na Marques e Silva

Effects of metoclopramide on the expression of metalloproteinases and interleukins in left colonic anastomoses. An experimental study

PURPOSE To evaluate the effects of metoclopramide on metalloproteinases (MMP) and interleukins (IL) gene expression in colonic anastomoses in rats. METHODS Eighty rats were divided into two groups for euthanasia on the 3rd or 7th postoperative day (POD), then into two subgroups for sepsis induction or not, and then into subgroups to receive either metoclopramide or saline solution. Left colonic anastomosis were performed and then analyzed. RESULTS On the 3rd POD, metoclopramide was associated with increased expression of MMP-1a, MMP-13, and TNF-α. On the 7th POD, the transcripts of all MMPs, TNF-α, IL-1β, IFN-γ, and IL-10 of the treated animals became negatively modulated. In the presence of sepsis, metoclopramide did not change MMPs and decreased IL-6, IL-1β, IFN-γ and IL-10 gene expression on the 3rd POD. On the 7th POD, increased expression of all MMPs, IFN-γ and IL-10 and negative modulated TNF-α and IL-6 gene expression. CONCLUSION Administration of metoclopramide increased metalloproteinases and interleukins gene expression on the 3rd postoperative day and negatively modulated them on the 7th POD. In the presence of abdominal sepsis, metoclopramide did not change MMPs and decreased ILs gene expression on the 3rd POD. On the 7th POD, the drug increased expression of all MMPs.

IS DIGITAL RECTAL EXAM RELIABLE IN GRADING ANAL SPHINCTER DEFECTS

Background Anal sphincter tone is routinely assessed by digital rectal examination in patients with fecal incontinence, although its accuracy in detecting sphincter defects or separating competent from incompetent muscles has not been established. Objective In this setting, we aimed to evaluate the accuracy of digital rectal examination in grading anal defects in order to separate small from extensive cases as depicted on 3D endoanal ultrasound, using a scoring sphincter defect and correlate anal tone to anal pressures. Methods Women with fecal incontinence were divided into two groups: small or extensive defects according to the ultrasound scoring system. Sensitivity, specificity, positive and negative predictive values of digital rectal examination in grading global and external sphincter defects were calculated. Anal tone at digital rectal examination was compared to resting and incremental pressures. Results A cohort of 76 consecutive incontinent women were enrolled. The median Wexner score was 9. Sixty-eight showed sphincter defects on 3D endoanal ultrasound. Anal tone at digital rectal examination was considered abnormal in 62 cases. Abnormal digital rectal examination showed a sensitivity of 90%, specificity of 27.78% in distinguishing small from extensive defects of both sphincters. Five out of eight women with no sphincter defects had only abnormal squeeze tone at digital rectal examination. Abnormal squeeze tone at digital rectal examination had a sensitivity of 65.31% in distinguishing small from extensive external anal sphincter defects. Digital rectal examination sensitivity increased linearly from small to extensive external anal sphincter defects (P=0.001). Women with abnormal resting tone had lower resting pressures than women with normal tone at digital rectal examination (P=0.0001). Women with abnormal squeeze tone had lower incremental pressures than women with normal tone at digital rectal examination (P=0.017). Conclusion Digital rectal examination had good sensitivity and poor specificity in discerning small from severe global anal sphincter defects. Moreover, digital rectal examination had fair sensitivity and poor specificity in grading external anal sphincter defects, and its best accuracy was on complete external anal sphincter lesions. Anal resting and squeeze tone were correlated to anal pressures.

Efeitos da bromoprida na cicatrização de anastomoses no cólon esquerdo de ratos

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.

Effects of metoclopramide on healing of colonic anastomoses in a rat model of abdominal sepsis.

ABSTRACT Introduction: Metoclopramide is often used in the treatment of postoperative nausea and vomiting, but a literature review failed to find reports on the influence of this drug on the healing of bowel anastomoses in the setting of abdominal sepsis. The aim of this study was to evaluate the effects of metoclopramide on the healing of left colonic anastomoses in rats with induced abdominal sepsis. Materials and Methods: Forty rats were divided into two groups of 20 animals each to receive either metoclopramide (experimental group: E) or saline (control group: C). Each group was further divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). A segmental resection of the left colon was performed, followed by end-to-end anastomosis. Sepsis was induced by cecal ligation and puncture. On the day of reoperation, the total number of adhesions was assessed and the anastomosed bowel segment was removed for tensile strength testing, histopathological analysis, measurement of hydroxyproline levels, and histomorphometric evaluation of collagen. Results: Intraoperative findings, number of intra-abdominal adhesions in the anastomosed area, and tensile strength before anastomosis rupture were similar among all subgroups at all assessments. On the third postoperative day, the anastomoses of animals treated with metoclopramide showed significantly lower hydroxyproline levels (p = 0.01) when compared with controls. Collagen content was similar among all subgroups. Conclusions: Metoclopramide does not have deleterious effects on the healing of bowel anastomoses in rats subjected to experimental abdominal sepsis.

Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.