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PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide, testosterone gel, tezosentan disodium, tipifarnib, tolvaptan, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Vardenafil hydrochloride hydrate; Xcellerated T cells, XR-5944; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziconotide.

Clinical Trials as Topic↗

PubMed2004

[The practice guideline 'Photo(chemo)therapy and systemic therapy in severe chronic plaque-psoriasis'].

The guideline for the treatment of adults with moderate to severe chronic plaque-type psoriasis vulgaris is based on published scientific evidence. The efficacy of the treatment, its safety, the side effects, the patients' discomfort, the patients' preference and the costs of treatment and follow-up are listed as criteria that play a role in the choice of treatment. Photo(chemo)therapy is the treatment of choice for severe forms of psoriasis. Phototherapy with ultraviolet-B light (UVB), especially narrow-band UVB, is preferred above photochemotherapy with ultraviolet-A light and psoralenes (PUVA). Of the oral treatments, methotrexate and ciclosporin are preferred above retinoids and fumarates because they yield a higher percentage of patients with partial or nearly complete remission. Fumarates are not officially registered in The Netherlands and Belgium.

Cyclosporine↗

PubMed2005

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort extract, synthetic human secretin; Taxus, telavancin hydrochloride, telithromycin, temoporfin, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, teriparatide, testosterone gel, TG-1024, tirapazamine, travoprost, travoprost/timolol; Valdecoxib, valganciclovir hydrochloride, voriconazole; Ximelagatran.

Clinical Trials as Topic↗

PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA; ValboroPro, valdecoxib, val-mCyd, valtorcitabine dihydrochloride: XP-828L.

Clinical Trials as Topic↗

PubMed2005

Gateways to clinical trials.

Clinical Trials as Topic↗

PubMedDate not supplied

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, ambrisentan, aminolevulinic acid methyl ester, armodafinil, aselizumab, asenapine maleate, azelnidipine; Bevacizumab, bexarotene, bimosiamose, biphasic insulin aspart, bortezomib, bosentan, BQ-123; C340, cannabidiol, caspofungin acetate, CC-4047, certolizumab pegol, cetuximab, ciclesonide, cilansetron, Cypher; Dabigatran etexilate, darbepoetin alfa, darifenacin hydrobromide, desloratadine, dexosome vaccine (melanoma), dimethyl fumarate, dronabinol/cannabidiol, drospirenone, drospirenone/estradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Efalizumab, eglumetad hydrate, emoxipin hydrochloride, eplerenone, erlotinib hydrochloride, escitalopram oxalate, etonogestrel/ethinylestradiol; Garenoxacin mesilate, gamma-hydroxybutyrate sodium, gefitinib; H5N1 pandemic influenza vaccine, human growth hormone-(177-191), human insulin; Indacaterol, INKP-100, INKP-102, insulin glargine, i.v. gamma-globulin; KLH; Lapatinib, L-arginine hydrochloride, lasofoxifene tartrate, levocetirizine, licochalcone A, LMI vaccine, lomefloxacin, lubiprostone, lumiracoxib; Miglustat, mycograb; Natalizumab, NCX-4016, nortopixantrone hydrochloride; Olmesartan medoxomil, omalizumab, oral insulin, OrM3; Parathyroid hormone (human recombinant), parecoxib sodium, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, pemetrexed disodium, pexelizumab, photochlor, pimecrolimus, pneumococcal 7-valent conjugate vaccine, polyphenon E; R-126638, R-411, resveratrol, roflumilast, RS-86, ruboxistaurin mesilate hydrate, rupatadine fumarate; Sipuleucel-T, somatropin, St. John's Wort extract; Tadalafil, Taxus, telbivudine, telithromycin, temsirolimus, teriparatide, teverelix, tigecycline, tiotropium bromide, tolterodine, tolvaptan, treprostinil sodium, typhoid vaccine; Vardenafil hydrochloride hydrate, vildagliptin, voriconazole; Ximelagatran; Zanolimumab, zileuton.

