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1.
J Org Chem ; 86(19): 13734-13743, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34541847

RESUMO

An efficient, facile, and eco-friendly synthesis of pyrimidine derivatives has been developed. It involves a [3 + 2 + 1] three-component annulation of amidines, ketones, and one carbon source. N,N-Dimethylaminoethanol is oxidized through C(sp3)-H activation to provide the carbon donor. One C-C and two C-N bonds are formed during the oxidative annulation process. The reaction shows good tolerance to many important functional groups in air, making this methodology a highly versatile alternative, and significant improvement to the existing methods for structuring a pyrimidine framework, especially 4-aliphatic pyrimidines.


Assuntos
Amidinas , Cetonas , Carbono , Catálise , Deanol , Pirimidinas
2.
J Oleo Sci ; 70(1): 59-65, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33431773

RESUMO

Quaternary ammonium compounds are widely used as antiseptic and disinfectant. It is been a concern that their widespread use will lead to an increase of environmental problems, therefore the development of biodegradable surfactants is necessary. The present research is aimed at the design of novel amphiphilic molecules with similar properties to those already known but more biodegradable. Based on benzalkonium chloride (BAC), novel carbonate cleavable surfactants (CBAC) were synthesized. The breakable carbonate sites make CBAC compounds more degradable and potentially more biodegradable than their non-cleavable BAC analogues. Natural products such as fatty alcohols (C8-C16) and N,N-dimethyl-2-aminoethanol were used as reagents for the synthesis of CBAC8-16. These amphiphilic compounds were characterized in terms of surface properties and antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and moulds. The novel surfactants showed similar surface activities in aqueous solutions when compared to BAC. Also, the surface activity/structure relationship revealed that carbonate cleavable surfactants with n-decyl group (CBAC10) showed the same behaviour as non-cleavable BAC. Furthermore, compounds containing n-octyl (CBAC8), n-decyl (CBAC10) and n-dodecyl (CBAC12) group showed strong antimicrobial activities.


Assuntos
Antibacterianos , Compostos de Benzalcônio/síntese química , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/farmacologia , Tensoativos/síntese química , Anti-Infecciosos Locais , Compostos de Benzalcônio/química , Compostos de Benzalcônio/farmacologia , Biodegradação Ambiental , Carbonatos , Deanol/química , Desinfetantes , Álcoois Graxos/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Indicadores e Reagentes/química , Compostos de Amônio Quaternário/química , Relação Estrutura-Atividade , Propriedades de Superfície
3.
Artigo em Russo | MEDLINE | ID: mdl-31851171

RESUMO

AIM: To study the effects of nooclerin (deanol aceglumate) on the structure of sleep disturbances in children with tension-type headache (TTH). MATERIAL AND METHODS: A blind randomized placebo-controlled study of the efficacy of nooclerin (deanol aceglumate), prescribed for 2 months to prevent TTH, was carried out. The study included 60 patients (30 boys and 30 girls), aged 9-16 years, with TTH. Patients were randomized into the nooclerin group (n=30) and the placebo group (n=30). Sleep disturbances were assessed before and after treatment with the Sleep Disturbance Scale for Children (SDSC). RESULTS: There was a significant positive dynamics (reduced total score on SDSC (p<0.001) and a significant decrease in the scores on scales 'Disorders of initiating and maintaining sleep', 'Disorders of excessive somnolence' (p<0.001), 'Sleep wake transition disorders' (p<0.01)) in the nooclerin group. No significant positive changes were detected in the placebo group. CONCLUSION: An anxiolytic action of nooclerin was confirmed. Further studies of the drug in child neurology and psychiatry using larger groups of patients are needed.


