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In vitro magnesium absorption and the role of intestinal motility.

Magnesium (Mg) is known as an inhibitor of spontaneously contracting muscular tissues. To increase extracellular Mg in vivo, high doses of Mg must be given orally. Therefore, we investigated the effect of different doses of Mg given from the mucosal side of the small intestine of rats. According to the model of Trendelenburg, a system for the perfusion of isolated small intestine was developed, which allows the simultaneous recording of absorption and muscle contractions. Increasing doses of Mg were applied serosally or intraluminally. Intramulinal Mg did not affect intestinal motility. In contrast, increasing concentrations of serosal Mg resulted in a 50% inhibition of motility at 2.9 mmol/l Mg. This indicates no influence on intestinal motility of high doses of Mg acting from the mucosal side. In further studies, the addition of citric acid or taurocholic acid did not alter Mg absorption. Serosally applied amiloride (1 mmol/l) inhibited absorption, but also resulted in complete loss of motility. Since in this model passive diffusion is the most important mechanism of Mg transport, a direct influence of amiloride on Mg absorption can be excluded. From these data, we conclude that intestinal motility influences absorption--also of ions in aqueous solution--and should therefore be taken into account in absorption studies.

Amiloride↗

[Effect of various methods of oxygenation in the isolated small intestine on the tryptophan and glycine accumulation].

The impact of various oxygenation types of intestinal preparations (mucosal, serosal and bilateral) on the transepithelial transport of amino acids and peptide according to the character of amino acids, their stereoisometry, incubation time, intestinal gradient and other factors, was investigated in fowl. Against-the-gradient-transport of L-tryptophan and glycine was observed at various oxygenation types, and its intensity decreased in the following sequence: bilateral, mucosal, serosal oxygenation. At various oxygenation types, the accumulation of L-tryptophan occurs more efficiently than that of DL-tryptophan and D-tryptophan. Using an in vitro bilateral intestinal oxygenation model system, we have demonstrated the plasma membrane of enterocyte microvilli to be rapidly impaired after oxidative stress. Glycine, but not L-tryptophan, attenuates oxidative injury in brush border membrane and alterations in amino acid transport activity. Overall, our data indicates that in vitro serosal oxygenation of the duodenum markedly improves glycine absorption, possibly involving the basolateral transporters.

Animals↗

[Pericarditis and exudative pleuritis in patients with systemic lupus erythematosus before and after therapy].

AIM OF THE STUDY: To establish the presence of pericarditis and exudative pleuritis in patients with systemic lupus erythematosus (SLE) prior to and after glicocorticoid and cytotoxic therapy. PATIENTS AND METHODS: In 43 patients, 39 women and 4 men, with SLE (disease was diagnosed according to revised American College of Rheumatology ACR criterias, 1997), aged between 20 and 61 and averaged disease duration of 5.54 +/- 5.74 years, heart/lung radiology and heart echosonography were performed in order to discover possible serositis (pericarditis and exudative pleuritis) prior to and after cytotoxic and glucocorticoid therapy. RESULTS: The presence of pericarditis and exudative pleuritis was established in 20 patients (47%) before the therapy. After the therapy pericarditis was present in 2 patients, average volume of 150 ml, and exudative pleuritis was also present in phrenicocostal sinus, but its volume was minimal. This table is showing the results of our study on patients with SLE and serositis. The results were compared with the results of European and Belgrade group in year 2000. [table: see text] CONCLUSION: Higher frequency of serositis (pericarditis and exudative pleuritis) in our study is probably a result of more active disease, and the effects of cytotoxic and glucocorticoid therapy were satisfing exept in two patients who were resistant on therapy. That is the reason why we had to consider plasmapheresis.

Adult↗

The role of CT scan in preoperative staging of colorectal carcinoma.

