Postoperative colonic motility increases after early food intake in patients undergoing colorectal surgery.

BACKGROUND: Stimulation of colonic motility by the gastrocolonic response may help to reduce inhibition of gastrointestinal motility after colorectal surgery. We aimed to investigate whether postoperative colonic motility is increased after early food intake. METHODS: Nineteen patients undergoing colorectal surgery and 7 healthy volunteers were investigated. Colonic motility was recorded with a combined manometry/barostat system, and the effect of a standard 500-kcal meal was evaluated once in healthy volunteers and in 15 patients on the first and second postoperative day. Four patients remained unfed, serving as controls. RESULTS: In patients, the colonic motility index increased from 12 +/- 5 at baseline to 65 +/- 24 mm Hg after the meal on postoperative day 1 (mean +/- SEM; P < .01), while barostat bag volumes decreased, indicating a rise in colonic tone. On day 2, the motility index was 62 +/- 17 mm Hg at baseline and did not change after the meal. In unfed controls, no change was observed during colonic motility recordings on both postoperative days. In healthy volunteers, the colonic motility index increased from 98 +/- 52 at baseline to 151 +/- 58 mm Hg postprandially (P < .05). CONCLUSIONS: As in healthy volunteers, there is a potential to stimulate colonic motility by early food intake in postoperative patients. This may help to improve prolonged colonic motility disorders after colorectal surgery.

Stimulation of fibroblast proliferation by lactate-mediated oxidants.

Lactate accumulation is a characteristic of wounds in which glycolysis, occurring both aerobically and anaerobically, contributes to its production. Cell proliferation is a critical component of healing wounds. Recently it has been shown that lactate can chelate iron and thus promotes production of hydroxyl radicals. We report here that exogenous lactate increases intracellular oxidants and that the oxidants promote cell growth in cultured dermal fibroblasts in a dose-dependent manner. The production of lactate-mediated oxidant requires iron and hydrogen peroxide and with increasing iron concentration oxidant production is raised as well. However, we found cell proliferation is retarded by 15 mM lactate in the presence of a high iron concentration (7.25 microM). The antioxidants catalase and mannitol abolish the inhibitory effect of high lactate. We conclude from these results that increased proliferation of cultured human fibroblasts by exogenous lactate is mediated by oxidant production.

Functional asymmetry of pelvic floor innervation and its role in the pathogenesis of fecal incontinence.

UNLABELLED: While the regular and symmetric innervation of the pelvic floor has been regarded as "established" for many years, recent data indicate that asymmetry of innervation of the sphincters may exists and may contribute to the occurrence and severity of incontinence symptoms in case of pelvic floor trauma. METHODS: A systematic review of published papers on asymmetry of sphincter innervation was performed including studies in healthy volunteers and patients with incontinence. 234 consecutive patients with fecal incontinence were investigated by means of side-separated mass surface EMG from the left and right side anal canal, these data were correlated to clinical and anamnestic findings. RESULTS: The literature survey indicates that asymmetry of sphincter innervation exists in a subgroup of healthy male and female volunteers, and may be a risk factor to become incontinent in case of trauma. Patients with incontinence in whom asymmetry of sphincter innervation could be shown more frequently reported a history of pelvic floor trauma during childbirth. Childbirth per se but not the number of deliveries predicted sphincter asymmetry. Asymmetrically innervated sphincters show a compromised sphincter function in routine anorectal manometry. CONCLUSION: Assessment of sphincter innervation asymmetry may be of value in clinical routine testing of patients with incontinence. However, a new technology is needed to replace mass surface EMG by multi-electrode arrays on a sphincter probe. This is one of the goals of the EU-sponsored research project OASIS.

Postoperative colonic motility in patients following laparoscopic-assisted and open sigmoid colectomy.

Clinical reports on laparoscopic-assisted sigmoid colectomy (LASC) suggest that the period of postoperative inhibition of gastrointestinal motility is shortened as compared to open sigmoid colectomy (OSC). We aimed to specifically investigate whether colonic motility increases more rapidly following LASC compared to OSC. LASC was performed in 11 patients and OSC in nine patients for recurrent diverticulitis or carcinoma. During surgery a manometry catheter was inserted into the colon via the anus, and the tip was placed in the splenic flexure. Continuous manometric recordings were performed from the day of surgery until postoperative day 3 with a four-channel microtransducer manometry system combined with a portable data logger. The postoperative colonic motility index was 101+/-18, 199+/-30, and 163+/-27 mm Hg/min on days 1, 2, and 3 after LASC, respectively, which was increased compared to indexes of 53+/-15, 71+/-18, and 76+/-23 following OSC (mean+/-standard error of the mean; P<0.05). The amplitude but not the frequency of contractions was higher following LASC compared to OSC. Following LASC, patients requested a similar amount of pain medication but resumed oral food more rapidly on postoperative days 2 and 3 (P<0.05), and they were discharged from the hospital earlier (P<0.05). Colonic motility in particular and the patient's condition in general seem to improve more rapidly following LASC compared to the open procedure.

Lactate and oxygen constitute a fundamental regulatory mechanism in wound healing.

