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1.
ACS Synth Biol ; 8(3): 474-481, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30721031

RESUMO

Enzymes are the ultimate entities responsible for chemical transformations in natural and engineered biosynthetic pathways. However, many natural enzymes suffer from suboptimal functional expression due to poor intrinsic protein stability. Further, stability enhancing mutations often come at the cost of impaired function. Here we demonstrate an automated protein engineering strategy for stabilizing enzymes while retaining catalytic function using deep mutational scanning coupled to multiple-filter based screening and combinatorial mutagenesis. We validated this strategy by improving the functional expression of a Type III polyketide synthase from the Atropa belladonna biosynthetic pathway for tropane alkaloids. The best variant had a total of 8 mutations with over 25-fold improved activity over wild-type in E. coli cell lysates, an improved melting temperature of 11.5 ± 0.6 °C, and only minimal reduction in catalytic efficiency. We show that the multiple-filter approach maintains acceptable sensitivity with homology modeling structures up to 4 Å RMS. Our results highlight an automated protein engineering tool for improving the stability and solubility of difficult to express enzymes, which has impact for biotechnological applications.


Assuntos
Aciltransferases/química , Aciltransferases/genética , Atropa belladonna/enzimologia , Biotecnologia/métodos , Ciência de Dados/métodos , Engenharia de Proteínas/métodos , Aciltransferases/metabolismo , Alcaloides de Belladona/metabolismo , Vias Biossintéticas , Códon sem Sentido , Estabilidade Enzimática/genética , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/metabolismo , Substâncias Luminescentes/química , Substâncias Luminescentes/metabolismo , Mutagênese , Mutação de Sentido Incorreto , Saccharomyces cerevisiae/metabolismo , Solubilidade , Temperatura de Transição
2.
Am J Obstet Gynecol ; 219(5): 488.e1-488.e7, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29902447

RESUMO

BACKGROUND: Intravesical injection with onabotulinum toxin A injection can be performed in-office under local anesthesia. Rectally administered pain medication presents a potentially feasible and previously uninvestigated adjunct to office-based anesthesia protocols. OBJECTIVE: The primary aim of this study was to determine whether adding a belladonna and opiate suppository to standard lidocaine instillation resulted in reduction of bladder injection pain during onabotulinum toxin A injection procedure. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study of patients undergoing onabotulinum toxin A bladder injection at a single clinic. Patients age ≥18 years, who met clinical criteria for invasive treatment of refractory urinary symptoms, had previously documented postvoid residual volumes <150 mL, and elected for in-office intravesical onabotulinum toxin A injection were eligible to participate. Participants were randomized by computer-generated block randomization to receive a belladonna and opiate (belladonna alkaloid with morphine 16.2/7.5 mg) or placebo suppository. Suppositories were placed immediately prior to lidocaine-based anesthesia, which all participants received. All participants underwent a standardized injection procedure using the same rigid cystoscope, needle type, and injection pattern (20 injections total). A 0-10 numeric rating scale was used to assess pain intensity before anesthesia and suppository, 40 minutes after administration of anesthesia and suppository, after first 10 bladder injections, and immediately after completion of 20 injections. Pain increase during procedure was calculated using the difference between score 40 minutes after administration of anesthesia and suppository and score after first 10 bladder injections. Postvoid residual were measured immediately postprocedure and 2 weeks later. Patient satisfaction with pain control was measured using a Likert scale. Our primary outcome was change in pain level from anesthetic baseline to midprocedure (score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository). A final sample size of 26 patients was needed to have 80% power (alpha = 0.05) to detect a 50% reduction in bladder injection pain during the procedure as defined by our primary outcome. An intent-to-treat approach was used for all analyses. RESULTS: In all, 26 participants were enrolled and randomized with 13 in each study arm. Participants in the treatment group were slightly older than in the placebo group (P = .05); there were no statistically significant differences in medical comorbidities. Median score after first 10 bladder injections to score 40 minutes after administration of anesthesia and suppository for the placebo group and treatment group was 4 (range 1-10) and 5 (range 0,9), respectively (P = .94). Median scores immediately after completion of 20 injections for the placebo group and treatment group were 3 (range 0-10) and 2 (range 0,8), respectively (P = .29). There were no significant differences in preinjection pain scores reported before anesthesia and suppository and at 40 minutes after administration of anesthesia and suppository. Postprocedure postvoid residual >200 mL was noted in 5 (38%) of the placebo group and 3 (23%) of the treatment group (P = .67). Two-week postprocedure postvoid residual >200 mL was noted in 3 (25%) of the placebo group and 2 (15%) of the treatment group (P = .64) for an overall rate of 20%. Eleven (84%) participants in each group reported being "mostly satisfied" or "very much satisfied" with pain control. CONCLUSION: Belladonna and opiate suppository use did not significantly reduce bladder injection pain, or increase risk of urinary retention immediately postprocedure or 2 weeks later. Satisfaction with pain control among onabotulinum toxin A injection patients is high.


