Serum C-reactive protein levels predict survival in hepatocellular carcinoma.

BACKGROUND/AIMS: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. METHOD: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients. RESULTS: The survival rate of patients of the H-CRP-positive group was lower than that of H-CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H-CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis. CONCLUSIONS: The prognosis of H-CRP-positive patients was poorer compared with H-CRP-negative patients. This study confirmed that H-CRP, like CRP, is a marker of poor prognosis in HCC patients.     

Chronic hepatitis C virus infection and lipoprotein metabolism

Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.     

Contractile response of guinea pig ileum by repetitive application of morphine.

1. The repetitive application of morphine gradually induced a contracture in the isolated guinea pig ileum. 2. The optimum conditions for induction of the contracture were as follows: the concentration, incubation time and washout time of morphine were 1 or 10 microM, 2 and 3 min, respectively. 3. Preincubation with naloxone or TTX blocked this morphine-induced contracture. 4. Among twitch-inhibiting drugs, only clonidine induced a contracture similar to that induced by morphine, while tetrodotoxin (TTX) and adenosine did not. 5. The contracture was also observed in the longitudinal muscle-myenteric plexus preparations. 6. These findings indicate that morphine has a dual inhibitory and excitatory action on the guinea pig ileum and that its repetitive application preferentially diminish the inhibitory one.     

A questionnaire about radiation safety management of the draining-water system at nuclear medicine facilities

We conducted a questionnaire survey about radiation-safety management condition in Japanese nuclear medicine facilities to make materials of proposition for more reasonable management of medical radioactive waste. We distributed a questionnaire to institutions equipped with Nuclear Medicine facilities. Of 1,125 institutions, 642 institutes (52.8%) returned effective answers. The questionnaire covered the following areas: 1) scale of an institution, 2) presence of enforcement of radiotherapy, 3) system of a tank, 4) size and number of each tank, 5) a form of draining-water system, 6) a displacement in a radioactive rays management area, 7) a measurement method of the concentration of medical radioactive waste in draining water system, 8) planned and used quantity of radioisotopes for medical examination and treatment, 9) an average displacement of hospital for one month. In most institutions, a ratio of dose limitation of radioisotope in draining-water system was less than 1.0, defined as an upper limitation in ordinance. In 499 hospitals without facilities of hospitalization for unsealed radioisotope therapy, 473 hospitals reported that sum of ratios of dose limits in a draining-water system was less than 1.0. It was calculated by used dose of radioisotope and monthly displacement from hospital, on the premise that all used radioisotope entered in the general draining-water system. When a drainage including radioactivity from a controlled area join with that from other area before it flows out of a institution, it may be diluted and its radioactive concentration should be less than its upper limitation defined in the rule. Especially, in all institutions with a monthly displacement of more than 25,000 m3, the sum of ratio of the concentration of each radionuclide to the concentration limit dose calculated by used dose of radioisotope, indicated less than 1.0.     

Effects of oral administration of Stephania tetrandra S. Moore on neovascularization of retinal and choroidal capillaries of diabetes in rats

In rats, an injection of streptozotocin (STZ) elevated blood levels of glucose 4 weeks later (STZ-induced diabetes) and an over-production of microvessels of retinal and choroidal capillaries of eyes developed. A previous study has shown that administration of Stephania tetrandra S. Moore (STSM) in culture prevented the over-production of microvessels of those capillaries of STZ-induced diabetes in vitro. Therefore, the study investigated whether or not orally administered STSM could inhibit over-production of microvessels of those capillaries of STZ injected rats in vivo. When STSM was given at the same time as the STZ injection and continued daily for 7 weeks, STSM prevented the elevation of blood glucose level and over-production of microvessels of those capillaries. When STSM was given after elevation of blood glucose level of glucose (4 weeks after STZ injection) and continued daily for 4 weeks, STSM lowered the elevated blood glucose level but had no effect on the over-production of microvessels of those capillaries. It was inferred that deposition of N(epsilon)(carboxymethyl) lysine in retinal and choroidal tissues, which is induced by STZ-induced diabetes may deteriorate the blood-retinal barrier and the blood-choroidal barrier. One might, therefore, speculate that advanced STZ-induced diabetes may deteriorate the blood-retinal barrier and blood-choroidal barrier. Therefore, STSM may not reach the retinal and choroidal tissues in the posterior ocular region in vivo.     

