醋酸棉酚对大鼠肾皮质形态结构的影响

醋酸棉酚每天30mg/kg(6次/周)给药6～8周后,大鼠肾曲小管线粒体肿胀,嵴模糊,伴有早期溶酶体增多、增大,形态多样,其后转而减少、变小。肾近曲小管微绒毛水肿,部分肾曲小管基底膜水肿。未见肾小球毛细血管内皮细胞、基膜和足细胞的超微结构明显变化。     

食管癌切除结肠代食管术44例

我们于１９８９年３月至１９９３年８月间，为４４例食管癌病人行食管癌切除、结肠代食管术。包括上段癌２３例，中段癌１８例，下段癌３例；其中上段癌病变长于７ｃｍ者６例，中段癌病变长于８ｃｍ者５例及下段癌中２例既往曾行胃大部切除术且病变长于９ｃｍ者均先行术前放疗，放疗剂量为３０～４０Ｇｙ。４０例（９０．９％）以结肠左动脉升支供血的横结肠行顺蠕动方向吻合，结果手术死亡１例，颈部吻合口瘘９例（２０．４５％）。我们认为本术式对中、上段癌病人疗效较满意，建议多采用以结肠左动脉为血供的横结肠作为移植段行顺蠕动方向吻合，为减少术后并发症，应注意加强病人围手术期的处置和护理。     

Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy

A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An "epidural morphine" group received general anesthesia and epidural morphine for postoperative pain relief, and an "epidural bupivacaine" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.     

Schedule-dependency of in vivo modulation of 5-fluorouracil by leucovorin and uridine in murine colon carcinoma

Summary The effect of leucovorin (LV) given in various doses and schedules on the in vivo antitumor activity and toxicity of 5-fluorouracil (5FU) was studied in two murine colon cancer lines, i.e., Colon 26 (relatively resistant to 5FU) and Colon 38 (5FU sensitive), maintained in Balb-c and C57B1/6 mice, respectively. Mice were treated weekly with 5FU at the maximum tolerated dose, alone and in combination with LV. In Colon 26, neither simultaneous administration of 5FU and LV nor 5FU combined with delayed administration of LV potentiated the antitumor activity of 5FU. LV given twice — 1 hr before (50 mg/kg) and then together (50 mg/kg) with 5FU (100 mg/kg) — gave significantly better delay of tumor growth of both tumor lines than 5FU did alone (100 mg/kg). No differences were found after a total LV dose of 100 or 200 mg/kg. Delayed administration of uridine (3500 mg/kg) allowed the use of higher 5FU doses, which improved the antitumor effect on Colon 26. Systemic toxicity led to moderate weight loss in treated mice, but was comparable for mice treated with 5FU alone or combined with LV. Hematological toxicity consisted of moderate leukopenia (nadir 40%), which was observed with the most active schedule and was less severe than with 5FU alone. This schedule did not cause thrombocytopenia, but after discontinuation the thrombocyte count showed an overshoot. Addition of uridine to this schedule reduced hematological toxicity only slightly. It is concluded that LV potentiated the antitumor activity of 5FU against two solid tumor lines, i.e., a relatively resistant and a sensitive murine colon carcinoma, and that toxicity was moderate.Abbreviations 5FU 5-fluorouracil - LV leucovorin (folinic acid, 5-formyl-tetrahydrofolate) - FdUMP 5-fluoro 2-deoxyuridine 5monophosphate - TS thymidylate synthase - CH2-THF 5-10 methylenetetrahydrofolate - UR uridine - GDF growth delay factor - TD tumor doubling time - MTD maximum tolerated dose - T/C mean tumor volume of treated mice divided by mean tumor volume of control mice     

Ultrastructure of early phase hepatic metastasis of human colon carcinoma cells with special reference to desmosomal junctions with hepatocytes

To demonstrate ultrastructural events in the early phase of hepatic metastasis of human colon carcinoma, we intrasplenically injected a highly metastasizable, human colon carcinoma cell line LM-H3 (1 x 10(6) cells) into nude mice, and electron microscopically investigated the hepatic metastasis. At 24 h, tumor cells adhered to the endothelial wall of terminal portal venules and periportal sinusoids. At 48-72 h, after extravasation, they deeply invaded the hepatic cell plate and the interstitial tissue of the portal tract, in which they underwent proliferation and made the metastatic foci. Tumor cells were linked with each other or with surrounding hepatocytes by desmosomes. Desmosomes were maintained during the mitosis. When invading tumor cells were exposed to the bile canaliculi, they generated microvilli on the surface. Microvilli were also formed at the luminal surface of intracytoplasmic inclusions. In the interstitial tissue of the portal tract, tumor cells were closely associated with fibroblasts. However, no junctional specializations were seen between them. The present study demonstrated that human colon carcinoma cell line LM-H3 formed desmosomes with hepatocytes soon after invasion of the hepatic cell plate, suggesting the regulatory role of an interaction with hepatocytes in the growth of metastatic foci within the liver parenchyma.     

Characterization of the antisecretory action of prostaglandin D2 in the rat colon

Previous studies have shown that prostaglandin D₂ (PGD₂) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD₂ was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D₂ inhibited the neuronally mediated short-circuit current evoked by prostaglandin I₂, which represents Cl^- secretion. The concentration-response curve for the inhibition by PGD₂ was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short-circuit current response induced by prostaglandin E₂ or iloprost, a stable prostaglandin I₂ analogue, suggesting an interaction of the blocker with receptors specific for PGD₂. A direct interaction of PGD₂ with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [³H]choline. Prostaglandin D₂ suppressed ³H release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD₂ on enteric cholinergic neurones is mediated by prostaglandin D receptors.     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.     

Chloride transport in the renal proximal tubule

The renal proximal tubule is responsible for most of the renal sodium, chloride, and bicarbonate reabsorption. Micropuncture studies and electrophysiological techniques have furnished the bulk of our knowledge about the physiology of this tubular segment. As a consequence of the leakiness of this epithelium, paracellular ionic transport--in particular that of Cl(-)--is of considerable importance in this first part of the nephron. It was long accepted that proximal Cl(-) reabsorption proceeds solely paracellularly, but it is now known that transcellular Cl(-) transport also exists. Cl(-) channels and Cl(-)-coupled transporters are involved in transcellular Cl(-) transport. In the apical membrane, Cl(-)/anion (formate, oxalate and bicarbonate) exchangers represent the first step in transcellular Cl(-) reabsorption. A basolateral Cl(-)/HCO(3)(-) exchanger, involved in HCO(3)(-) reclamation, participates in the rise of intracellular Cl(-) activity above its equilibrium value, and thus also contributes to the creation of an outwardly directed electrochemical Cl(-) gradient across the cell membranes. This driving force favours Cl(-) diffusion from the cell to the lumen and to the interstitium. In the basolateral membrane, the main mechanism for transcellular Cl(-) reabsorption is a Cl(-) conductance, but a Na(+)-driven Cl(-)/HCO(3)(-) exchanger may also participate in Cl(-) reabsorption.     

Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis

Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 × 10⁻⁴v 1.4 × 10⁻⁴, Mann-Whitney U, P < .02). The level in CD (4.0 × 10⁻⁴) was similar to FAR Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAR This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.