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1.
Int J Colorectal Dis ; 35(11): 2055-2064, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32632501

ABSTRACT

PURPOSE: The purpose of this study was to reveal whether a transanal tube (TAT) could act as an alternative to a diverting stoma (DS) after laparoscopic low anterior resection. PATIENTS AND METHODS: A total of 89 consecutive rectal cancer patients whose tumors were located within 15 cm from the anal verge who underwent laparoscopic low anterior resection without a DS at our institution between May 12, 2015 and August 31, 2019 were included. All patients received a postoperative Gastrografin enema study (GES) through a TAT between the 3rd and 10th postoperative day. We planned two study protocols. From May 12, 2015 to March 31, 2017, we conducted a second operation including a DS construction immediately when radiological anastomotic leakage (rAL) was detected (Group A, n=46). From April 1, 2017 to August 31, 2019, we continued TAT drainage even if rAL was detected and repeated the GES weekly until the rAL was healed (Group B, n=43). RESULTS: In Group A (n=46), 14 cases of rAL were included, 11 of which underwent stoma construction. The remaining 3 patients who refused stoma construction were treated conservatively. In Group B (n=43) rAL was encountered in 10, and 7 of these patients were treated successfully by TAT continuous drainage. The rate of DS in Group B (7.0%) was significantly lower than that in Group A (23.9%) (p=0.028). CONCLUSIONS: A TAT could act as a DS to mitigate the symptoms of anastomotic leakage after laparoscopic low anterior resection.


Subject(s)
Laparoscopy , Proctectomy , Rectal Neoplasms , Surgical Stomas , Anastomosis, Surgical/adverse effects , Anastomotic Leak/etiology , Anastomotic Leak/prevention & control , Humans , Laparoscopy/adverse effects , Rectal Neoplasms/surgery , Retrospective Studies , Surgical Stomas/adverse effects
2.
Gan To Kagaku Ryoho ; 45(6): 997-999, 2018 Jun.
Article in Japanese | MEDLINE | ID: mdl-30026431

ABSTRACT

Aggressive angiomyxoma is an uncommon mesenchymal tumor that mostly involves the pelvic and perineal regions in young women.We herein report an extremely rare case of aggressive angiomyxoma in a 75-year-old man. The patient had undergone follow-up for an intraductal papillary mucinous neoplasm.In September 2015, CT detected a tumor measuring 33 mm in diameter around the pelvis, and the tumor showed gradual increase in size.MRI revealed a relatively sharply marginated tumor with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.For treatment and diagnosis, we laparoscopically resected the tumor. Histopathologically, the specimen showed spindle tumor cells within a myxoid background and vascular structures.The tumor was diagnosed as aggressive angiomyxoma, and surgical margins were negative for tumor cells. The patient is currently doing well without any signs of recurrence as of 18 months postoperatively.


Subject(s)
Myxoma/blood supply , Pelvic Neoplasms/blood supply , Aged , Humans , Magnetic Resonance Imaging , Male , Myxoma/diagnostic imaging , Myxoma/surgery , Pelvic Neoplasms/diagnostic imaging , Pelvic Neoplasms/surgery , Treatment Outcome
3.
Nutr Res ; 42: 71-84, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28633873

ABSTRACT

Amino acids can exert protective effects on the liver either when administered as a medication or following an operation. In this study, we examined the protective effects of amino acids on the liver using in vitro and in vivo models by studying their influence on the induction of inducible nitric oxide synthase (iNOS) and nitric oxide production as a liver injury marker in cultured hepatocytes and liver-protective effects in d-galactosamine and lipopolysaccharide (GalN/LPS)-treated rats, respectively. Primary cultured rat hepatocytes were treated with interleukin (IL)-1ß in the presence or absence of Elental® amino acid component (EleAA; 17 amino acids). Rats were pretreated with either EleAA or a diet containing selected amino acids followed by GalN/LPS injection. Survival rate and mRNA expression were analyzed. EleAA inhibited iNOS induction through reduction of mRNA synthesis and stability in cultured hepatocytes, indicating prevention of liver injury, but did not show a liver-protective effect in GalN/LPS rats. Among EleAA, Lys, Trp, His, and Arg (4AA) markedly decreased nitric oxide production and inhibited nuclear factor-κB (NF-κB) activation. In GalN/LPS rats, 4AA (3% of each amino acid in diet) increased survival rate by 50% and decreased mRNA expression of iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 in the liver. 4AA reduced NF-κB activation induced by GalN/LPS. 4AA inhibited the expression of inflammatory mediators, in part through inhibition of NF-κB activation in cultured hepatocytes and GalN/LPS-treated rats. The results suggest that EleAA has therapeutic potential for organ injuries including liver.