Contralateral Lung Injury Associated With Single-Lung Ischemia-Reperfusion Injury

Background. There have been very few studies on the effect of single-lung ischemia-reperfusion on the function of the contralateral lung. This study was designed to clarify the effect.

Methods. Fifteen mongrel dogs were divided into two groups. In group 1 (n = 7), the left lung was subjected to ischemia without ventilation for 90 minutes, and then reperfused. In group II (n = 8), the lung was not subjected to ischemia, and was ventilated during the 90-minute ischemia of group I. Arterial blood gas, hemodynamics, extravascular lung water, and airway pressure were measured. Pulmonary biopsy was performed to evaluate adenine nucleotide levels. The protein concentration and phosphorous concentration of phospholipids in bronchoalveolar lavage fluid were measured.

Results. Group I, with perfusion and ventilation of the right lung alone, was significantly inferior to group II with respect to arterial blood gas, right pulmonary compliance, extravascular lung water of the right lung, and the protein concentration in the bronchoalveolar lavage fluid of the right lung after the 90-minute period.

Conclusions. These results indicate that 90 minutes of warm ischemia and reperfusion of the left lung caused deterioration of not only the left but also contralateral right pulmonary function.     

Systemic Delivery of Synthetic MicroRNA-16 Inhibits the Growth of Metastatic Prostate Tumors via Downregulation of Multiple Cell-cycle Genes

Recent reports have linked the expression of specific microRNAs (miRNAs) with tumorigenesis and metastasis. Here, we show that microRNA (miR)-16, which is expressed at lower levels in prostate cancer cells, affects the proliferation of human prostate cancer cell lines both in vitro and in vivo. Transient transfection with synthetic miR-16 significantly reduced cell proliferation of 22Rv1, Du145, PPC-1, and PC-3M-luc cells. A prostate cancer xenograft model revealed that atelocollagen could efficiently deliver synthetic miR-16 to tumor cells on bone tissues in mice when injected into tail veins. In the therapeutic bone metastasis model, injection of miR-16 with atelocollagen via tail vein significantly inhibited the growth of prostate tumors in bone. Cell model studies indicate that miR-16 likely suppresses prostate tumor growth by regulating the expression of genes such as CDK1 and CDK2 associated with cell-cycle control and cellular proliferation. There is a trend toward lower miR-16 expression in human prostate tumors versus normal prostate tissues. Thus, this study indicates the therapeutic potential of miRNA in an animal model of cancer metastasis with systemic miRNA injection and suggest that systemic delivery of miR-16 could be used to treat patients with advanced prostate cancer.     

Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression

Background  

Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells.     

Effect of Toki-Shakuyaku-San (TJ-23) on the activity of choline acetyltransferase in the brain of menopausal rats

This study was designed to examine the effect of TJ-23 on the synthesis of acetylcholine menopausal rats. TJ-23 (500 mg/kg body weight) was administered daily through drinking water for either 1 or 3 months. Treatment with TJ-23 for 1 month resulted in an increase in the choline acetyltransferase (ChAT) activity in the ventral hippocampus, but there was no statistically significant change in the frontoparietal cerebral cortex. Treatment with TJ-23 for 3 months resulted in a decrease in the ChAT activity in the frontoparietal cortex, but there was no statistically significant change in the hippocampus. Furthermore, treatment with TJ-23 for 3 months resulted in a decrease in the ChAT activity in the amygdala-pyriform cortex complex. From these observations, it is inferred that TJ-23 treatment brings on the synthesis of acetylcholine in the frontoparietal cerebral cortex and hippocampus, and furthermore, treatment with the same regimen brings on different time sequences of acetylcholine synthesis in the frontoparietal cerebral cortex and hippocampus in menopausal rats.