Assuntos
Ansiolíticos , Deanol , Glutamatos , Transtornos do Sono-Vigília , Cefaleia do Tipo Tensional , Adolescente , Ansiolíticos/uso terapêutico , Criança , Deanol/uso terapêutico , Feminino , Glutamatos/uso terapêutico , Humanos , Masculino , Sono , Transtornos do Sono-Vigília/congênito , Transtornos do Sono-Vigília/tratamento farmacológico , Cefaleia do Tipo Tensional/complicações , Cefaleia do Tipo Tensional/tratamento farmacológico
4.
Toxicol Appl Pharmacol ; 378: 114592, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100288

RESUMO

Dimethylaminoethanol (DMAE) and its salts have been used to treat numerous disorders in humans and hence safety of its use is a concern. DMAE is a close structural analog of choline, an essential nutrient. Exposure to DMAE may affect choline uptake and synthesis. The current investigation characterizes: 1) the absorption, distribution, metabolism, and excretion (ADME) of DMAE in Wistar Han rats and B6C3F1 mice following a single gavage or intravenous (IV) administration of 10, 100 or 500 mg/kg [14C]DMAE, and 2) the ADME of [14C]choline (160 mg/kg) and the effect on its disposition following pre-treatment with DMAE (100 or 500 mg/kg). In both rats and mice, following gavage administration, DMAE was excreted in urine (16-69%) and as exhaled CO2 (3-22%). The tissue retention was moderate (21-44%); however, the brain concentrations were low and there was no accumulation. Serum choline levels were not elevated following administration of DMAE. The DMAE metabolites in urine were DMAE N-oxide and N,N-dimethylglycine; the carcinogen, N-N-dimethylnitrosamine, was not detected. The pattern of disposition of [14C]choline following gavage administration was similar to that of [14C]DMAE. Prior treatment with DMAE had minimal effects on choline disposition. The pattern of disposition of [14C]DMAE and [14C]choline following IV administration was similar to gavage administration. There were minimal dose-, sex- or species-related effects following gavage or IV administration of [14C]DMAE or [14C]choline. Data from the current study did not support previous reports that: 1) DMAE alters choline uptake and distribution, or 2) that DMAE is converted into choline in vivo.


Assuntos
Colina/administração & dosagem , Colina/metabolismo , Deanol/administração & dosagem , Deanol/metabolismo , Administração Intravenosa , Administração Oral , Animais , Dimetilnitrosamina/metabolismo , Feminino , Masculino , Camundongos , Ratos , Ratos Wistar , Distribuição Tecidual/fisiologia
5.
Zh Nevrol Psikhiatr Im S S Korsakova ; 118(1. Vyp. 2): 45-51, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29658504

RESUMO

AIM: To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. MATERIAL AND METHODS: A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). RESULTS AND CONCLUSION: Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.


Assuntos
Alcoolismo , Antidepressivos , Deanol , Síndrome de Abstinência a Substâncias , Antidepressivos/uso terapêutico , Deanol/uso terapêutico , Etanol , Humanos , Síndrome de Abstinência a Substâncias/tratamento farmacológico
6.
Artigo em Russo | MEDLINE | ID: mdl-29460904

RESUMO

AIM: To study clinical and pathophysiological symptoms of autonomic dysfunction syndrome in children and adolescents and assess the efficacy of its treatment with nooclerin. MATERIAL AND METHODS: Fifty-three patients, aged from 10 to 15 years, with autonomic dysfunction syndrome were examined. All patients underwent neurological examination, assessment with the A.M. Vein's questionnaire of autonomic disorders, the 10 point Visual Analogous scale for headache and fatigue, the Spielberger-Khanin scale for anxiety, Kerdo index, Hildebrandt's coefficient, electrocardiography with clinoorthostatic test, electroencephalography, and TOVA psychophysiological test. RESULTS AND CONCLUSION: The signs of the asthenic-autonomic syndrome were characteristic of the clinical picture of disease. EEG results demonstrated the deficit of activation effects, predominance of synchronized effects of thalamic structures which led to the insufficient activation of cortical structures. These data support the high efficacy of nooclerin.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Deanol/uso terapêutico , Glutamatos/uso terapêutico , Adolescente , Ansiedade/diagnóstico , Astenia/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Criança , Eletroencefalografia , Fadiga/diagnóstico , Feminino , Humanos , Masculino , Exame Neurológico , Inquéritos e Questionários , Síndrome , Resultado do Tratamento , Escala Visual Analógica
7.
Artigo em Russo | MEDLINE | ID: mdl-29053118