OBJECTIVES: To evaluate the role of CT scan in preoperative staging of colorectal carcinoma by comparing it with the surgical-pathologic staging and pathologic findings. MATERIAL AND METHOD: The CT scans of twenty four patients with pathological proven primary colorectal carcinoma from January 1998 to December 2002 at Srinagarind hospital Khon Kaen University were review. The CT findings were analyzed according to serosal and or pericolic fat invasion, involvement of lymphnodes, liver or other metastases, and correlated the CT staging with TNM staging. RESULTS: The CT imaging had 100% sensitivity, 57% specificity, 87.5% accuracy for evaluating serosal and/or pericolic fat invasion, 93.2% sensitivity, 54% specificity, 75% accuracy for evaluating involvement of the lymph nodes. In the present study, the distant metastases was not detected CONCLUSION: The role of CT in preoperative staging of colorectal carcinoma in this report can be summarized as: (1) The sensitivity in detecting serosal and/or pericolic fat invasion is relatively higher than in previous reports. (2) The criteria for evaluation of nodal disease increased accuracy of CT and its high sensitivity is considered clinically useful.

Adult↗

[Clinicopathological analysis of synchronous liver metastasis in gastric cancer and evaluation of surgical outcomes].

OBJECTIVE: To analyze the clinicopathological factors affecting synchronous liver metastasis in gastric cancer,and evaluate its surgical outcome. METHODS: Clinical data of 44 patients with synchronous hepatic metastasis from gastric cancer from Aug. 1994 to Feb. 2004 were reviewed retrospectively, and compared with those of 576 gastric cancer patients without hepatic metastasis to analyze the clinicopathological factors affecting synchronous liver metastasis from gastric cancer. The survivals after radical resection, palliative and exploratory operation were compared. RESULTS: Univariate analysis revealed that ascites, pelvic and peritoneal seeding, serosal invasion, lymph node metastasis, involvement of neighboring organs, Borrmann types,depth of infiltration were correlated with synchronous hepatic metastasis from gastric cancer (P< 0.01). Logistic regression showed peritoneal seeding (P=0.003, OR=1.629), serosal infiltration (P=0.000, OR=3.000), lymph node metastasis (P=0.081, OR=1.689) were independent risk factors for synchronous hepatic metastasis from gastric cancer. Sixteen (36.4%) patients received radical excision, 15 (34.1%) patients palliative operation, and 13 (29.5 %) patients exploratory operation,and the median survival times were 19.5, 11.0 and 6.2 months respectively (P< 0.05). CONCLUSIONS: Peritoneal seeding,serosal infiltration, lymph node metastasis are most important risk factors for synchronous hepatic metastasis from gastric cancer. Radical resection of gastric primary lesion and hepatic metastases can significantly prolong survival time.

Aged↗

[A novel technique for the closure of the pancreatic remnant using jejunal serosa following distal pancreatectomy].

Postoperative complication rate after distal pancreatectomy is as high as 10-30% in the published literature. Intraabdominal abscess formation and pancreatic fistula are the most common and clinically relevant complications, and they are thought to depend on surgical technique and skills. Using a novel method, we covered the pancreatic stump with the serosal surface of the first jejunal loop. Our aim was to compare the efficacy of this new technique to the traditional "stapling and handsewn suturing" method in terms of postoperative complication rate. Between 2002 and 2005, 50 patients, who underwent distal pancreatectomy, were randomized prospectively into two groups. In the first group of patients (n=23) the remnant of the pancreas was closed by the novel technique using the serosal surface of the first jejunal loop. In the second group (n=27) the pancreatic stump was closed in the traditional way using a combination of stapler and handsewn suture method. The incidence of postoperative pancreatic fistula and/or intra-abdominal abscess formation were compared using Fischer's test. Pancreatic fistula was defined as a loss of greater than 100 ml fluid drainage beyond postoperative day 5. We found a significantly lower postoperative complication rate using the novel technique compared to the traditional way to cover the pancreatic stump after distal pancreatectomy (8.7% vs. 33% (P = 0.0458). However, there was no significant difference in postoperative hospital stay. We concluded that using the serosal surface of the first jejunal loop is a simple, quick and secure method of closure of the proximal pancreas in terms of surgical practicability. This new technique significantly decreases the rate of postoperative fistula or abscess formation after distal pancreatectomy.

