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Biomedical subjects

Tomohiko Akahoshi

Publications and source records attributed to Tomohiko Akahoshi.

13 recordsLinked to original sources
PubMed2005

Selective cyclooxygenase (COX) inhibition causes damage to portal hypertensive gastric mucosa: roles of nitric oxide and NF-kappaB.

Portal hypertension (PHT) is associated with increased susceptibility of the gastric mucosa to injury by a variety of factors, including nonsteroidal anti-inflammatory drugs (NSAIDs) that nonselectively inhibit both isoforms of cyclooxygenase (COX-1 and -2). PHT gastric mucosa also has excessive nitric oxide (NO) production that contributes to the general increased susceptibility to injury. Using a rat model of PHT, we studied whether selective COX inhibition, which does not damage normal (normotensive) gastric mucosa, is sufficient to cause PHT gastric damage and, if so, whether and how excessive NO is involved. Indomethacin, a nonselective NSAID, caused 2.4-fold more gastric injury to PHT vs. normotensive sham-operated (SO) control rats. Neither NS-398 nor celecoxib, selective COX-2 inhibitors, caused gastric damage in either SO or PHT rats. SC-560, a selective COX-1 inhibitor, did not cause gastric damage in SO rats but dose-dependently caused gastric damage in PHT rats. There was a compensatory increase in COX-2 expression and activity in SC-560-treated SO rats but not SC-560-treated PHT rats. Partial inhibition of NO production restored gastric COX-2 expression and activity levels in SC-560-treated PHT rats to those of SC-560-treated SO rats, by a mechanism consistent with induction of NF-kappaB, and significantly reduced gastric damage. These studies indicate that, in contrast to normotensive gastric mucosa, inhibition of COX-1 alone is sufficient to cause PHT gastric damage as a result of excessive NO that prevents the induction of NF-kappaB and the compensatory increase in COX-2.

Animals↗
PubMed2005

Survivin: a novel target for indomethacin-induced gastric injury.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal erosions and ulcers. Apoptosis is one of the mechanisms. The role of survivin, an antiapoptosis protein, in NSAID-induced gastric injury is unknown. We examined the role of survivin in NSAID-induced gastric mucosal and gastric cell injury. METHODS: We examined: (1) the effects of indomethacin (nonselective NSAID), celecoxib and NS-398 (cyclooxygenase [COX]-2-selective NSAIDs), SC-560 (a COX-1-selective NSAID), and SC-560 plus celecoxib on survivin expression and extent of injury in rat gastric mucosa; (2) the effects of indomethacin, NS-398, SC-560, and SC-560 plus NS-398 on survivin expression and injury in gastric epithelial (RGM-1) cells; and (3) the effects of survivin suppression with small interfering RNA (siRNA) on RGM-1 cell integrity at baseline and following indomethacin injury. RESULTS: Indomethacin treatment dose-dependently reduced survivin protein levels and caused severe injury of gastric mucosa and RGM-1 cells. Suppression of survivin expression with siRNA in RGM-1 cells caused cell damage and increased susceptibility to injury by indomethacin. Celecoxib treatment caused exfoliation of the mucosal surface epithelium, but neither caused deep erosions or altered survivin expression. Neither NS-398 nor SC-560 treatment altered survivin levels or produced injury in vivo or in vitro. COX-1 and COX-2 inhibitor combination caused injury in vivo and in vitro but did not decrease survivin expression. CONCLUSIONS: (1) Indomethacin, but not selective COX-1 or COX-2 inhibitors alone or in combination, reduces survivin expression in gastric mucosal cells and (2) significant reduction of survivin precedes greater severity of gastric injury.

Animals↗
PubMed2004

Propranolol alone may not be acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients: randomized controlled trial.

