Molecular biology and ontogeny of glutamate receptors in the mammalian central nervous system

Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic terminals, glutamate binds to both ionotropic and metabotropic receptors to mediate fast, slow, and persistent effects on synaptic transmission and integrity. There are three types of ionotropic glutamate receptors. N-Methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA), and kainate receptors are principally activated by the agonist bearing its name and are permeable to cationic flux; hence, their activation results in membrane depolarization. All ionotropic glutamate receptors are believed to be composed of four distinct subunits, each of which is topologically arranged with three transmembrane-spanning and one pore-lining (hairpin loop) domain. In contrast, metabotropic glutamate receptors are G protein (guanine nucleotide-binding protein) -coupled receptors linked to second-messenger systems. Group I metabotropic glutamate receptors are linked to phospholipase C, which results in phosphoinositide hydrolysis and release of calcium from intracellular stores. Group II and group III metabotropic glutamate receptors are negatively linked to adenylate cyclase, which catalyzes the production of cyclic adenosine monophosphate. Each metabotropic glutamate receptor is composed of seven transmembrane-spanning domains, similar to other members of the superfamily of metabotropic receptors, which includes noradrenergic, muscarinic acetylcholinergic, dopaminergic, serotonergic (except type 3 receptors), and gamma-aminobutyric acid (GABA) type B receptors. This review summarizes the relevant molecular biology and ontogeny of glutamate receptors in the central nervous system and highlights some of the roles that they can play during brain development and in certain disease states.     

New Polyacetylenes, DGAT inhibitors from the roots of Panax ginseng

The petroleum ether extract of Panax ginseng showed a significant inhibition of the diacylglycerol acyltransferase (DGAT) enzyme from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of two new polyacetylenic compounds, (9 R,10 S)-epoxyheptadecan-4,6-diyn-3-one ( 1) and 1-methoxy-(9 R,10 S)-epoxyheptadecan-4,6-diyn-3-one ( 2). Their chemical structures were elucidated on the basis of spectroscopic evidence and asymmetric synthesis. IC50 values of 9 microg/mL ( 1) and 32 microg/mL ( 2) were obtained.     

Effects of organic matrix proteins on the interfacial structure at the bone-biocompatible nacre interface in vitro

The biocompatibility and potential osteoinductivity of nacre have favored its use as a bone-grafting material. The present study is to investigate the interfacial structure at the bone-nacre interface resulting from organic matrix proteins, which emphasizes the mechanism of bone-bonding ability and biocompatibility of the shell tissues such as nacre and biogenic calcite. To understand the interfacial reaction, the zeta potential measurements, provide for a unique method to quantify the actual state of the interface in situ, were used for synthetic and biogenic calcium carbonate suspensions with respect to pH and the organic matrix as an additive. The zeta potentials and surface charge density show that the organic matrix proteins are main charge regulators, resulting in the stabilized tissue properties as compared with synthetic crystals. Also, in forming calcium carbonate crystals with the additives, the conformation of organic matrix has an important role in the understanding of the newly formed interfacial structure. The result provides the primary role of the organic matrix proteins in controlling the formation of interfacial structure and biocompatibility with bone as well as the stability of biogenic tissues. And it gives a new insight into the usefulness of zeta potential measurement to describe the in vivo interaction between the bone and implants.     

Inhibitory effects of the root cortex of Paeonia suffruticosa on interleukin-8 and macrophage chemoattractant protein-1 secretions in U937 cells

In an effort to elucidate the mechanism of the anti-inflammatory effect of mudanpi, the root cortex of Paeonia suffruticosa Andrews (Ranunculaceae), we determined the effects of the methanolic extract of mudanpi (MEM) on the secretions of interleukin (IL)-8, a major mediator of acute neutrophil-mediated inflammation, and macrophage chemoattractant protein (MCP)-1, a major mediator of chronic macrophage-mediated inflammation, in human monocytic U937 cells stimulated with phorbol myristate acetate (PMA). MEM significantly inhibited PMA-induced secretions of IL-8 and MCP-1 proteins in a dose-dependent manner. The inhibition of these chemokines by MEM was due to its suppression of IL-8 and MCP-1 genes. In addition, 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, one of major constituents isolated from MEM, inhibited PMA-induced secretions of IL-8 and MCP-1 proteins by its suppression of IL-8 and MCP-1 genes. Thus, one possible anti-inflammatory mechanism of mudanpi, an anti-inflammatory Chinese crude drug, may be to inhibit the secretions of inflammatory chemokines.     