RESUMO

BACKGROUND: This work is devoted to the combined therapy of asthenic syndrome in psychiatric patients due to the importanmce of studies of clinical signs of asthenic disorders and their comorbidity with psychiatric and somatic diseases. AIM: To evaluate the efficacy and safety of deanoli aceglumas (nooklerin) in treatment of asthenic and cognitive disorders in patients with borderline psychopathological conditions. MATERIAL AND METHODS: Sixty patients were enrolled in the study (30 patients of the main group and 30 patients of the control group). All patients received psychopharmacological treatment. Nooklerin was administered as add-on in the daily dose of 1000 mg in the main group. Psychopathological and psychometric examinations were conducted. The duration of treatment with nooklerin was 30 days. RESULTS: There was a significant reduction of asthenic and cognitive disorders in the main group compared to the controls. The good tolerability of nooklerin in the absence of a negative effect on the main disease was shown. CONCLUSION: The possibility of using deanoli aceglumas (nooklerin) as a drug of choice in combined treatment of asthenic and cognitive disorders in patients with borderline psychopathological conditions is confirmed.


Assuntos
Astenia/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Deanol/uso terapêutico , Glutamatos/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Adulto Jovem
8.
Drug Deliv ; 23(7): 2183-2192, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25182481

RESUMO

Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its Cmax and AUC0-t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.


Assuntos
Encéfalo/metabolismo , Flurbiprofeno/administração & dosagem , Flurbiprofeno/metabolismo , Animais , Linhagem Celular , Deanol/química , Portadores de Fármacos/química , Células Endoteliais/metabolismo , Flurbiprofeno/química , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual/fisiologia
9.
J Drugs Dermatol ; 14(9): 997-1002, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26355619

RESUMO

INTRODUCTION: With many effective anti-aging solutions for the face, consumer focus is now turning to other parts of the body including the delicate skin on the neck. This study investigates the effect of a new neck cream on the appearance of texture, fine lines and wrinkles, laxity, and hydration. METHODS: 85 adult females ages 35-65 with Fitzpatrick skin types I through IV applied the test neck cream twice daily for a 3-month study period. Screening was conducted at Baseline, 2, 30, 60, and 90 days via a virtual trial. Subjects rated satisfaction in each of 4 anti-aging categories including hydration, texture, appearance of wrinkles, and appearance of laxity as well as three product attributes including application, feel, and smell. RESULTS: Improvement was statistically significant for all measured categories (hydration, texture, appearance of wrinkles, and appearance of laxity) with 94% of study subjects noting improvement in one or more of the measured categories. Further, the quantity of "Satisfied" and "Highly Satisfied" assessments increased 8-fold from baseline with a 94x increase in the quantity of "Highly Satisfied" assessments. DISCUSSION: The results demonstrate the product's rapid and continuing ability to improve the self-perceived signs of aging in the neck area including improvement in skin texture on the neck and a reduction in the appearance of wrinkles and laxity along the jawline. Future studies are recommended to determine the primary action mechanisms and to assess the degree of improvement by blinded physician assessment.


Assuntos
Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/uso terapêutico , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Adulto , Idoso , Antioxidantes/uso terapêutico , Biotina/uso terapêutico , Deanol/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Higroscópicos/uso terapêutico , Pessoa de Meia-Idade , Sesquiterpenos Monocíclicos , Pescoço , Satisfação do Paciente , Sesquiterpenos/uso terapêutico , Envelhecimento da Pele/patologia , Envelhecimento da Pele/fisiologia , Complexo Vitamínico B/uso terapêutico , Vitamina E/uso terapêutico
10.
Anal Bioanal Chem ; 407(17): 5079-89, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25633216

