Topical Analgesia with Lidocaine Plus Diclofenac Decreases Pain in Benign Anorectal Surgery: Randomized, Double-blind, and Controlled Clinical Trial.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of a topical formulation containing lidocaine plus diclofenac (CLIFE1) compared to lidocaine (CLIFE2), to decrease pain in benign anorectal surgery (BARS) to date not evaluated. More than 50% of patients undergoing BARS, especially hemorrhoidectomy, suffer from moderate and severe postoperative pain. This remains an unresolved problem that could be addressed with the new CLIFE1 topical treatment. METHODS: A multicenter, randomized double-blind, active-controlled parallel-group superiority trial, was conducted in two Spanish hospitals. Patients undergoing BARS (hemorrhoids, anal fistula and anal fissure) were randomized at the end of surgery at a 1:1 ratio to receive first dose either CLIFE1 (n = 60) or CLIFE2 (n = 60) anorectal topical treatment, and after every 12 h for the first three postoperative days and once a day from the fourth to sixth. The primary outcome was average of pain decrease after topical treatment, measured with visual analogue scale (VAS) by the patients themselves, the evening in the surgery day and four times daily for the first three postoperative days. RESULTS: The results of 120 patients included out of 150 selected undergoing BARS show a decrease in pain after CLIFE1 topical treatment (7.47 ± 13.09) greater than with CLIFE2 (4.38 ± 6.75), difference -3.21 95% CI (-5.75; -0.68), p = 0.008, decreasing significantly postoperative pain ( ≥ 9 mm, VAS) in 35% of patients undergoing benign anorectal surgery, compared to 18.33 % treated with lidocaine. CONCLUSIONS: The CLIFE1 topical treatment shows better analgesic efficacy than CLIFE2 in BARS.

Hydration and Nanoconfined Water: Insights from Computer Simulations.

The comprehension of the structure and behavior of water at interfaces and under nanoconfinement represents an issue of major concern in several central research areas like hydration, reaction dynamics and biology. From one side, water is known to play a dominant role in the structuring, the dynamics and the functionality of biological molecules, governing main processes like protein folding, protein binding and biological function. In turn, the same principles that rule biological organization at the molecular level are also operative for materials science processes that take place within a water environment, being responsible for the self-assembly of molecular structures to create synthetic supramolecular nanometrically-sized materials. Thus, the understanding of the principles of water hydration, including the development of a theory of hydrophobicity at the nanoscale, is imperative both from a fundamental and an applied standpoint. In this work we present some molecular dynamics studies of the structure and dynamics of water at different interfaces or confinement conditions, ranging from simple model hydrophobic interfaces with different geometrical constraints (in order to single out curvature effects), to self-assembled monolayers, proteins and phospholipid membranes. The tendency of the water molecules to sacrifice the lowest hydrogen bond (HB) coordination as possible at extended interfaces is revealed. This fact makes the first hydration layers to be highly oriented, in some situations even resembling the structure of hexagonal ice. A similar trend to maximize the number of HBs is shown to hold in cavity filling, with small subnanometric hydrophobic cavities remaining empty while larger cavities display an alternation of filled and dry states with a significant inner HB network. We also study interfaces with complex chemical and geometrical nature in order to determine how different conditions affect the local hydration properties. Thus, we show some results for protein hydration and, particularly, some preliminary studies on membrane hydration. Finally, calculations of a local hydrophobicity measure of relevance for binding and self-assembly are also presented. We then conclude with a few words of further emphasis on the relevance of this kind of knowledge to biology and to the design of new materials by highlighting the context-dependent and non-additive nature of different non-covalent interactions in an aqueous nanoenvironment, an issue that is usually greatly overlooked.

Anti-inflammatory effects of ischemic preconditioning on rat small bowel allografts.