Abdominal Abscess↗

Effects of bombesin on mucosal ion transport in the mouse isolated jejunum.

The effects of bombesin (BBS) on ion transport in the mouse isolated jejunum were studied in full thickness (intact) or serosal stripped (mucosal) sheets of jejunum mounted in Ussing chambers. Although serosal BBS (0.1-30 nM) induced a concentration-related increase in transmural potential difference (PD) and short-circuit current (Isc) without altering conductance in both preparations, the peptide was more potent and efficacious in mucosal than in intact tissues. In all preparations, pretreatment with BBS abolished the effects of a subsequent administration of BBS showing the rapid development of desensitization. In intact tissues, serosal pretreatment with either chlorisondamine (3 microM) or tetrodotoxin (0.1 microM) decreased, but did not abolish BBS action. Meanwhile, atropine pretreatment (3 microM) did not affect the BBS response. In these tissues, previous blockade of NaCl cotransport by furosemide (300 microM) decreased BBS (30 nM) stimulation of PD or Isc. In mucosal preparations, tetrodotoxin pretreatment (0.1 microM) similarly reduced but did not eliminate BBS (3 nM) stimulation of PD or Isc, whereas atropine pretreatment (1 microM) again had no effect on BBS action. In contrast in these mucosal tissues, furosemide pretreatment (300 microM) did not modify the BBS response. Furthermore, carbachol pretreatment (10 microM) prevented completely the tetrodotoxin-resistant action of BBS. These findings in vitro suggest that the increase of PD and Isc following BBS administration in isolated mouse jejunum is associated with three different levels of action of this peptide: BBS may act on noncholinergic nerves, at pre- and post-ganglionic levels, as well as directly on the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of carbamazepine on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine 3',5'-cyclic phosphate and theophylline.

Carbamazepine has been reported to decrease urine output and increase urinary concentration in patients with diabetes insipidus. The effects of the drug on the osmotic water permeability of the bladder of the toad, Bufo marinus, were studied. Carbamazepine had no effect on osmotic water flow when present in the serosal or mucosal bathing media. The submaximal or maximal increase in osmotic water flow caused by vasopressin was inhibited by serosal carbamazepine concentrations as low as 0.01 mM. Higher concentrations of carbamazepine in the mucosal solution also inhibited the submaximal antidiuretic hormone (ADH) response. The response to 2 mM cyclic AMP was inhibited by 0.5 mM serosal carbamazepine. Carbamazepine did not affect the response to 20 mM theophylline. Significant inhibition of the ADH response occurred only after preincubation of the bladders with the drug for at least 1 hour. The inhibition was reversed by rinsing the drug from the bladders before ADH was added. The mechanism of action of carbamazepine in diabetes insipidus remains obscure. In the toad bladder, the drug neither directly increases osmotic water flow nor potentiates the response to vasopressin.

Animals↗

Pertinent risk factors and gastric carcinoma with synchronous peritoneal dissemination or liver metastasis.

From 1965 to 1985, of 1108 patients with advanced gastric cancer who underwent gastric resection in our department, 216 patients (19.5%) had synchronous peritoneal dissemination (PD) or liver metastasis (LM). The 1-year survival rate was 22.5% for PD, 14.7% for LM, and 4.8% for PD plus LM (p less than 0.01). With PD, patients were younger, tumor was larger, Borrmann type 3 and 4 and undifferentiated lesions were more frequent, and the incidence of serosal invasion was higher. Histologic findings showed a pattern of infiltrative growth. With LM, patients were more likely to be male, Borrmann type 2 and 3 and differentiated lesions were frequent, and the antral region was often involved. The degree of serosal invasion was less than with PD. The pattern of growth was the expansive type and vascular involvement was prominent. Rate of lymph node metastasis was high in both groups. The route of metastasis was partly linked to features of the primary lesion. Multivariate analysis showed that independent risk factors involved in the occurrence of each metastasis are serosal invasion, lymph node metastasis, and undifferentiated tissue type for PD, and lymph node metastasis and vascular involvement for LM. When designing treatment in an attempt to suppress a recurrence, even after curative resection, all of these risk factors must be kept in mind.

