Reduction of inflammation and colon injury by a Pennyroyal phenolic extract in experimental inflammatory bowel disease in mice.

PURPOSE: Little is known about the pharmacological effects of the phenolic compounds of Pennyroyal (Mentha pulegium). This Mediterranean aromatic plant, used as a gastronomic spice and as food preservative by the food industry has been studied mainly due to its essential oil antibacterial properties, composed primarily by monoterpenes. With this work, we aimed to evaluate the effects of a phenolic extract of pennyroyal in the impairment of inflammatory processes in Inflammatory Bowel Diseases (IBD) and in the potential inhibition of progression to colorectal cancer (CRC). METHODS: To that purpose, we evaluated the effect of pennyroyal extract administration in a model of TNBS-induced colitis in mice and further determined its effect on human colon carcinoma cell proliferation and invasion. RESULTS: The phenolic extract of pennyroyal exhibited antioxidant properties in in vitro assays and administration of the extract in a rat model of carrageenan-induced paw oedema led to significant anti-inflammatory effects. Further results evidenced a beneficial effect of the phenolic extract in the attenuation of experimental colitis and a potential antiproliferative effect on cultured colon cancer cells, effects not previously described, to our knowledge. A reduction in several markers of colon inflammation was observed following administration of the extract to colitis-induced mice, including functional and histological indicators. A successful inhibition of cancer cell invasion and proliferation was also observed in in vitro studies with HT-29 cells. Furthermore, the extract also led to a reduced expression of iNOS/COX-2 in the colon of colitis-induced mice, both being crucial mediators of intestinal inflammation. CONCLUSIONS: Taking into consideration the central role of inflammation in the pathophysiology of CRC and the recognised connection between inflammatory events and cancer, these results enlighten the relevance of the phenolic constituents of pennyroyal as important pharmacological sources in the investigation of new treatment options for patients with inflammatory bowel diseases.

Explosively Puffed Ginseng Ameliorates Ionizing Radiation-Induced Injury of Colon by Decreasing Oxidative Stress-Related Apoptotic Cell Execution in Mice.

Although radiation therapy (RT) is a feasible treatment approach for early colorectal cancer, RT is considerably toxic to normal tissues due to the increased reactive oxygen species production, which can induce tissue damage. Ginseng, a natural antioxidant agent, exhibits the protective effects against ionizing radiation (IR)-induced damage in in vitro and in vivo models. The explosive puffing of ginseng has been investigated as a process to improve the efficacy of ginseng due to the resulting physicochemical changes in its functional components. In this study, we provided the evidence for promotion in the beneficial role of puffed ginseng extract (PGE) and associated mechanisms of action, in comparison with white ginseng extract (WGE), against IR-induced colorectal injury, using in vivo study on a mouse model. To study the role of PGE in preventing IR-induced damage, we examined colorectal injury and apoptotic changes in mice exposed to 137Cs at 8 Gy. High-performance liquid chromatography analysis showed that PGE had an increased total ginsenoside concentration with new generation of Rg3, Rg5, and Rk1, compared with the concentrations in WGE. Administering PGE, but not WGE, significantly ameliorated IR-induced colorectal cell death through negative regulation of apoptotic signaling pathways. These antiapoptotic effects of PGE were linked to the capacity to suppress the p53-mediated DNA damage response and NF-κB-mediated apoptotic signaling. Moreover, IR-induced oxidative stress in the colorectal epithelium was markedly reduced by PGE administration. Collectively, this study establishes a mechanism of action by which PGE counteracts IR-induced colorectal injury as a novel radioprotective agent.

Hyaluronidase inhibits reactive adipogenesis and inflammation of colon and skin.

