The relationship between n-3 long-chain polyunsaturated fatty acids and pulse wave velocity in diabetic and non-diabetic patients under long-term hemodialysis. A horizontal study.

BACKGROUND: Diabetes mellitus (DM) and deficiency in n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are known to increase the incidence of cardiovascular disease (CVD). However, it has not yet been reported whether n-3 LCPUFAs are related to arteriosclerosis in patients under long-term hemodialysis (HD). METHODS: Pulse wave velocity from the brachium to the ankle (baPWV) was measured as a marker of arteriosclerosis with a volume-plethysmographic apparatus in 147 long-term HD patients (non-diabetic (non-DM): 51 males/42 females, 62 +/- 14 y; and DM: 33 males/21 females, 67 +/- 9 y). The fatty acid composition of the total phospholipid fraction from washed RBCs was analyzed by gas chromatography. Analyses were adjusted for age, sex, diastolic blood pressure, pulse, body mass index, duration of HD treatment, smoking status, LDL/HDL-cholesterol ratios and diabetes mellitus (DM). RESULTS: The mean baPWV was 18.9 +/- 5.2 and 23.7 +/- 6.3 m/s in non-DM and DM patients, respectively. The mean baPWV in DM patients was significantly higher than that of non-DM patients after adjustment (p = 0.0002). Multiple regression analysis showed that there was a significant inverse association between baPWV and docosahexaenoic acid (DHA) levels (p = 0.017) and DHA/arachidonic acid (AA) ratios (p = 0.012) in RBC in non-DM patients after adjustment but not in DM patients. CONCLUSIONS: We suggest that n-3 LCPUFAs may be a negative risk factor of CVD also in non-DM HD patients. In DM patients the effects of n-3 PUFAs on the vascular system became undetectable probably because DM overwhelmingly affected PWV. Further studies in a prospective manner are necessary.

Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors.

Omega-3 polyunsaturated fatty acids (PUFAs) are essential nutrients demonstrated to have health benefits, such as decreasing the risk of coronary heart disease, improving parameters associated with metabolic syndrome, and decreasing anxiety symptoms and depression risk. Previous intervention studies indicated the association between blood or tissue PUFA levels and the gut microbiota; however, the details remain incompletely elucidated. We conducted a cross-sectional study to examine the association between PUFAs and the gut microbiota among breast cancer survivors. Adults who had been diagnosed with invasive breast cancer more than one year ago and were not currently undergoing chemotherapy were enrolled. Capillary blood and faecal samples were obtained to assess the blood PUFA levels and gut microbiota compositions. The mean age (n=124) was 58.7 years, and 46% of the participants had a history of chemotherapy. Multiple regression analysis controlling for possible confounders indicated that an increased relative abundance of Actinobacteria was significantly associated with increased levels of docosahexaenoic acid (DHA, beta=0.304, q<0.01). At the genus level, the abundance of Bifidobacterium was positively associated with the level of DHA (beta=0.307, q<0.01). No significant association between omega-6 PUFAs and the relative abundances of gut microbiota members was observed. In addition, analyses stratified by the history of chemotherapy indicated significant associations of PUFA levels with the abundance of some bacterial taxa, including the phylum Actinobacteria (DHA, beta=0.365, q<0.01) and Bacteroidetes (EPA, beta=-0.339, q<0.01) and the genus Bifidobacterium (DHA, beta=0.368, q<0.01) only among participants without a history of chemotherapy. These findings provide the first evidence of positive associations between the abundances of Bifidobacterium among the gut microbiota and the levels of omega-3 PUFAs in the blood. Further studies are required to gain additional insight into these associations in healthy subjects as well as into the causality of the relationship.

Omega-3 polyunsaturated fatty acids and psychological intervention for workers with mild to moderate depression: A double-blind randomized controlled trial.

