Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and secretions of apolipoprotein B-containing lipoprotein and bile acids in HepG2

We studied the effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl) ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on intracellular cholesterol esterification and the secretion of apolipoprotein B100 (apoB)-containing lipoprotein and bile acids in the human hepatoma cell line HepG2. NTE-122 markably inhibited [3H]oleate incorporation into cholesteryl esters in HepG2 cells incubated with 5 microg/ml 25-hydroxycholesterol as a stimulus for ACAT (IC50=6.0 nM). On the other hand, NTE-122 did not affect [3H]oleate incorporation into triglycerides and phospholipids and [14C]acetate incorporation into cholesterol. The stimulation of ACAT by 25-hydroxycholesterol caused significant increases in the secretion of radiolabeled cholesteryl esters, radiolabeled triglycerides and apoB mass. NTE-122 pronouncedly inhibited the secretion of radiolabeled cholesteryl esters in proportion to the inhibition of cellular cholesterol esterification, and it significantly reduced the secretion of radiolabeled triglycerides and apoB mass in HepG2 cells incubated with 25-hydroxycholesterol. Furthermore, NTE-122 increased the secretion of bile acids synthesized from [14C]-cholesterol. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing both the cholesterol content and the amount of secreted very low-density lipoprotein and enhancing the excretion of bile acid from the liver.     

Effects of NTE-122, a novel acyl-CoA:cholesterol acyltransferase inhibitor, on cholesterol esterification and high-density lipoprotein-induced cholesterol efflux in macrophages

We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.     

Some observations in the fine structure of age changes of the mouse retinal pigment epithelium

Summary Age changes of the fine structure in the CF-1 mouse retinal pigment epithelium were studied from 1–24 months old. The change most characteristic of the senescence of the retinal pigment epithelium was found to be the appearance of wavy undulating 12 nm wide filaments having a periodicity of about 80 nm after the 12th month. In addition, the retinal pigment epithelial cells of the aging eye were found to have a marked accumulation of lysosomal dense bodies measuring about 0.3 to 1.2 m in diameter especially in the apical portion of the cytoplasm. Extended and enlarged basal cytoplasmic infoldings of the retinal pigment epithelial cells were another prominent age change in the old mouse. In these basal infoldings densely fixed amorphous materials by tannic acid and very fine filaments are recognized. Age-related changes of the retinal pigment epithelial cell of the CF-1 mouse may take place as the degeneration of cytoplasmic materials, the appearance of bundles consisting of parallel undulating filaments, and the extending process of basal infolding from the choroid side.     

Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent

Summary To determine whether E-643, a new -blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine--hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 151±28/89±14 mmHg), sitting (158±22/101±11 138±28/89±15 mmHg) and standing (153±32/103±21 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 69±10 beats/min), but was increased in the sitting (68±10 73±9 beats/min) and standing (73±10 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine--hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine--hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.     

A study on the psychological status of perioperative patients (II)]

In order to study the changes of the psychological status during perioperative period, we performed four different psychological tests, Spielberger's rating scale "The State-Trait Anxiety Inventory (STAI)", Self-rating Depression Scale (SDS), Maudsley Personality Inventory (MPI) and Baum test, in 63 patients who received simple total hysterectomy for myoma of uterus. The anxiety ratings showed a significant decrease postoperatively. On the contrary, the SDS index that expresses the level of depressive mood showed no significant change during perioperative period. Moreover the patients who had shown a tendency of nervousness in MPI kept the high level of the SDS index during perioperative period than the other patients who had not shown a tendency of nervousness in MPI. In Baum test, more than 75% of patients manifested psychologic fragility or lability. These results suggest that depressive mood affects strictly the psychological status in postoperative period more than anxiety. We presume that the depressive mood during perioperative period is responsible for the postoperative psychological disturbance.     