Assuntos
Analgésicos , Alcaloides de Belladona/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Morfina/administração & dosagem , Bexiga Urinária/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Anestesia , Alcaloides de Belladona/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções , Lidocaína/administração & dosagem , Pessoa de Meia-Idade , Morfina/efeitos adversos , Medição da Dor , Satisfação do Paciente , Placebos , Estudos Prospectivos , Supositórios , Resultado do Tratamento , Retenção Urinária/induzido quimicamente , Retenção Urinária/epidemiologia
4.
Cardiol Young ; 28(7): 922-927, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29747708

RESUMO

IntroductionPallid breath-holding spells are common and dramatic forms of recurrent syncope in infancy. They are very stressful despite their harmless nature and sometimes require treatment. OBJECTIVE: The objective of this study was to evaluate the efficacy of belladonna in severe breath-holding spells. METHODS: This is a multicentric, retrospective series involving 84 children with severe pallid breath-holding spells. Inclusion criteria were >1 pallid breath-holding spell with loss of consciousness, paediatric cardiology evaluation, and follow-up >6 months. In total, 45 patients received belladonna and 39 patients did not receive treatment, according to physician preference. RESULTS: Mean age was 11 months, ranging from 4 to 18 months, with 54% of males. Mean spell duration was 30 seconds (interquartile range 15, 60), and the frequency was four episodes per month (interquartile range 0.5, 6.5). Comparison of baseline characteristics between groups showed similar demographics, with the single difference in the severity of the spells, being more severe in the treated group. When comparing the treated and non-treated groups at 3 months, only two (5%) patients had a complete remission in the first group, whereas 20 (44%) had remission in the belladonna group (p<0.01). When considering the characteristics of the spells before and after the initiation of treatment with belladonna, 75% of the patients presented a positive response, with 44% of the patients presenting with complete resolution of the spells (p<0.01). No major adverse reaction was reported, with only 5% minor adverse events. CONCLUSIONS: Belladonna is highly effective to alleviate severe breath-holding spells in young children, without any major adverse effects.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Alcaloides de Belladona/uso terapêutico , Ferro/uso terapêutico , Transtornos Respiratórios/tratamento farmacológico , Síncope/prevenção & controle , Anemia Ferropriva/complicações , Apneia/etiologia , Alcaloides de Belladona/efeitos adversos , Cianose/etiologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Lactente , Masculino , Transtornos Respiratórios/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
Eksp Klin Farmakol ; 79(2): 9-13, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27416676

RESUMO

In a placebo-controlled study, changes in psychophysiological status of operators (38 healthy male volunteers aged 23-35 years) performing 4-hour model operator activity were evaluated after a single oral administration of typical representatives of the different classes of drugs (haloperidol, proroxan, yohimbine hydrochloride, propranolol, mesocarb, isoprenaline, Belladonna extract, anabasine hydrochloride, valproate sodium, and phenazepam), which are used for the treatment, rehabilitation and prophylaxis of common diseases. It was found that all the drugs modified to a greater or lesser extent some components of the model operator activity. Isoprenaline and phenazepam had the most negative effect on the psychophysiological indicators and quality of the modeled operator activity. The results should be considered before administration of such drugs to working operators.