INTRODUCTION: Minimizing the inflammatory events that follow intestinal transplantation may influence immediate graft function and improve outcome. Ischemic preconditioning (IPc) has been shown to ameliorate early inflammatory responses, and it may also attenuate the potentially damaging inflammation after intestinal transplantation. Herein, we examine the influence of intestinal IPc on inflammatory indices (tissue expression of ICAM-1, CD11a, and CD44 and serum levels of the soluble ICAM-1, sICAM-1) after heterotopic intestinal transplantation. METHODS: Lewis rats received full-length preconditioned or non-preconditioned Brown Norway intestinal allografts in the absence of immunosuppression. Preconditioned grafts were subjected to 1 cycle of 10 minutes of ischemia-reperfusion. Preconditioned and non-preconditioned isografts acted as controls. Blood was collected on alternate days post-transplant, and graft tissue harvested on sacrifice. ICAM-1, CD44, and CD11a expression was determined by immunohistochemistry, and the area of staining was quantified using image analysis. Serum soluble ICAM-1 levels were determined using an R&D Systems Quantikine enzyme immunoassay. RESULTS: (1) IPc ameliorated serum levels of sICAM-1 until severe rejection (day 7) overcame this down-regulation when compared to non-preconditioned allografts (day 3: 34,304 vs 40,479 pg/mL; day 5: 52,441 vs 61,593 pg/mL; day 7: 75,114 vs 73,309 pg/mL; day 9: 72,872 vs 76,314 pg/mL, respectively). (2) ICAM-1 expression was significantly lower in preconditioned allografts (1.02 vs 2.01 mm(2)). (3) CD44 tissue levels were also found to be lower in preconditioned allografts (0.86 vs 1.13 mm(2)). (4) There was a significant relationship between tissue ICAM-1 expression and serum levels of soluble ICAM-1 (P < .02). CONCLUSIONS: IPc improves inflammatory indices in the early stages following intestinal transplantation, and this might lead to a preserved cellular, architectural, and functional graft status. Furthermore, our results support the use of soluble ICAM-1 as a marker of endothelial activation, and thence of inflammation and developing rejection.

Comparison of the long-term outcome of two therapeutic strategies for the management of abdominal abscess complicating Crohn's disease: percutaneous drainage or immediate surgical treatment.

AIM: The management of abdominal abscesses complicating Crohn's disease is complex and involves a difficult choice between medical, radiological and surgical procedures. The long-term outcome was compared for two strategies for the management of abdominal abscess: percutaneous drainage (PD) followed by rescue surgery in the case of failure vs direct immediate surgery (IS). We also compared the results of IS with surgery performed after PD failure. METHODS: We retrospectively identified 44 patients with Crohn's disease with an abdominal abscess from January 2000 to December 2009. Therapeutic success was defined as abscess resolution and no reappearance within 1 year of follow-up. RESULTS: The first therapeutic approach was PD in 22 cases and IS in the other 22 cases. IS had a higher therapeutic success rate than PD (95.5% vs 27.2% respectively; P < 0.001). PD was the only independent variable related to treatment failure in the multivariate analysis after adjustment for possible confounders such as abscess size, multilocularity, presence of fistula and corticosteroid use (OR 88.26, 95% CI 7.38-1055.36; P < 0.001). Surgery after failure of PD (n = 16) was associated with longer total hospitalization (56.12 ± 35.89 vs 27.52 ± 15.11 days; P = 0.017) and longer postoperative stay (44.0 ± 83.7 vs 14.3 ± 30 days; P = 0.179) and needed a second operation more often (5/16, 31% vs 1/22, 4.5%; P = 0.065) than IS. CONCLUSIONS: Percutaneous drainage provided durable abscess resolution in only one-third of the patients compared with more than 90% of those treated with IS. In addition, surgery performed after PD failure results in a poorer outcome than IS.

Long-term results of surgery plus fibrin sealant for anal fistula.

AIM: The long-term recurrence rate of fibrin glue treatment was analysed in patients with trans-sphincteric cryptoglandular fistula operated by a two-phase procedure: (i) fistulectomy with seton placement; (ii) fibrin sealant (Tissucol Duo®, Baxter) insertion in the track. METHOD: Clinical data were collected prospectively for all patients operated between 2004 and 2010. The statistical association of clinical variables and recurrence was analysed and a disease-free curve was constructed using the Kaplan-Meier method. RESULTS: Twenty-eight consecutive patients (mean age 48.3 ± 13.3 years; 22 men) were enrolled in the study. Middle and high trans-sphincteric fistulae were diagnosed in 20 (71.4%) and eight (28.6%) patients. Seven (25%) had secondary track formation. The mean interval between the first operation and the fibrin sealant treatment was 12.5 ± 7.6 months. There were no complications related to the procedure. Nine (32.1%, 95% CI 17.9-50.7%) patients developed recurrence between 3 and 27 months after fibrin sealant treatment. Disease-free curves showed that the highest probability of recurrence occurred in the first 2 years. No incontinence was found at a mean follow-up of 20.6 (3-60) months among the 67.8% patients with no evidence of recurrence. CONCLUSION: Fibrin sealant is safe and simple. The healing rate is satisfactory without the risk of incontinence.

