AzetinesResearch: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Egypt: A country in northern Africa, bordering the Mediterranean Sea, between Libya and the Gaza Strip, and the Red Sea north of Sudan, and includes the Asian Sinai Peninsula Its capital is Cairo.Research Personnel: Those individuals engaged in research.Research Support as Topic: Financial support of research activities.Schistosomiasis: Infection with flukes (trematodes) of the genus SCHISTOSOMA. Three species produce the most frequent clinical diseases: SCHISTOSOMA HAEMATOBIUM (endemic in Africa and the Middle East), SCHISTOSOMA MANSONI (in Egypt, northern and southern Africa, some West Indies islands, northern 2/3 of South America), and SCHISTOSOMA JAPONICUM (in Japan, China, the Philippines, Celebes, Thailand, Laos). S. mansoni is often seen in Puerto Ricans living in the United States.Biomedical Research: Research that involves the application of the natural sciences, especially biology and physiology, to medicine.Molluscacides: Agents destructive to snails and other mollusks.Citrobacter freundii: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria found in humans and other animals including MAMMALS; BIRDS; REPTILES; and AMPHIBIANS. It has also been isolated from SOIL and WATER as well as from clinical specimens such as URINE; THROAT; SPUTUM; BLOOD; and wound swabs as an opportunistic pathogen.Cardiac Myosins: Myosin type II isoforms found in cardiac muscle.Sarcomeres: The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cardiomyopathy, Hypertrophic: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).Chemistry, Analytic: The branch of chemistry dealing with detection (qualitative) and determination (quantitative) of substances. (Grant & Hackh's Chemical Dictionary, 5th ed)Myosins: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.Spiramycin: A macrolide antibiotic produced by Streptomyces ambofaciens. The drug is effective against gram-positive aerobic pathogens, N. gonorrhoeae, and staphylococci. It is used to treat infections caused by bacteria and Toxoplasma gondii.Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Prenylamine: A drug formerly used in the treatment of angina pectoris but superseded by less hazardous drugs. Prenylamine depletes myocardial catecholamine stores and has some calcium channel blocking activity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1406)Anesthetics, Local: Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site.Supreme Court Decisions: Decisions made by the United States Supreme Court.Cimicidae: A family of wingless, blood-sucking insects of the suborder HETEROPTERA, including the bedbugs and related forms. Cimex (BEDBUGS), Heamatosiphon, and Oeciacus are medically important genera. (From Dorland, 28th ed)Civil Rights: Legal guarantee protecting the individual from attack on personal liberties, right to fair trial, right to vote, and freedom from discrimination on the basis of race, color, religion, sex, age, disability, or national origin. (from accessed 1/31/2003)Histiocytosis, Sinus: Benign, non-Langerhans-cell, histiocytic proliferative disorder that primarily affects the lymph nodes. It is often referred to as sinus histiocytosis with massive lymphadenopathy.PiperazinesAfrica, Southern: The geographical area of Africa comprising ANGOLA; BOTSWANA; LESOTHO; MALAWI; MOZAMBIQUE; NAMIBIA; SOUTH AFRICA; SWAZILAND; ZAMBIA; and ZIMBABWE.Williams Syndrome: A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.Hemagglutinins, Viral: Specific hemagglutinin subtypes encoded by VIRUSES.Influenza A virus: The type species of the genus INFLUENZAVIRUS A that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is usually by aerosol (human and most non-aquatic hosts) or waterborne (ducks). Infected birds shed the virus in their saliva, nasal secretions, and feces.Influenza, Human: An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia.Hemagglutinin Glycoproteins, Influenza Virus: Membrane glycoproteins from influenza viruses which are involved in hemagglutination, virus attachment, and envelope fusion. Fourteen distinct subtypes of HA glycoproteins and nine of NA glycoproteins have been identified from INFLUENZA A VIRUS; no subtypes have been identified for Influenza B or Influenza C viruses.Hemagglutinins: Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc.Influenza A Virus, H1N1 Subtype: A subtype of INFLUENZA A VIRUS with the surface proteins hemagglutinin 1 and neuraminidase 1. The H1N1 subtype was responsible for the Spanish flu pandemic of 1918.Influenza A Virus, H3N2 Subtype: A subtype of INFLUENZA A VIRUS comprised of the surface proteins hemagglutinin 3 and neuraminidase 2. The H3N2 subtype was responsible for the Hong Kong flu pandemic of 1968.