For many years, lactate has been known to accelerate collagen deposition in cultured fibroblasts and, without detailed explanation, has been presumed to stimulate angiogenesis. Similarly, hypoxia has been linked to angiogenic effects and collagen deposition from cultured cells. Paradoxically, however, wound angiogenesis and collagen deposition are increased by breathing oxygen and decreased by hypoxia. Lactate accumulates to 4-12 mM in wounds for several reasons, only one of which is the result of hypoxia. Oxygen in wounds is usually low but can be increased by breathing oxygen (without change in lactate). We have reported that lactate elicits vascular endothelial growth factor (VECF) from macrophages, as well as collagen, some heat shock proteins, and VECF from endothelial cells, and collagen from fibroblasts, even in the presence of normal amounts of oxygen. Hypoxia exerts many of these same effects in cultured cells. In this study, we elevated extracellular lactate in wounds by implanting purified solid-state, hydrolysable polyglycolide. A steady-state 2-3 mM additional elevation of lactate resulted. With it, there was a significant short-term elevation of interleukin-1beta, a long-term elevation of VECF (2x) and transforming growth factor-beta1 (2-3x), a 50% elevation in collagen deposition, and a large reduction of insulin-like growth factor-1 (- 90%). We propose that lactate induces a biochemical "perception" of hypoxia and instigates several signals that activate growth factor/cytokine signals while the continued presence of molecular oxygen allows endothelial cells and fibroblasts to reproduce and deposit collagen. The data are consistent with ADP-ribosylation effects and oxidant signaling. (WOUND REP REG 2003;11:504-509)

Comparison of inflammatory and systemic sources of growth factors in acute and chronic human wounds.

Inflammatory cells are generally assumed to be the primary source of most growth factors/cytokines that participate in wound healing. Correspondingly, most attempts to enhance wound healing have been directed at the wound itself. However, certain key factors such as insulin-like growth factor-I (IGF-I) and related proteins are present in blood in sufficient quantities to suggest significant contributions from outside the wound. Because little is known of the dynamics of IGF family members in wounds, particularly in human wounds, we serially measured the mRNAs and proteins of the IGF family in fluid and tissues taken from acute as well as chronically inflamed human wounds and compared them to their corresponding concentrations in blood. We also measured transforming growth factor-beta1 and -beta3, vascular endothelial growth factor, interleukin-1beta, matrix metalloproteinases and selected isomers/receptors, all of which are associated with inflammation. All IGF proteins reached their highest concentrations immediately after injury. No difference between IGF-I mRNA expression between acute and inflamed wounds was found. As a group, IGF-related proteins, in contrast to transforming growth factor-beta, vascular endothelial growth factor, and interleukin-1beta, are highly correlated to and are generally below their concentrations in blood and are not elevated by inflammation. The IGF family therefore appears to enter wounds, even inflamed wounds, mainly from blood. If blood IGF-I is low, wound levels are lower. This data suggests that healing impairment due to IGF-I deficiency can be readily detected and is, at least in part, easily and safely correctable.

Xanthogranulomatous cholecystitis resembling carcinoma with extensive tumorous infiltration of the liver and colon.

BACKGROUND: Xanthogranulomatous cholecystitis is a macrophage-rich inflammatory condition of the gallbladder that occasionally presents with tumorlike appearance. CASE PRESENTATION: In the present case the inflammation involved all the layers of the gallbladder, the surrounding connective tissue, and part of the right lobe of the liver and right transverse colon. The clinical and radiological findings were suggestive of advanced carcinoma of the gallbladder. However, intraoperative frozen section investigation revealed xanthogranulomatous cholecystitis, for which simple cholecystectomy is the treatment of choice. CONCLUSIONS: The original cause of the condition is unclear in most cases. In the present case it is possible that rupture of the gallbladder in association with the patient's known history of trauma have initiated the process.

Total gastrectomy severely alters the central regulation of food intake in rats.

OBJECTIVE: To investigate the central regulation of food intake by quantifying neuron activation of the nucleus of the solitary tract (NTS) after injection of cholecystokinin (CCK) or food intake in gastrectomized rats. SUMMARY BACKGROUND DATA: Total gastrectomy is followed by early satiety, low calorie intake, and weight loss in the majority of patients. The etiology of these effects is unknown. Sixty percent to 70% of patients remain underweight after total gastrectomy, the weight loss averaging 25% of preoperative body weight. About two thirds of gastrectomized patients report early satiety, and about 60% do not reach the recommended daily calorie intake. The NTS is a brain stem center involved in the regulation of food intake; thus, the extent and pattern of neuronal activation provide information on the process involved in the initiation of satiation and the regulation of food intake. METHODS: The authors investigated neuronal activation in the NTS using c-fos immunohistochemistry following CCK injection or food intake in healthy control rats, sham-operated control rats, age-matched control rats, weight-matched control rats, and vagotomized or gastrectomized rats. RESULTS: Neuronal activation in the NTS after CCK injection was significantly decreased 21 days after total gastrectomy, but increased by up to 51% 3 months and by up to 102% 12 months after surgery compared to age-matched unoperated control rats. Neuronal activation in the NTS in response to feeding was markedly increased up to fivefold in gastrectomized rats. This increase was early in onset and sustained, and occurred despite significantly reduced food intake. Administration of MK329, a CCK-A receptor antagonist, significantly reduced the number of postprandially activated neurons in both gastrectomized and control rats. CONCLUSIONS: The early postprandial activation of NTS neurons after total gastrectomy in rats may correspond to early satiety reported by patients, while the sustained activation of NTS neurons after a meal could contribute to a reduced daily calorie intake. These data suggest that a disturbed central regulation of food intake might contribute to early satiety, reduced food intake, and weight loss after total gastrectomy.