Subject(s)
Amino Acids/pharmacology , Hepatocytes/drug effects , Liver Diseases/drug therapy , Acute Disease , Animals , Cells, Cultured , Disease Models, Animal , Galactosamine/pharmacology , Hepatocytes/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , L-Lactate Dehydrogenase/metabolism , Lipopolysaccharides/pharmacology , Liver/cytology , Liver/drug effects , Liver/metabolism , Male , NF-kappa B/genetics , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Phosphatidylinositol 3-Kinase/genetics , Phosphatidylinositol 3-Kinase/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar , Signal Transduction , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
4.
Gan To Kagaku Ryoho ; 44(12): 1982-1984, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29394841

ABSTRACT

We herein report 2 cases of successful surgical treatment of reconstructed gastric tube-bronchial fistulas caused by leakage after esophagectomy for esophageal cancer. One patient was a 56-year-old man who developed a reconstructed gastric tube-bronchial fistula, and the fistula was closed by conservative treatment. However, he developed pneumonia on postoperative day 117, and the reconstructed gastric tube-bronchial fistula was found to have recurred. Fibrin glue was endoscopically injected into the fistula, but this treatment was unsuccessful. The other patient was a 60-year-old man who developed a reconstructed gastric tube-bronchial fistula and severe pneumonia, and his condition did not improve by conservative treatment. We performed a reoperation for both patients using a pedunculated latissimus dorsi flap, and both patients recovered well.


Subject(s)
Bronchial Fistula/surgery , Esophageal Fistula/surgery , Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Bronchial Fistula/etiology , Esophageal Fistula/etiology , Humans , Male , Middle Aged , Reoperation , Surgical Flaps
5.
Surg Laparosc Endosc Percutan Tech ; 26(4): 338-42, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27438177

ABSTRACT

PURPOSE: We report a duodenal stump reinforcement procedure in laparoscopic distal gastrectomy with Roux-en-Y reconstruction. METHODS: We retrospectively reviewed the data of 223 patients who underwent laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer. We compared 2 groups: group NR (not reinforced, n=102, June 2009 to December 2011) when we did not perform reinforcement of the duodenal stump, and group R (reinforced, n=121, January 2012 to July 2014) when we did the reinforcement. The duodenum was divided with an endoscopic linear stapler. In group R, the duodenal staple line was reinforced by hand-sewn Lembert's sutures. RESULTS: There were no significant differences between group NR and R in patients' characteristics. Duodenal stump leakage occurred in 2 patients in group NR (2.0%). By contrast, in R group, no patients had duodenal stump leakage or fistula. CONCLUSIONS: Duodenal stump leakage can be avoided by using reinforcement with Lembert's sutures.


Subject(s)
Gastrectomy/methods , Gastroscopy/methods , Stomach Neoplasms/surgery , Anastomosis, Roux-en-Y/methods , Female , Humans , Male , Middle Aged , Postoperative Hemorrhage/etiology , Surgical Stapling/methods , Suture Techniques
6.
Gan To Kagaku Ryoho ; 43(3): 385-7, 2016 Mar.
Article in Japanese | MEDLINE | ID: mdl-27067862

