.
Bull Exp Biol Med ; 171(4): 416-420, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542744

RESUMO

Adhesions in rat abdominal cavity were studied after laparotomy and subsequent single intraperitoneal injection of 2 ml of 5% aqueous solution of oxidized dextran (OD) with a molecular weight of 40 kDa (oxidation degree 10%). On days 7 and 21 after laparotomy, the number of adhesions in OD-treated rats was lower by 7.5 and 4 times than in animals not receiving OD. The number of neutrophils in adhesions on day 21 was manyfold lower in OD-treated rats. In 7 and 21 days after laparotomy, the number of fibroblasts in the adhesions of rats receiving and not receiving OD was similar, but 2-fold higher than in the peritoneum of non-operated rats. The content of collagen in adhesions on day 21 after laparotomy in OD-treated rats was 10-fold lower than in animals no receiving OD.


Assuntos
Dextranos/farmacologia , Laparotomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Cavidade Abdominal/patologia , Cavidade Abdominal/cirurgia , Animais , Dextranos/administração & dosagem , Modelos Animais de Doenças , Injeções Intraperitoneais , Masculino , Peritônio/efeitos dos fármacos , Peritônio/patologia , Ratos , Ratos Wistar , Resultado do Tratamento
7.
Arch Gynecol Obstet ; 301(5): 1113-1115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32206876

RESUMO

PURPOSE: Deep ovarian endometriosis surgery is likely to be associated with diffuse bleeding, intraoperative ovarian tissue destruction and perioperative adhesion formation. A new surgical approach is hereby proposed to avoid the negative short-term impact of classic laparoscopic cystectomy on ovarian reserve. RESULTS: The need for intraoperative periovarian coagulation after endometrioma excision was avoided by combining the gold standard minimal-access endometrioma stripping technique with a purely plant-based medical product with high-hemostatic and antiadhesion barrier properties. CONCLUSION: Endometrioma stripping followed by the application of a polysaccharide agent could avoid ovarian failure and at same time could reduce adhesion formation, thereby preserving tubo-ovarian function in endometrioma surgery. We encourage other surgically working groups to investigate middle- and long-term effects of this combined technique.


Assuntos
Endometriose/cirurgia , Infertilidade/cirurgia , Doenças Ovarianas/cirurgia , Reserva Ovariana/fisiologia , Aderências Teciduais/cirurgia , Feminino , Humanos
8.
Arch Gynecol Obstet ; 302(4): 879-886, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32666127

RESUMO

PURPOSE: To examine whether the presence of peritoneal adhesions at the second cesarean delivery (CD), attributable to the first CD, are associated with maternal intra-operative organ injury and adverse neonatal outcomes. METHODS: A retrospective cohort study was conducted, comparing severe maternal intra-operative organ injury and adverse neonatal outcomes, between women with and without peritoneal adhesions. All women with two CDs during the follow-up period were included. Women with adhesions diagnosed during the first CD, history of other abdominal or pelvic surgery, pelvic infection or pelvic inflammatory disease, endometriosis, uterine Mullerian anomalies and newborns with known chromosomal or structural abnormalities were excluded, resulting in 7925 women. Intra-operative peritoneal organ injury was defined as a composite of bladder injury, ureteral injury, small bowel injury or hysterectomy. The examined adverse neonatal outcomes were low 1 and 5 min Apgar scores, intrapartum death (IPD) and postpartum death (PPD). Multivariate logistic regression was performed. RESULTS: Peritoneal adhesions at the second CD, attributable to the first CD were diagnosed in 32.6% of patients (n = 2581). The presence of peritoneal adhesions was not found to be independently associated with intra-operative organ injury nor with 5 min Apgar scores, IPD and PPD. Second CDs complicated with adhesions were found to be associated with low (< 7) 1 min Apgar scores (adjusted OR 1.38, CI 1.20-1.58, p < 0.001). CONCLUSION: Adhesions attributable to a previous CD do not seem to increase the risk for intra-operative organ injury and adverse neonatal outcomes. These findings may assist in reassuring patients who are facing a second CD.