The superficial femoral vein: a valuable conduit for a short renal vein in kidney transplantation.

A variety of techniques have been developed to improve the problem with a short renal vein in kidney transplantation. Those techniques range from thorough mobilization of the recipient common and external iliac veins (iliac vein transposition) to donor vein elongation with a saphenous or gonadal vein or a polytetrafluoroethylene graft. Right renal vein extension using the inferior vena cava represents an excellent option for cadaveric kidney transplantation; however, for kidneys from living donors, that is not a suitable alternative. We present two cases where the superficial femoral vein was used as a conduit with good results; there was no additional morbidity for the patient. Although uncommon, renal vein extensions are sometimes needed in kidney transplantation. The superficial femoral vein comes close to representing the ideal conduit for a short renal vein when compared with a synthetic or an autologous graft due to its diameter and harvesting technique.

Time course of necrosis/apoptosis and neovascularization during experimental gastric conditioning.

Apoptosis, necrosis and neovascularization are three processes that occur during ischemic preconditioning in a range of organs. In the stomach, the effect of this preconditioning (the delay phenomenon) has helped to improve gastric vascularization prior to esophagogastric anastomosis after esophagectomy. Here we present a sequential study of the histological recovery of the gastric fundus and the phenomena of apoptosis, necrosis and neovascularization in an experimental model of partial gastric ischemia. Partial gastric devascularization was performed by ligature of the left gastric vessels in Sprague-Dawley rats. Rats were assigned to groups in accordance with their evaluation period: control, 1, 3, 6, 10, 15 and 21 days. Histological analysis, caspase-3 activity, DNA fragmentation and vascular endothelial cell proliferation (Ki-67) were measured in tissue samples after sacrifice. After 24 h of partial gastric ischemia, rates of apoptosis and necrosis were higher in the experimental groups than in controls. Tissue injury was higher 3 and 6 days post-ischemia. From day 10 after partial gastric ischemia, apoptosis and necrosis started to decrease, and on days 15 and 21 showed no differences in relation to controls. Neovascularization began between days 1 and 3, reaching its peak at 15 days after ischemia and coinciding with complete histological recovery. Both necrosis and apoptosis play a role in tissue injury during the first days after partial gastric ischemia. After 15 days, the evolution of both the histology and the neovascularization suggested that this is the optimal time for performing gastric transposition.

[Current status of follow-up of the upper digestive tract in familial adenomatous polyposis]. / Estado actual del seguimiento del área gastroduodenal en la poliposis adenomatosa familiar.

Familiar adenomatous polyposis (FAP) is a hereditary disease characterized by the development of multiple adenomatous polyps in the gastrointestinal tract and colorectal cancer in practically all patients who do not receive appropriate treatment. Although the most commonly involved region in this disease is the colorectal area, it is well known that adenomas can also develop in the upper gastrointestinal tract, mainly in the periampullary area of the duodenum. Because of the possibility of malignant transformation of these polyps, adequate monitoring is required, even though the optimal follow-up schedule has not yet been defined. In the present article, we report a case of a gastric adenocarcinoma detected during the follow-up of a patient diagnosed with FAP, as well as a review of the literature on this subject. We stress the need for early detection and appropriate management of this disease. Sufficient information is available to support the use of upper gastrointestinal endoscopy with lateral vision and serial biopsies of the periampullary region in these patients. The first endoscopy in patients with FAP should be performed at the age of 20 years or at diagnosis. Subsequently, a follow-up schedule should be designed, according to the number and histological characteristics of the polyps observed.

Long-term urinary dysfunction after rectal cancer surgery.