ABSTRACT

A woman in her 50s visited our hospital in February 2015 with a complaint of dull abdominal pain in the right lower quadrant. She had a medical history of appendectomy for appendicitis in her 20s. Computed tomography(CT)revealed a tumor 90 mm in diameter near the ileocecum. Elective surgery was planned under the suspicion of gastrointestinal tumor, malignant lymphoma, or ileal cancer. She was emergently hospitalized 1 day earlier than scheduled because of high fever and severe abdominal pain. CT revealed that the tumor had increased to 120 mm in diameter without free air. Her white blood cell count was not elevated, and her symptoms improved readily with medical treatment. Thus, we performed the operation as scheduled. A tumor with a dark red recess on the surface had invaded the transverse colon intraoperatively, and a small amount of purulent ascites was present at the pouch of Douglas. We performed ileocecal resection with partial transverse colectomy. Histopathological examination led to the diagnosis of desmoid tumor in the mesentery of the terminal ileum. The surgical margins were negative for tumor cells. The tumor surface around the recess showed peritonitis, and the ascites showed no bacteria or tumor cells. The patient had been doing well without recurrence after discharge. Some cases of desmoid tumor with peritonitis have been reported, but most were caused by tumor penetration into the intestinal tract. We report herein a rare case of intra-abdominal desmoid tumor with abacterial peritonitis.


Subject(s)
Fibromatosis, Aggressive/diagnosis , Ileal Neoplasms/pathology , Ileal Neoplasms/surgery , Peritonitis/etiology , Ascites/etiology , Female , Fibromatosis, Aggressive/complications , Fibromatosis, Aggressive/surgery , Humans , Ileal Neoplasms/complications , Middle Aged , Tomography, X-Ray Computed , Treatment Outcome
7.
JPEN J Parenter Enteral Nutr ; 40(7): 1033-41, 2016 09.
Article in English | MEDLINE | ID: mdl-25754438

ABSTRACT

BACKGROUND: Japanese herbal medicine, Kampo saireito, is used for treatments in patients with digestive diseases, including chronic hepatitis and cirrhosis. However, few studies demonstrate scientific evidence for liver-protective effects of saireito. In inflamed liver, proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß stimulate the induction of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production. Excessive levels of NO synthesized by iNOS have been implicated as one of the factors in liver injury, so it is essential to reduce the induction of iNOS for the prevention of liver injury. In this study, we examined IL-1ß-stimulated hepatocytes as a simple "in vitro injury model" to investigate liver-protective effects of saireito. METHOD: Primary cultured rat hepatocytes were treated with IL-1ß in the presence or absence of saireito. The induction of NO production and iNOS and its signaling pathway were analyzed. RESULTS: Saireito inhibited the production of NO dose and time dependently and reduced the expression of iNOS messenger RNA (mRNA) and its protein. Saireito had no effect on IκB degradation but inhibited the translocation of nuclear factor (NF)-κB to the nucleus and its DNA binding. Saireito also inhibited the activation of Akt, resulting in the reduction of type I IL-1 receptor (IL-1RI) mRNA and protein expression. CONCLUSION: These findings demonstrate that saireito suppresses iNOS gene expression through the inhibition of NF-κB and IL-1RI-dependent pathways, leading to the reduction of NO production. Saireito may have therapeutic potential for organ injuries, including liver.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Hepatocytes/drug effects , Liver/drug effects , Medicine, Kampo , Nitric Oxide Synthase Type II/antagonists & inhibitors , Animals , Cells, Cultured , Cytokines/metabolism , Hepatocytes/metabolism , Japan , Liver/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Wistar , Signal Transduction
8.
Nitric Oxide ; 44: 81-7, 2015 Jan 30.
Article in English | MEDLINE | ID: mdl-25512333