Effect of L-azetidine-2-carboxylic acid on glycosylations of collagen in chick-embryo tendon cells. (1/17)

The glycosylations of hydroxylysine during collagen biosynthesis in isolated chick-embryo tendon cells were studied by using pulse-chase labelling experiments with [14C]-lysine. The hydroxylation of lysine and the glycosylations of hydroxylysine continued after a 5 min pulse label for up to about 10 min during the chase period. These data differ from those obtained previously in isolated chick-embryo cartilage cells, in which, after a similar 5 min pulse label, these reactions continued during the chase period for up to about 20 min. The collagen synthesized by the isolated chick-embryo tendon cells differed markedly from the type I collagen of adult tissues in its degree of hydroxylation of lysine residues and glycosylations of hydroxylysine residues. When the isolated tendon cells were incubated in the presence of L-azetidine-2-carboxylic acid, the degree of glycosylations of hydroxylysine during the first 10 min of the chase period was identical with that in cells incubated without thcarboxylic acid for at least 60 min, whereas no additional glycosylations took place in the control cells after the 10 min time-point. As a consequence, the collagen synthesized in the presence of this compound contained more carbohydrate than did the collagen synthesized by the control cells. Additional experiments indicated that azetidine-2-carboxylic acid did not increase the collagen glycosyltransferase activities in the tendon cells or the rate of glycosylation reactions when added directly to the enzyme incubation mixture. Control experiments with colchicine indicated that the delay in the rate of collagen secretion, which was observed in the presence of azetidine-2-carboxylic acid, did not in itself affect the degree of glycosylations of collagen. The results thus suggest that the increased glycosylations were due to inhibition of the collagen triple-helix formation, which is known to occur in the presence of azetidine-2-carboxylic acid.  (+info)

Incorporation of L-azetidine-2-carboxylic acid into hemoglobin in rabbit reticulocytes in vitro. (2/17)

L-Azetidine-2-carboxylic acid is the naturally occurring lower homologue of L-proline. Reticulocytes from anemic rabbits incubated with DL-[14-C]azetidine-2-carboxylic acid synthesized radiolabeled hemoglobin, which when isolated from cell lysates co-chromatographed with unlabeled hemoglobin on Sephadex G-100 columns. Amino acid analysis of hemoglobin from reticulocytes incubated with DL-[14-C]-azetidine-2-carboxylic acid suggested that the homologue was incorporated into hemoglobin intact and unaltered. Alternatively, another amino acid analogue, 1-aminocyclopentane-[1-14-C]carboxylic acid, which is purported to be a valine antagonist, was not incorporated into hemoglobin under these conditions. Incubation of reticulocytes with 1, 5, and 10 mM L-azetidine-2-carboxylic acid reduced L-[U-14-C]proline (0.10 mM) incorporation into hemoglobin by 25, 58, and 72%, respectively. Conversely, 1.45 and 145 muM L-proline reduced radiolabeled azetidine-2-carboxylic acid (0.8 mM) in corporation into hemoglobin by 45 and 92%, respectively. Incorporation of L-[U-14-C]leucine and L-[U-14-C]lysine (0.1 mM each) into hemoglobin was unaffected at these concentrations of L-azetidine-2-carboxylic acid. These results suggest that L-azetidine-2-carboxylic acid is incorporated into hemoglobin without reducing the rate of globin synthesis in rabbit reticulocytes in vitro. The alpha and beta chains of hemoglobin into which [14-C]azetidine-2-carboxylic acid had been incorporated in rabbit reticulocytes in vitro were resolved electrophoretically on sodium dodecyl sulfate-polyacrylamide gels. The ratio of total radioactivity in the alpha and beta chains separately extracted from gels was in good agreement with the known 7:4 ratio of prolyl residues in the respective chains. Autoradiograms of two-dimensional tryptic peptide maps of rabbit globin into which either [14-C]azetidine-2-carboxylic acid or [14-C]proline had been incorporated showed nearly identical patterns of radioactivity. These results suggest that azetidine-2-carboxylic acid substitutes specifically for prolyl residues during in vitro hemoglobin synthesis in rabbit reticulocytes.  (+info)

18F-ZW-104: a new radioligand for imaging neuronal nicotinic acetylcholine receptors--in vitro binding properties and PET studies in baboons. (3/17)