OBJECTIVE: Urinary dysfunction is a well-known complication of rectal surgery, secondary to injury to the autonomic nervous plexus. The object of this study was to evaluate the incidence, prevalence and type of micturition disorders following rectal cancer surgery and their reversibility during long-term follow-up. PATIENTS AND METHODS: A prospective study of 45 patients who underwent surgery for rectal cancer between 1993 and 1998 was undertaken. Those with pre-operative urinary dysfunction were excluded after sequential uroflowmetry and clinical interview. Ten of the surgical interventions were high anterior resections, 18 low anterior resections, and 17 abdominoperineal amputations. Pre-operative radiotherapy was performed in 47.9% of patients. All patients underwent sequential uroflowmetry and a clinical interview 3 and 12 months after the intervention. Subjects who presented micturition disorders underwent urodynamic examination The follow up period was three years. RESULTS: Three months after surgery alterations were found in 14 (31.3%) patients; the most frequent were stress incontinence, urinary tenesmus and the urge to urinate. At the 12-month assessment only 6 (13.3%) patients had urinary symptomatology or uroflowmetry abnormalities. After three years, micturition disorders persisted in 3 (6.6%) patients. CONCLUSION: Urinary dysfunction after rectal cancer excision is associated with a high degree of reversibility. Seventy-eight percent of the alterations detected after three months and 50% of those that persisted after a year disappeared during follow up.

Immunodulation with tacrolimus (FK506): results of a prospective, open-label, non-controlled trial in patients with inflammatory bowel disease.

UNLABELLED: Tacrolimus (FK506) is widely used in the organ transplant setting, but not in the treatment of IBD. OBJECTIVE: the aim of this study was to analyse the effectiveness of tacrolimus in specific clinical presentations of inflammatory bowel disease (IBD) in which recurrence is likely. PATIENTS AND METHODS: inclusion criteria were: perianal Crohn's disease (PCD), CD in rectal stump, pouchitis and cuffitis with severely impaired function of the ileoanal pouch (IPAA), and proven refractoriness to other therapies. Clinical assessment: Hughes' classification (PCD); Oresland index (OI) in IPAA, endoscopy-biopsy and Quality of life (QoL) using the Spanish version of the IBDQ. Response was determined as complete (CP), partial (PR) or non-existent (NR). Tacrolimus was administered orally at a dose of 0.1 mg/kg/day (levels 5-15 .g/L). RESULTS: nineteen patients entered the study. Mean duration of treatment was 9.6 +/- 6.3 months. In PCD, CR was reported in 66% of cases and PR in 33%, with disappearance of inflammation, stenosis and ulcers. In patients with pouchitis and cuffitis,77% presented either CR or PR. The OI scores and QoL improved significantly after treatment (p<0.006 and p<0.002, respectively). Adverse effects were minor and controlled by regulating the dose. CONCLUSION: oral administration of tacrolimus is easy to per-form and has few adverse effects when used to treat IBD in certain clinical presentations with a high likelihood of recurrence.

Role of nitric oxide in apoptosis and cell necrosis for intestinal transplantation.

INTRODUCTION: Nitric oxide (NO) is an important mediator of both physiological and pathological responses. Its dual role in the ischemia-reperfusion syndrome is still a matter of controversy. The aim of this study was to analyze the effect of NO on apoptosis and cell necrosis associated with heterotopic small bowel transplant. METHODS: Sprague-Dawley rats underwent heterotopic small bowel transplants with 3 hours of cold ischemia and 5 hours of reperfusion. Animals were assigned to the following study groups: Sham; bowel transplant (Trp); bowel transplant + NO donor (Trp + NONOS); bowel transplant + NO synthesis inhibitor (Trp + L-NAME). We studied histological changes and bacterial translocation in mesenteric nodes, liver and spleen as parameters of cell necrosis and caspase-3 activity as a parameter of apoptosis. RESULTS: Histological changes and bacterial translocation showed that exogenous administration of NO protected the transplant. Simple bowel transplant, with or without inhibition of NO synthesis, did not display this protective effect. Significantly greater levels of apoptosis were observe in grafts among the group administered NO at pharmacological doses. CONCLUSIONS: In experimental bowel transplantation rats administered exogenous NO show less necrosis but at the same time stimulation of apoptosis.

Biological relevance of the polymorphism in the CCR5 gene in refractory and non-refractory rheumatoid arthritis in Mexicans.

OBJECTIVE: The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA. METHODS: We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively. RESULTS: In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05). CONCLUSION: Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.

Protective effect of ischemic preconditioning on cold preservation and reperfusion injury associated with rat intestinal transplantation.