RESUMO

A new type of low-mass substituted 4-oxazolin product ions of [M + H](+) precursor ions of aminophospholipids (glycerophosphatidylethanolamine, glycerophosphatidyl-N-methylethanolamine, glycerophosphatidyl-N,N-dimethylethanolamine, glycerophosphatidylserine) resulting from high-energy collision-induced dissociation (matrix-assisted laser desorption/ionization time-of-flight/reflectron time-of-flight mass spectrometry) and low-energy collision-induced dissociation (e.g., electrospray ionization quadrupole reflectron time-of-flight mass spectrometry) with accurate mass determination is described; these were previously misidentified as CHO-containing radical cationic product ions. The mechanism for the formation of these ions is proposed to be via rapid loss of water followed by cyclization to an 11-membered-ring transition state for the sn-1 fatty acid substituent and to a ten-membered-ring transition state for the sn-2 fatty acid substituent, and via final loss of monoacylglycerol phosphate, leading to substituted 4-oxazolin product ions. The minimum structural requirement for this interesting skeletal rearrangement fragmentation is an amino group linked to at least one hydrogen atom (i.e., ethanolamine, N-methylethanolamine, serine). Therefore, N,N-dimethylethanolamine derivates do not exhibit this type of fragmentation. The analytical value of these product ions is given by the fact that by post source decay and particularly high-energy collision-induced dissociation achieved via matrix-assisted laser desorption/ionization time-of-flight/reflectron time-of-flight mass spectrometry, the sn-2-related substituted 4-oxazolin product ion is always significantly more abundant than the sn-1-related one, which is quite helpful for detailed structural analysis of complex lipids. All other important product ions found are described in detail (following our previously published glycerophospholipid product ion nomenclature; Pittenauer and Allmaier, Int. J. Mass. Spectrom. 301:90-1012, 2011).


Assuntos
Deanol/química , Etanolaminas/química , Oxazóis/química , Fosfatidiletanolaminas/química , Fosfatidilserinas/química , Íons/química , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
11.
Mol Divers ; 19(1): 87-101, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25528441

RESUMO

A variety of organocatalysts has been screened for the synthesis of arylaminonaphthols. It has been shown that (N,N-dimethylethanolamine) is a highly efficient organocatalyst for the direct synthesis of a novel class of arylaminonaphthols via three-component condensation of 2-naphthol, aldehydes, and arylamines under solvent-free conditions. Mild, one-pot, and green reaction conditions, relatively short reaction times and good yields make this protocol highly significant. 25 new compounds have been synthesized by this method.


Assuntos
Aldeídos/química , Aminas/química , Deanol/química , Naftóis/química , Naftóis/síntese química , Técnicas de Química Sintética , Modelos Moleculares
12.
ScientificWorldJournal ; 2014: 507351, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133239

RESUMO

A lasting dream of human beings is to reverse or postpone aging. In this study, dimethylaminoethanol (DMAE) and compound amino acid (AA) in Mesotherapy were investigated for their potential antiaging effects on D-galactose induced aging skin. At 18 days after D-gal induction, each rat was treated with intradermal microinjection of saline, AA, 0.1% DMAE, 0.2% DMAE, 0.1% DMAE + AA, or 0.2% DMAE + AA, respectively. At 42 days after treatment, the skin wound was harvested and assayed. Measurement of epidermal and dermal thickness in 0.1% DMAE + AA and 0.2% DMAE + AA groups appeared significantly thicker than aging control rats. No differences were found in tissue water content among groups. Hydroxyproline in 0.1% DMAE + AA, 0.2% DMAE + AA, and sham control groups was much higher than all other groups. Collagen type I, type III, and MMP-1 expression was highly upregulated in both 0.1% DMAE + AA and 0.2% DMAE + AA groups compared with aging control. In contrast, TIMP-1 expression levels of various aging groups were significantly reduced when compared to sham control. Coinjection of DMAE and AA into target tissue has marked antiaging effects on D-galactose induced skin aging model of rat.