Assuntos
Recesariana/estatística & dados numéricos , Cesárea/efeitos adversos , Período Pós-Parto , Aderências Teciduais/complicações , Adulto , Feminino , Humanos , Histerectomia , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Reoperação , Estudos Retrospectivos , Aderências Teciduais/etiologia
9.
Biomed Microdevices ; 21(4): 78, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414228

RESUMO

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG-b-PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG-b-PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG-b-PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.


Assuntos
Eletricidade , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Membranas Artificiais , Doenças Peritoneais/prevenção & controle , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Nanofibras/química , Doenças Peritoneais/metabolismo , Doenças Peritoneais/patologia , Poliésteres/química , Polietilenoglicóis/química , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle
10.
Drug Dev Ind Pharm ; 45(5): 695-702, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30560692

RESUMO

The purpose of this study was to prepare a novel cryptotanshinone-loaded nanoemulsion (Cry LN) and to evaluate its prevention effect on the postoperative peritoneal adhesions (PPA). The Cry LN was prepared by high-pressure homogenization method, and various methods were used to investigate the physicochemical properties. The results showed that Cry LN has nanoscale particle size with uniform distribution and could slowly release the incorporated drug compared with Cry solution. With superior safety, Cry LN could increase the ratio of tissue plasminogen activator (tPA)/plasminogen activator inhibitor-1 (PAI-1) up to 673% compared with control group. Furthermore, in vivo animal study confirmed the Cry LN activated the fibrinolytic system and successfully prevented PPA formation in rat. In conclusion, Cry nanoemulsion could be considered as a potentially promising and effective strategy for PPA treatment.


Assuntos
Fibrinólise/efeitos dos fármacos , Doenças Peritoneais/prevenção & controle , Fenantrenos/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Animais , Linhagem Celular , Modelos Animais de Doenças , Emulsões , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Doenças Peritoneais/etiologia , Doenças Peritoneais/patologia , Fenantrenos/farmacocinética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/etiologia , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Ativador de Plasminogênio Tecidual/metabolismo
11.
J Surg Res ; 223: 198-206, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29433874

RESUMO

BACKGROUND: Peritoneal adhesions are nonanatomical connections that bind organs to the abdominal wall or among them. They arise after peritoneal injury, which triggers an inflammatory response followed by a healing process that leads to fibrotic tissue formation. Mesenchymal stem cells and their secretion products, also referred to as acellular derivatives (ACDs), have anti-inflammatory, fibrinolytic, and antifibrogenic properties. The aim of this study was to determine the effect of intraoperative administration of ACD on the appearance, severity, and progression of peritoneal adhesions, in an animal model. MATERIALS AND METHODS: Cecal erosions were mechanically induced in adult mice. Before closure, the vehicle, ACD, or Seprafilm was administered. Seven days later, the presence and grade of peritoneal adhesions were assessed macroscopically. One, 3, and 7 d after intervention, molecular and cellular markers of inflammation, fibrinolysis, and fibrogenesis were evaluated both locally and systemically. RESULTS: ACDs avoided the appearance of clinically relevant peritoneal adhesions. The vehicle had no effect, and Seprafilm reduced them inconsistently. The antiadhesive effect of ACD was associated with an early reduction of proinflammatory cytokine (tumor necrosis factor-alpha and interferon-gamma) secretion and leukocyte (polymorphonuclears, mononuclears, and macrophages) infiltration. High levels of D-dimer, low fibrin deposits, low myofibroblasts infiltration, and less fibrosis were also observed. CONCLUSIONS: ACD administered at the end of abdominal surgeries prevents the formation of peritoneal adhesions due to the modulation of inflammatory, fibrinolytic, and fibrogenic processes.