In this study we evaluated the role of hyaluronan (HA) in reactive adipogenesis, a local expansion of preadipocytes that provides host defense by release of antimicrobial peptides. We observed that HA accumulated during maturation of adipocytes in vitro and was associated with increased expression of preadipocyte factor 1, zinc finger protein 423, and early B cell factor 1. Although HA is normally abundant in the extracellular matrix, a further increase in HA staining occurred in mice at sites of reactive adipogenesis following injury of colon by dextran sodium sulfate or injury of skin from infection with Staphylococcus aureus. HA also abundantly accumulated around adipocytes seen in the colons of patients with inflammatory bowel disease. This HA was necessary for adipocyte maturation because digestion of HA by administration of soluble hyaluronidase or transgenic expression of hyaluronidase 1 inhibited adipogenesis in vitro and in vivo. Furthermore, hyaluronidase also suppressed inflammation of both skin and colon and decreased antimicrobial peptide expression by developing preadipocytes. This resulted in increased bacterial transit across the epithelial barrier despite decreased tissue injury from inflammation. These observations suggest HA plays an important role in reactive adipogenesis and host defense after injury.

Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed. Effects on regional gut growth and intraluminal growth factor activity were then determined. Despite calorie intake being similar in all groups, soya rich feed caused 20% extra total body weight gain. Stomach weight was highest on soya and casein diets. Soya enhanced diet caused greatest increase in small intestinal weight and preserved luminal growth factor activity at levels sufficient to increase proliferation in vitro. Regional small intestinal proliferation was highest in proximal segment in ED fed animals whereas distal small intestine proliferation was greater in soya fed animals. Colonic weight and proliferation throughout the colon was higher in animals receiving soya or whey supplemented feeds. We conclude that specific protein supplementation with either soya, casein or whey may be beneficial to rest or increase growth in different regions of the bowel through mechanisms that include differentially affecting luminal growth factor bioactivity. These results have implications for targeting specific regions of the bowel for conditions such as Crohn's disease and chemotherapy.

Role of Multidetector Computed Tomography in the Diagnosis of Colorectal Perforations.

Colonic perforations can be classified into perforations that occur at the site of a localized pathologic process and cecal perforations that occur secondary to distal colonic obstructions. Rectal perforations may result from foreign bodies inserted into the rectum; moreover, deep rectal biopsies, polypectomy, improper cleansing enema, or thermometer placement may also lead to rectal perforation. Correct identification of the cause and site of the perforation is crucial for appropriate management and surgical planning. Multidetector row computed tomography has a pivot role in planning the type of operative treatment, the prognosis, and in assessing those patients who have clinical symptoms of peritonitis but no radiographic signs of perforation.

Effect of glutamine supplementation on left colon healing in rats with extrahepatic biliary obstruction.

PURPOSE: To evaluate the influence of glutamine and obstructive jaundice on left colon healing in rats. METHODS: Sixteen male rats were allocated across four groups: LG--Common bile duct ligation followed by colotomy and bowel suture on postoperative day 7. Supplementation with glutamine 2% from day 4 after duct ligation until euthanasia. L--Common bile duct ligation followed by colotomy and bowel suture on postoperative day 7. No glutamine supplementation. M--Common bile duct manipulation followed by colotomy and bowel suture on postoperative day 7. No glutamine supplementation. MG--Common bile duct manipulation followed by colotomy and bowel suture on postoperative day 7. Supplementation with glutamine 2% from day 4 after duct manipulation until euthanasia. On the day of euthanasia, bursting pressure of the sutured bowel segment was measured and samples were collected for histopathological analysis. RESULTS: There were no differences in bursting pressure among groups : LG vs. M (110 ± 28 vs. 173 ± 12; p = 0.08). Groups L and MG were not different from group M (156 ± 12 and 118 ± 22. Glutamine supplementation was associated with less edema, polymorphonuclear lymphocyte infiltration, bacterial colonies, and abscess formation, as well as with increased collagen formation. CONCLUSION: Obstructive jaundice had no negative effect and glutamine supplementation had no positive effect on colonic scar strength in rats.