Female↗

Responses of the colonic epithelium to auranofin: evidence for involvement of enteric nerves.

Auranofin, the orally effective gold compound, stimulated the canine colonic epithelium in vitro. It increased short circuit currents across both the innervated mucosal and functionally "nerve-free" epithelial preparation, when added to either the luminal or serosal solutions. Serosal responses were inhibited by tetrodotoxin (TTX). A hydrophilic gold compound, sodium aurothiosulphate produced similar effects but only on serosal addition. Gold compounds can thus alter colonic transport activating enteric nerves and releasing a neurotransmitter. Thus gold induced diarrhea could have a significant neural component.

Animals↗

[Clinical effect of intraperitoneal hyperthermochemotherapy on the survival rate for advanced gastric cancer patients].

Intraperitoneal hyperthermic perfusion (IPHP) was performed right after surgery for 31 advanced gastric cancer patients with serosal invasion and/or peritoneal dissemination. The survival rate in the IPHP group, was compared with that in the control group, 30 patients who underwent surgery alone within the same period of time. The 1-year survival rates for IPHP group and control group were 81.9% and 40.3%, respectively. The 2-year survival rates were 52.1% and 11.8%, and the 3-year survival rates were 26.1% and 0%, respectively. The survival rate for IPHP group was better than that for control group, with p = 1.46 x 10(-4). IPHP and control group with peritoneal dissemination included 21 and 9 patients respectively, and 50% survival rates were 18 months and 4.2 months, respectively. IPHP and control group with serosal invasion included 10 and 21 patients, respectively, and 8 out of 10 patients survived in the IPHP group, while 17 out of 21 patients died in the control group. These results suggest that IPHP is effective for gastric cancer patients with peritoneal dissemination and/or serosal invasion.

Aged↗

Prostaglandin F2 alpha inhibits acidification in H(+)-secreting epithelia.

The role of prostaglandins in the regulation of acidification mechanisms in H(+)-secreting epithelia has been investigated in the abdominal skin of the southern leopard frog, Rana pipiens. Exogenous administration of prostaglandin (PG) E2 and PGF1 alpha (10(-7) M) to the serosal media of paired skins mounted in modified Ussing chambers showed no significant alteration on H+ excretion rates. PGF2 alpha exhibited a dose-dependent inhibition of acidification in both the mucosal and serosal media of animals in normal acid-base states. The ED50 was determined to be 5 X 10(-8) M. Animals placed in an NH4Cl-induced chronic metabolic acidosis demonstrated enhanced H+ excretion from normal which was inhibited by PGF2 alpha (10(-8) M). Frogs treated with ibuprofen (30 mg/kg/day for 3 days) stimulated mucosal acidification to a magnitude similar to the chronic metabolic acidosis animal, and this was inhibited by PGF2 alpha (10(-8) M) during the recovery phase. PGF2 alpha produced effects on both the mucosal proton excretion system and the serosal Na+/H+ exchanger mechanism. PGF2 alpha appears to function in this H(+)-secreting epithelia to maintain a low basal H+ excretion rate and to regulate intracellular pH.

Acidosis↗

Relationship between thiamin phosphorylation and intestinal transport in vitro: effect of chloroethylthiamin.