BACKGROUND AND AIM: In Japan, endoscopic injection sclerotherapy (EIS) is widely used to prevent first esophageal variceal bleeding, in contrast to pharmacological therapy which is the main treatment used in the rest of the world. The present study investigated if propranolol alone is acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients. This was compared with EIS. METHODS: Twenty-five Japanese cirrhotic patients with endoscopically proven, likely to bleed esophageal varices were randomly assigned for propranolol administration (12 patients; group A) and EIS (13 patients; group B) to prevent first esophageal variceal bleeding. Complications, non-recurrence rate, bleeding rate and probability of survival were compared between the two groups. RESULTS: One patient in group A had severe bradycardia with loss of consciousness that seriously worsened his quality of life. The cumulative non-recurrence rate of group A was significantly lower compared with that of group B (P < 0.05). In group A, 2 of the 12 patients requested to discontinue taking propranolol and were excluded from the trial. The EIS treatment (group B) showed excellent results. No patient in group A or group B bled from esophageal varices throughout this study. The two groups showed no statistically significant differences in probability of survival. CONCLUSIONS: Propranolol alone may not be acceptable to prevent first esophageal variceal bleeding in Japanese cirrhotic patients.

Adrenergic beta-Antagonists↗
PubMed2003

Abnormal PTEN expression in portal hypertensive gastric mucosa: a key to impaired PI 3-kinase/Akt activation and delayed injury healing?

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual-specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids. PTEN inhibits activation of Akt, the downstream effector of PI 3-kinase, which is integral to cell proliferation, migration, survival, and angiogenesis essential for tissue injury healing. PTEN expression and activation during injury healing remain unexplored. Portal hypertensive (PHT) gastric mucosa has impaired injury healing, but the underlying mechanisms remain unknown. We investigated whether impaired healing of injured PHT gastric mucosa is due to abnormal PTEN expression/activation that leads to decreased Akt activation. We also investigated the possible involvement of Egr-1, which regulates PTEN in some cells (e.g., fetal kidney epithelial cells), and TNF-alpha, which can induce Egr-1 expression. In PHT gastric mucosa 6 h after injury, PTEN protein levels were increased by 2.7-fold; unphosphorylated PTEN (reflecting activated PTEN) was increased by 2.4-fold; Akt phosphorylation (reflecting Akt activation) was reduced by 2-fold; and Egr-1 expression was increased by 3.3-fold vs. normal gastric mucosa. TNF-alpha neutralization reversed all of the above abnormalities in PHT gastric mucosa, reduced mucosal injury, and enhanced healing. We conclude that, in injured PHT gastric mucosa, overexpressed/activated PTEN leads to the reduced activation of the PI 3-kinase/Akt pathway that results in impaired injury healing.

Animals↗
PubMed2003

A robotic surgery system (da Vinci) with image guided function--system architecture and cholecystectomy application.

We have developed a data fusion system for the robotics surgery system "da Vinci". The data fusion system is composed of an optical 3D location sensor and a digital video processing system. The 3D location sensor is attached to the da Vinci's laparoscope and measures its location and direction. The digital video processing system captures the laparoscope's view and superimposes 3D patient's organ models onto the captured view in real-time. We applied the system to "da Vinci" and examined this system during a cholecystectomy. In this experiment, the surgeon was able to observe the inner conditions of the organs with a stereo view.

Cholecystectomy↗
PubMed2002

Role of the spleen in liver fibrosis in rats may be mediated by transforming growth factor beta-1.