Assuntos
Transplante de Células-Tronco Mesenquimais , Doenças Peritoneais/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Fibrinólise , Fibrose , Inflamação/prevenção & controle , Camundongos
12.
J Pathol ; 243(2): 137-147, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28722107

RESUMO

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Doenças Peritoneais/fisiopatologia , Peritônio/fisiologia , Doenças Autoimunes/etiologia , Endometriose/etiologia , Endometriose/imunologia , Endometriose/fisiopatologia , Feminino , Humanos , Imunidade Celular/fisiologia , Doenças Peritoneais/etiologia , Doenças Peritoneais/imunologia , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/imunologia , Fibrose Peritoneal/fisiopatologia , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/fisiopatologia , Peritônio/anatomia & histologia , Peritônio/imunologia , Peritonite/etiologia , Peritonite/patologia , Peritonite/fisiopatologia , Serosite/etiologia , Cicatrização/fisiologia
13.
Surg Innov ; 24(6): 543-551, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28877644

RESUMO

BACKGROUND: To investigate the early and late antiadhesive effect and any changes of fibrin matrix regulation enzymes on rat peritoneum, after local administration of bevacizumab. METHODS: Rats were subjected to cecal abrasion. Bevacizumab (5 mg/kg) against placebo was given intraperitoneally. On the 2nd, 14th, and 28th postoperative days adhesions were scored, and tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), degree of fibrosis, and angiogenesis were measured in abrased cecum and in intact parietal peritoneum. RESULTS: Bevacizumab significantly reduced adhesions up to 15% on the 2nd, 52.5% on the 14th, and 55% on the 28th postoperative day, and significantly increased tPA concentrations in peritoneum. PAI-1 was decreased, and a significantly higher tPA/PAI-1 ratio along with an increase of MMP-9 was measured at all time points. Fibrosis and angiogenesis were significantly lower on the 14th and 28th postoperative days. CONCLUSIONS: Local bevacizumab administration has a strong early and late antiadhesive action on rat peritoneum, mediated by changes in the tPA/PAI-1 and MMP balance in favor of fibrinolysis up to 28 days after operations.


Assuntos
Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Ceco/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Peritônio/efeitos dos fármacos , Aderências Teciduais/prevenção & controle , Animais , Ceco/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Peritônio/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ratos , Ratos Wistar , Ativador de Plasminogênio Tecidual/metabolismo
14.
J Cell Mol Med ; 20(4): 632-43, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26828859

RESUMO

Intra-abdominal adhesions are major post-operative complications for which no effective means of prevention is available. We aimed to evaluate the efficacy of exogenous pulmonary surfactant administration in the prevention of post-operative abdominal adhesions. Rats were randomly assigned to undergo laparotomy (L) or gastroenterostomy (GE) and then treated with surfactant (groups L-S and GE-S, respectively). Intra-abdominal adhesions, collagen fibre content, metalloproteinase (MMP)-9, expression of growth factors (TGF-ß, KGF and VEGF), type III procollagen (PCIII) and pro-caspase 3, as well as isolectin B4 and ED1-positive cells expressing MMP-9, were evaluated. Groups treated with surfactant (GE-S and L-S) exhibited fewer adhesions. A significant reduction in collagen fibre content was observed in GE-S compared to GE animals (P < 0.001). In situ and gelatin zymography analysis showed higher MMP-9 expression and activity in the GE-S group compared to the GE group (P < 0.05). ED1-positive cell counts were significantly higher in the GE-S group (P < 0.001) than in the GE group. Virtually all cells positive for ED1 were MMP-9+. Double-labelling of MMP-9 with IB4 showed no significant differences between GE-S and GE groups. TGF-ß, KGF, PCIII and pro-caspase-3 mRNA expression decreased significantly in GE-S compared to GE animals (P < 0.05). Surfactant administration also reduced apoptosis in the GE-S group. These findings suggest that surfactant reduces the intra-abdominal adhesions triggered by laparotomy and gastrointestinal anastomosis, thus preventing fibrosis formation at the peritoneal surfaces. This preclinical study suggests an innovative treatment strategy for intra-abdominal adhesions with surfactant and to endorse its putative mechanism of action.