Assuntos
Aminoácidos/farmacologia , Deanol/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Animais , Colágeno/genética , Colágeno/metabolismo , Galactose/farmacologia , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Ratos , Ratos Wistar , Pele/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo
13.
Int J Syst Evol Microbiol ; 64(Pt 6): 1978-1983, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24614846

RESUMO

A novel, strictly anaerobic, methylotrophic marine methanogen, strain SLH33(T), was isolated from deep sediment samples covered by an orange microbial mat collected from the Napoli Mud Volcano. Cells of strain SLH33(T) were Gram-stain-negative, motile, irregular cocci that occurred singly. Cells utilized trimethylamine, dimethylamine, monomethylamine, methanol, betaine, N,N-dimethylethanolamine and choline (N,N,N-trimethylethanolamine) as substrates for growth and methanogenesis. The optimal growth temperature was 30 °C; maximum growth rate was obtained at pH 7.0 in the presence of 0.5 M Na(+). The DNA G+C content of strain SLH33(T) was 43.4 mol%. Phylogenetic analyses based on 16S rRNA gene sequences placed strain SLH33(T) within the genus Methanococcoides. The novel isolate was related most closely to Methanococcoides methylutens TMA-10(T) (98.8% 16S rRNA gene sequence similarity) but distantly related to Methanococcoides burtonii DSM 6242(T) (97.6%) and Methanococcoides alaskense AK-5(T) (97.6%). DNA-DNA hybridization studies indicated that strain SLH33(T) represents a novel species, given that it shared less than 16% DNA-DNA relatedness with Methanococcoides methylutens TMA-10(T). The name Methanococcoides vulcani sp. nov. is proposed for this novel species, with strain SLH33(T) ( = DSM 26966(T) = JCM 19278(T)) as the type strain. An emended description of the genus Methanococcoides is also proposed.


Assuntos
Fontes Hidrotermais/microbiologia , Methanosarcinaceae/classificação , Filogenia , Composição de Bases , Betaína/metabolismo , Colina/metabolismo , DNA Bacteriano/genética , Deanol/metabolismo , Mar Mediterrâneo , Methanosarcinaceae/genética , Methanosarcinaceae/isolamento & purificação , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
14.
Artigo em Inglês | MEDLINE | ID: mdl-24269909

RESUMO

This paper described the preparation and application of a new dimethylethanolamine aminated polychloromethyl styrene nano-latex (DMEAPL) coated capillary column (ccc-DMEAPL) in the determination of four tetracycline antibiotics (TCA) including tetracycline (TC), oxytetracycline (OTC), doxycycline (DC) and chlorotetracycline (CTC) in pig plasma. The ccc-DMEAPL column was characterized with steady EOF values of ca. 1.5-5.2×10(-5)cm(2)/Vs at pH 1.8-6.3. The optimized conditions for field-amplified sample stacking open-tubular capillary electrochromatography (FASS-OT-CEC) were as following: background electrolyte, 10mmol/L Na2HPO4+15mmol/L citric acid (pH 3.2); ccc-DMEAPL, 50µm i.d.×50cm (effective length 41.5cm), separation voltage, 18kV; column temperature, 25°C; UV detection wavelength, 270nm; water-plug injection: 30mbar×10s; sample electrokinetic injection, 10kV×20s. The four TCA were extracted with the solution of 10mmol/L Na2HPO4+15mmol/L citric acid+4g/L EDTA-2Na (pH 3.2). The FASS-OT-CEC method was validated in terms of linearity, sensitivity, selectivity, precision and accuracy. The LODs ranged from 3 to 7ng/mL, the recoveries for the four TCA were all more than 80%. The developed method was successfully applied for the determination of TCs in the actual pig plasma samples.


Assuntos
Antibacterianos/sangue , Eletrocromatografia Capilar/instrumentação , Eletrocromatografia Capilar/métodos , Deanol/química , Nanopartículas/química , Tetraciclinas/sangue , Animais , Antibacterianos/química , Látex/química , Limite de Detecção , Modelos Lineares , Poliestirenos/química , Reprodutibilidade dos Testes , Suínos , Tetraciclinas/química
15.
Appl Radiat Isot ; 78: 26-32, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23665261