BACKGROUND: The effect of the spleen on the cirrhotic liver is unknown. Transforming growth factor-beta 1 (TGF-beta 1), which plays a crucial role in the matrix production during liver fibrosis, is an inhibitory factor regarding the regeneration of hepatocytes. In this study, we investigated the TGF-beta 1 production in the spleen of cirrhotic rats and the effects of a splenectomy on the healing process from liver fibrosis. METHODS: Thirty-six Wistar male rats were used. Thioacetamide (TAA) was administered intraperitoneally for 24 weeks. The rats underwent either a sham operation (TAA + Sham) or a splenectomy (TAA + SPL). The improvements in liver fibrosis and liver regeneration were investigated 10, 30 and 60 days after the operations in each group. The effect of a splenectomy on the plasma concentration of TGF-beta 1 in the portal vein was investigated by ELISA. The TGF-beta 1 expressions in the spleen were measured using immunohistochemical staining and the degree of such expression was measured using RT-PCR. The activity of TGF-beta 1 in the portal vein of TAA + Sham and TAA + SPL was assessed by the inhibiting effect of rat parenchymal hepatocyte proliferation in primary culture. RESULTS: Liver regeneration (PCNA-labeling index) in the TAA + SPL rats was stimulated more at 10 and 30 days after the operation (P < 0.05) than in the TAA + Sham rats, and the improvement of liver fibrosis (fibrosis rate) in the TAA + SPL rats was higher at 60 days (P < 0.05) than in the TAA + Sham rats. The plasma concentration of TGF-beta1 of the portal vein in TAA + SPL rats was significantly lower than in the TAA + Sham rats for each period. Immunohistochemically, TGF-beta1-positive stained cells were recognized in the spleen macrophages in the red pulp of cirrhotic rats. The plasma of the TAA + Sham rats at 10 and 30 days after the operation was significantly stronger than that of the TAA + SPL rats in inhibiting the proliferation of rat hepatocytes of primary culture. Inhibitory effects were then dose-dependently neutralized by monoclonal TGF-beta 1 antibody. CONCLUSION: Spleen-derived TGF-beta 1 may thus play an inhibitory role in the healing of liver cirrhosis by inhibiting the regeneration of the damaged liver.

Animals↗
PubMed2002

Endoscopic injection sclerotherapy in the management of 2105 patients with esophageal varices.

BACKGROUND: The objective of this study is to examine the overall clinical results of endoscopic injection sclerotherapy (EIS) for patients with esophageal varices in our institution. METHODS: From January 1982 to May 2001, 2105 patients with esophageal varices were treated with EIS, which included prophylactic injections for patients with risky varices according to our criteria. Follow-up endoscopy was performed every 3 months, and recurrent varices were treated with additional EIS. RESULTS: Acute variceal bleeding was controlled in 468 of 473 patients (98.9%). Esophageal varices were completely eradicated in 1757 of 2105 patients (83.5%) with 3.8 +/- 1.6 sessions of EIS. The cumulative recurrence rates were 32.2% at 5 years, 36.5% at 10 years, and 37.8% at 15 years. The cumulative nonbleeding rates were 92.3% at 5 years, 90.1% at 10 years, and 89.5% at 15 years. The survival rate of acute bleeders was significantly lower than for both elective and prophylactic cases (P <.05). The overall cumulative survival rate was 28.2% at 10 years. CONCLUSIONS: EIS is the first choice of treatment for esophageal variceal bleeding, and rebleeding was shown to be well controlled in a long-term follow-up with endoscopy and additional EIS. The lower survival rate observed in acute bleeders may therefore justify the use of prophylactic EIS.

Acute Disease↗
PubMed2002

Long-term results of endoscopic Histoacryl injection sclerotherapy for gastric variceal bleeding: a 10-year experience.

BACKGROUND: The long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) were evaluated as the initial treatment for bleeding gastric varices. PATIENTS AND METHODS: Fifty-two patients with bleeding gastric varices underwent endoscopic injections of Histoacryl for hemostasis over a 10-year period. Histoacryl was injected intravariceally. Among these 52 patients, 32 had active bleeding and 20 had recent bleeding. Most of the varices were large (F2 or F3, 48 cases). After Histoacryl injection, the patients were followed endoscopically with retreatment administered as necessary. The patients were followed for a mean 28.1 months. RESULTS: The rate of initial hemostasis (no bleeding occurred for 48 hours after sclerotherapy) was 96.2%. Cumulative nonbleeding rates were 64.7%, 52.7%, and 48.2% at 1, 5, and 10 years, respectively. When rebleeding occurred, 80.0% was within 1 year after initial injection. Recurrent bleeding was easily stopped with the reinjection of Histoacryl in most patients. The treatment failure-related mortality rate was 4.0% (2 of 52). The cumulative survival rates were 66.9%, 60.4%, and 55.5% at 1, 5, and 10 years, respectively. The mortality depended on either malignancy or liver function (Child-Pugh classification). CONCLUSIONS: These results suggest that Histoacryl injection sclerotherapy is highly effective for the treatment of bleeding gastric varices, with rare complications occurring both acutely and long-term. Therefore, Histoacryl injection sclerotherapy is considered to be the first choice of treatment for bleeding gastric varices, but the rate of recurrent bleeding is so high that further methods or devices still need to be developed in order to prevent gastric variceal rebleeding.