BACKGROUND: This study assessed whether a combined intervention of omega-3 polyunsaturated fatty acids (PUFAs) and psychoeducation better improved mild to moderate depression in workers compared to psychoeducation alone. METHODS: This study was a double-blinded, parallel group, randomized controlled trial that compared the intervention group, receiving omega-3 fatty acids, with a control group, receiving a placebo supplement. Participants receiving omega-3 fatty acids took 15 × 300 mg capsules per day for 12 weeks. The total daily dose of omega-3 PUFAs was 500 mg docosahexaenoic acid and 1000 mg eicosapentaenoic acid (EPA). The Beck Depression Inventory®-II (BDI-II) was used to assess the severity of depression after treatment. RESULTS: After 12 weeks of treatment, BDI-II scores were significantly lower in the placebo and omega-3 group, when compared to their respective baseline scores (Placebo: t = - 4.6, p < 0.01; Omega-3: t = - 7.3, p < 0.01). However, after 12 weeks of treatment, we found no significant difference between both groups with respect to changes in the BDI-II scores (0.7; 95% CI, - 0.7 to 2.1; p = 0.30). LIMITATIONS: This study did not measure blood omega-3 fatty acid concentration and presented a high-dropout rate. Moreover, our results may not be generalizable to other regions. CONCLUSIONS: The results show that a combination of omega-3 fatty acids and psychoeducation and psychoeducation alone can contribute to an improvement in symptoms in people with mild to moderate depression. However, there is no difference between the interventions in ameliorating symptoms of depression.

Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors.

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.

Fatty acid composition of the postmortem corpus callosum of patients with schizophrenia, bipolar disorder, or major depressive disorder.

BACKGROUND: Studies investigating the relationship between n-3 polyunsaturated fatty acid (PUFA) levels and psychiatric disorders have thus far focused mainly on analyzing gray matter, rather than white matter, in the postmortem brain. In this study, we investigated whether PUFA levels showed abnormalities in the corpus callosum, the largest area of white matter, in the postmortem brain tissue of patients with schizophrenia, bipolar disorder, or major depressive disorder. METHODS: Fatty acids in the phospholipids of the postmortem corpus callosum were evaluated by thin-layer chromatography and gas chromatography. Specimens were evaluated for patients with schizophrenia (n=15), bipolar disorder (n=15), or major depressive disorder (n=15) and compared with unaffected controls (n=15). RESULTS: In contrast to some previous studies, no significant differences were found in the levels of PUFAs or other fatty acids in the corpus callosum between patients and controls. A subanalysis by sex gave the same results. No significant differences were found in any PUFAs between suicide completers and non-suicide cases regardless of psychiatric disorder diagnosis. CONCLUSIONS: Patients with psychiatric disorders did not exhibit n-3 PUFAs deficits in the postmortem corpus callosum relative to the unaffected controls, and the corpus callosum might not be involved in abnormalities of PUFA metabolism. This area of research is still at an early stage and requires further investigation.

Dietary fish, n-3 polyunsaturated fatty acid consumption, and depression risk in Japan: a population-based prospective cohort study.

Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan. A total of 12 219 subjects were enrolled from the Saku area in 1990. Of these, we extracted 1181 participants aged 63-82 years who completed food frequency questionnaires in both 1995 and 2000 and also underwent a mental health examination in 2014-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for MDD according to fish intake and PUFA quartiles were calculated. Current MDD was diagnosed in 95 patients. We found a reduced risk of MDD in the third quartile for fish intake (111.1 g per day, OR=0.44, 95% CI=0.23-0.84), second quartile for EPA (307.7 mg per day, OR=0.54, 95% CI=0.30-0.99) and third quartile for docosapentaenoic acid (DPA) (123.1 mg per day, OR=0.42, 95% CI=0.22-0.85). ORs adjusted for cancer, stroke, myocardial infarction and diabetes remained significant for fish and DPA intake. Our results suggest that moderate fish intake could be recommended for the prevention of MDD in aged Japanese individuals.

Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes.