Assuntos
Atenção/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Análise e Desempenho de Tarefas , Tranquilizantes/farmacologia , Adulto , Anabasina/farmacologia , Atenção/fisiologia , Alcaloides de Belladona/farmacologia , Benzodiazepinas/farmacologia , Dioxanos/farmacologia , Método Duplo-Cego , Haloperidol/farmacologia , Humanos , Isoproterenol/farmacologia , Masculino , Propranolol/farmacologia , Psicofisiologia , Sidnonas/farmacologia , Ácido Valproico/farmacologia , Ioimbina/farmacologia
7.
Am J Ther ; 23(1): e74-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-24263161

RESUMO

The belladonna alkaloids can be isolated from a number of plants, which contain hallucinogens that represent a serious danger to infants, children, and adolescents. Roots, leaves, and fruits of the plant contain the alkaloids atropine, hyoscyamine, and scopolamine, which can lead to an anticholinergic toxidrome; however, not all characteristics of the toxidrome are necessarily present in each case of poisoning. A retrospective chart review of all children seen following anticholinergic ingestions, between April 2001 and November 2010, at the Hospital for Sick Children in Toronto. Ten children, with a mean age of 15.5 years (range, 15-18 years), were identified; 5 had used jimsonweed and the others had a variety of tablets containing atropine. All 10 presented with severe anticholinergic symptoms and 2 with suicide attempts. Treatments included charcoal, benzodiazepines, haloperidol, and physostigmine, and 2 patients were intubated. Ingestion and subsequent severe anticholinergic toxidrome occurred exclusively in adolescents. It is important to educate this age group regarding the toxicity and potential risks associated with the recreational use of these plants and substances. Physostigmine can help in both the diagnosis and management of patients intoxicated with these substances.


Assuntos
Alcaloides de Belladona/envenenamento , Adolescente , Hospitais Pediátricos , Humanos , Fisostigmina/uso terapêutico , Estudos Retrospectivos , Atenção Terciária à Saúde
8.
J Exp Psychol Gen ; 143(2): 835-49, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23815456

RESUMO

The present research examined how decision reversibility can affect motivation. On the basis of extant findings, it was suggested that 1 way it could affect motivation would be to strengthen different regulatory foci, with reversible decision making, compared to irreversible decision making, strengthening prevention-related motivation relatively more than promotion-related motivation. If so, then decision reversibility should have effects associated with the relative differences between prevention and promotion motivation. In 5 studies, we manipulated the reversibility of a decision and used different indicators of regulatory focus motivation to test these predictions. Specifically, Study 1 tested for differences in participants' preference for approach versus avoidance strategies toward a desired end state. In Study 2, we used speed and accuracy performance as indicators of participants' regulatory motivation, and in Study 3, we measured global versus local reaction time performance. In Study 4, we approached the research question in a different way, making use of the value-from-fit hypothesis (Higgins, 2000, 2002). We tested whether a fit between chronic regulatory focus and focus induced by the reversibility of the decision increased participants' subjective positive feelings about the decision outcome. Finally, in Study 5, we tested whether regulatory motivation, induced by decision reversibility, also influenced participants' preference in specific product features. The results generally support our hypothesis showing that, compared to irreversible decisions, reversible decisions strengthen a prevention focus more than a promotion focus. Implications for research on decision making are discussed.


