Catechol-O-methyltransferase and Parkinson's disease

Parkinson's disease (PD) is one of the main causes of neurological disability in the elderly. Levodopa is the gold standard for treating this disease, but chronic levodopa therapy is complicated by motor fluctuation and dyskinesia. The catechol-O-methyltransferase (COMT) inhibitors represent a new class of antiparkinsonian drugs. When coadministered with levodopa/decarboxylase inhibitor, 2 COMT inhibitors, tolcapone and entacapone have been shown to improve the clinical benefit of levodopa. COMT activity is genetically polymorphic, and individuals with the low activity (COMT(L/L)) genotype have a thermolabile COMT protein; studies suggest that this genotype is less common in Asians than in Caucasians. Differences in COMT activity may determine the individual response to levodopa and result in ethnic differences in PD susceptibility. Our recent study suggests that the COMTL allele can interact with the MAOB gene to increase the occurrence of PD in Taiwanese. In order to understand this new class of antiparkinsonian drugs, we review their basic properties, pharmacology, and clinical efficacy. The frequency distribution of COMT genetic polymorphisms among different populations and its implications in the etiology and drug response is also discussed.     

Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.     

PKC- and PI3K-dependent but ERK-independent proliferation of murine splenic B cells stimulated by chondroitin sulfate B

High molecular weight polyanions such as dextran sulfate are known to be weak polyclonal activators of murine B cells, but the molecular mechanism of their mitogenic activitiy is not fully elucidated. Although chondroitin sulfate A (CSA), B (CSB) and C (CSC) are highly charged polyanions, little is known about their effects on the proliferation of B cells. In this study, we demonstrated that CSB stimulated proliferation of murine B cells as markedly as did anti-IgM antibody, more markedly than did dextran sulfate and much more markedly than did CSA, CSC, heparin and hyaluronic acid. CSB caused translocation of protein kinase C (PKC) isoform beta from cytosol to membrane fractions and increased phosphorylation of Akt but not phosphorylation of extracellular signal-regulated kinase (ERK) of B cells. CSB-induced B cell proliferation was almost completely blocked by either the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or the PKC inhibitor GF109203X but was not significantly inhibited by the ERK kinase inhibitor PD98059. The mitogenic effect of anti-IgM was significantly inhibited by all the three inhibitors, while the mitogenic effect of LPS was inhibited only by LY294002. These findings indicate that CSB stimulated proliferation of murine B cells more markedly than did dextran sulfate and suggest that PKC and PI3K are crucial but that ERK is less important for the mitogenic activity of CSB, the signaling pathways of which may be at least partly distinct from those of anti-IgM and LPS.     

腹腔镜微创技术在门脉高压症外科治疗中瓶颈与术式变迁

门静脉高压症大多是由肝脏自身病变、肝内外胆管疾病、门静脉血管病变等引起的一类症候群。门静脉高压常常引起严重的临床症状体征,主要有脾大、脾功能亢进充血性脾大、大量腹水形成、门体侧枝循环的形成、门静脉高压性胃肠血管病(portalhypertensivegastrointestinalvasculopathy,PHGIV)、肝性脑病。其中上消化道出血是最严重的并发症。临床治疗方法多是以控制上消化道出血、提高患者的生存质量为目的。内科治疗方法中包括药物硬化、内镜套扎及介入栓塞治疗。外科治疗方法包括活体肝脏移植、分流术、断流术三种。由于我国活体供肝资源短缺,到目前为止肝脏移植开展的医院并不是很多且技术并不成熟。目前公认且可取的断流术是贲门周围离断术联合脾切除术,分流术是选择性远端脾肾分流术。传统开腹手术创伤较大、术后恢复时间较长、术后并发症多。随着腔镜外科的迅猛发展,微创外科如同核武器般占据着手术发展的主流,所以一个敞亮的切口已经不再是解决一个复杂手术的好武器。目前越来越多的门静脉高压患者接受腹腔镜微创技术的治疗,但是仍然缺少大样本的临床研究。因此,尚需要进行大样本、多中心的临床和循证医学研究,旨在为门静脉高压的外科治疗提供治疗策略,为临床应用和研究提供基础。     

Extraction and Properties of Black Rice Pigment

Pharmaceutical Chemistry Journal - Two black rice pigment components, BR1 and BR2, were obtained by thin layer chromatography. From five experiments for in vitro testing of the scavenging ability,...     

Etiology and management of the hypertensive phase in glaucoma drainage-device surgery

Insertion of glaucoma drainage devices has become a mainstay in the surgical management of multiple forms of glaucoma, and the indications for this procedure continue to expand. A unique clinical challenge in the postoperative care of these devices is the hypertensive phase, a period of postoperative intraocular pressure elevation in the first three months after surgery. We discuss the influence of a variety of factors on the development of the hypertensive phase after glaucoma drainage implantation, including type of device, device material, and device surface area. Furthermore, several intraoperative and postoperative interventions are investigated as attempts to mitigate this phenomenon. Included among these are the use of antimetabolites, collagen matrix, and a variety of approaches to postoperative inflammation and intraocular pressure control. We provide an overview of our current knowledge of the etiology and management of the hypertensive phase.