Adolescent↗
PubMed2002

Laparoscopic splenectomy for hematologic diseases.

BACKGROUND: Laparoscopic splenectomy has been demonstrated to be technically feasible and safe for the treatment of hematologic diseases. METHODS: The study comprised 64 consecutive patients with chronic immune thrombocytopenia purpura (ITP) who were admitted to our hospital from 1992 to 2000 and underwent laparoscopic splenectomy. Forty-one consecutive patients with ITP who underwent open splenectomy performed at the same hospital by the same surgical team between 1986 and 2000 were selected as the control group. RESULTS: We performed laparoscopic splenectomies for ITP, hereditary spherocytosis (HS), malignant lymphoma, autoimmune hemolytic anemia, and cryoglobulinemia. Laparoscopic surgery as compared with open surgery in ITP revealed a significantly lower pain medication requirement, an earlier resumption of oral intake, and a shorter hospital stay, but a longer operative time. During the present study (range: 3.8-80 months), the cumulative rate of nonrecurrence was 67.9% at 5 years after surgery, which was similar to the rate for the previous open splenectomy. CONCLUSIONS: Laparoscopic splenectomy is considered to be a suitable alternative therapeutic modality in the treatment of hematologic diseases.

Anemia, Hemolytic↗
PubMedDate not supplied

Pulmonary embolism following laparoscopic surgery: a report of two cases.

Laparoscopic abdominal surgery is considered a low-risk procedure for postoperative complications because of reduced surgical stress and earlier mobilization. We report two patients who experienced pulmonary embolism following laparoscopic surgery; one patient underwent umbilical hernia repair and the other cholecystectomy. Although pulmonary embolism is indeed rare after laparoscopic surgery, early detection and early treatment are determinative factors for a good prognosis. Therefore, medical caregivers must remember that pulmonary embolism can be a critical complication after laparoscopic surgery and preventive measures should be employed for high-risk subjects.

Adult↗
PubMedDate not supplied

Laparoscopic splenectomy for portal hypertension.

BACKGROUND/AIMS: Laparoscopic splenectomy is now increasingly being performed. However, controversy remains regarding the effectiveness of a laparoscopic splenectomy for patients with portal hypertension. METHODOLOGY: Seventy-three patients with portal hypertension who underwent a laparoscopic splenectomy from February 1992 until October 2000 were reviewed and the effectiveness of the procedures for portal hypertension was evaluated. Forty-two patients had esophagogastric varices and twenty had a concomitant hepatocellular carcinoma. The indications for surgery were bleeding tendency due to thrombocytopenia (n = 40), difficulty in receiving treatment for hepatocellular carcinoma due to thrombocytopenia (n = 18), and sclerotherapy-resistant esophagogastric varices (n = 15). RESULTS: A laparoscopic splenectomy was successfully performed in all the patients. The rate of conversion to conventional open surgery was 9.6% (7/73). The mean operative time was 210.1 +/- 101.9 minutes, and the estimated blood loss was 374.7 +/- 352.4 mL. There were no cases of mortality, and morbidity was encountered in 11.0% of patients. The increase in the platelet count correlated significantly to the spleen weight (P < 0.001). The platelet count had been maintained at over 10 x 10(4)/mm3 for over three years. Eighteen patients with hepatocellular carcinoma successfully underwent treatment for hepatocellular carcinoma after surgery and no recurrence of esophagogastric varices was encountered. CONCLUSIONS: A laparoscopic splenectomy resulted in the successful secondary treatment of hepatocellular carcinoma and esophagogastric varices. Portal hypertension was not a contraindication. A laparoscopic approach is therefore the procedure of choice for a splenectomy in portal hypertension.

Aged↗