ABSTRACT

Pyroglutamyl leucine (pyroGlu-Leu), which is a peptide isolated from wheat gluten hydrolysate, has been reported to be a hepatoprotective compound in acute liver failure. In inflamed liver, proinflammatory cytokines including interleukin (IL)-1ß and tumor necrosis factor (TNF)-α stimulate the induction of inducible nitric oxide synthase (iNOS). Excess production of nitric oxide (NO) by iNOS is an inflammatory biomarker in liver injury. We examined proinflammatory cytokine-stimulated hepatocytes as a simple "in vitro inflammation model" to determine liver protective effects of pyroGlu-Leu and its mechanisms of action. We hypothesized that pyroGlu-Leu inhibits the induction of iNOS gene expression, resulting in the attenuation of hepatic inflammation. Hepatocytes were isolated from rats by collagenase perfusion and cultured. Primary cultured cells were treated with IL-1ß in the presence or absence of pyroGlu-Leu. The induction of iNOS and its signaling pathway were analyzed. IL-1ß stimulated the enhancement of NO production in hepatocytes and this effect was inhibited by pyroGlu-Leu. pyroGlu-Leu decreased the expression of iNOS protein and its mRNA. Transfection experiments with iNOS-luciferase constructs revealed that pyroGlu-Leu inhibited both of iNOS promoter transactivation and its mRNA stabilization. pyroGlu-Leu also decreased the expression of an iNOS gene antisense transcript, which is involved in iNOS mRNA stability. However, pyroGlu-Leu had no effects on IκB degradation and NF-κB activation. Results demonstrate that pyroGlu-Leu inhibited the induction of iNOS gene expression at transcriptional and post-transcriptional steps through IκB/NF-κB-independent pathway, leading to the prevention of NO production. pyroGlu-Leu may have therapeutic potential for liver injury through the suppression of iNOS.


Subject(s)
Dipeptides/pharmacology , Hepatocytes/drug effects , Interleukin-1beta/metabolism , Nitric Oxide Synthase Type II/metabolism , Pyrrolidonecarboxylic Acid/analogs & derivatives , Transcriptional Activation/drug effects , Animals , Cells, Cultured , Hepatocytes/metabolism , Male , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/genetics , Pyrrolidonecarboxylic Acid/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar
9.
Asian J Endosc Surg ; 7(3): 260-3, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25131324

ABSTRACT

A 74-year-old woman who developed schwannoma of the sigmoid colon was referred to our hospital for colonography to determine the cause of her stool occult blood. Colonoscopy revealed a submucosal tumor, which measured 3 cm in diameter, in the sigmoid colon. Endoscopic ultrasonography revealed a low echoic, homogeneous and demarcated submucosal tumor that continued into the fourth layer of the colonic wall. Gastrointestinal stromal, myogenic or neurogenic tumor was suspected, and thus, laparoscopic sigmoidectomy was carried out. We used two ports during the operation, a SILS Port in the umbilical region and a 12-mm port in the right lower abdominal wall, and performed sigmoidectomy with D2 lymph node dissection. Histological findings revealed spindle-like tumor cells with multiform nuclei. The tumor was diagnosed by immunostaining as benign schwannoma of the sigmoid colon. The conventional surgical treatment for schwannoma of the digestive tract is partial resection, but if preoperative diagnosis is unknown, radical resection with lymphadenectomy is acceptable for submucosal tumors in the digestive tract. In this case, laparoscopic reduced port surgery using only one or two ports may be more feasible and beneficial with regard to cosmesis and reduced postoperative pain than conventional laparoscopic colectomy.


Subject(s)
Colectomy , Laparoscopy , Neurilemmoma/surgery , Sigmoid Neoplasms/surgery , Aged , Female , Humans , Neurilemmoma/pathology , Sigmoid Neoplasms/pathology
10.
Nitric Oxide ; 40: 75-86, 2014 Aug 31.
Article in English | MEDLINE | ID: mdl-24878381

ABSTRACT

Supplementation of active hexose correlated compound (AHCC) improved the prognosis of postoperative hepatocellular carcinoma patients. Excess production of nitric oxide (NO) by inducible NO synthase (iNOS) is an inflammatory biomarker in liver injury. AHCC suppressed iNOS induction in hepatocytes, suggesting that AHCC has a potential liver-protective effect. However, the active component in AHCC responsible for NO suppressive activities has not been identified. The objective of this study was to identify this NO suppressive component and to investigate its mechanisms of action. AHCC was subjected to fractionation by cation exchanger, size exclusion chromatography, and normal- and reversed-phase HPLC. Aliquots of the fractions were added to primary cultured rat hepatocytes stimulated with interleukin (IL)-1ß, and NO production was assayed. By activity-guided fractionation and electron spray ionization mass spectrometry analysis, adenosine was identified as one of the NO suppressive components in AHCC. Adenosine inhibited NO production, and reduced the expression of iNOS protein and mRNA. It had no effects on IκB degradation, but it inhibited NF-κB activation. Adenosine also inhibited the upregulation of type I IL-1 receptor (IL-1RI). Experiments with iNOS promoter-luciferase constructs revealed that adenosine decreased the levels of iNOS mRNA at the promoter transactivation and mRNA stabilization steps. Adenosine decreased the expression of the iNOS gene antisense transcript, which is involved in iNOS mRNA stability. Adenosine in AHCC suppressed iNOS induction by blocking NF-κB activation and the upregulation of the IL-1RI pathways, resulting in the inhibition of NO production.