The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood. In the PUFA-deprived mouse group, we observed lower motivation and higher sensitivity to a hallucinogenic drug resembling the prodromal symptoms in schizophrenia. Furthermore, a working-memory task-evoked hyper-neuronal activity in the medial prefrontal cortex was also observed, along with the downregulation of genes in the prefrontal cortex involved in oligodendrocyte integrity and the gamma-aminobutyric acid (GABA)-ergic system. Regulation of these genes was mediated by the nuclear receptor genes Rxr and Ppar, whose promoters were hyper-methylated by the deprivation of dietary AA and DHA. In addition, the RXR agonist bexarotene upregulated oligodendrocyte- and GABA-related gene expression and suppressed the sensitivity of mice to the hallucinogenic drug. Notably, the expression of these nuclear receptor genes were also downregulated in hair-follicle cells from schizophrenia patients. These results suggest that PUFA deficiency during the early neurodevelopmental period in mice could model the prodromal state of schizophrenia through changes in the epigenetic regulation of nuclear receptor genes.

Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study.

N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9-14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ⩾ 9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ⩾ 13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations.

The response of human T lymphocytes against alloantigens following Fas-mediated activation-induced cell death.

We examined the response of T lymphocytes activated with specific alloantigens following Fas-mediated apoptosis; using a mixed lymphocyte culture (MLC) system. Cells obtained from an MLC after 6 or 7 days of culture were incubated for are additional 24 hours in the presence or absence of the agonistic monoclonal antibody (MoAb), 7C11, or the antagonistic MoAb, ZB4. We assessed DNA fragmentation/specific cytotoxiy of the MoAb-treated cells. Cells harvested after 4 days of culture were sensitive to apoptosis induced by 7C11 with maximum DNA fragmentation observed on day 6. ZB4 slightly inhibited apoptosis of the cells compared with controls. The simultaneous addition of recombinant interleukin-2 (rIL-2) with the MoAbs significantly inhibited DNA fragmentation in control and ZB4-treated cells, but had little effect on the 7C11-treated cells. Control and ZB4-treated MLC cells showed cytotoxic activities against specific target cells, namely >10%. In contrast, the 7C11-treated cells showed <5% cytotoxicity. Although the addition of rIL-2 increased specific percentage cytotoxicity of control and ZB4-treated cells, it had little effect on the specific cytotoxic activity of the 7C11-treated MLC cells. These results suggest that specific cytotoxic T lymphocytes may be eliminated via apoptosis mediated by the Fas/Fas ligand system.

Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial.

Our open-label pilot study showed that supplementation with docosahexaenoic acid (DHA) increased serum brain-derived neurotrophic factor (BDNF) levels and that there might be an association between changes in serum BDNF levels and reduced psychological distress. Animal research has indicated that a DHA-enriched diet increases BDNF in the brain. In this randomized double-blind controlled trial of severely injured patients vulnerable to posttraumatic stress disorder (PTSD) and depression, we examined whether DHA increases serum BDNF levels and whether changes in BDNF levels are associated with subsequent symptoms of PTSD and depression. Patients received 1470 mg per day of DHA plus 147 mg per day of eicosapentaenoic acid (EPA; n = 53) or placebo (n = 57) for 12 weeks. Serum levels of mature BDNF and precursor pro-BDNF at baseline and 12-week follow-up were measured using enzyme-linked immunosorbent assay kits. At 12 weeks, we used the Clinician-Administered PTSD Scale to assess PTSD symptoms and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. We found a significant increase in serum BDNF levels during the trial in the DHA and placebo groups with no interaction between time and group. Changes in BDNF levels were not associated with PTSD severity but negatively associated with depression severity (Spearman's ρ = -0.257, P = 0.012). Changes in pro-BDNF were also negatively associated with depression severity (Spearman's ρ = -0.253, P = 0.013). We found no specific effects of DHA on increased serum levels of BDNF and pro-BDNF; however, evidence in this study suggests that increased BDNF and pro-BDNF have a protective effect by minimizing depression severity.

