A Randomized Double-blind Placebo-controlled Trial on the Effect of Magnesium Oxide in Patients With Chronic Constipation

BACKGROUND/AIMS: Magnesium oxide (MgO) has been frequently used as a treatment for chronic constipation (CC) since the 1980s in Japan. The aim of this study is to evaluate its therapeutic effects of MgO in Japanese CC patients. METHODS: We conducted a randomized, double-blind placebo-controlled study. Thirty-four female patients with mild to moderate constipation were randomly assigned to either placebo (n = 17) or MgO group (n = 17) 0.5 g × 3/day for 28 days. Primary endpoint was overall improvement over the 4-week study period. Secondary endpoints were changes from baseline in spontaneous bowel movement (SBM), response rates of complete spontaneous bowel movement (CSBM), stool form, colonic transit time (CTT), abdominal symptom, and quality of life. RESULTS: One patient failed to complete the medication regimen and was omitted from analysis: data from 16 placebo and 17 MgO patients were analyzed. The primary endpoint was met by 25.0% of placebo vs 70.6% of MgO group (P = 0.015). MgO significantly improved SBM changes compared to placebo (P = 0.002). However, MgO did not significantly improved response rates of CSBM compared to placebo (P = 0.76). In addition, MgO significantly improved Bristol stool form scale changes (P < 0.001) and significantly improved CTT compared to the placebo group (P < 0.001). MgO significantly improved the Japanese version of the patient assessment of constipation quality of life (P = 0.003). CONCLUSION: Our placebo-controlled study demonstrated that MgO was effective treatment for improving defecation status and shortened CTT in Japanese CC patients with mild to moderate symptoms.

Mechanism of hepatocyte apoptosis in rats with liver fibrosis induced by lipogenic methionine-choline-deficient diet / 中华病理学杂志

<p><b>OBJECTIVE</b>To clarify the effects of endoplasmic reticulum stress (ER stress) and mitogen-activated protein kinase (MAPK) on hepatocyte apoptosis in rats with non-alcoholic fatty liver fibrosis induced by methionine-choline-deficient diet (MCDD).</p><p><b>METHODS</b>Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by giving a MCDD for 10 weeks (group M). A methionine-choline-control diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental group (group R). Steatosis, fibrosis and inflammation were determined by tissue staining. The activation of hepatic stellate cells and oxidative stress were determined by immunostaining, immunoblotting or real time-PCR (RT-PCR), respectively. Hepatocyte apoptosis was determined by TUNEL staining. Expressions of glucose-regulated protein 78 (GRP78), caspase-12, caspase-7, cleaved caspase-7, caspase-3, cleaved caspase-3, and caspase-9 were evaluated to clarify the presence of ER stress. Expressions of c-Jun, ERK1/2, p-ERK1/2 were evaluated to clarify the states of MAPK signaling.</p><p><b>RESULTS</b>Changing the diet from MCDD to MCCD triggered the reduction of fat in hepatocytes, a decrease in inflammatory response, oxidative stress, and fibrosis. The protein expressions of ERP78, caspase-12, caspase-7, and cleaved caspase-7 were increased significantly in group M compared with normal control group (group N, P < 0.05 or P < 0.01), the mRNA expressions of ERP78, caspase-12, and caspase-7 were also increased significantly in group M compared with group N (3.03 ± 0.41 vs 2.12 ± 0.37, 1.86 ± 0.36 vs 0.78 ± 0.20, and 2.38 ± 0.19 vs 1.84 ± 0.13, respectively, P < 0.05 or P < 0.01), while they recovered immediately in group R. In contrast, the protein levels of caspase-3, cleaved caspase-3 and mRNA expressions of caspase-3 and caspase-9 revealed no significant differences in three groups (P > 0.05). The mRNA expressions of c-Jun and protein levels of ERK1 and p-ERK1 were increased significantly in group M compared with group N (P < 0.01), while they recovered immediately after changing the diet from MCDD to MCCD.</p><p><b>CONCLUSIONS</b>ER stress plays a role in the development and regression of non-alcoholic fatty liver fibrosis induced by MCDD, however, ER stress-related caspase-12 pathway may not be the main mechanism of hepatic apoptosis, and MAPK signaling may play an important role in hepatic apoptosis in the model.</p>