Subject(s)
Adenosine/pharmacology , Hepatocytes/drug effects , Nitric Oxide Synthase Type II/antagonists & inhibitors , Polysaccharides/chemistry , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Hepatocytes/cytology , Hepatocytes/metabolism , Male , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar , Structure-Activity Relationship
11.
Dig Dis Sci ; 59(9): 2126-35, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24781162

ABSTRACT

BACKGROUND: Dextran sodium sulfate (DSS)-induced colitis in rats is widely used as an experimental model for elucidating the etiology of ulcerative colitis (UC) and developing its novel remedy. We investigated the temporal and spatial changes in inflammatory mediators such as tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the regions of rectum and distal colon and examined whether statins, which were designed to lower plasma cholesterol levels, influenced those mediators. METHODS: Colitis was induced in rats by oral administration of 5 % DSS for 5 days, followed by 2 % DSS for 10 days. 5 % DSS rats were treated with fluvastatin (20 mg/kg) concomitantly for 5 days. The expression of inflammatory mediators of a sequence of four regions in rectum (R) and distal colon (D0, D1, and D2) was determined by quantitative RT-PCR. RESULTS: The peak of colitic damage, which was confirmed clinically and histopathologically, was found on days 4-6. The expression of TNF-α, iNOS, cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1ß, and IL-6 mRNA increased in R time dependently, showing the peak on days 4-6, and then decreased thereafter. The levels of mRNAs reduced from R to D0, D1, and D2 region dependently. Fluvastatin decreased the expression of these markers in addition to the prevention of DSS-induced damage. CONCLUSIONS: Results demonstrated that the expression of inflammatory biomarkers had time and region specificity and was markedly inhibited by fluvastatin. To obtain a precise drug effect for UC, it is important to elucidate the temporal and spatial dependence of inflammatory biomarkers in DSS colitis model.


Subject(s)
Colitis/metabolism , Colitis/pathology , Colon/metabolism , Fatty Acids, Monounsaturated/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Indoles/therapeutic use , RNA, Messenger/metabolism , Rectum/metabolism , Animals , Biomarkers/metabolism , Chemokine CXCL1/genetics , Colitis/chemically induced , Colon/pathology , Dextran Sulfate , Disease Models, Animal , Fluvastatin , Interleukin-1beta/genetics , Male , Nitric Oxide Synthase Type II/genetics , Rats , Rats, Wistar , Rectum/pathology , Time Factors , Tumor Necrosis Factor-alpha/genetics
12.
Nitric Oxide ; 30: 9-16, 2013 Apr 01.
Article in English | MEDLINE | ID: mdl-23348570

ABSTRACT

Natural antisense transcripts (asRNAs) are frequently transcribed from mammalian genes. Recently, we found that non-coding asRNAs are transcribed from the 3' untranslated region (3'UTR) of the rat and mouse genes encoding inducible nitric oxide synthase (iNOS), which catalyzes the production of the inflammatory mediator nitric oxide. The iNOS asRNA stabilizes iNOS mRNA by interacting with the mRNA 3'UTR. Furthermore, single-stranded 'sense' oligonucleotides corresponding to the iNOS mRNA sequence were found to reduce iNOS mRNA levels by interfering with mRNA-asRNA interactions in rat hepatocytes. This method was named natural antisense transcript-targeted regulation (NATRE) technology. In this study, we detected human iNOS asRNA expressed in hepatocarcinoma and colon carcinoma tissues. The human iNOS asRNA harbored a sequence complementary to an evolutionarily conserved region of the iNOS mRNA 3'UTR. When introduced into hepatocytes, iNOS sense oligonucleotides that were modified by substitution with partial phosphorothioate bonds and locked nucleic acids or 2'-O-methyl nucleic acids greatly reduced levels of iNOS mRNA and iNOS protein. Moreover, sense oligonucleotides and short interfering RNAs decreased iNOS mRNA to comparable levels. These results suggest that NATRE technology using iNOS sense oligonucleotides could potentially be used to treat human inflammatory diseases and cancers by reducing iNOS mRNA levels.