Effect on electroencephalogram of chewing flavored gum

The objective of the present study was to evaluate the effect on the electroencephalogram (EEG) of a chewing gum with and without our prepared new flavor. Electroencephalograms were obtained after the following three tests: chewing pure gumbase with sucrose (standard gumbase), chewing flavored standard gum and the inhalation of flavored aromatic oil. As the control, we used the pre-stimulus control EEG record without a stimulus. We examined the relationship between the pre-stimulus control record and the post-stimulus record using the changes of power in four bands. Chewing the standard gumbase led to an increase in the alpha wave and a decrease in the beta wave. Chewing the flavored standard gum and inhaling the flavored aromatic oil each increased the alpha and beta waves. In addition, chewing the flavored standard gum led to a change in the ratio of theta wave in the frontal area. The difference in the theta, alpha and beta bands in chewing gum with and without the added flavor suggested that the flavor as well as chewing could induce concentration with a harmonious high arousal state in brain function.     

De novo uterine sarcoma with good response to neo-adjuvant chemotherapy

Abstract.  Numa F, Umayahara K, Ogata H, Nawata S, Sakaguchi Y, Emoto T, Kawasaki K, Hirakawa H, Sase M, Oga A, Kato H. De novo uterine sarcoma with good response to neoadjuvant chemotherapy. We report here the extremely rare case of a 28-year-old woman with advanced stage uterine sarcoma arising soon after a cesarean section. She underwent an abdominal cesarean section because of a breech presentation. At the time of the procedure, there were no abnormal findings such as leiomyoma of the uterus in the abdominal cavity. One year later, she was referred to our hospital because of a large abdominal tumor. Transabdominal power Doppler ultrasonography and magnetic resonance imaging (MRI) showed a large hypervascular tumor in the abdominal cavity. Her serum levels, for the two tumor markers carbohydrate antigen CA125 and LDH, were elevated, at 219 U/ml (< 35 U/ml) and 862 IU/l (115 U/ml−217 U/ml), respectively. On the basis of a diagnosis of malignant tumor of gynecological origin, exploratory laparotomy was performed, and through biopsy, the tumor was found to be advanced undifferentiated uterine sarcoma. She exhibited a good response to neoadjuvant chemotherapy consisting of cisplatin, epirubicin, and dimethyltriazenoimidazole carboxamide (DTIC) every 28 days, which was successfully followed by a hysterectomy.     

Effects of low-energy laser irradiation on bone remodeling during experimental tooth movement in rats

BACKGROUND AND OBJECTIVE: Low-energy laser irradiation has many anabolic effects such as the acceleration of bone formation. However, its effects on tooth movement, performed by bone resorption and formation, have not been well characterized. STUDY DESIGN/MATERIALS AND METHODS: A total of 10 g of orthodontic force was applied to rat molars to cause experimental tooth movement. A Ga-Al-As diode laser was used to irradiate the area around the moved tooth, and after 12 days, the amount of tooth movement was measured. Calcein was injected subcutaneously to label the newly formed alveolar bone for quantitative analysis. Immunohistochemical staining of proliferating cell nuclear antigen was performed to evaluate cellular proliferation. TRAPase staining was also performed to facilitate the identification of osteoclasts. RESULTS: In the laser irradiation group, the amount of tooth movement was significantly greater (1. 3-fold) than that of the nonirradiation group in the end of the experiment. The amount of bone formation and rate of cellular proliferation in the tension side and the number of osteoclasts in the pressure side were all significantly increased in the irradiation group when compared with the nonirradiation group (P < 0. 01). CONCLUSION: These findings suggest that low-energy laser irradiation can accelerate tooth movement accompanied with alveolar bone remodeling.     

An alternative method of arterial reconstruction after hepatic arterial thrombosis following living-related liver transplantation

BACKGROUND: Hepatic artery thrombosis (HAT) remains an important cause of graft loss after liver transplantation. Emergency rearterialization methods are limited in cases of living-related liver transplantation in which the graft hepatic artery is thin and short. CASE: A 19-year-old woman who underwent living-related liver transplantation for biliary atresia developed HAT on the 4th postoperative day. During the emergency laparotomy the recipient hepatic artery was found to be too short to anastomose, so the recipient's right gastroepiploic artery was anastomosed to the graft hepatic artery. The patient is now alive and well 6 months after reoperation, and she has experienced no further episode of HAT. CONCLUSION: The right gastroepiploic artery can be used easily and safely for hepatic graft revascularization without causing ischemia of the stomach. An additional skin incision is not required, and the artery is long enough to anastomose to the graft artery directly. The method of hepatic graft rearterialization described here is an important option for patients who undergo living-related or split liver transplantation.