Effect of glutamine supplementation on left colon healing in rats with extrahepatic biliary obstruction

PURPOSE: To evaluate the influence of glutamine and obstructive jaundice on left colon healing in rats. METHODS: Sixteen male rats were allocated across four groups: LG - Common bile duct ligation followed by colotomy and bowel suture on postoperative day 7. Supplementation with glutamine 2% from day 4 after duct ligation until euthanasia. L - Common bile duct ligation followed by colotomy and bowel suture on postoperative day 7. No glutamine supplementation. M - Common bile duct manipulation followed by colotomy and bowel suture on postoperative day 7. No glutamine supplementation. MG - Common bile duct manipulation followed by colotomy and bowel suture on postoperative day 7. Supplementation with glutamine 2% from day 4 after duct manipulation until euthanasia. On the day of euthanasia, bursting pressure of the sutured bowel segment was measured and samples were collected for histopathological analysis. RESULTS: There were no differences in bursting pressure among groups : LG vs. M (110 ± 28 vs. 173 ± 12; p = 0.08). Groups L and MG were not different from group M (156 ± 12 and 118 ± 22. Glutamine supplementation was associated with less edema, polymorphonuclear lymphocyte infiltration, bacterial colonies, and abscess formation, as well as with increased collagen formation. CONCLUSION: Obstructive jaundice had no negative effect and glutamine supplementation had no positive effect on colonic scar strength in rats. .

Effects and mechanisms of auricular electroacupuncture on visceral pain induced by colorectal distension in conscious rats.

OBJECTIVE: To investigate the effects and mechanisms of action of auricular electroacupuncture (AEA) on visceral pain induced by colorectal distension (CRD). METHODS: Twenty-nine female Sprague-Dawley rats were randomly divided into four groups: control; untreated CRD; CRD+AEA; and CRD+sham electroacupuncture (SEA). An electromyogram (EMG) was recorded for 120 min in the conscious state. After a 30 min baseline recording, CRD was performed in untreated CRD, AEA and SEA groups and lasted for 90 min. AEA and SEA were started at 30 min and lasted for 30 min. The EMG was recorded and analysed to evaluate the severity of visceral pain, indicated by the magnitude of the vasomotor response (VMR). mRNA expression of the 5-hydroxytryptamine 1a (5-HT1a) receptor was measured separately in the colon and raphe nuclei using real-time fluorescent quantitative PCR. RESULTS: No differences were seen in the baseline EMG among the four groups (p>0.05). During pre-stimulation, VMR magnitude in the CRD, AEA and SEA groups increased compared with that in the control group (p<0.05). During stimulation, the VMR magnitude was significantly decreased in AEA but not SEA groups relative to the (untreated) CRD group. Similarly, mRNA expression of the 5-HT1a receptor in both the colon and raphe nuclei was lower in AEA but not SEA groups compared with the CRD group (p<0.05). CONCLUSIONS: AEA can ameliorate CRD-induced visceral pain in rats, and increase mRNA expression of the 5-HT1a receptor peripherally (in the colon) and centrally (in the raphe nuclei), suggesting a serotonergic mechanism of action.

Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate.

Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1ß), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1ß) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia). Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation.

Use of defatted flaxseed meal reduces precancerous colon lesions in C57BL/6 mice

PURPOSE: To investigate the hemopreventive effect of defatted flaxseed meal in C57BL/6 mice after induction of precancerous colon lesions with 1.2-dimethylhydrazine (DMH). METHODS: Thirty-six 12-week-old C57BL/6 mice were divided into three treatment groups(n=12 in each group): (1) diet with 10% defatted flaxseed meal; (2) diet with defatted flaxseed meal and precancerous colon lesions induced by DMH; and (3) precancerous colon lesions induced by DMH, without defatted flaxseed meal. The incidence of aberrant crypt foci (ACF), oxidative processes, expression of tumor suppressor proteins and cyclins, as well as the profile of short-chain fatty acids (SCFA) in animal feces were investigated in the presence and absence of DMH. RESULTS: The rats consuming defatted flaxseed meals showed lesions with lower multiplicity and a reduced incidence of lesions. No changes in the expression of tumor suppressor proteins and those involved in cell cycle control were detected. CONCLUSION: Defatted flaxseed meal protected the distal colon of mice from precancerous lesions.

Use of defatted flaxseed meal reduces precancerous colon lesions in C57BL/6 mice.