The effect of Chloroethylthiamin (CET), a structural analog of thiamin, on thiamin pyrophosphokinase (TPKase) activity of the supernatant of rat isolated enterocytes was compared with that on thiamin intestinal transport by rat everted jejunal sacs. Thiamin- thiazol-2(14C) was used as a substrate both for TPKase activity and for thiamin serosal transport and uptake. CET strongly inhibited TPKase activity of isolated enterocytes: at molar concentrations 10 or 100 times higher than labeled thiamin, the inhibition was 57 and 100% respectively. The inhibition was of the competitive type, with a Ki = 15 microM. At a molar concentration 10 times higher than labeled thiamin, CET lowered the thiamin serosal transport by 60%, and the sac wall content of free and phosphorylated thiamin by 54 and 42% respectively. At the 1:10 thiamin: CET molar ratio, the extent of the reductions of TPKase activity (57%) and of phosphorylated thiamin content of intestinal sac walls (42%) were of the same order. This indicates a relationship between the two events. Moreover, since TPKase activity inhibition alone resulted in the lowering of labeled thiamin serosal transport, thiamin phosphorylation and transport are probably two strictly related processes.

Animals↗

Nuclear morphometry as a prognostic indicator in colorectal carcinoma resected for cure.

The prognostic value of nuclear morphometry in addition to clinical and pathologic features was retrospectively studied in 64 cases of colorectal carcinoma resected for cure with a minimum of five years of follow-up. By univariate analysis, patient outcome was found to correlate with the presence of serosal involvement (P = .003), the presence of lymph node involvement (P = .01), the number of involved lymph nodes (P = .0001) and the mean nuclear area (P = .02). With multivariate analysis, only the number of involved lymph nodes significantly correlated with the survival (P = .0001). In a subsequent multivariate model expressing lymph node status as the presence or absence of metastasis, the presence or absence of serosal involvement and the mean nuclear area were both found to independently correlate with the outcome (P = .003 and P = .02, respectively). Linear regression analysis revealed significant colinearity between the mean nuclear area and the number of involved lymph nodes (P = .03). Accelerated failure time models based on determination of serosal involvement and then either specification of the number of involved lymph nodes or calculation of the mean nuclear area were of comparable predictive value to the determination of the number of involved lymph nodes alone. The former appeared to be better at identifying a subgroup of patients with good prognosis. This study demonstrates that two or more models based on pathologic features may be of comparable predictive value in colorectal carcinoma resected for cure, including models that incorporate mean nuclear area.

Adenocarcinoma↗

Inhibition of the hydrosmotic response to antidiuretic hormone by 3,3'-diallyldiethylstilbestrol (DADES).

3,3'-diallyldiethylstilbestrol (DADES), a blocker of the facilitated diffusion of glucose, was found to interfere markedly with the hydrosmotic response to antidiuretic hormone and its related agonists. Frog urinary bladders were isolated and monitored for transmural net water flow. DADES was added either to the serosal or to the apical medium at concentrations ranging from 10(-4) M to 10(-6) M. Pretreatment for 30 min with apical 10(-4) M DADES drastically reduced the subsequent hydrosmotic response: (a) to oxytocin (4.4 x 10(-8) M) by 91.7 +/- 17.6% versus 6.2 +/- 7.8 in control; (b) to 8-bromo 3',5'-cyclic AMP by 93.5 +/- 19.4% versus 19.4 +/- 11.4%; (c) to serosal hyperosmolarity (mannitol 220 mOsm) by 99.3 +/- 0.5% versus 12.3 +/- 18.2%. This effect was dose-dependent. Inhibitory action of DADES was more effective on the apical side than on the serosal side (97.0 +/- 1.5 versus 45.8 +/- 10.8). Freeze-fracture studies revealed a modified distribution of the particles and unusual endocytotic pits and vesicles in the apical membrane of both granular and mitochondria-rich epithelial cells. These observations point to multiple and complex effects of the drug. Thus, it seems that DADES has numerous effects on urinary epithelium, which makes it a nonspecific inhibitor of water permeation. Conclusions on its use should therefore be drawn with suitable caution.

8-Bromo Cyclic Adenosine Monophosphate↗

[Hemostatic effect of local intramural injection of dehydrated ethanol in the canine gastrointestinal tract].