Assuntos
Tomada de Decisões , Motivação , Atenção , Alcaloides de Belladona , Combinação de Medicamentos , Escina , Feminino , Humanos , Masculino , Controles Informais da Sociedade , Tetracaína , Adulto Jovem
10.
Rev. toxicol ; 28(2): 119-134, jul.-dic. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-94021

RESUMO

Los textos cervantinos constituyen una interesante fuente para el estudio de la sociedad española tardorrenacentista. Nosotros hemos abordado las obras de Cervantes desde la óptica de la toxicología, analizando el uso de agentes tóxicos y venenosos, fundamentalmente alucinógenos y narcóticos en el ámbito de la práctica de la brujería y hechicería (ungüentos de brujas, filtros de amor, pócimas venenosas, etc.), así como las menciones a las hipotéticas sustancias dotadas de acción alexifármaca, como la verbena (Verbena officinalis), el cuerno de unicornio, las piedras bezoares o el castóreo. Las obras cervantinas en las que se hace referencia a estos preparados son las novelas El Quijote, La Galatea, Viaje del Parnaso y cuatro Novelas Ejemplares (La española inglesa, El licenciado Vidriera, El celoso extremeño y El coloquio de los perros), así como en las comedias Pedro de Urdemalas, La entretenida y El laberinto del amor. Entre los agentes tóxicos de origen herbal citados expresamente por Cervantes en el contexto analizado se encuentran el beleño (Hyoscyamus niger / albus), el tabaco (Nicotiana tabacum), la adelfa (Nerium oleander), el tártago (Euphorbia lathyris), el ruibarbo (Rheum officinale, Rumex alpinus) y, de forma enmascarada, el opio (Papaver somniferum). En relación con el resto de preparados dotados de actividad tóxica, Cervantes no identifica sus ingredientes, aunque, a tenor de la sintomatología descrita por el autor, podrían ser plantas de la familia de las solanáceas, como el beleño, el solano, la datura, la belladona o la mandrágora. Con respecto a los tóxicos minerales, únicamente hay referencias a los efectos del mercurio o azogue. El Dioscórides comentado por Andrés Laguna pudo ser la fuente técnica utilizada por Cervantes para documentarse en esta materia (AU)


Cervantine texts are an interesting source for the study of Spanish late Renaissance society. We have studied the works of Cervantes from the toxicology viewpoint, analyzing the use of toxic and poisonous substances, essentially hallucinogenic and narcotic agents in the field of witchcraft and sorcery practice (witches ointments, love filters, poisonous potions, etc.), as well as references to hypothetical substances endowed with alexipharmic action, as the vervain (Verbena officinalis), unicorn horn, bezoar stones or castoreum. Cervantine works which refers to these preparations are the novels Don Quixote, The Galatea, Voyage to Parnassus and four Exemplary Novels (The Spanish-English Lady, The Licentiate of Glass, The Jealous Extremaduran and The Colloquy of the Dogs), as well as the comedies Pedro de Urdemalas, The Amusing Woman and The Labyrinth of Love. Toxic agents of herbal origin mentioned explicitly by Cervantes in the analyzed context include the henbane (Hyoscyamus niger / albus), tobacco (Nicotiana tabacum), oleander (Nerium oleander), spurge (Euphorbia lathyris), rhubarb (Rheum officinale, Rumex alpinus), and masked way, opium (Papaver somniferum). In relation to the rest of preparations endowed with toxic activity, Cervantes does not identify its ingredients, though, within the meaning of the symptoms described by the author, they could be plants of the Solanaceae family, as the henbane, nightshade, jimsonweed, belladonna or mandrake. Concerning toxic minerals, only there are references to the effects of mercury (“azogue”). The Dioscorides commented by Andrés Laguna could be the technical font used by Cervantes to document in this matter (AU)


Assuntos
Humanos , Masculino , Feminino , Toxicologia/história , Alucinógenos/toxicidade , Ópio/toxicidade , Atropa belladonna/toxicidade , Alcaloides de Belladona/toxicidade , Mandragora officinarum/toxicidade , Mandragora/toxicidade , Medicina nas Artes , Solanaceae/toxicidade , Datura stramonium/toxicidade , Datura/toxicidade , Intoxicação por Mercúrio/fisiopatologia
12.
J Womens Health (Larchmt) ; 19(4): 703-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20350198