Clinical Trials as Topic↗

PubMed2006

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium, mycophenolate mofetil, mycophenolic acid sodium salt; Nitisinone; Omalizumab, omapatrilat, ONYX-015, oxaliplatin; Paclitaxel, paclitaxel nanoparticles, panitumumab, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pertuzumab, phosphatidylcholine-rich phospholipid mixture, pimecrolimus, pioglitazone hydrochloride, pramlintide acetate, prasterone; QR-333; Ranelic acid distrontium salt, ranolazine, rasagiline mesilate, RFB4(dsFv)-PE38, ribavirin, rifabutin, risperidone, rituximab, rofecoxib, rosiglitazone maleate, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; S-236, salmeterol xinafoate, sarizotan hydrochloride, sildenafil, sildenafil citrate, sunitinib malate; Tadalafil, tegaserod maleate, temozolomide, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, trabectedin, treprostinil sodium; Vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, vinflunine, virosome influenza vaccine, voriconazole; Zidovudine.

Clinical Trials as Topic↗

PubMedDate not supplied

[Investigation of the catabolism of acetate and peptides in the new anaerobic thermophilic bacterium Caldithrix abyssi].

This work is concerned with the metabolism of Caldithrix abyssi-an anaerobic, moderately thermophilic bacterium isolated from deep-sea hydrothermal vents of the Mid-Atlantic Ridge and representing a new, deeply deviated branch within the domain Bacteria. Cells of C. abyssi grown on acetate and nitrate, which was reduced to ammonium, possessed nitrate reductase activity and contained cytochromes of the b and c types. Utilization of acetate occurred as a result of the operation of the TCA and glyoxylate cycles. During growth of C. abyssi on yeast extract, fermentation with the formation of acetate, propionate, hydrogen, and CO2 occurred. In extracts of cells grown on yeast extract, acetate was produced from pyruvate with the involvement of the following enzymes: pyruvate:ferredoxin oxidoreductase (2.6 micromol/(min mg protein)), phosphate acetyltransferase (0.46 micromol/(min mg protein)), and acetate kinase (0.3 micromol/(min mg protein)). The activity of fumarate reductase (0.14 micromol/(min mg protein)), malate dehydrogenase (0.17 micromol/(min mg protein)), and fumarate hydratase (1.2 micromol/(min mg protein)), as well as the presence of cytochrome b, points to the formation of propionate via the methyl-malonyl-CoA pathway. The activity of antioxidant enzymes (catalase and superoxide dismutase) was detected. Thus, enzymatic mechanisms have been elucidated that allow C. abyssi to switch from fermentation to anaerobic respiration and to exist in the gradient of redox conditions characteristic of deep-sea hydrothermal vents.

Acetate Kinase↗

PubMedDate not supplied

[The new facultatively chemolithoautotrophic, moderately halophilic, sulfate-reducing bacterium Desulfovermiculus halophilus gen. nov., sp. nov., isolated from an oil field].

The new mesophilic, chemolithoautotrophic, moderately halophilic, sulfate-reducing bacterium strain 11-6 could grow at a NaCl concentration in the medium of 30-230 g/l, with an optimum at 80-100 g/l. Cells were vibrios motile at the early stages of growth. Lactate, pyruvate, malate, fumarate, succinate, propionate, butyrate, crotonate, ethanol, alanine, formate, and H2 + CO2 were used in sulfate reduction. Butyrate was degraded completely, without acetate accumulation. In butyrate-grown cells, a high activity of CO dehydrogenase was detected. Additional growth factors were not required. Autotrophic growth occurred, in the presence of sulfate, on H2 + CO2 or formate without other electron donors. Fermentation of pyruvate and fumarate was possible in the absence of sulfate. Apart from sulfate, sulfite, thiosulfate, and elemental sulfur were able to serve as electron acceptors. The optimal growth temperature was 37 degrees C; the optimum pH was 7.2. Desulfoviridin was not detected. Menaquinone MK-7 was present. The DNA G+C content was 55.2 mol %. Phylogenetically, the bacterium represented a separate branch within the cluster formed by representatives of the family Desulfohalobiaceae in the subclass Deltaproteobacteria. The bacterium was assigned to a new genus and species, Desulfovermiculus halophilus gen. nov., sp. nov. The type strain is 11-6T (= VKM B-2364), isolated from the highly mineralized formation water of an oil field.

Carboxylic Acids↗

PubMed2006

Gateways to clinical trials.

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus-eluting stent, sitaxsentan sodium, solifenacin succinate, Staphylococcus aureus vaccine; Tadalafil, talactoferrin alfa, talaporfin sodium, Taxus, tecadenoson, tegaserod maleate, telithromycin, temsirolimus, tenofovir disoproxil fumarate, teriparatide, terutroban sodium, tesaglitazar, tesmilifene hydrochloride, TG-100115, tigecycline, torcetrapib; Ularitide; Valproic acid, sodium, voriconazole; Zotarolimus, zotarolimus-eluting stent.