The relative value of a subserosal injection of 98% ethanol (0.2 ml x 4) in controlling acute and chronic bleeding from serosal vessels was assessed in dogs. Blood flow was measured from gastric serosal vessels (average diameter 1.6 mm) severed immediately after, 24 hours after, and 48 hours after ethanol injection. Blood flow from severed colonic serosal vessels (averaging diameter 1.0 mm) was measured prior to and immediately after ethanol injection. The safety of ethanol injection was tested by endoscopically guided submucosal injection which were sequentially observed endoscopy at one hour, 24 hours, and weekly for weeks after injection. Ethanol injection had no effect on bleeding from larger gastric vessels unless the injection was made 24 or 48 hours prior to vessel severence. Ethanol injection was effective in reducing bleeding from the smaller colonic vessels when done immediately prior to vessel severence. Gastric submucosal injections led to ulcers which extended into the muscle layer at on week and healed completely by three weeks; none perforated or bleed. These data support the potential efficacy of therapeutic ethanol injection for the control of small vessel (1.0 mm diameter) bleeding and the potential prophylactic value against rebleeding from larger vessels. Further studies are needed to determine if these findings are organ related as opposed to being diameter specific.

Animals↗

[Clinico-pathological study on recurrent gastric cancer after curative resection].

Among 675 patients who had undergone curative resection of gastric cancer during last 13 years, 113 died of cancer recurrence. One hundred and forty-five patients who had survived longer than 5 years were used as controls. In the recurrence group, the primary lesion was larger and the lymph node metastasis more common as compared with the surviving controls. Moreover, these lesions were often located at the upper third of the stomach and exhibited Borrmann 3 or 4 type. Prognostic serosal invasion was positive in 75 per cent of the recurrence group and negative in 84 per cent of the surviving controls. The most frequent mode of recurrence was hematogenous metastasis in negative prognostic serosal invasion (54%) and peritoneal disseminated metastasis in positive prognostic serosal invasion (52%). There were no differences in the distribution of gross and histological types of cancer in the modes of recurrence. It was found that peritoneal dissemination and/or local recurrence dominated as the mode of recurrence (51%), followed by hematogenous metastasis (34%), but that lymph node recurrence was uncommon (15%). In peritoneal disseminated cases, long-term survival following reoperation should not be expected. It was suggested that in order to improve the prognosis in the case of hematogenous metastasis, postoperative immunochemotherapy should be applied.

Adenocarcinoma↗

Effects of putative thromboxane receptor agonists and antagonists on rat small intestinal ion transport.

Effects of a thromboxane mimic, U46619, on electrolyte transport were examined in vitro using stripped segments of rat ileal mucosa mounted in Ussing chambers. Addition of U46619 to the serosal bathing solution elicited a transient increase in short-circuit current (Isc) and decrease in transepithelial conductance (Gt). The increase in Isc was accompanied by a transient increase in Cl- secretion and decrease in Na+ absorption. In the steady-state, Isc was not increased whereas Gt remained decreased and Na+ and Cl- absorption were inhibited. Removal of Cl- or pretreatment with serosal and mucosal indomethacin (1 microM) or the thromboxane receptor antagonist, SK&F 88046, added to the serosal bathing solution, inhibited the increase in Isc stimulated by U46619 (apparent KB approximately 8 nM). The effects of U46619 on both Isc and Gt are qualitatively similar to those resulting from stimulation with leukotriene D4. However, the changes in Isc with leukotriene D4 (10 microM) are antagonized by SK&F 88046 only at high concentrations (1-10 microM). In addition, the secretagogues prostaglandin F2 alpha, lys-bradykinin, serotonin and histamine, produce qualitatively similar changes in Isc to those seen with U46619 without altering Gt. With the exception of prostaglandin F2 alpha, the effects of these secretagogues are not inhibited by SK&F 88046 (10 microM). These results indicate that U46619 acts at a thromboxane receptor to stimulate intestinal Cl- secretion and inhibit Na+ and Cl- absorption. These changes are inhibited selectively by the thromboxane receptor antagonist, SK&F 88046.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