Subject(s)
Nitric Oxide Synthase Type II/genetics , RNA, Antisense/genetics , RNA, Messenger/metabolism , 3' Untranslated Regions , Animals , Colonic Neoplasms/chemistry , Colonic Neoplasms/metabolism , Hepatocytes/cytology , Hepatocytes/metabolism , Humans , Liver Neoplasms/chemistry , Liver Neoplasms/metabolism , Male , Nitric Oxide Synthase Type II/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Nucleic Acid Conformation , RNA, Antisense/metabolism , RNA, Messenger/genetics , Rats , Rats, Wistar , Statistics, Nonparametric
13.
Hepatol Res ; 43(7): 775-84, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23198837

ABSTRACT

AIM: Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors), which were originally designed to lower plasma cholesterol levels, are increasingly recognized as anti-inflammatory agents. In the inflamed liver, pro-inflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS). Overproduction of NO by iNOS has been implicated as a factor in liver injury. We examined pro-inflammatory cytokine-stimulated hepatocytes as a simple in vitro injury model to determine liver-protective effects of statins. We hypothesized that statins are involved in the downregulation of iNOS, resulting in decreased hepatic inflammation. METHODS: Hepatocytes were isolated from rats by collagenase perfusion and centrifugation. Primary cultured hepatocytes were treated with interleukin (IL)-1ß in the presence or absence of fluvastatin. The induction of iNOS and its signaling pathway were analyzed. RESULTS: IL-1ß produced increased levels of NO. This effect was inhibited by fluvastatin, which exerted its maximal effects at 100 µM. Fluvastatin decreased the levels of iNOS protein and its mRNA expression. Fluvastatin had no effects on IκB degradation and nuclear factor-κB activation. However, fluvastatin inhibited the upregulation of type I IL-1 receptor mRNA and protein expression. Transfection experiments demonstrated that fluvastatin suppressed iNOS induction by the inhibition of promoter transactivation and mRNA stabilization. Fluvastatin reduced the expression of an iNOS gene antisense-transcript, which is involved in iNOS mRNA stability. CONCLUSION: Results indicate that fluvastatin inhibits the induction of iNOS at both transcriptional and post-transcriptional steps, leading to the prevention of NO production. Fluvastatin may provide therapeutic potential in iNOS induction involved in various liver injuries.

14.
Surg Today ; 42(10): 973-7, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22619001

ABSTRACT

Cavernous hemangioma of the adrenal gland is a rare tumor, which does not usually have endocrinological function. We report to our knowledge, the third documented case of a functioning adrenal hemangioma. Interestingly, this tumor indicated glucocorticoid hypersecretion, whereas the two previous cases showed mineralocorticoid hypersecretion. The tumor was 5 cm in diameter with typical computed tomography and magnetic resonance imaging findings. Subclinical Cushing's syndrome was diagnosed preoperatively, as there was insufficient suppression of cortisol by low-dose dexamethasone, a low adrenocorticotropic hormone (ACTH) concentration, and diminished ACTH and cortisol circadian rhythms without the typical clinical manifestation and symptoms of hypercortisolism. Intraoperative hypotension occurred immediately after tumor removal and following postoperative adrenal insufficiency, which support that the tumor was hyperfunctioning. The postoperative adrenal insufficiency had recovered completely by 12 months after the operation.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Cushing Syndrome/etiology , Hemangioma, Cavernous/diagnosis , Adrenal Gland Neoplasms/complications , Aged , Cushing Syndrome/diagnosis , Female , Hemangioma, Cavernous/complications , Humans
15.
Dig Dis Sci ; 57(4): 943-51, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22212728