Clinical Trials as Topic↗

PubMed2006

Gateways to clinical trials.

Clinical Trials as Topic↗

PubMed1975

Lactate dehydrogenase-catalyzed stereospecific hydrogen atom transfer from reduced nicotinamide adenine dinucleotide to dicarboxylate radicals.

The dicarboxylate radical -OOC--CH--CH(OH)COO- was generated in an N2O-saturated fumarate solution by high energy ionizing radiation. When NADH was present in the solution, product analysis indicated a stoichiometry of 2 molecules of the radical reacted with 1 NADH molecule to form 2 malate and 1 enzymatically active NAD+ molecules. In a similar experiment using tritium label on position A of NADH, due to an isotope effect, only 10% of the label was transferred to malate; most of the remaining tritium was found in the NAD+ formed. When lactate dehydrogenase was added, however, no la bel was detectable in NAD+, and over 80% of the tritium lost from NADH was found in malate. The stereospecific transfer of the hydrogen atom from lactate dehydrogenase-bound NADH to the dicarboxylate radical suggested that the free radical reaction must have taken place at the active site. The hydrogen atom transfer was inhibited by oxamate. Results from flow experiments in which an irradiated fumarate solution was mixed with a solutionof lactate dehydrogenase and NADH are in support of a mechanism in which the hydrogen atom transfer occurs in the first oxidation step.

Animals↗

PubMed1976

NAD+-malic enzyme. Regulatory properties of the enzyme from Ascaris suum.

The regulatory properties of the NAD-dependent malic enzyme from the mitochondria of Ascaris suum have been studied. The malate saturation curve exhibits sigmoidicity and the degree of this sigmoidicity increases as the pH is increased. Fumarate was the only compound tested that stimulated the enzyme activity, whereas oxalacetate was the most powerful inhibitor. Activation by low levels of fumarate was found to be competitive with malate. It is proposed that this stimulation has physiological significance in controlling the dismutation reaction in the parasite. The branched-chain volatile fatty acid excretion products, tiglate, 2-methylbutanoate, and 2-methylpentanoate, inhibited the enzyme activity and this inhibition was competitive with malate. The Ki values for these compounds are in the physiological range of their concentrations; therefore, it is suggested that they may aid in controlling the malic enzyme activity in vivo. Oxalacetate inhibition of malic enzyme activity was competitive with malate, and the Ki values decreased with an increase in pH. Two alternatives are proposed which could account for the lack of oxalacetate decarboxylation by the ascarid malic enzyme.

Animals↗

PubMed1991

Urinary excretion of CGS 5,649 and its conjugated glucuronide and sulfate in man.

Experiments in animals have indicated that CGS 5,649 B [6-(2-isopropylaminopropyl)-3-pyridinol fumarate] might enhance memory and learning processes and might be a valuable drug for treatment of impairment of vigilance and mental performance in the elderly. CGS 5,649 (I) is extensively metabolized. Therefore, we investigated the excretion of the drug and its conjugates (I-SULF,I-GLUC) into urine after oral administration of 1200 mg of the fumarate salt of I to one healthy male volunteer. Three HPLC methods were developed to analyze the three compounds in urine: a. Solid-phase extraction and UV-measurement at 280 nm; b. Dansylation followed by fluorometric detection (lambda ex 340, lambda em 525 nm); c. Direct injection of diluted urine, gradient system with ion-pair reagent and UV-detection at 280 nm. The conjugates were measured after enzymatic hydrolysis with glucuronidase/sulfatase and sulfatase. I-GLUC was also measured directly since a synthetic sample had become available. Results from the different analytical methods showed agreement: about 100% of the administered dose was excreted within 24 h; the relative amounts of I, I-SULF and I-GLUC were about 1:2:2; after oral administration, CGS 5,649 B is rapidly and completely absorbed; it is eliminated from plasma by conjugation and direct excretion into urine.

Chromatography, High Pressure Liquid↗

PubMed1990

Mutagenesis, cloning and complementation analysis of C4-dicarboxylate transport genes from Rhodobacter capsulatus.