Assuntos
Peritônio/cirurgia , Surfactantes Pulmonares/farmacologia , Aderências Teciduais/prevenção & controle , Animais , Caspase 3/genética , Caspase 3/metabolismo , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Gastroenterostomia , Regulação da Expressão Gênica , Laparotomia , Lectinas/genética , Lectinas/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Peritônio/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Aderências Teciduais/genética , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
15.
J Surg Res ; 197(2): 291-300, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25976855

RESUMO

BACKGROUND: Peritoneal adhesions, organized as fibrous bands after abdominal surgery, are related with considerable morbidity and repeated hospitalization. Phospholipids, natural constituents of the peritoneal fluid, seem to display excellent antiadhesive properties. The aim of this study was to investigate whether intraperitoneal application of phospholipids is capable of reducing postoperative adhesions and the possible underlying mechanisms. MATERIALS AND METHODS: Twenty male Wistar rats were subjected to a midline laparotomy and a standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus of 3 mL of phospholipids (12 mg/mL) or NaCl (placebo) was given intraperitoneally. Seven days later, the quality and the quantity of adhesions, as well as serum proinflammatory and/or profibrotic mediators, were blindly assessed. Human colonic subepithelial myofibroblasts were isolated from normal controls and cultured with transforming growth factor-ß1 (TGFß1, 5 ng/mL) in the presence of phospholipids (30-300 µg/mL). Collagen production in culture supernatants and migratory activity of myofibroblasts were also assessed. RESULTS: Phospholipids reduced intra-abdominal adhesions (P < 0.001), with respect to their intensity and area, and serum levels of cytokines (interleukin 1ß, interleukin 6, platelet-derived growth factor-1, and TGFß1) compared with placebo-treated rats. Stimulation of myofibroblasts with TGFß1 significantly increased (P < 0.001) the basic collagen production. The presence of phospholipids significantly reduced (P < 0.001) both the TGFß1 induced and the basic collagen production. Using a wound healing assay, phospholipids were found to reduce the basic and the TGFß1-induced migration of myofibroblasts in a concentration-dependent manner. CONCLUSIONS: Intraperitoneal phospholipids might be involved in the prevention of postoperative adhesions formation via the reduction of proinflammatory and/or profibrotic mediators and by inhibiting fibrogenic properties of mesenchymal cells.


Assuntos
Miofibroblastos/efeitos dos fármacos , Fosfolipídeos/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Biomarcadores/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Humanos , Injeções Intraperitoneais , Laparotomia , Masculino , Miofibroblastos/metabolismo , Peritônio/cirurgia , Fosfolipídeos/farmacologia , Complicações Pós-Operatórias/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Aderências Teciduais/etiologia , Aderências Teciduais/metabolismo
16.
Lasers Surg Med ; 47(10): 817-23, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26415104

RESUMO

BACKGROUND: Adhesions commonly occur after abdominal surgery and can cause bowel obstruction, chronic abdominal pain, and infertility. Their prevention remains a challenge. OBJECTIVES: To evaluate the effects of the application of low-level lasers on the prevention of adhesions and scarring of the skin after peritoniectomia. METHOD: Twenty-four New Zealand breed male rabbits, approximately 2 months of age, were randomly divided into 3 groups (n = 8): GC-control group not subjected to laser, GL1-group with laser application at a dose of 0.2 J, and GL2-group with laser application at a dose of 3.6 J. All animals received a longitudinal midline incision and a bilateral resection of the peritoneal fragment, measuring 3 × 1 cm(2) . The animals received a laser treatment of one application every 24 hours, beginning at the time of surgery and lasting for a period of 4 days. After 14 days post-surgery, the animals were killed and adhesion formation was evaluated qualitatively and quantitatively by means of a laparotomy shaped inverted "U", which allowed for the verification of the broad wall of the abdominal cavity and organs. Differences were considered significant at P < 0.05. RESULTS: The adhesion formation was observed in 100% of the rabbits from groups GC and GL1, as compared to 37.5% of the rabbits from group GL2 (P < 0.01). The evaluation of the vascularization and tenacity of adhesions among the groups showed no significant difference. In groups CG and GL1, 72% and 83% of adhesions were verified between visceras, respectively whereas in GL2 occurred among abdominal wall. The tensile strength of the skin between the groups was not significant (P = 0.3106). The resistance of abdominal wall segments without skin he resistance of skin segments between groups GL2 and GC were higher than in GL1 (P = 0.01). CONCLUSION: Low-level LASER is effective in preventing intra-abdominal adhesions in rabbits without compromising strength and healing of the abdominal wall.


