Sodium butyrate enhances Fas-mediated apoptosis of human hepatoma cells

BACKGROUND/AIMS: Human hepatoma cells have been reported to be resistant to Fas-mediated apoptosis. Sodium butyrate (SB) induced apoptosis of several cancer cells. We investigated the effects of SB on Fas-mediated apoptosis of hepatoma cells. METHODS: In hepatoma cells (HuH-6, HuH-7, Hep-G2, and PLC/PRF/5), susceptibility to Fas-mediated apoptosis and Fas expression were assessed. Caspase-3 activation and cell cycle progression were evaluated in HuH-6. A cDNA microarray assay was performed to screen the changes in the expression of mRNAs. RESULTS: Pretreatment with SB caused an enhancement of the sensitivity to anti-Fas-mediated cytotoxicity, though it did not increase the expression of Fas. The cDNA microarray assay revealed up-regulation of pro-apoptotic Bik, Bak, Bid and c-Jun N-terminal protein kinase-1, and down-regulation of anti-apoptotic Bag-1 and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitor protein. In some molecules, expression of the proteins was confirmed by Western blotting. An increase in truncated-Bid accompanying the reduction in Bid was also observed. CONCLUSIONS: SB enhances the susceptibility of hepatoma cells to anti-Fas-mediated cytotoxicity by altering the mRNA and protein expression and/or the activation status of proteins that could be involved in the Fas signaling pathway. SB may have an important role in the elimination of hepatoma cells.     

Maternal thyroid function during pregnancy and puerperal period

It has been noted that hypothyroidism in pregnant women can adversely affect the children's subsequent psychoneurotic development. Also, transient elevation of serum free thyroxine is occasionally seen in the first trimester of normal pregnancy. However, normal thyroid function during pregnancy and the puerperal period has not been clearly defined in Japan. The aim of this study was to assess maternal thyroid function during pregnancy and puerperal period in Japan. The concentrations of thyroid stimulating hormone (TSH), free triiodo-thyronine (free T(3)), free thyroxine (free T(4)) and thyroid binding capacity (TBC) of 522 normal pregnant and puerperal women (119 in the first trimester; 132 in the second trimester; 135 in the third trimester and 136 in the early puerperium) were measured by electrochemiluminescence immunoassay. We compared the measured data with those of healthy nonpregnant control. Twenty-six (21.8%) of 119 women in the first trimester had lower TSH levels and 23 (16.9%) of 136 women in the early puerperium had higher TSH levels than the normal range of healthy nonpregnant controls. Free T(3) gradually decreased during pregnancy, although it remained within the normal control range. Eight (6.7%) of 119 women in the first trimester had high free T(4) levels, which gradually decreased during pregnancy. Sixty (44.4%) of 135 women in the third trimester had low free T(4) levels. The values of TBC in the second trimester increased compared with the first trimester and did not change in the third trimester and decreased after delivery. There were no correlations between maternal TSH and levels of thyroid hormones (free T(3) or free T(4)), except for TSH and free T(4) in the first trimester. In conclusion, we showed that maternal thyroid function, especially TSH and free T(4), changed during the course of pregnancy. In assessing the thyroid function associated with pregnancy, one needs to keep in mind the tendency toward low free T(4) levels in the third trimester and high TSH levels in the early puerperal period.     

Churg-Strauss syndrome complicated by colon erosion, acalculous cholecystitis and liver abscesses

We report on a case of Churg-Strauss syndrome (CSS) with colon erosion, cholecystitis and liver abscesses. A 21-year-old woman with a history of bronchial asthma for 3 years was admitted with a complaint of abdominal pain. Laboratory findings included remarkable leukocytosis and eosinophilia, and a colonoscopy revealed erosion from the rectum to the ileocecal region. In addition, a colonic biopsy specimen showed necrotizing vasculitis and marked eosinophilic infiltration. On the basis of the clinical features and histopathological findings, she was diagnosed with CSS and subsequently treated with oral prednisolone, after which the eosinophilia and abdominal pain disappeared. However, on the 15th d in hospital she developed cholecystitis and liver abscesses. She was therefore treated with antibiotics and as a result went into clinical remission.     

The harmful effect of exercise on reducing taurine concentration in the tissues of rats treated with CCl<Subscript>4</Subscript> administration

Background We have previously reported that oral taurine administration reduced the frequency of painful muscle cramps in patients with liver cirrhosis, and that skeletal muscle taurine concentration was significantly decreased after exercise. The aim of this study was to examine taurine concentration in various tissues of a liver damaged with fibrosis (LD) in a rat model before and after exercise.Methods Rats were divided into normal (NML) and LD groups. The LD group received CCl₄ injection for 10 weeks. Thereafter, both groups were divided into control (NML/CTL, LD/CTL) and exercise (NML/EX, LD/EX) groups, respectively. The rats in the EX groups were subjected to treadmill running. Plasma, liver, brain, heart, and skeletal muscle taurine concentration, as well as plasma and liver lipid peroxidase (LPO) concentration, were measured.Results The liver, brain, and skeletal muscle taurine concentration in the LD groups was significantly decreased compared to that in the respective NML groups. Furthermore, the taurine concentration in the heart and skeletal muscles in the LD/CTL group was significantly decreased post exercise. The respective plasma and liver LPO concentration in the LD groups was significantly increased compared to that in the corresponding NML group. Moreover, plasma LPO concentration in the LD/EX group was significantly higher than in the LD/CTL group.Conclusions Tissue taurine concentration, particularly in skeletal muscle, was significantly decreased in the LD model rats induced by CCl₄ administration, and furthermore, the significantly decreased concentration, except for liver, was aggravated by exercise, even though at lower intensity.     