Fish consumption and depressive symptoms in undergraduate students: A cross-sectional analysis.

BACKGROUND: Emerging evidence suggests that fish consumption may have beneficial effects on mood disorders. However, no study has been reported on this issue in young adults to date. The aim of this study was to investigate the relationship between fish consumption and depressive symptoms in Japanese undergraduate students. METHODS: The 20-item Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms with a cut-off score of 16. A total of 4190 completed questionnaires (from 2124 men and 2066 women) were received for analysis. RESULTS: Multivariate logistic analysis showed that fish intake was inversely associated with risk of depressive symptoms in undergraduate students. After adjustment for possible confounders, the odds-ratios (95% confidence intervals) for fish intake 1-2 times/month, 1-2 times/week, 3-4 times/week, and almost every day (compared with "almost never") were 0.78 (0.62-0.99), 0.70 (0.56-0.87), 0.67 (0.53-0.85) and 0.65 (0.46-0.92), respectively. This association tended to be stronger in women than in men. CONCLUSIONS: Frequent fish consumption in undergraduate students seems to moderate depressive symptoms. Further research is warranted to clarify the causality.

Hepatectomy under extracorporeal circulation.

BACKGROUND: Resection of hepatic tumors located near the confluence of the hepatic vein or invading the inferior vena cava has become technically feasible and relatively safe by using venovenous bypass. However, some technical problems remain to be solved. METHODS: We performed three cases of hepatic resection under extracorporeal circulation combined with hypothermic perfusion. RESULTS: An unexpected hemorrhage was observed in all three cases for different causes. The patient of case 2 died of liver failure developed from fatty liver. Bile duct stenosis was observed in cases 1 and 3. CONCLUSIONS: Although hepatectomy under total vascular exclusion by use of Biopump is now considered a safe procedure, attention should be paid when this procedure is performed because some technical problems still remain.

Effects of ulinastatin on polymorphonuclear leukocyte elastase and interleukin 6 levels after hepatectomy.

Eight patients undergoing hepatectomy received 15 x 10(4) U of ulinastatin during and after surgery and then twice daily for 4 days, and 11 hepatectomized patients served as untreated controls. Between-group differences in age, duration of surgery, volume of blood loss and transfusion, weight of resected liver, and results of preoperative liver function tests were not significant. On postoperative day 1, mean (+/- SD) polymorphonuclear leukocyte elastase levels were significantly lower in the treated patients than in the controls (310 +/- 69 micrograms/L vs 519 +/- 382 micrograms/L; P < 0.05); interleukin 6 levels also tended to be lower in the treated patients than in controls (42.4 +/- 34.0 pg/mL vs 63.3 +/- 43.1 pg/mL). The results indicate that ulinastatin has beneficial effects on host defenses after surgery.

Oxygen-dependent fragmentation of cellular DNA by nitric oxide.

Although active oxygen species and related metabolites, such as nitric oxide (NO), have been postulated to play important roles in the apoptosis of various cells, a precise mechanism leading to cell death remains to be elucidated. Recently we found that the lifetime of NO depends greatly on the concentration of environmental oxygen and that NO reversibly inhibits mitochondrial respiration and ATP synthesis; the inhibitory effect is stronger at physiologically low oxygen tension than under atmospheric conditions (Arch. Biochem. Biophys. 323, 27-32, 1995). The present work describes the effects of the NO-generating agent, 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC 18) and oxygen tension on the respiration, ATP synthesis and apoptosis of HL-60 cells. When respiration was inhibited by NOC 18, cellular ATP levels decreased significantly and DNA fragmentation was elicited. Both events were enhanced by decreasing oxygen tension and suppressed by adding NO-trapping agents, such as 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and oxyhemoglobin. The fragmentation of cellular DNA was inhibited in a dose dependent manner by herbimycin A, a tyrosine kinase inhibitor. Fragmentation of the DNA of HL-60 cells was also induced either by peroxynitrite, superoxide or hydroxyl radical by some mechanism which was diminished by lowering the oxygen tension. These results indicated that the decrease in cellular ATP and activation of tyrosine kinase might play important roles in NO-induced apoptosis particularly under physiologically low oxygen tensions.