RESUMO

BACKGROUND: Prior research has not examined the association of patient expectations or preparation by providers for the postpartum experience with depressive symptoms. We investigated whether lack of preparation for the postpartum experience and physical health after uncomplicated childbirth were associated with early postpartum depressive symptoms. METHODS: We conducted a telephone survey of 720 early postpartum mothers in New York City. Mothers reported on depressive symptoms, physical symptoms, provider preparation for the postpartum experience, and other factors. RESULTS: Nearly 39% of patients reported depressive symptoms; 24% did not feel adequately prepared by their provider for the postpartum experience. Mothers reported a range of physical symptoms: 98% reported daily vaginal bleeding, 79% reported cesarean section or episiotomy site pain, 82% reported breast pain, and 32% reported urinary incontinence. Patients who reported inadequate preparation by their provider were more likely to report depressive symptoms compared with patients who reported adequate preparation (53% vs. 35%, p < 0.001). In a multivariable model predicting postpartum depressive symptoms, adjusted odds ratios (ORs) remained elevated for perceived lack of preparation for the postpartum experience, more physical symptoms, and more physical functional limitations. CONCLUSIONS: Further research is needed to investigate whether preparing patients for expected health consequences after pregnancy may reduce the incidence of early postpartum depressive symptoms.


Assuntos
Depressão Pós-Parto/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Nível de Saúde , Educação de Pacientes como Assunto , Adulto , Alcaloides de Belladona/uso terapêutico , Cicloexanóis/uso terapêutico , Combinação de Medicamentos , Ergotaminas/uso terapêutico , Feminino , Humanos , Isoflavonas/uso terapêutico , Bem-Estar Materno/psicologia , Análise Multivariada , Cidade de Nova Iorque , Fenobarbital/uso terapêutico , Gravidez , Resultado da Gravidez , Cloridrato de Venlafaxina , Saúde da Mulher , Adulto Jovem
14.
Electrophoresis ; 29(10): 2112-6, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18425749

RESUMO

This short communication describes the characterization of seven tropane alkaloid compounds in Atropa belladonna L. Thus a rapid and easy CE-electrospray interface (ESI)-TOF-MS procedure is developed to analyze these compounds in a pharmaceutical preparations of A. belladonna L. leaf extract. Optimum electrophoretic separation is obtained using an alkaline solution of 60 mM ammonium acetate at pH 8.5 containing 5% isopropanol. Under the optimum CE-ESI-TOF-MS conditions several important compounds such as tropine, belladonnine, norhyoscyamine, apoatropine, hyoscyamine, 6beta-hydroxyhyoscyamine, and scopolamine have been simultaneously identified from A. belladonna L. CE-ESI-IT-MS has been used to discriminate the putative presence of littorine. The sensitivity, together with mass accuracy and true isotopic pattern of the TOF-MS, allowed the identification of a broad series of tropane alkaloid compounds present in pharmaceutical preparations of A. belladonna L. leaf extract.


Assuntos
Atropa belladonna/química , Alcaloides de Belladona/análise , Eletroforese Capilar/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Alcaloides de Belladona/química , Extratos Vegetais/análise , Extratos Vegetais/química , Espectrometria de Massas em Tandem/métodos
15.
Clin J Oncol Nurs ; 11(6): 805-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18063538

RESUMO

CASE STUDY: Ms. G, a 78-year-old woman with a history of heart failure and a left ventricular ejection fraction of 45%, had an exploratory laparotomy with colon resection and colostomy two days ago for an obstructive stage IIIB adenocarcinoma of the colon. She is a patient on a general surgical unit. Upon assessment at 7 am, Ms. G was easily aroused and oriented. She has a patient-controlled analgesia (PCA) pump for postoperative pain control with 1 mg of morphine available every 30 minutes; she used a total of 4 mg of morphine via IV since midnight. Ms. G requires belladonna and opium suppositories about every eight hours to treat bladder spasms associated with her urinary catheter.