Involvement of endoplasmic reticulum stress in development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study role of endoplasmic reticulum stress in the development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats.</p><p><b>METHODS</b>Non-alcoholic steatohepatitis was induced by 10 weeks- methionine-choline-deficient diet (MCDD), Markers of endoplasmic reticulum stress were determined by immunoblotting and real-time PCR.</p><p><b>RESULTS</b>The number of apoptotic hepatocytes, The expression levels of endoplasmic reticulum stress markers were increased significantly in MCDD group compared to control group (probability value less than 0.05 or probability value less than 0.01), while ratio of hepatocyte proliferation/apoptosis was decreased in MCDD group (probability value less than 0.01). The number of hepatocytes apoptosis, and the expression levels of endoplasmic reticulum stress markers were decreased significantly 2 weeks after the feeding with normal diet in MCDD group (probability value less than 0.05 or probability value less than 0.01).</p><p><b>CONCLUSION</b>MCDD induces endoplasmic reticulum stress and fibrosis in rats.</p>

Acute Stanford Type B Aortic Dissection after Endoluminal Grafting for the Treatment of Descending Thoracic Aortic Aneurysms / 日本心臓血管外科学会雑誌

A 65-year-old patient underwent successful transluminally placed endoluminal prosthetic grafts (TPEGs) of a descending thoracic aortic aneurysm (dTAA). Two hours after TPEGs, the patient suddenly complained of chest, back pain and right leg pain. Angiography and computed tomography showed acute type B aortic dissection. Re-TPEGs was immediately performed, and the entry was successfully closed. This case suggests that TPEGs for the treatment of acute aortic dissection may be useful for selected patients.

A Case of Chest Pain as an Initial Symptom of Coronary-Pulmonary Arterial Fistula / 日本心臓血管外科学会雑誌

A 51-year-old woman suffered from a sudden onset of anterior chest pain and was referred to our hospital on the suspicion of an anginal attack. The exercise ECG showed findings of an anterior lesion and ischemia. Coronary angiography also revealed left anterior descending branch fistula and circumflex branch fistula connecting to the main pulmonary artery trunk. Direct closure was performed for both intra-pulmonary openings under cardiopulmonary bypass. The postoperative course was uneventful and the patient did not show any precordial pain. Coronary angiography showed no coronary organic narrowing, but contrast medium remained in the fistulae although there was no left to right shunt. Ligation of the fistulae had to be performed simultaneously to confirm complete obstruction of the coronary-pulmonary arterial fistulae. The antiplatlet agent is administered to the patient to prevent occurring myocardial infarction caused by thrombus which might be formed in fistulae.

Long Term Results with Tilting Disk and Bileallet Prostheses in Mitral Valve Replacement / 日本心臓血管外科学会雑誌

A total of 35 patients who underwent mitral valve replacement were followed up for more than 5 years. Their hemodynamics and valve function were analyzed using transthoracic and esophageal Doppler ultrasound echocardiography and cineangiography. They were classified and evaluated according to valve function. The tilting disk valve replacement group (group I) consisted of 24 cases, the bileaflet valve replacement group (group II) consisted of 11 cases. There were 4 mechanical valve dysfunction cases in group I. The function of group II tended to be superior to group I, even excluding those with valve dysfunction. However, the hemodynamic recovery of the latter was as good as that of group II. The left cardiac function parameters of LVEF, %FS and CI were comparable in both groups, but in valve dysfunction cases LVEDVI decreased because of prosthetic stenosis and there was some right ventricular overload with severe tricuspid regurgitation.

Hemodynamics and Surgical Results of Chronic Venous Insufficiency with Skin Changes in the Lower Limbs / 日本心臓血管外科学会雑誌

Preoperative hemodynamics in the lower limbs in 174 limbs of 103 patients were measured and investigated and the surgical results were evaluated. The subjects were divided into the C_4-6-group, which included 51 limbs with skin changes, and the C_{2, 3}-group, which consisted of 123 limbs without skin changes. Plethysmography showed that the maximum venous outflow was significantly higher, and the refilling time was shorter in the C_4-6-group compared to the C_{2, 3}-group. All C_4-6-group patients had reflux of the long saphenous vein, and the reflux velocity and volume was significantly greater than in the C_{2, 3}-group. Limbs with deep vein reflux accounted for 45% of the C_4-6-group. We performed angioscopic deep vein external valvuloplasty in 23 of those limbs. There was no case of reccurence of skin changes at a mean follow-up of 22 months. However chronic venous insufficiency often was associated with multisegmental reflux lesions and in such cases it might be necessary to perform multiple surgical procedures to eliminate the reflux.