OBJECTIVE: To define the protective effect of ischemic preconditioning on cold ischemia and reperfusion injury associated with intestinal transplantation, and the role of nitric oxide in this process. SUMMARY BACKGROUND DATA: Ischemia/reperfusion injury continues to be a significant obstacle in small bowel transplantation. Preconditioning is a mechanism that protects against this injury. METHODS: To study the capacity of preconditioning to prevent cold ischemia-associated injury and the inflammatory response associated with intestinal transplantation, the authors studied a control group of animals, cold ischemia groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS, and intestinal transplantation groups with or without previous preconditioning and with or without previous administration of L-NAME or NONOS. RESULTS: Histologic findings and the release of lactate dehydrogenase into the preservation solution showed that preconditioning protects against cold ischemic preservation-associated injury. Preconditioning also prevented the inflammatory response associated with intestinal transplantation, measured by the above parameters and by neutrophil recruitment in the intestine. Inhibition of nitric oxide eliminates the protective effect. CONCLUSIONS: Preconditioning protects the intestinal grafts from cold preservation and reperfusion injury in the rat intestinal transplantation model. Nitric oxide is involved in this protection.

Prognostic factors for mortality in left colonic peritonitis: a new scoring system.

BACKGROUND: Perforating lesions of the colon affect a heterogeneous group of patients, often elderly, and usually present as abdominal emergencies, with high morbidity and mortality. The aims of this study were to assess the prognostic value of specific factors in patients with left colonic peritonitis and to evaluate the utility of a scoring method that allows one to define groups of patients with different mortality risks. STUDY DESIGN: Between January 1994 and December 1999, 156 patients (77 men and 79 women), with a mean (SD) age of 63.2 years (15.5 years) (range 22 to 87 years), underwent emergency operation for a distal colonic perforation. Intraoperative colonic lavage was the first choice operation and it was performed in 74 patients (47.4%). There were three alternative procedures: the Hartmann operation was performed in 69 patients (44.2%), subtotal colectomy in 9, and colostomy in 4 patients. We analyzed specific variables for their possible relation to death including gender, age, American Society of Anesthesiologists (ASA) score, immunocompromised status, etiology, and degree of peritonitis, preoperative organ failure, time (hours) between hospital admission and surgical intervention, and degree of temperature elevation (38 degrees C). Univariate relations between predictors and outcomes (death) were analyzed using logistic regression. Multivariate logistic regression analysis was used to assess the prognostic value of combinations of the variables. Significant factors identified in univariate and multivariate logistic regression analyses were used to define a left colonic Peritonitis Severity Score (PSS). Factors that were significant only in univariate analysis scored 2 points if present and 1 if not. Variables significant in multivariate analysis were scored from 1 to 3 points. Patients were randomly split into two groups, one to calculate the scoring system and the other to validate it. RESULTS: Overall postoperative mortality rate was 22.4%. Septic-related mortality was observed in 24 patients (15.4%). Age, peritonitis grade, ASA score, immunocompromised status, and ischemic colitis were significant for postoperative death in univariate analysis. But only ASA score and preoperative organ failure were significantly associated with postoperative mortality in multivariate logistic regression analysis. The PSS, as defined in this study, was related to outcomes of patients. Mortality rate increased from 0%, when PSS was 6 points (minimum possible score), to 100% in patients with a PSS of 13 (maximum possible PSS = 14). CONCLUSIONS: Left colonic peritonitis continues to have a persistently high mortality in patients with septic complications. ASA score and preoperative organ failure are the only factors that are significantly associated with mortality in the multivariate analysis. The PSS classification may help uniformly define the mortality risk of patients with distal large bowel peritonitis, and may help to increase the comparability of studies carried out at different centers.

Liver xenotransplantation: changes in lipid and lipoprotein concentration after long-term graft survival.

BACKGROUND/AIMS: Today, scientists devote considerable effort to the study of mechanisms of xenograft rejection, but with liver xenotransplantation (XTx) researchers face the added problem of metabolic incompatibility between species. To date, there have been few studies of molecular xenogeneic interactions, perhaps because little progress has been made in solving immunological problems. This study is an initial analysis of lipoprotein metabolism in a hamster-to-rat hepatic xenotransplantation model. METHODS: There were 6 experimental groups (n=8): (1) male Sprague-Dawley (S.D.) rats (220-280 g); (2) male Golden Syrian hamsters (100-150 g); (3) S.D. rats, "sham" operation with immunosuppression; (4) S.D. rat-to-S.D. rat alloTx; (5) S.D. rat-to-S.D. rat alloTx with immunosuppression; (6) XTx hamster G.S-to-S.D. rat with immunosuppression. Mofetil mycophenolate (25 mg/kg/d) was administered for 14 days and FK506 (0.2 mg/kg/d) for 45 days (groups 3, 5 and 6). After 24 h fasting, animals were sacrificed (day +50 postransplantation) and a complete lipoprotein profile was determined. Serum lipoproteins were subfractioned by ultracentrifugation in density gradient. RESULTS: There was a large increase in serum lipid levels in xenografted rats compared with control rats and allografted rats. Xenografted rats presented a severely altered lipoprotein profile compared with normal rats. Surprisingly, the characterisation of lipoproteins in xenografted rats displayed the same composition as donor animals. Histological study did not show signs of alteration of the hepatic architecture. CONCLUSIONS: Since the liver is the main solid organ co-ordinator of metabolic pathways, such as lipid metabolism, hepatic xenotransplantation makes changes in lipid concentrations in the recipient and also changes in lipid compositions of lipoproteins. Hepatic xenotransplantation is not a feasible solution given the organ's metabolic complexity.