Antihypertensive effect of CS-905, a novel dihydropyridine calcium blocker, in conscious hypertensive dogs. (4/17)

CS-905, (+-)-3-(1-diphenylmethylazetidin-3-yl)5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxy lat e, is a novel dihydropyridine calcium blocker. Both CS-905 and nicardipine, when administered orally, produced a dose-dependent fall of blood pressure in conscious perinephritic hypertensive dogs. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in the heart rate and plasma renin activity (PRA). The lack of both tachycardia and increase of PRA is probably mostly due to the slow onset of antihypertensive action following CS-905.  (+info)

Generation and electrophile trapping of N-Boc-2-lithio-2-azetine: synthesis of 2-substituted 2-azetines. (5/17)


Effects of a new thyrotropin-releasing hormone derivative on behavioral changes after focal cerebral ischemia in rats. (6/17)

We observed the effects of a new thyrotropin-releasing hormone derivative, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on behavioral changes in rats for 3 weeks after focal cerebral ischemia. Under halothane anesthesia, the left middle cerebral artery was occluded via a transretro-orbital approach. YM-14673 was administered just after the operation and once a day for 3 weeks. Neurologic deficits, including hemiplegia and abnormal posture, and disturbance of passive avoidance learning were present in solvent-treated control rats for the entire 3 weeks. YM-14673 at 0.1 or 0.3 mg/kg i.p. or 1 mg/kg p.o. significantly accelerated the recovery of neurologic deficits and ameliorated cognitive disturbance compared with the solvent-treated controls although the drug at 0.1 and 0.3 mg/kg i.p. did not influence the size of the ischemic infarct. YM-14673 mitigated the behavioral disturbances in this model of chronic focal cerebral ischemia. We also discuss the suitability of this model for the evaluation of drugs.  (+info)

Beneficial renal effects of CS-905, a novel dihydropyridine calcium blocker, in SHR. (7/17)

CS-905 is a potent dihydropyridine calcium blocker that has a gradual and long-lasting antihypertensive action with little tachycardia in SHR. In this study, we investigated chronic and acute effects of CS-905 on renal functions in SHR. To examine the chronic effects, 23 week-old male SHR were treated with CS-905 (1 or 3 mg/kg/day, p.o.) or 0.3% CMC (carboxymethylcellulose). After the 15 week-treatment, the agent dose-relatedly lowered systolic blood pressure measured 24 hr after the final administration (184 +/- 2 and 173 +/- 3 mmHg at 1 and 3 mg/kg/day vs. 218 +/- 4 mmHg for the control group). Natriuresis and the reduction of urinary protein excretion were also observed in the CS-905 treated groups. Urinary NAG (N-acetyl-beta-D-glucosaminidase) activity tended to decrease, but not significantly. Histopathological changes observed in the SHR kidney were reduced by chronic treatment with CS-905. On a single oral administration in 38 week-old SHR, CS-905 caused natriuresis at a dose of 3 mg/kg, but did not affect urinary protein excretion and urinary NAG activity. These effects of CS-905 on renal functions may be beneficial in the treatment of hypertension.  (+info)

Interference with thyroid histogenesis by inhibitors of collagen synthesis. (8/17)

Histogenesis of thyroid follicles in the chick embryo begins with a penetration by cells of the mesenchymal capsule into a solid epithelial primordium. Before penetration occurs, slits containing fibrillar material form between the epithelial cells. The fibrillar material is an epithelial cell product as shown by its formation within channels that form in cultures of isolated epithelial primordia. The drugs L-azetidine-2-carboxylic acid (LACA) and alpha, alpha'-dipyridyl, which interfere with collagen synthesis, prevent the formation of fibrils in cultured epithelial primordia and in cultures of whole thyroids. Furthermore, mesenchymal cells do not invade when whole thyroid primordia are cultured in the presence of either drug. The effects of alpha, alpha'-dipyridyl are reversed by washing out the drug; the effects of LACA are reversed by incubation with equimolar or greater amounts of L-proline added to the medium along with the drug. The results are interpreted to mean that the fibrillar material is collagen of epithelial origin, that the collagen in some way plays a role in mesenchymal penetration of the epithelial primordium, and that the epithelium is responsible for the pattern of lobulation within the developing gland.  (+info)