PURPOSE: To investigate the hemopreventive effect of defatted flaxseed meal in C57BL/6 mice after induction of precancerous colon lesions with 1.2-dimethylhydrazine (DMH). METHODS: Thirty-six 12-week-old C57BL/6 mice were divided into three treatment groups(n=12 in each group): (1) diet with 10% defatted flaxseed meal; (2) diet with defatted flaxseed meal and precancerous colon lesions induced by DMH; and (3) precancerous colon lesions induced by DMH, without defatted flaxseed meal. The incidence of aberrant crypt foci (ACF), oxidative processes, expression of tumor suppressor proteins and cyclins, as well as the profile of short-chain fatty acids (SCFA) in animal feces were investigated in the presence and absence of DMH. RESULTS: The rats consuming defatted flaxseed meals showed lesions with lower multiplicity and a reduced incidence of lesions. No changes in the expression of tumor suppressor proteins and those involved in cell cycle control were detected. CONCLUSION: Defatted flaxseed meal protected the distal colon of mice from precancerous lesions.

Prilling for the development of multi-particulate colon drug delivery systems: pectin vs. pectin-alginate beads.

This paper proposes a multi-particulate drug delivery system produced by prilling technique in combination with an enteric coating. Optimization of process parameters, such as feed viscosity at nozzle, selection of cross-linker, pH of the gelling solution and cross-linking time, allows to obtain beads with strong gelled matrix. Results showed that dextran/piroxicam beads demonstrated high encapsulation efficiency, very narrow dimensional distribution and high sphericity. Coated beads retained shape and narrow size distribution of the uncoated particles. Moreover, the strength of the produced Zn(2+)-pectinate beads allows to reduce Eudragit coating thickness. Piroxicam loaded multi-particulate systems show an interesting prolonged drug release in intestinal fluids. Hence, such platforms could be proposed for the treatment of inflammatory bowel diseases.

Iatrogenic perforation at colonic imaging.

AIM: Adequate colonic imaging is generally an invasive procedure with attendant risks, particularly perforation. Endoscopy, barium enema and computed tomographic colonography (CTC) are the main techniques for investigating patients with symptoms of, or screening for, colorectal cancer. The potential complications of these investigations have to be weighed against the benefits. This article reviews the literature on the incidence, presentation and management of iatrogenic colonic perforation at colonic imaging. METHOD: A literature review of relevant studies was undertaken using PubMed, Cochrane library and personal archives of references. Manual cross-referencing was performed, and relevant references from selected articles were reviewed. Studies reporting complications of endoscopy, barium enema and CT colonography were included in this review. RESULTS: Twenty-four studies were identified comprising 640,433 colonoscopies, with iatrogenic perforation recorded in 585 patients (0.06%). The reported perforation rate with double-contrast barium enema was between 0.02 and 0.24%. Serious complications with CTC were infrequent, though nine perforations were reported in a case series of 24,365 patients (0.036%) undergoing CTC. CONCLUSION: Perforation remains an infrequent and almost certainly under-reported, complication of all colonic imaging modalities. Risk awareness, early diagnosis and active management of iatrogenic perforation minimizes an adverse outcome.

Application of manuka honey and GENADYNE A4 negative pressure wound therapy system in a 55-year-old woman with extensive phlegmonous and necrotic lesions in the abdominal integuments and lumbar region after traumatic rupture of the colon.

BACKGROUND: Antibiotic resistance of bacteria is on the rise and thus, the discovery of alternative therapeutic agents is urgently needed. Honey possesses good therapeutic potential, including wound healing properties and antimicrobial activity. CASE REPORT: The authors report on the case of a 55-year-old woman with extensive phlegmonous and necrotic lesions of the abdominal integuments and the lumbar area following traumatic colonic rupture, treated with Manuka honey wound dressings and the GENADYNE A4 negative pressure wound healing system. CONCLUSIONS: The application of the Manuka honey and the GENADYNE A4 negative pressure wound healing system in treating phlegmonous lesions of the abdominal integuments after rupture of the colon brought good effects, ultimately enabling skin autografting on the wound site and complete wound healing.

CT colonography: perforation rates and potential radiation risks.