RESUMO

INTRODUCTION: A novel one-pot method for preparing [(18)F]fluoromethylcholine ([(18)F]FCH) via in situ generation of [(18)F]fluoromethyl tosylate ([(18)F]FCH2OTs), and subsequent [(18)F]fluoromethylation of dimethylaminoethanol (DMAE), has been developed. METHODS: [(18)F]FCH was prepared using a GE TRACERlab FXFN, although the method should be readily adaptable to any other fluorine-(18) synthesis module. Initially ditosylmethane was fluorinated to generate [(18)F]FCH2OTs. DMAE was then added and the reaction was heated at 120 °C for 10 min to generate [(18)F]FCH. After this time, reaction solvent was evaporated, and the crude reaction mixture was purified by solid-phase extraction using C(18)-Plus and CM-Light Sep-Pak cartridges to provide [(18)F]FCH formulated in USP saline. The formulated product was passed through a 0.22 µm filter into a sterile dose vial, and submitted for quality control testing. Total synthesis time was 1.25 h from end-of-bombardment. RESULTS: Typical non-decay-corrected yields of [(18)F]FCH prepared using this method were 91 mCi (7% non-decay corrected based upon ~1.3 Ci [(18)F]fluoride), and doses passed all other quality control (QC) tests. CONCLUSION: A one-pot liquid-phase synthesis of [(18)F]FCH has been developed. Doses contain extremely low levels of residual DMAE (31.6 µg/10 mL dose or ~3 ppm) and passed all other requisite QC testing, confirming their suitability for use in clinical imaging studies.


Assuntos
Colina/análogos & derivados , Deanol/química , Deanol/isolamento & purificação , Contaminação de Medicamentos/prevenção & controle , Marcação por Isótopo/instrumentação , Robótica/instrumentação , Colina/síntese química , Colina/isolamento & purificação , Desenho de Equipamento , Análise de Falha de Equipamento , Marcação por Isótopo/métodos , Robótica/métodos
17.
Appl Environ Microbiol ; 78(23): 8298-303, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23001649

RESUMO

Choline (N,N,N-trimethylethanolamine), which is widely distributed in membrane lipids and is a component of sediment biota, has been shown to be utilized anaerobically by mixed prokaryote cultures to produce methane but not by pure cultures of methanogens. Here, we show that five recently isolated Methanococcoides strains from a range of sediments (Aarhus Bay, Denmark; Severn Estuary mudflats at Portishead, United Kingdom; Darwin Mud Volcano, Gulf of Cadiz; Napoli mud volcano, eastern Mediterranean) can directly utilize choline for methanogenesis producing ethanolamine, which is not further metabolized. Di- and monomethylethanolamine are metabolic intermediates that temporarily accumulate. Consistent with this, dimethylethanolamine was shown to be another new growth substrate, but monomethylethanolamine was not. The specific methanogen inhibitor 2-bromoethanesulfonate (BES) inhibited methane production from choline. When choline and trimethylamine are provided together, diauxic growth occurs, with trimethylamine being utilized first, and then after a lag (∼7 days) choline is metabolized. Three type strains of Methanococcoides (M. methylutens, M. burtonii, and M. alaskense), in contrast, did not utilize choline. However, two of them (M. methylutens and M. burtonii) did metabolize dimethylethanolamine. These results extend the known substrates that can be directly utilized by some methanogens, giving them the advantage that they would not be reliant on bacterial syntrophs for their substrate supply.


Assuntos
Colina/metabolismo , Deanol/metabolismo , Microbiologia Ambiental , Metano/metabolismo , Methanosarcinaceae/isolamento & purificação , Methanosarcinaceae/metabolismo , DNA Arqueal/química , DNA Arqueal/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Etanolamina/metabolismo , Methanosarcinaceae/classificação , Methanosarcinaceae/genética , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
18.
Eksp Klin Farmakol ; 75(4): 17-9, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22702105

RESUMO

Experiments on mice with streptozotocin-induced diabetes mellitus and stress-induced erosive ulcerous damage of the mucous membrane of stomach showed evidence of the preventive activity of deanol aceglumate in the course of peroral introduction at a dose of 250 mg/kg per 24 h during 4 days. This effect is accompanied by activation of the peristalsis of bowels and by an increase in the blood flow in the wall of stomach.


