Effects of bromopride on the healing of left colon anastomoses of rats

Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group- C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day

Research of working area development parameters in conditions of deep steep deposit finalizing

Отримано формули розрахунку об’єму запасів корисних копалин в приконтурній та глибинній зоні. Встановлено характер впливу параметрів доробки глибоких крутоспадних родовищ відкритим способом на доцільне положення поточних та проектних контурів кар’єру. Встановлено, що найменший середній коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу в проектному положенні. Найменший поточний коефіцієнт розкриву досягається при мінімальному значенні суми обсягів корисної копалини приконтурної зони лежачого і висячого боків покладу, а також робочого борту кар'єру в поточному положенні

Estudo da formação de aderências e da cicatrização de anastomoses colônicas em ratos com sepse peritoneal induzida

OBJETIVO: Avaliar os efeitos da sepse abdominal sobre a formação de aderências e a cicatrização de anastomoses colônicas em ratos. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para anastomose do cólon esquerdo na presença (grupo S) ou ausência (grupo N) de indução de sepse por ligadura e punção do ceco (CLP). Cada grupo foi dividido em subgrupos para eutanásia no terceiro (N3 e S3) ou sétimo (N7 e S7) dia de pós-operatório (DPO). Foi avaliada a quantidade de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, força de ruptura, hidroxiprolina e conteúdo de colágeno tecidual. RESULTADOS: Os animais submetidos à CLP apresentaram maior quantidade de aderências intra-abdominais tanto no 3° DPO (p=0,00) quanto no 7° DPO (p=0,00). Tiveram menores valores de força de ruptura no 3° DPO (p=0,00), porém maiores valores no 7° DPO (p=0,00). Não houve diferença na variação da concentração de hidroxiprolina, conteúdo de colágeno e histopatologia. CONCLUSÕES: A infecção peritoneal desencadeada por CLP aumentou a quantidade de aderências intra-cavitárias. Houve diminuição da resistência de anastomoses cólicas no 3° DPO, com posterior aumento no 7° DPO, sem efeito sobre os outros parâmetros da cicatrização. ________________________________________________________________________________ ABSTRACTPURPOSE: To evaluate the effects of abdominal sepsis on adhesion formation and colon anastomosis healing in rats. METHODS: Forty rats were distributed in two groups containing 20 rats each for left colon anastomosis in the presence (Group S) or absence (Group N) of induced sepsis by cecal ligation and puncture. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 or S7) post-operative day. The amount of adhesions was evaluated and a segment of the colon was removed for histopathologic analysis, bursting strength assessment, hydroxyproline and the determination of tissue collagen. RESULTS: The subjects which underwent cecal ligation and puncture presented a higher amount of intra-abdominal adherences in both third (p=0,00) and seventh (p=0,00) post-operatory days. Smaller bursting strengths were found in the S3 subgroup, and greater bursting strengths were found in the S7 subgroup. There was no difference in the variations on the concentrations of hydroxyproline, tissue collagen and histopathology. CONCLUSIONS: The peritoneal infection which was developed by cecal ligation and puncture raised the amount of intra-cavitary adhesions. There was a decrease in the amount of colonic anastomosis on the third post-operatory day with a following raise on the seventh without any effects on other healing parameters

Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

<p>Abstract</p> <p>Background</p> <p>Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.</p> <p>Methods</p> <p>A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO₂insufflation at the 10 cm of water. TIR was evaluated at the 24^th, 72^nd, 120^thand 168^thhour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.</p> <p>Results</p> <p>More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24^thand 72^nd; p < 0.01 - 120^thand p < 0.001 - 168^thhrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.</p> <p>Conclusions</p> <p>MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO₂insufflation however, led to moderate inflammation and less adhesion formation.</p

The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

<p>Abstract</p> <p>Background</p> <p>To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions.</p> <p>Methods</p> <p>78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody.</p> <p>Results</p> <p>VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma.</p> <p>Conclusion</p> <p>Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.</p

A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

<p>Abstract</p> <p>Background</p> <p>Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.</p> <p>Methods/Design</p> <p>This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part^®Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.</p> <p>Discussion</p> <p>This trial aims to assess, whether the intra-peritoneal application of A-Part^®Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.</p> <p>Trial registration</p> <p>NCT00646412</p

Thymidine phosphorylase in cancer cells stimulates human endothelial cell migration and invasion by the secretion of angiogenic factors

BACKGROUND: Thymidine phosphorylase (TP) is often overexpressed in tumours and has a role in tumour aggressiveness and angiogenesis. Here, we determined whether TP increased tumour invasion and whether TP-expressing cancer cells stimulated angiogenesis. METHODS: Angiogenesis was studied by exposing endothelial cells (HUVECs) to conditioned medium (CM) derived from cancer cells with high (Colo320TP1 = CT-CM, RT112/TP = RT-CM) and no TP expression after which migration (wound-healing-assay) and invasion (transwell-assay) were determined. The involvement of several angiogenic factors were examined by RT-PCR, ELISA and blocking antibodies. RESULTS: Tumour invasion was not dependent on intrinsic TP expression. The CT-CM and RT-CM stimulated HUVEC-migration and invasion by about 15 and 40%, respectively. Inhibition by 10 mu M TPI and 100 mu M L-dR, blocked migration and reduced the invasion by 50-70%. Thymidine phosphorylase activity in HUVECs was increased by CT-CM. Reverse transcription-polymerase chain reaction revealed a higher mRNA expression of bFGF (Colo320TP1), IL-8 (RT112/TP) and TNF-alpha, but not VEGF. Blocking antibodies targeting these factors decreased the migration and invasion that was induced by the CT-CM and RT-CM, except for IL-8 in CT-CM and bFGF in RT-CM. CONCLUSION: In our cell line panels, TP did not increase the tumour invasion, but stimulated the migration and invasion of HUVECs by two different mechanisms. Hence, TP targeting seems to provide a potential additional strategy in the field of anti-angiogenic therapy

A randomised, multi-centre, prospective, double blind pilot-study to evaluate safety and efficacy of the non-absorbable Optilene® Mesh Elastic versus the partly absorbable Ultrapro® Mesh for incisional hernia repair

<p>Abstract</p> <p>Background</p> <p>Randomised controlled trials with a long term follow-up (3 to 10 years) have demonstrated that mesh repair is superior to suture closure of incisional hernia with lower recurrence rates (5 to 20% versus 20 to 63%). Yet, the ideal size and material of the mesh are not defined. So far, there are few prospective studies that evaluate the influence of the mesh texture on patient's satisfaction, recurrence and complication rate. The aim of this study is to evaluate, if a non-absorbable mesh (Optilene^®Mesh Elastic) will result in better health outcomes compared to a partly absorbable mesh (Ultrapro^®Mesh).</p> <p>Methods/Design</p> <p>In this prospective, randomised, double blind study, eighty patients with incisional hernia after a midline laparotomy will be included. Primary objective of this study is to investigate differences in the physical functioning score from the SF-36 questionnaire 21 days after mesh insertion. Secondary objectives include the evaluation of the patients' daily activity, pain, wound complication and other surgical complications (hematomas, seromas), and safety within six months after intervention.</p> <p>Discussion</p> <p>This study investigates mainly from the patient perspective differences between meshes for treatment of incisional hernias. Whether partly absorbable meshes improve quality of life better than non-absorbable meshes is unclear and therefore, this trial will generate further evidence for a better treatment of patients.</p> <p>Trial registration</p> <p>NCT00646334</p