Serotonin receptor blockade increases food intake and body weight after total gastrectomy in rats.

BACKGROUND: Total gastrectomy often results in early satiety and loss of body weight. Serotonin inhibits food intake, and postprandial serotonin release is increased after total gastrectomy. Serotonin might contribute to early satiety and loss of body weight after total gastrectomy. METHODS AND MATERIALS: Food intake and body weight were investigated with an automated recording system in gastrectomized rats 1-12 months postoperatively. Rats were treated with metergoline, a 5-hydroxytryptamine (5-HT)(1/2) receptor antagonist, two different 5-HT(3) receptor antagonists, a combination of metergoline and devazepide, a cholecystokinin (CCK) a receptor antagonist, or vehicle. In addition, metergoline or vehicle was applied continuously by an intraperitoneal osmotic minipump for 7, 28, or 84 days after total gastrectomy. RESULTS: Metergoline treatment resulted in a dose-dependent increase in food intake in gastrectomized rats. 5-HT(3) receptor antagonist treatment had no effect, and devazepide in addition to metergoline did not further stimulate food intake. Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% (24-h cumulative food intake [FI], 6 months: vehicle 3.83 +/- 0.10, metergoline 5.52 +/- 0.15 g/100 g body weight (BW), P < 0.0001). Chronic metergoline treatment for 7, 28, or 84 days significantly increased food intake after total gastrectomy compared to vehicle treatment (FI 7 days: vehicle 30.83 +/- 0.71, metergoline 36.27 +/- 0.85 g/100 g BW; P < 0.0002; average weekly FI during 28 days; vehicle 31.23 +/- 0.22, metergoline 36.83 +/- 0.33 g/100 g BW, P < 0.0001; average weekly FI during 84 days: vehicle 33.02 +/- 0.59, metergoline 35.07 +/- 0.48 g/100g BW, P < 0.008), and there was a significant body weight increase compared to vehicle treatment (7 days: DeltaBW vehicle -0.7 +/- 1.2 g vs DeltaBW metergoline 9.0 +/- 2.1 g, P < 0.001; 28 days: DeltaBW vehicle 0.3 +/- 2.2 vs DeltaBW metergoline 13.0 +/- 2.3, P < 0.001; 84 days: DeltaBW vehicle 25.7 +/- 10.2 vs DeltaBW metergoline 49.5 +/- 7.2, P < 0.04). Treatment for 84 days resulted in a significant body weight gain, while vehicle treatment had no effect (vehicle: 438 +/- 11 g vs 464 +/- 12 g, P < 0.2, n.s.; metergoline: 448 +/- 9 g vs 498 +/- 10 g, P < 0.007). CONCLUSIONS: Inhibition of food intake by serotonin might contribute to early satiety and loss of body weight after total gastrectomy.

Human duodenal spheroids for noninvasive intracellular pH measurement and quantification of regulation mechanisms under physiological conditions.

Three-dimensional cell cultures (spheroids) of biopsies of human duodenum were used to develop a new noninvasive method for studying intercellular and intracellular mechanisms. Through examinations of intracellular pH regulation, high functional similarity to native tissue could be shown, as already evidenced morphologically. A special microperfusion chamber was developed to fix individual spheroids physically to a nylon net, via laminar perfusion flow through the chamber. A significant improvement over current fixation methods was shown by the increase of cell viability almost up to 100%. Viability of the spheroids was confirmed by trypan blue exclusion, by a LIVE/DEAD viability/cytotoxicity kit, and by BCECF distribution. Intracellular pH was measured by use of the pH-sensitive fluorescence dye BCECF. To investigate the intracellular pH regulation, spheroid-like vesicles were acidified by NH4Cl prepulse technique. The subsequent active intracellular pH recovery was blocked with Na+-free Krebs Henseleit (KH) solution, with amiloride KH (inhibitor of the Na+-H+-exchanger), or with H2DIDS KH (inhibitor of the HCO3(-)-Cl(-)-exchanger and Na+-HCO3(-)-cotransporter). The intracellular pH of the spheroids was 7.31 +/- 0.05. pH-backregulation after acidification was prevented by sodium-free buffer, amiloride, and H2DIDS. These experiments indicated the presence of a Na+-H+-exchanger and a Na+-HCO3(-)-cotransporter. In conclusion, the human duodenal spheroid is an excellent physiological system for in vitro studies of the human duodenum.