Carcinoma originating from aberrant breast tissue of the right upper anterior chest wall : a case report

Aberrant breast tissue is usually found in proximity to the normal breast, that is, in the axillary, sternal or clavicular regions. Carcinoma occurs more frequently in the aberrant tissue of the axilla than the extra-axillary site though the overall incidence of tumors of aberrant breast tissue is low. To our knowledge, studies regarding the carcinoma of aberrant breast tissue of the extra-axillary site have been reported rarely. Here we report a recent case of carcinoma originating from the extra-axillary aberrant breast tissue, presenting as a subcutaneous nodule on the right upper anterior chest wall. It is suggested that subcutaneous nodules of uncertain origin around the periphery of the breast should be suspected for breast carcinoma as a differential diagnosis and treated properly.     

Molecular biology and ontogeny of gamma-aminobutyric acid (GABA) receptors in the mammalian central nervous system

gamma-Aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian central nervous system. After release from nerve terminals, GABA binds to at least two classes of postsynaptic receptors (ie, GABAA and GABAB), which are nearly ubiquitous in the brain. GABAA receptors are postsynaptic heteropentameric complexes that display unique physiologic and pharmacologic properties based on subunit composition. Activation of GABAA receptors in mature neurons results in membrane hyperpolarization, which is mediated principally by inward chloride flux, whereas in early stages of brain development, GABAA receptor activation causes depolarization of the postsynaptic membrane. GABA, receptors reside both presynaptically and postsynaptically, exist as heterodimers and are coupled to voltage-dependent ion channels through interactions with heterotrimeric G proteins. This review summarizes the molecular biology and ontogeny of GABAA and GABAB receptors, highlighting some of their putative roles during normal brain development as well as in disease states such as epilepsy.     

The treatment of lacrimal apparatus obstruction with the use of an inner canthal Jones tube insertion via a transcaruncular route

BACKGROUND AND OBJECTIVE: To evaluate the clinical utility of the lacrimal bypass surgery using Bowman's probe in treatment of obstruction of the lacrimal apparatus. PATIENTS AND METHODS: This study evaluated 124 cases of obstruction of the lacrimal passage systems with mean epiphora of 2.7 years. An incision was made on the side of the caruncle, and the lacrimal bone was penetrated between the lacrimal sac and the nasal mucosa by Bowman #0. Insertion of a Jones tube was made at the new lacrimal pathway, a puctum dilator or scissors was introduced through the caruncle and dilated across the lacrimal bone into the nasal cavity. The Jones tube was introduced over the probe into the nasal cavity, and fixed at the caruncle with nonabsorbable suture material. RESULTS: Complete resolution of epiphora was accomplished in 120 (96.8%) of 124 eyes; only 4 (3.2%) eyes failed during a mean of 17.1 months of follow-up. CONCLUSION: This procedure is simple and safe with no facial scarring, short operation time, high success rate, and can be performed under local anesthesia. Therefore, the clinical utility of this procedure seems to be of value in treatment of complicated obstruction of the lacrimal apparatus.     

Molecular ontogeny of major neurotransmitter receptor systems in the mammalian central nervous system: norepinephrine, dopamine, serotonin, acetylcholine, and glycine

Neurotransmitter receptors are critical elements in intercellular signaling within the central nervous system and are divided into two major types based on their molecular structure and biophysical properties. The first are ionotropic receptors--ligand-gated ion channels that directly affect the membrane potential via passage of permeant ions (such as sodium and calcium) and mediate fast synaptic transmission. The second type are slower metabotropic receptors that are also ligand gated but depend on an interaction with guanine nucleotide-binding proteins and mediate signal transduction by activating second-messenger systems within the cell. In the past two decades, a wealth of information has emerged regarding the molecular biology and pharmacology of classic neurotransmitter receptors (including adrenergic, dopaminergic, serotonergic, cholinergic, glycine, gamma-aminobutyric acid [GABA(A)], and glutamate receptors). Further, the distribution of subunits comprising these receptors has been extensively studied. This review focuses on the molecular ontogeny of several of the major neurotransmitter receptor systems in the mammalian central nervous system, highlighting the role that some of these may play during brain development and in certain pathologic states.