Assuntos
Parede Abdominal/cirurgia , Cicatriz/prevenção & controle , Terapia com Luz de Baixa Intensidade , Doenças Peritoneais/prevenção & controle , Peritônio/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Animais , Cicatriz/etiologia , Masculino , Doenças Peritoneais/etiologia , Coelhos , Distribuição Aleatória , Aderências Teciduais/etiologia , Cicatrização
17.
J Obstet Gynaecol Res ; 41(12): 1942-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26419644

RESUMO

AIM: We aimed to evaluate the preventive effect of the ligustrazine nanoparticles nano spray (LNNS) for postoperative peritoneal adhesions in female rat models. MATERIAL AND METHODS: Fifty Wistar female rats weighting 250-300 g were randomly assigned to seven equal groups. All animals in the seven groups underwent midline laparotomy and ceca were abraded with sterile rasp. Group 1 underwent sham operations without treatment. In group 2, a postoperative peritoneal adhesion model was created, but no medication was given. In group 3, a postoperative peritoneal adhesion model was treated with LNNS, 2.5 mg/kg. In group 4, a postoperative peritoneal adhesion model was treated with LNNS, 5 mg/kg. In group 5, a postoperative peritoneal adhesion model was treated with LNNS, 10 mg/kg. In group 6, a postoperative peritoneal adhesion model was treated with polylactic acid (PLA) nanoparticle. In group 7, a postoperative peritoneal adhesion model was treated with ligustrazine, 2.5 mg/kg. Ten days after surgery, macroscopic and pathologic assessments were performed, and peritoneal fluid samples were collected in each group. The levels of tumor necrosis factor-α, tissue plasminogen activator and plasminogen activator inhibitor-1 in peritoneal fluid were determined by enzyme-linked immunosorbent assay. RESULTS: The adhesion score and extent of groups 4 and 5 was lower than that of group 2 in macroscopic assessment (P < 0.05). A comparison of tumor necrosis factor-α and tissue plasminogen activator level in the peritoneal fluid also demonstrated significant differences among groups 2, 4 and 5 (P < 0.05). The levels of plasminogen activator inhibitor-1 in peritoneal fluid in the LNNS groups were decreased compared to group 1. CONCLUSION: We suggest that LNNS could reduce peritoneal adhesion formation and it could be applied as a novel intervention for postoperative peritoneal adhesion.


Assuntos
Nanopartículas/administração & dosagem , Doenças Peritoneais/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Pirazinas/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Líquido Ascítico/química , Ensaio de Imunoadsorção Enzimática , Feminino , Doenças Peritoneais/patologia , Inibidor 1 de Ativador de Plasminogênio/análise , Ratos , Ratos Wistar , Aderências Teciduais/patologia , Fator de Necrose Tumoral alfa/análise
18.
J Surg Res ; 187(2): 699-711, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24332552

RESUMO

BACKGROUND: Adhesions commonly appear in patients after abdominal surgery, with considerable individual variation in adhesion composition and severity of the repair process. Here, we address the influence of transforming growth factor (TGF)-ß3 and betaglycan in this response, in relation to TGF-ß1, in an adhesiogenic rabbit model. MATERIALS AND METHODS: Omental adhesions were recovered 3, 7, 14, and 90 d after the implantation of a polypropylene mesh on the parietal peritoneum in New Zealand White rabbits. Omentum from nonoperated animals served as control. Tissue specimens were examined for TGF-ß3 and TGF-ß1 (Western blotting, reverse transcription-polymerase chain reaction), and TGF-ß1:TGF-ß3 messenger RNA and protein expression ratios were analyzed. Immunohistochemical detection of TGF-ß3 and betaglycan was performed. RESULTS: Injury to the omentum led to mobilization of TGF-ß3 and betaglycan-expressing cells from milky spots. Fibrous zones in adhesions were simultaneous to the presence of TGF-ß1 and the membrane-bound form of betaglycan (7-d adhesions), whereas soluble betaglycan appeared in TGF-ß1-positive areas showing limited fibrosis (3-d adhesions). The elevated expression of TGF-ß3 concurrent with the presence of membrane-bound form of betaglycan was observed in zones of adipose regeneration (14-d adhesions), whereas zones of fibrous consistency were negative for TGF-ß3. CONCLUSIONS: Milky spots on the omentum contain inflammatory/immune cells positive for TGF-ß3, TGF-ß1, and betaglycan, playing a role in the damaged omentum repair. Our observations support the contribution of TGF-ß3 to tissue repair through adipose tissue regeneration and the profibrotic role of TGF-ß1 and suggest that these effects on the local wound repair response could be driven by the expression of betaglycan in its soluble or membrane-bound form.


