Effects of Cilnidipine on Heart Rate and Uric Acid Metabolism in Patients With Essential Hypertension.

Background: The relation between hypertension and hyperuricemia has been established by epidemiological studies. Calcium channel blockers are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine is a new calcium channel blocker acting by blocking both L- and N-type calcium channels.

KirrelL, a member of the Ig-domain superfamily of adhesion proteins, is essential for fusion of primary mesenchyme cells in the sea urchin embryo.

In the sea urchin embryo, primary mesenchyme cells (PMCs) adhere to one another and fuse via filopodia, forming cable-like structures within which skeletal rods are deposited. Although this process was first described more than a century ago, molecules that participate in PMC adhesion and fusion have not been identified. Here we show that KirrelL, a PMC-specific, Ig domain-containing transmembrane protein, is essential for PMC fusion, probably by mediating filopodial adhesions that are a pre-requisite for subsequent membrane fusion.

Comparative analysis of use of porous orbital implant with mucus membrane graft and dermis fat graft as a primary procedure in reconstruction of severely contracted socket.

Purpose: The purpose of our study is to present a surgical technique of primary porous orbital ball implantation with overlying mucus membrane graft (MMG) for reconstruction of severely contracted socket and to evaluate prosthesis retention and motility in comparison to dermis fat graft (DFG).

Study Design: Prospective comparative study.

Materials And Methods: A total of 24 patients of severe socket contracture (Grade 2-4 Krishna's classification) were subdivided into two groups, 12 patients in each group.

COPS5 (Jab1) protein increases β site processing of amyloid precursor protein and amyloid β peptide generation by stabilizing RanBP9 protein levels.

Increased processing of amyloid precursor protein (APP) and accumulation of neurotoxic amyloid β peptide (Aβ) in the brain is central to the pathogenesis of Alzheimer's disease (AD). Therefore, the identification of molecules that regulate Aβ generation is crucial for future therapeutic approaches for AD. We demonstrated previously that RanBP9 regulates Aβ generation in a number of cell lines and primary neuronal cultures by forming tripartite protein complexes with APP, low-density lipoprotein-related protein, and BACE1, consequently leading to increased amyloid plaque burden in the brain.

Striking reduction of amyloid plaque burden in an Alzheimer's mouse model after chronic administration of carmustine.

Background: Currently available therapies for Alzheimer's disease (AD) do not treat the underlying cause of AD. Anecdotal observations in nursing homes from multiple studies strongly suggest an inverse relationship between cancer and AD. Therefore, we reasoned that oncology drugs may be effective against AD.

Primary dermatofibrosarcoma protuberans of orbit--a rare entity.

Primary Dermatofibrosarcoma Protuberance (DFSP) is a rare neoplasm of dermal origin. Though it is a locally aggressive tumor with high recurrence rate, however distant metastasis can also occur. Orbital DFSP is an uncommon phenomenon.

Chronic cladribine administration increases amyloid beta peptide generation and plaque burden in mice.

Background: The clinical uses of 2-chloro-2'-deoxyadenosine (2-CDA) or cladribine which was initially prescribed to patients with hematological and lymphoid cancers is now extended to treat patients with multiple sclerosis (MS). Previous data has shown that 2-CDA has high affinity to the brain and readily passes through the blood brain barrier reaching CSF concentrations 25% of that found in plasma. However, whether long-term administration of 2-CDA can lead to any adverse effects in patients or animal models is not yet clearly known.

Patterns of gene expression in Drosophila InsP3 receptor mutant larvae reveal a role for InsP3 signaling in carbohydrate and energy metabolism.

Background: The Inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an InsP(3) gated intracellular Ca(2+)-release channel. Characterization of Drosophila mutants for the InsP(3)R has demonstrated that InsP(3)-mediated Ca(2+) release is required in Drosophila larvae for growth and viability.

Methodology/principal Findings: To understand the molecular basis of these growth defects a genome wide microarray analysis has been carried out with larval RNA obtained from a strong InsP(3)R mutant combination in which 1504 independent genes were differentially regulated with a log(2) of fold change of 1 or more and P<0.

Molecular mechanism of insulin resistance.

Free fatty acids are known to play a key role in promoting loss of insulin sensitivity,thereby causing insulin resistance and type 2 diabetes.However,the underlying mechanism involved is still unclear.In searching for the cause of the mechanism,it has been found that palmitate inhibits insulin receptor (IR)gene expression,leading to a reduced amount of IR protein in insulin target cells.

Fatty acid represses insulin receptor gene expression by impairing HMGA1 through protein kinase Cepsilon.

It is known that free fatty acid (FFA) contributes to the development of insulin resistance and type2 diabetes. However, the underlying mechanism in FFA-induced insulin resistance is still unclear. In the present investigation we have demonstrated that palmitate significantly (p <0.

A Lupinoside prevented fatty acid induced inhibition of insulin sensitivity in 3T3 L1 adipocytes.

The decrease in insulin sensitivity to target tissues or insulin resistance leads to type 2 diabetes mellitus, an insidious disease threatening global health. Numerous evidences made free fatty acids (FFAs) responsible for insulin resistance and type 2 diabetes. We demonstrate here that the damage of insulin acitivity by a free fatty acid, palmitate could be prevented by a lupinoside.

Involvement of novel PKC isoforms in FFA induced defects in insulin signaling.

Involvement of novel PKCs (nPKCs) in the negative regulation of insulin-signaling pathway is a current interest of many workers investigating the cause for insulin resistance and type 2 diabetes. Free fatty acids (FFAs) are recently shown to be the major players in inducing insulin resistance in insulin target cells. They are also found to be involved in activating nPKCs associated with the impairment of insulin sensitivity.

Inhibition of insulin receptor gene expression and insulin signaling by fatty acid: interplay of PKC isoforms therein.

Fatty acids are known to play a key role in promoting the loss of insulin sensitivity causing insulin resistance and type 2 diabetes. However, underlying mechanism involved here is still unclear. Incubation of rat skeletal muscle cells with palmitate followed by I(125)- insulin binding to the plasma membrane receptor preparation demonstrated a two-fold decrease in receptor occupation.