Assuntos
Antidiscinéticos/farmacologia , Deanol/farmacologia , Diabetes Mellitus Experimental/prevenção & controle , Úlcera Gástrica/prevenção & controle , Estresse Fisiológico , Animais , Diabetes Mellitus Experimental/fisiopatologia , Camundongos , Peristaltismo/efeitos dos fármacos , Estômago/irrigação sanguínea , Estômago/fisiopatologia , Úlcera Gástrica/fisiopatologia
19.
J Biol Chem ; 287(20): 16289-99, 2012 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-22451671

RESUMO

The obligate intracellular and promiscuous protozoan parasite Toxoplasma gondii needs an extensive membrane biogenesis that must be satisfied irrespective of its host-cell milieu. We show that the synthesis of the major lipid in T. gondii, phosphatidylcholine (PtdCho), is initiated by a novel choline kinase (TgCK). Full-length (∼70-kDa) TgCK displayed a low affinity for choline (K(m) ∼0.77 mM) and harbors a unique N-terminal hydrophobic peptide that is required for the formation of enzyme oligomers in the parasite cytosol but not for activity. Conditional mutagenesis of the TgCK gene in T. gondii attenuated the protein level by ∼60%, which was abolished in the off state of the mutant (Δtgck(i)). Unexpectedly, the mutant was not impaired in its growth and exhibited a normal PtdCho biogenesis. The parasite compensated for the loss of full-length TgCK by two potential 53- and 44-kDa isoforms expressed through a cryptic promoter identified within exon 1. TgCK-Exon1 alone was sufficient in driving the expression of GFP in E. coli. The presence of a cryptic promoter correlated with the persistent enzyme activity, PtdCho synthesis, and susceptibility of T. gondii to a choline analog, dimethylethanolamine. Quite notably, the mutant displayed a regular growth in the off state despite a 35% decline in PtdCho content and lipid synthesis, suggesting a compositional flexibility in the membranes of the parasite. The observed plasticity of gene expression and membrane biogenesis can ensure a faithful replication and adaptation of T. gondii in disparate host or nutrient environments.


Assuntos
Colina Quinase/biossíntese , Regulação Enzimológica da Expressão Gênica/fisiologia , Mutagênese , Fosfatidilcolinas/biossíntese , Proteínas de Protozoários/biossíntese , Toxoplasma/enzimologia , Sequência de Bases , Colina Quinase/genética , Deanol/metabolismo , Dados de Sequência Molecular , Mutação , Fosfatidilcolinas/genética , Multimerização Proteica/fisiologia , Proteínas de Protozoários/genética , Toxoplasma/genética
20.
J Alzheimers Dis ; 29(3): 527-35, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22330824

RESUMO

New criteria related to prodromal Alzheimer's disease (AD) have been proposed to overcome the issue of heterogeneity of patients with mild cognitive impairment (MCI) and to better define patients in early stage AD. Only few therapeutic trials, if any, have been reported using this newly defined population. The objective of this study was to assess the clinical efficacy and safety of a novel pro-cholinergic drug (V0191) in patients with prodromal AD. Two hundred forty two (242) patients with a diagnosis of prodromal AD were randomized in an approximately 1 : 1 ratio to receive either 1500 mg V0191 or matching placebo once daily for 24 weeks. Changes in global cognitive functioning were assessed using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog; responder rate as primary efficacy measure). Standardized measures of memory, executive function, attention, functional capacity, and apathy were also obtained. Despite some interesting trends at week 12 and conversion rates favoring V0191, no statistically significant differences in cognitive function between V0191 and placebo were noted. In addition to the absence of drug efficacy on this population, several design features may have hindered this study, including insufficient powering to assess changes in cognition over time, a relatively short duration of treatment, and the lack of validated clinical trial measures designed to assess the prodromal AD population. Lessons learned in AD study design optimization, including those presented in this paper, could be valuable for further investigation with pro-cholinergic drugs such as V0191.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipsicóticos/uso terapêutico , Colinérgicos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Deanol/análogos & derivados , Deanol/uso terapêutico , Método Duplo-Cego , Feminino , Glutamatos/uso terapêutico , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Resultado do Tratamento
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