Computed tomographic colonography (CTC) has emerged as an alternative screening tool for colorectal cancer due to the potential to provide good efficacy combined with greater acceptability than optical colonoscopy or fecal occult blood testing. However, some organizations have raised concerns about the potential harms, including perforation rates and radiation-related cancer risks, and have not recommended that it currently be used as a screening tool in the general population in the US. In this article the authors review the current evidence for these potential harms from CTC and compare them to the potential harms from the alternatives including colonoscopy and double-contrast barium enema.

La colonoscopia: ¿es un estudio pre-operatorio indispensable para la restitución del tránsito intestinal en pacientes jóvenes: portadores de colostomía por traumatismo abdominal penetrante? / Colonoscopy: is a necessary pre-operatory study for intestinal transit restitution in young patients carrying a colostomy by penetrating abdominal trauma?

Determinar el impacto de la colonoscopia como procedimiento preoperatorio requisito para la restitución del tránsito intestinal en una población portadora de colostomía por un traumatismo abdominal penetrante. Estudio descriptivo, retrospectivo observacional, donde se evalúan informes de endoscopias digestivas inferiores realizadas por el servicio de Gastroenterología del Hospital General del Oeste "Dr. José Gregorio Hernández" de Caracas, como requisito preoperatorio para la restitución del transito intestinal en pacientes portadores de colostomía por traumatismo abdominal penetrante, en el período comprendido entre enero 2004 y diciembre 2008. De una población total de 46 pacientes, se les realizó una colonoscopia a 34 (73,91%). Los 12 restantes (26,08%), no cumplían con los criterios de inclusión. de los 34 pacientes incluidos para evaluación, 22 (64,70%), presentaron colitis y recidivas por deprivación, 7 (20,59%) con estudio normal y 4 (11,76%) presentaron alguna alteración en la endoscopia digestiva inferior. En este estudio no hay evidencia que sugiera que la realización de una colonoscopia preoperatoria en la cirugía electiva de restitución de tránsito intestinal, evite la aparición de complicaciones, ni permita el diagnóstico de patologías de relevancia en la población estudiada, no teniendo ésta la importancia que se le ha otorgado hasta la actualidad.

To determine the impact of the colonoscopy as pre-operating procedure as a requirement in the population carrying of colostomy by abdominal penetrating trauma for the restitution of the intestinal transit. Descriptive, retrospective and observational study, where the inferior digestive endoscopy made by the service of Gastroenterology in Hospital General del Oeste "Dr. José Gregorio Hernández", Caracas, was valued as pre-operating requirement in carrying patients of colostomy by abdominal penetrating trauma for the restitution of the intestinal transit, in the period between January 2004 to December 2008. In a population of 46 patients, only 34 (73.91%) were included to do the colonoscopy, the others 12 (26,08%) didn't fulfill the inclusion criteria. Of the 34 patients included, 22 (64.70%) were displayed colitis and rectitis by deprivation, 7 (20.59%) were normal study and 4 (11.76%) presented others alteration in the inferior digestive endocopy. In this study there is not evidence to suggest that the realization of preoperatory colonoscopy for surgery in the restitution of intestinal transit, avoid complications or permit diagnosis of diseases in the study population, doing less important the evidence exposed until present.

Forensic application of ESEM and XRF-EDS techniques to a fatal case of sodium phosphate enema intoxication.

Sodium phosphate enemas and laxatives are widely used for the treatment of constipation, even if a number of cases of significant toxicity due to alterations of the fluid and electrolyte equilibria (hypernatremia, hyperphosphatemia, and hypocalcemia) have been reported. We present the case of an 83-year-old man who died of fecal and chemical peritonitis secondary to an iatrogenic colon perforation (produced performing a Fleet enema through the patient's iliac colostomy) with peritoneal absorption of sodium phosphate. Environmental scanning electron microscopy coupled with an X-ray fluorescence energy dispersive spectrometry discovered multiple bright crystals formed of calcium, phosphorus, and oxygen in the brain, heart, lung, and kidney sections of the victim. The absence of these kinds of precipitates in two control samples chronically treated with Fleet enemas led us to assume that the deceased had adsorbed a great quantity of phosphorus ions from the peritoneal cavity with subsequent systemic dissemination and precipitation of calcium phosphate bindings.