ABSTRACT

BACKGROUND/AIMS: α-Lipoic acid (α-LA) has been reported to reduce ischemia-reperfusion injury (IRI). Proinflammatory cytokines stimulate the induction of inducible nitric oxide synthase (iNOS) gene expression, leading to excess production of NO and resulting in liver injury including IRI. We hypothesized that inhibition of iNOS induction underlies the protective effects of α-LA on the liver. The objective was to investigate whether α-LA directly influences iNOS induction in cultured hepatocytes, which is used as a simple in vitro injury model, and the mechanism involved. METHODS: Primary cultured rat hepatocytes were treated with interleukin (IL)-1ß in the presence or absence of α-LA. The induction of iNOS and NO production and its signal were analyzed. RESULTS: α-LA inhibited the expression of iNOS mRNA and protein dose- and time-dependently, resulting in decreases in NO production. α-LA had no effects on the degradation of IκB proteins and activation of NF-κB. In contrast, α-LA inhibited the upregulation of type I IL-1 receptor stimulated by IL-1ß, although α-LA had no effect on Akt activation. Transfection experiments with iNOS promoter-luciferase constructs revealed that α-LA had no effect on the transactivation of the iNOS promoter, but decreased the stabilization of iNOS mRNA. Further, α-LA inhibited the expression of an iNOS gene antisense-transcript, which is involved in iNOS mRNA stability. CONCLUSIONS: Results indicate that α-LA inhibits the induction of iNOS gene expression at a posttranscriptional step via iNOS mRNA stabilization, rather than promoter activation. It may provide useful therapeutic effects through the suppression of iNOS induction involved in liver injury.


Subject(s)
Antioxidants/pharmacology , Gene Expression/drug effects , Hepatocytes/metabolism , Interleukin-1beta/pharmacology , Nitric Oxide Synthase Type II/metabolism , RNA Stability/drug effects , RNA, Messenger/metabolism , Thioctic Acid/pharmacology , Animals , Cells, Cultured , Hepatocytes/drug effects , L-Lactate Dehydrogenase/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/genetics , Promoter Regions, Genetic/drug effects , Rats , Rats, Wistar , Receptors, Interleukin-1/metabolism , Transcriptional Activation/drug effects
16.
J Nutr Metab ; 2011: 374542, 2011.
Article in English | MEDLINE | ID: mdl-21773019

ABSTRACT

Eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA), n-3 polyunsaturated fatty acids (PUFAs), have a variety of biological activities including anti-inflammatory and anticancer effects. We hypothesized that their peroxidized products contributed in part to anti-inflammatory effects. In the liver, the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as one of the factors in hepatic inflammation and injury. We examined whether the peroxidation of EPA/DHA influences the induction of iNOS and NO production in proinflammatory cytokine-stimulated cultured hepatocytes, which is in vitro liver inflammation model. Peroxidized EPA/DHA inhibited the induction of iNOS and NO production in parallel with the increased levels of their peroxidation, whereas unoxidized EPA/DHA had no effects at all. Peroxidized EPA/DHA reduced the activation of transcription factor, NF-κB, and the expression of the iNOS antisense transcript, which are involved in iNOS promoter transactivation (mRNA synthesis) and its mRNA stabilization, respectively. These findings demonstrated that peroxidized products of EPA/DHA suppressed the induction of iNOS gene expression through both of the transcriptional and posttranscriptional steps, leading to the prevention of hepatic inflammation.

17.
Surg Today ; 41(7): 1011-5, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21748624

ABSTRACT

A pancreatic endometrial cyst is an extremely rare disease. Since 1984, only 7 cases have been reported, including the current case. A 35-year-old woman with a history of recurrent severe left upper abdominal pain of 3 months' duration was found to have a cyst in the pancreatic body on the diagnostic imaging findings. With a preoperative diagnosis of mucous cystic adenoma, she underwent a distal pancreatectomy. The histopathological examination of the specimen revealed a pancreatic endometrial cyst. She complained about severe periodic abdominal pain during the convalescence, without any surgical complications. This study reviews previous reports of pancreatic endometrial cysts, and also discusses the clinicopathological features, pathogenesis, and appropriate treatment for this disease.