Assuntos
Analgesia Controlada pelo Paciente/efeitos adversos , Analgésicos Opioides/efeitos adversos , Delírio/induzido quimicamente , Adenocarcinoma/cirurgia , Idoso , Alcaloides de Belladona/efeitos adversos , Causalidade , Neoplasias do Colo/cirurgia , Colostomia/efeitos adversos , Delírio/diagnóstico , Delírio/prevenção & controle , Diagnóstico Precoce , Feminino , Humanos , Morfina/efeitos adversos , Avaliação em Enfermagem , Ópio/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/enfermagem , Cateterismo Urinário/efeitos adversos
16.
Georgian Med News ; (140): 47-50, 2006 Nov.
Artigo em Russo | MEDLINE | ID: mdl-17179588

RESUMO

For study of the sweat secretion in 27 patients suffered by local hyperhidrosis method of colorimetric determination of functioning sudoriferous glands number and a Minor's tests were used. The confines and intensity of sweat secretion have been determined. Study was carried out before and during the treatment as well as at the moment of clinical recovery. Revealing of vegetative syndromes was provided by Vein's inquirer. In patients with hyperhidrosis vegetative abnormalities were combined with asthenic disorders. Duration of illness had impact on frequency and character of neurasthenic syndrome manifestation. Offered scheme of local hyperhidrosis treatment with staged use of belladonna and antihistaminic preparation "hydroxyzine" (having antimuscarinic action) could be characterized as a well endurable and significantly ameliorative of patient's clinical status.


Assuntos
Alcaloides de Belladona/uso terapêutico , Glândulas Écrinas/metabolismo , Ergotaminas/uso terapêutico , Hiperidrose/metabolismo , Fenobarbital/uso terapêutico , Adolescente , Adulto , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiopatologia , Colorimetria , Combinação de Medicamentos , Glândulas Écrinas/efeitos dos fármacos , Glândulas Écrinas/inervação , Feminino , Seguimentos , Humanos , Hiperidrose/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Cryo Letters ; 27(2): 65-72, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16794738

RESUMO

Atropa belladonna hairy roots (clone M8) were successfully cryopreserved by using the vitrification method. A. belladonna hairy root tips were precultured on a half strength of Murashige and Skoog (MS) solid medium with 0.1 mg per L 2,4-D or without phytohormone for 1 day, and then dehydrated with PVS2 solution for 15 minutes prior to immersion into liquid nitrogen for 1 day, 1 week, 1 month and 3 months. Hairy root tips kept in liquid nitrogen were rapidly thawed at 36 degree C in a water bath. The root tips were recultured on half strength MS medium. The hairy root tips, precultured with 2,4-D before cryopreservation, showed a higher survival rate than those precultured without phytohormone. The hairy root tips, precultured with 2,4-D, showed an average survival rate of 83 percent. There was no significant difference in the viability of the hairy roots cryopreserved for different periods. The regrowth of cryopreserved hairy roots was similar to that of untreated hairy roots and tropane alkaloid productivity became stable after 4th subculture. PCR analysis of hairy roots demonstrated the conservation of the T-DNA in cryopreserved hairy roots. These results indicate that cryopreservation by vitrification method is useful to preserve A.belladonna hairy root clone M8.