Oxygen concentration regulates NO-dependent relaxation of aortic smooth muscles.

Nitric oxide (NO) functions as an endothelium-derived relaxation factor and regulates vascular resistance. Recent studies in this laboratory(Arch.Biochem.Biophys.323, 27-32, 1995) revealed that the lifetime of NO significantly increased at physiologically low levels of oxygen concentrations and, hence, this gaseous radical strongly inhibited mitochondrial electron transport for a fairly long duration at low oxygen concentrations. The present work describes the effect of oxygen concentration on NO-induced relaxation and guanylate cyclase (GC) activity of endothelium-denuded aorta of the rat. Both NO and 2,2 '-(hydroxynitrosohydrazono)bis-ethanamine (NOC18), an NO donor, induced the relaxation of endothelium-denuded helical segments of rat aorta which were contracted by norepinephrine. NO-dependent relaxation of arterial specimens was enhanced by lowering oxygen concentration in the medium with concomitant increase in their cGMP levels. Anoxia induced the relaxation of the aorta by some NO-enhanceable and methylene blue-insensitive mechanism. These results suggested that local concentrations of oxygen might play important roles in the regulation of NO-dependent GC activity and vascular tonus of resistance arteries.

Molecular mechanisms of apoptosis in HL-60 cells induced by a nitric oxide-releasing compound.

Nitric oxide (NO) generated from 1-hydroxy-2-oxo-3, 3-bis(2-aminoethyl)-1-triazene (NOC 18), an NO-releasing compound, induced monocytic differentiation of human promyelocytic leukemia HL-60 cells as assessed by expression of nonspecific esterases and morphologic maturation. Simultaneously, DNA fragmentation and morphological alterations typical of apoptosis were also induced. To investigate the mechanisms of apoptosis during differentiation of HL-60 cells induced by NO, the endogenous levels of Bcl-2 and Bax were assessed by immunoblotting. Treatment of cells with NOC 18 slightly reduced the level of Bcl-2 followed by Bax. These changes might be involved in the induction of apoptosis. The involvement of the activation of the interleukin-1 beta converting enzyme (ICE) family of proteases (caspases), such as ICE and CPP32, in the pathways was also investigated. CPP32, but not ICE, was strongly activated in response to NOC 18 stimulation, thereby implicating CPP32-like activity in the induction of apoptosis. Moreover, the possible involvement of tyrosine phosphorylation in apoptosis was investigated. Pretreatment of cells with herbimycin A, an inhibitor of tyrosine kinases, suppressed DNA fragmentation and CPP32-like activity, whereas pretreatment with vanadate, an inhibitor of tyrosine phosphatases, enhanced both parameters, suggesting that tyrosine phosphorylation might be involved in the pathways of apoptosis in HL-60 cells induced by NO.

Heterotopic gastric mucosa in the gallbladder.

We report on a case of heterotopic gastric mucosa in the body of the gallbladder. A 39-year-old man, who was asymptomatic, visited our hospital because of a polypoid lesion in the gallbladder, discovered during a routine health screening. Ultrasonography (US) revealed a broad-based polypoid lesion 1.7 cm in diameter in the body of the gallbladder, which was free of gallstones. The gallbladder mass was faintly enhanced by helical computed tomography. Laparoscopic cholecystectomy was performed because of the possibility of malignancy. The specimen revealed a 1.7 x 1.3 cm polypoid lesion with deep delle in the body, with no gallstones in the gallbladder. Intraoperative frozen examination yielded a diagnosis of hyperplastic polyp of the gallbladder. Histologically, the polypoid lesion consisted of gastric fundic glands located in the whole wall of the gallbladder. The surrounding mucosa consisted of almost normal epithelium without any metaplastic changes. Postoperative technetium 99m-pertechnetate scintigraphy demonstrated no evidence of gastric heterotopia elsewhere in the body. We also review 18 other reports of heterotopic gastric mucosa in the gallbladder in the Japanese medical literature.