Protective effects of lazaroid U74389G on intestinal graft after heterotopic small bowel transplantation in rats.

BACKGROUND: Experimental studies have shown that 21-aminosteroids (21-A) are powerful inhibitors of superoxide-mediated iron-dependent lipid peroxidation. This study was aimed at determining how far the blocking effect of one of these substances (lazaroid U74389G) on lipid peroxidation protects intestinal grafts morphologically and biologically in a heterotopic transplant model (SBT) in rats. ANIMALS AND METHODS: Heterotopic LEW were performed using Ringer lactate (4 degrees C) as preservation solution. In Group 1 (n = 7) the donor and recipient animals received 3 and 6 mg/kg of the 21-A U74389G, respectively. Group 2 (n = 7) received the same doses of the vehicle of the drug. Sham group underwent only a laparotomy. Bacterial translocation (BT) was determined in mesenteric lymph nodes (MLN), liver (L), and spleen (S) 60 min after reperfusion. Tissue myeloperoxidase (MPO), malondialdehyde (MDA), and percentage conversion xanthine dehydrogenase/xanthine oxidase (XD/XO) were also determined in the ileal graft. Histological damage was graded according to Park's classification. RESULTS: Tissue MDA (nmol/mg prot) was significantly lower in Group 1 (0.53 +/- 0.09) than in Group 2 (3.66 +/- 1, P < 0.05) and showed levels similar to those of the sham-operated group (0.40 +/- 0.05). Injury grades were also significantly different in both study groups (Group 1, 0-1; Group 2, 2-3, P < 0.05). BT (log CFU/g tissue) in Group 1 were MLN, 0; L, 0.36; and S, 0. In Group 2, MLN, 1.07; L, 0.81; and S, 1.49 (P < 0.05 in MLN). Increase in MPO activity (U/g prot) in comparison with sham-operated animals was similar in the two study groups (Group 1, 1.49 +/- 0.58; Group 2, 1.22 +/- 0.46; Sham, 0.34 +/- 0.37 (P < 0.05 1,2 vs sham). Conversion of XD to XO was unaffected by the supplementation of the drug. CONCLUSION: 21A U74389G inhibits lipid peroxidation, protects intestinal graft, and reduces BT after heterotopic SBT in rats.

Effect of oral supplementation of ornithine-alpha-ketoglutarate on the intestinal barrier after orthotopic small bowel transplantation.

The aim of this study was to analyze the possible protective effects of a glutamine and arginine precursor (ornithine-alpha-ketoglutarate [OKG]) on the mucosa of a transplanted intestine when administered with either a defined formula oral diet (DFD) or a standard chow. Isogenic male Lewis rats (250 g) were submitted to a laparotomy (groups 1 and 2) or to an orthotopic small bowel transplantation (SBT; groups 3-6). Groups 1, 3, and 5 received a DFD 14 days after surgery. Groups 2, 4, and 6 received standard chow. In addition, groups 5 and 6 received a daily oral supplementation of 1.4 g/kg of OKG. Weight changes and food intake were recorded daily. At the end of the study, bacterial translocation (BT) was measured in mesenteric lymph nodes, liver, and spleen. The protein/DNA index was also determined in intestinal mucosa. SBT induced BT in all transplanted groups, especially in those fed DFD. Addition of OKG (groups 5 and 6) significantly reduced BT in comparison with groups 3 and 4 and improved the protein/DNA index as well as weight gain. It is concluded that OKG supplementation protects the intestinal barrier after SBT, and that this effect is more marked when it is added to a standard chow.