Transposon mutagenesis was used to isolate insertion mutants of the photosynthetic bacterium Rhodobacter capsulatus which were unable to grow under aerobic conditions in the dark on malate, succinate or fumarate as sole carbon sources. Of five mutants isolated, all were deficient in C4-dicarboxylate transport. However, these mutants were still capable of photoheterotrophic growth, although at a slower rate than the wild type, on malate and succinate (but not fumarate). The mutated locus (designated dct) was complemented in trans using a cosmid gene bank. Subcloning and complementation analysis indicated that at least three closely linked genes essential for aerobic dicarboxylate transport were contained within an 8.3 kb region of the Rhodobacter capsulatus chromosome.

Biological Transport↗

PubMed1990

[Long-term follow-up of pulmonary hypertension of unknown etiology].

Since 1967, 166 patients with primary pulmonary hypertension of unknown etiology have been followed-up at the Department of Cardiology at the University of Vienna. Although an exact etiopathogenetic differentiation was not possible, three groups of patients were identified clinically: patients with so-called primary pulmonary hypertension (PPH)--group 1; patients with pulmonary hypertension induced by anorexipens (aminorex fumarate)--group 2; and patients with pulmonary hypertension due to emboli in the large pulmonary vessels--group 3. In addition to non-invasive echocardiographic assessment of pulmonary pressures, regular cardiac catheterizations were carried out, which revealed right atrial mean pressure, cardiac output, and mixed venous saturation to be prognostic predictive factors. Patients with anorexigen-induced pulmonary hypertension have a clearly better life expectancy than those with PPH. Owing to the temporally limited effect of the pulmonary hypertension-inducing agent, aminorex fumarate (Menocil), patients with anorexigen-induced pulmonary hypertension may be considered a model group for drug-induced vascular pathology.

Aminorex↗

PubMed1977

Effect of extracellular pH and inhibitors on the gluconeogenesis and ammoniagenesis relationship in rat kidney cortex slices.

1. Gluconeogenesis from glutamine, fumarate, pyruvate, glutamine plus fumarate, and glutamine plus pyruvate, was generally higher at pH 7.1 than at pH 7.4 and 7.7, whereas ammoniagenesis did not depend on the pH of the medium. 2. The intermediates of the Krebs cycle decreased ammonia formation from glutamine, raising at the same time gluconeogenesis. 3. Arsenite, malonate, maleate, hydrazine and 2,4-dinitrophenol inhibited gluconeogenesis, and enhanced simultaneously ammonia formation irrespective of the pH of the medium.

Ammonia↗

PubMed1989

Studies of glycogen synthesis and the Krebs cycle by mass isotopomer analysis with [U-13C]glucose in rats.

Starved rats were infused intragastrically via indwelling duodenal cannulae with glucose at a rate of 30 mg/min/kg. The infusate contained [U-13C]glucose at an enrichment of 32 or 17%. At the end of the infusion, after 160 min, glucose and lactate were isolated from arterial and portal blood and from liver, and liver glycogen was isolated and hydrolyzed to glucose. The enrichment in glucose and lactate and the isotopomer distribution in glucose of masses from 180 to 186 were determined by gas chromatography-mass spectrometry (GC-MS). From analysis of these data we determined (a) gluconeogenesis proceeds at half the basal rate in the presence of a large infused glucose load, (b) one-quarter of the hepatic pyruvate pool is derived from nonglucose carbon, (c) half of the labeled molecules in liver glycogen are of mass 186 from the infused glucose and half are of masses 181-183, (d) the contribution of the indirect path from pyruvate when corrected for synthesis from unlabeled pyruvate ranges from 55 to 65%, (e) the rate of pyruvate carboxylase averages 90% that of citrate synthase, and (f) the rate of exchange of oxaloacetate with fumarate is about three times the rate of flux in the Krebs cycle (four times in the "forward" direction), and the enrichment in carbon 1 of oxaloacetate was 2.3 times that in carbon 4. In the Appendix a method to obtain the isotopomer distribution of newly formed glucose and glycogen glucose is described. An algorithm to correct for the contribution of natural abundance of 13C and the presence of 12C in commercial [U-13C]glucose is presented. A novel mathematical analysis to obtain the parameters of the Krebs cycle from the isotopomer distribution is developed in the Appendix. Equations to calculate the relative rates of pyruvate carboxylase (y), and the equilibration of oxaloacetate with fumarate from the isotopomer distribution are derived. Mass isotopomer analysis provides a novel and powerful tool for the study of carbohydrate metabolism and the operation of the Krebs cycle.

Animals↗