Assuntos
Atropa belladonna/fisiologia , Criopreservação/métodos , Raízes de Plantas/fisiologia , Alcaloides de Belladona/metabolismo , DNA Bacteriano/genética , DNA de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento
18.
Phytochemistry ; 67(4): 327-37, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16426652

RESUMO

Two stereospecific oxidoreductases constitute a branch point in tropane alkaloid metabolism. Products of tropane metabolism are the alkaloids hyoscyamine, scopolamine, cocaine, and polyhydroxylated nortropane alkaloids, the calystegines. Both tropinone reductases reduce the precursor tropinone to yield either tropine or pseudotropine. In Solanaceae, tropine is incorporated into hyoscyamine and scopolamine; pseudotropine is the first specific metabolite on the way to the calystegines. Isolation, cloning and heterologous expression of both tropinone reductases enabled kinetic characterisation, protein crystallisation, and structure elucidation. Stereospecificity of reduction is achieved by binding tropinone in the respective enzyme active centre in opposite orientation. Immunolocalisation of both enzyme proteins in cultured roots revealed a tissue-specific protein accumulation. Metabolite flux through both arms of the tropane alkaloid pathway appears to be regulated by the activity of both enzymes and by their access to the precursor tropinone. Both tropinone reductases are NADPH-dependent short-chain dehydrogenases with amino acid sequence similarity of more than 50% suggesting their descent from a common ancestor. Putative tropinone reductase sequences annotated in plant genomes other that Solanaceae await functional characterisation.


Assuntos
Oxirredutases do Álcool/metabolismo , Alcaloides de Belladona/metabolismo , Regulação da Expressão Gênica , Oxirredutases do Álcool/química , Oxirredutases do Álcool/genética , Alcaloides/metabolismo , Sequência de Aminoácidos , Atropina/metabolismo , Alcaloides de Belladona/química , Sítios de Ligação , Cinética , Dados de Sequência Molecular , NADP/metabolismo , Escopolamina/metabolismo , Solanaceae/metabolismo , Estereoisomerismo , Especificidade por Substrato , Tropanos/metabolismo
19.
Oncol Nurs Forum ; 32(5): 969-78, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16136195

RESUMO

PURPOSE/OBJECTIVES: To critically evaluate and synthesize intervention research related to hot flashes in the context of cancer and to identify implications and future directions for policy, research, and practice. DATA SOURCES: Published, peer-reviewed articles and textbooks; editorials; and computerized databases. DATA SYNTHESIS: Although a variety of pharmacologic and nonpharmacologic treatments are available, they may not be appropriate or effective for all individuals. CONCLUSIONS: The large and diverse evidence base and current national attention on hot flash treatment highlight the importance of the symptom to healthcare professionals, including oncology nurses. IMPLICATIONS FOR NURSING: Using existing research to understand, assess, and manage hot flashes in the context of cancer can prevent patient discomfort and improve the delivery of evidence-based care.


Assuntos
Fogachos/etiologia , Fogachos/terapia , Neoplasias/complicações , Neoplasias/terapia , Antidepressivos/uso terapêutico , Antineoplásicos/uso terapêutico , Alcaloides de Belladona , Cimicifuga , Terapia Combinada/métodos , Terapias Complementares/métodos , Combinação de Medicamentos , Interações Medicamentosas , Ergotaminas/uso terapêutico , Feminino , Humanos , Hypericum , Masculino , Metisergida/uso terapêutico , Neurotransmissores/uso terapêutico , Fenobarbital/uso terapêutico , Progestinas/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do Tratamento , Vitamina E/uso terapêutico
20.
Artigo em Inglês | MEDLINE | ID: mdl-15985780

RESUMO

Homeopathic pathogenetic trials (or provings) provide the foundations for the clinical practice of homeopathy. The most recent review of proving studies indicated that provings are generally of poor methodological quality. Methods to improve the quality and scientific rigour are needed to critically assess the clinical basis of homeopathy. This article describes a methodology using a symptom diary with a selection of predefined remedy specific symptoms (proving questionnaire). The proving questionnaire was developed as an alternative to the traditional qualitative proving methods in an attempt to provide a quantitative method that could rigorously validate the original provings. This article considers the advantages and disadvantages of this approach and provides suggestions for future work in this area.


Assuntos
Materia Medica/normas , Atropa belladonna , Alcaloides de Belladona/uso terapêutico , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
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