Effects of gastrectomy on motility, perfusion pressure, and caerulein-induced relaxation of sphincter of Oddi in dogs.

The effects of subtotal-gastrectomy (gastrectomy) on the spontaneous motility and caerulein-induced relaxation of the sphincter of Oddi (SO) were investigated in the dog. The spontaneous motility and the response to caerulein of the SO were recorded using perfusion method. The basal perfusion pressure (5.1 +/- 0.5 cmH2O) and the frequency of phasic contractions (6.1 +/- 0.5 cycles/min, c/min) of the SO increased to 8.2 +/- 0.6 cmH2O (p < 0.05) and 9.3 +/- 0.4c/min (p < 0.05) after gastrectomy, respectively. They were observed one month after operation (7.8 +/- 0.5 cmH2O and 9.1 +/- 0.9 c/min, p < 0.05), but did not change by vagotomy with sympathectomy (vagosympathectomy). In the spontaneous motility of the SO, the motility index increased to 143.7 +/- 18.7% (p < 0.05) at 4 hrs and 135.0 +/- 9.1% (p < 0.05) at one month after gastrectomy, but did not increase after vagosympathectomy. Caerulein had an inhibitory effect on the SO motility in the normal animal 48.0 +/- 4.2%). Gastrectomy reversed to the excitatory effect from the inhibitory effect to caerulein at 4 hrs (127.6 +/- 5.3%, p < 0.05) and at one month (126.6 +/- 5.3%, p < 0.05) after operation, but not reversed by vagosympathectomy and sham gastrectomy. The excitatory response to caerulein after gastrectomy was not effected by vagosympathectomy. It is concluded that gastrectomy induced the SO dysfunction, an increase of the perfusion pressure and the frequency of phasic contractions of the SO, and a change of the response to caerulein of the SO. These alterations suggests that one of the mechanisms of the regulation of the SO motility exist as the reflex from the stomach and/or uppermost duodenum through intrinsic nervous pathways.

[Effects of gabexate mesilate (FOY) on the gallbladder, sphincter of Oddi and duodenum of the normal and gastrectomized dogs].

FOY induced a dose-dependent inhibitory response on the gallbladder, sphincter of Oddi and duodenum of normal and gastrectomized dogs, although it induced an excitatory response in some dogs. The inhibitory response was not reduced or terminated by pretreatment with atropine, guanethidine, hexamethonium or/and proglumide. The FOY-induced inhibitory response reversed to the excitatory response in the sphincter of Oddi and duodenum by pretreatment with tetrodotoxin, but not in the gallbladder. These results suggested that the FOY-induced inhibitory response of the sphincter of Oddi and duodenum was caused by stimulation of nonadrenergic noncholinergic inhibitory neurons, not by FOY-induced cholecystokinin secretion. The excitatory response was induced by direct stimulation of their smooth muscles. The inhibitory response of the gallbladder to FOY was induced by direct stimulation of the smooth muscles.

Reduced metastatic potential and c-myc overexpression of colon adenocarcinoma cells (Colon 26 line) transfected with nm23-R2/rat nucleoside diphosphate kinase alpha isoform.

Increased expression of nm23/nucleoside diphosphate kinase (NDP kinase) has been reported to be associated with both reduced metastatic potential in breast carcinoma and tumor progression in colon adenocarcinoma and lung adenocarcinoma. We examined effects of expression of nm23-R2 rat NDP kinase alpha isoform on mouse adenocarcinoma cells (Colon 26 line) and found a significant reduction of metastatic potential along with overexpression of c-myc. We also found that the proliferation rate of the transformed cells was the same as that of the control cells in culture. These results indicate that the cell growth potential in vitro is irrelevant to metastatic potential of the cells in vivo.