Subject(s)
Cystadenoma/diagnosis , Endometrial Neoplasms/diagnosis , Pancreatic Neoplasms/diagnosis , Abdominal Pain/pathology , Adult , Cystadenoma/pathology , Cystadenoma/surgery , Endometrial Neoplasms/pathology , Endometrial Neoplasms/surgery , Female , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery
18.
Gan To Kagaku Ryoho ; 38(6): 1021-4, 2011 Jun.
Article in Japanese | MEDLINE | ID: mdl-21677500

ABSTRACT

A 60-year-old man was hospitalized for urodynia. Clinical examinations demonstrated a locally advanced sigmoid colon cancer with direct extension to the bladder, rectum, and pelvic wall. We considered that curative resection was not possible and performed temporary colostomy for fecal diversion. After colostomy, he was treated with neoadjuvant chemoradiotherapy(NACRT)for down staging. The radiation therapy was delivered with 45 Gy(1. 8 Gy/fraction; 5 days/week×5 weeks), and the concurrent chemotherapy was performed with capecitabine(825mg/m2 twice daily on radiotherapy days). CT scan confirmed a dramatic response with downstaging of the tumor following NA-CRT(clinical response, PR in the RECIST criteria). Invasion of the tumor to pelvic wall disappeared on CT scan, and[18F]fluorodeoxyglucose positron emission tomography( FDG-PET)failed to demonstrate any distant metastasis. We considered that the tumor was hence resectable and performed total pelvic exenteration(TPE)1 month after NACRT. A pathological examination of surgical specimens confirmed a R0 resection. The patient made an unremarkable postoperative recovery. He went on to receive adjuvant capecitabine chemotherapy, completing four cycles. He remains well and disease-free 10 months following surgery. NACRT with capecitabine appears effective even for unresectable locally advanced sigmoid colon cancer.


Subject(s)
Adenocarcinoma/drug therapy , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoadjuvant Therapy , Sigmoid Neoplasms/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Capecitabine , Combined Modality Therapy , Deoxycytidine/therapeutic use , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Positron-Emission Tomography , Sigmoid Neoplasms/pathology , Sigmoid Neoplasms/radiotherapy , Sigmoid Neoplasms/surgery , Tomography, X-Ray Computed
19.
Med Mol Morphol ; 43(1): 60-4, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20340008

ABSTRACT

A case of solitary fibrous tumor (SFT) arising in the soft tissue of the left inguinal region is reported. A 57-year-old Japanese woman presented with a nonadherent, well-defined, oval mass that was 2 x 3 cm in diameter and located in the inguinal soft tissue. Microscopic evaluation showed proliferation of spindle-shaped, fibroblast-like cells by the coexistence of hypo- and hypercellular areas with mast cell infiltration separated by hemangiopericytoma-like blood vessels. Immunohistochemistry revealed strong expression of CD34 and CD99 in the fibroblast-like cells, supporting the diagnosis of SFT. Although the patient was free of symptoms such as hypoglycemia, immunoreactive insulin-like growth factor (IGF)-II was localized in the socalled Golgi area of the spindle-shaped cells. In conclusion, immunoreactive IGF-II was detected in SFT that was not associated with hypoglycemia.


Subject(s)
Abdominal Neoplasms/diagnosis , Inguinal Canal , Solitary Fibrous Tumors/diagnosis , 12E7 Antigen , Abdominal Neoplasms/chemistry , Abdominal Neoplasms/surgery , Antigens, CD/analysis , Antigens, CD34/analysis , Cell Adhesion Molecules/analysis , Female , Golgi Apparatus/chemistry , Humans , Hypoglycemia/metabolism , Immunohistochemistry , Insulin-Like Growth Factor II/analysis , Middle Aged , Solitary Fibrous Tumors/chemistry , Solitary Fibrous Tumors/surgery
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