Assuntos
Omento/lesões , Omento/metabolismo , Proteoglicanas/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Aderências Teciduais/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Cicatrização/fisiologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Tecido Adiposo Branco/ultraestrutura , Animais , Modelos Animais de Doenças , Masculino , Microscopia Eletrônica de Transmissão , Omento/patologia , Omento/cirurgia , Peritônio/lesões , Peritônio/metabolismo , Peritônio/cirurgia , Polipropilenos/efeitos adversos , Proteoglicanas/genética , RNA Mensageiro/metabolismo , Coelhos , Receptores de Fatores de Crescimento Transformadores beta/genética , Transdução de Sinais/fisiologia , Telas Cirúrgicas/efeitos adversos , Aderências Teciduais/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta3/genética
19.
J Obstet Gynaecol Res ; 40(2): 532-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24102983

RESUMO

AIM: We aim to evaluate the effect of Nigella sativa oil (NSO) on postoperative peritoneal adhesion formation in female rats. This experimental study is the first on the prevention of postoperative adhesion formation by NSO. METHODS: Twenty-four Wistar albino female rats were randomly assigned to three groups of eight rats each. Rats in group 1 were each injected i.p. with 1 mL of NSO. In group 2, an adhesion model was created with no injection of NSO. In group 3, an adhesion model was created and the area was covered with 1 mL of NSO. The rats were killed on postoperative day 8, and the severity of adhesions was evaluated macroscopically and histopathologically. RESULTS: There was a statistically significant difference in adhesion scores between group 2 (control) and group 3 (NSO-treated) (P = 0.003). Statistically significant differences in angiogenesis, fibrosis and inflammation were observed between the control and Nigella sativa groups (P = 0.002, P = 0.001 and P = 0.004, respectively). CONCLUSION: Covering peritoneal surfaces with NSO after peritoneal trauma is effective in decreasing peritoneal adhesion formation.


Assuntos
Doenças Peritoneais/prevenção & controle , Óleos de Plantas/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Animais , Feminino , Peritônio/cirurgia , Distribuição Aleatória , Ratos , Ratos Wistar , Índice de Gravidade de Doença , Aderências Teciduais/prevenção & controle
20.
Int J Gynaecol Obstet ; 164(2): 650-655, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37503788

RESUMO

OBJECTIVE: To examine demographic and obstetrical factors that are associated with adhesion formation following cesarean delivery. METHODS: We conducted a population-based study that included all women over 18 years og age who underwent two cesarean deliveries between the years 1988 and 2016 in a large tertiary medical center. We excluded women with adhesions already diagnosed during the first cesarean delivery, history of other abdominal or pelvic surgery, history of pelvic infection or pelvic inflammatory disease, history of endometriosis and history of uterine Müllerian anomalies. In addition, women with a classical or T-shaped uterine incision, non-singleton pregnancies, and fetal chromosomal or structural abnormalities were excluded. RESULTS: During the study period, 32.6% (n = 2283) of women were diagnosed with peritoneal adhesions during the second cesarean delivery. Factors found to be significantly associated with peritoneal adhesions were maternal age 35 years or older at the first cesarean delivery, Bedouin Arab ethnicity, composite of intrapartum and postpartum infectious morbidity, and cesarean deliveries that were performed after the onset of labor. In contrast, having a previous vaginal birth was found to be protective. CONCLUSIONS: Our results suggest that a woman's characteristics at her first cesarean delivery and her obstetrical history may be predictive of the likelihood of adhesion formation.


Assuntos
Cesárea , Anormalidades Urogenitais , Nascimento Vaginal Após Cesárea , Gravidez , Feminino , Humanos , Pré-Escolar , Cesárea/efeitos adversos , Idade Materna , Útero , Aderências Teciduais/epidemiologia , Aderências Teciduais/etiologia , Estudos Retrospectivos
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