Sludge and stone formation in the gallbladder in bedridden elderly patients with cerebrovascular disease: influence of feeding method

Purpose. The incidence of gallbladder sludge or gallstone formation in bedridden patients with cerebrovascular disease (CVD) remains obscure. The aim of this study was to determine the incidence, relationship to feeding method, and mechanisms of gallbladder sludge and gallstone formation in elderly patients with CVD. Methods. Using ultrasonography, we determined the development of gallbladder sludge and gallstone over a 12-month period, the area of the gallbladder, the gallbladder contractile response to cerulein, and fasting levels of plasma cholecystokinin (CCK) in 40 bedridden elderly patients with CVD. The patients were divided into three groups based on the feeding method: oral ingestion (OI), nasogastric feeding (NF), and total parenteral nutrition (TPN). Results. Gallbladder sludge and gallstone were not observed in any of the 14 OI patients, but occurred in 6 and 1 of the 11 NF patients, and in 14 and 3 of the 15 TPN patients, respectively. Fasting gallbladder areas were significantly larger in the TPN group than in the other two groups. The TPN group showed a marked decrease in cerulein-induced gallbladder contractility. Fasting plasma CCK levels were lower in the TPN group than in the OI group. Conclusions. Our results indicate that elderly patients with CVD confined to bed over long periods are not necessarily at risk of gallbladder sludge or gallstone formation, and the development of these features may be associated with the feeding method. The predisposition of CVD patients on TPN to gallbladder disease is probably caused by failure of gallbladder contraction, resulting from insufficient secretion of CCK and impaired sensitivity of the gallbladder to CCK. Received: August 1, 2000 / Accepted: December 1, 2000     

Simple way to improve accuracy in diagnosis of quadrant inflammatory disease: how to avoid adverse laparotomy by using plain CT

BACKGROUND/AIMS: It has been reported that contrast computed tomography (CT) provides a rapid and accurate diagnosis of acute appendicitis, and could potentially prevent adverse appendectomy. In the present study, we evaluated the diagnostic value of precontrast CT combined with that of serum C reactive protein (CRP) concentration for right lower quadrant inflammatory diseases. METHODOLOGY: One hundred consecutive patients who had rebound tenderness and muscular rigidity or guarding on right lower quadrant underwent an emergency abdominal CT without contrast medium and laboratory tests. Based on the CT findings, 10 patients with peritonitis and 41 patients with definite acute appendicitis underwent emergency operations. Of 19 patients with negative CT findings, 11 patients who had positive CRP levels also underwent emergency appendectomies. The remaining patients, of whom 8 had negative CRP levels and 30 had CT findings of other inflammatory diseases, underwent conservative therapy and were examined again later on. RESULTS: The final diagnosis was acute appendicitis in 58 cases, other intestinal diseases in 21, gynecological disease in 6, urolithiasis in 1, and unknown in 14. Among 86 patients who underwent emergency operations and had a pathological diagnosis, CT had a sensitivity of 81% for the diagnosis of appendicitis, with a specificity of 89%, and an accuracy of 84%. CT combined with serum CRP concentration yielded a sensitivity of 100%, an accuracy of 97%, and a specificity of 89%. The adverse appendectomy rate was 3%. None of the patients underwent a delayed appendectomy. CT differentiated other inflammatory diseases from acute appendicitis in 23 patients. CONCLUSIONS: It may be concluded that precontrast CT scan combined with serum CRP can provide a rapid and accurate diagnosis of acute appendicitis and other right lower quadrant inflammatory diseases.     

Atrial septal pacing to resynchronize atrial contraction and improve atrial transport function

OBJECTIVES: Atrial septal pacing via a trans-septal breakthrough site within the right atrial septum can shorten global atrial activation time, resulting in significant reduction of recurrence of atrial fibrillation events. This study examined whether this pacing method will lead to resynchronization of atrial contraction and its benefit on hemodynamic function can be maintained for 24 months. METHODS: Thirty patients with atrial fibrillation and delayed atrial conduction were enrolled (17 males, 13 females, mean age 73 +/- 7 years). Trans-septal breakthrough site within the right atrial septum was identified through pacing from the dorsal left atrium. Continuous atrial septal pacing at the trans-septal breakthrough site was performed for 24 months. Time difference (TD) between right and left atrial contractions was measured during atrial septal pacing and sinus rhythm by pulse Doppler echocardiography of the trans-tricuspid (P-At) and mitral (P-Am) blood flows (TD = P-Am - P-At). RESULTS: The atrial lead was screwed near the fossa ovalis in 29 of 30 patients. Atrial septal pacing yielded significantly shorter P wave duration (101.9 +/- 10.4 vs 139.6 +/- 14.7 msec, p < 0.001), leading to significant reduction of TD in atrial contraction (-8.8 +/- 10.0 vs 29.8 +/- 13.6 msec, p < 0.001)as compared to sinus rhythm. Both shorter P wave duration and reduced TD during atrial septal pacing remained statistically significant during the follow-up period as compared to sinus rhythm. Both left atrial diameter and A to E ratio of filling waves at mitral valve were significantly decreased at 12 months and remained decreased at 24 months. CONCLUSIONS: Atrial septal pacing at the trans-septal breakthrough site can resynchronize atrial contraction and results in improved hemodynamic effects during 24 months of follow-up.     

Comparison of the performance of zotarolimus- and everolimus-eluting stents by optical coherence tomography and coronary angioscopy

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.