RESUMO
5-hydroxytryptophan (5-HTP) is an intermediate molecule in the biosynthesis of serotonin, an important neurotransmitter, regulating a series of metabolic and psychological functions in humans. In this work, we studied the heterologous production of Human tryptophan hydroxylase (TPH1) in Escherichia coli, for the synthesis of 5-hydroxytryptophan (5-HTP) from Tryptophan (Trp). To quantify TPH1 activity, a simple fluorescence-based microtiter plate assay was established, based on the changes in fluorescence emission at 340 nm between substrate and product when excited at 310 nm, allowing quick and reliable quantification of released 5-HTP. To increase enzyme production, heterologous TPH1 production was studied in stirred tank bioreactor scale. The effect of rate of aeration (0.25, 0.50 and 0.75 vvm) and agitation (150, 250 and 500 rpm) was evaluated for biomass production, pH, volumetric oxygen transfer coefficient (kLa) and volumetric TPH1 activity. We determined that high agitation and low aeration allowed reaching the maximum measured enzyme activity. Under such conditions, we observed a 90% substrate conversion, obtaining 90 µM (~0.02 g/L) 5-HTP from a 100 µM Tryptophan substrate solution. Finally, we observed that the addition of Tween 20 (0.1%) in the culture broth under production conditions expanded the pH operation range of TPH1. Our results establish a base for a biocatalytic approach as a potential alternative process for the synthesis of 5-HTP using recombinant TPH1.
Assuntos
5-Hidroxitriptofano , Triptofano Hidroxilase , Humanos , Serotonina , Tensoativos , Triptofano , Triptofano Hidroxilase/genéticaRESUMO
The tobacco industry promotes electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) as a safer alternative to conventional cigarettes with misleading marketing sustained by studies with conflict of interest. As a result, these devices sell without regulations and warnings about their adverse effects on health, with a growing user base targeting young people. This systematic review aimed to describe the adverse effects on the respiratory system in consumers of these devices. We conducted a systematic review and bibliometric analysis of 79 studies without conflict of interest evaluating ENDS and HTP effects in the respiratory system in experimental models, retrieved from the PubMed database. We found that the damage produced by using these devices is involved in pathways related to pulmonary diseases, involving mechanisms previously reported in conventional cigarettes as well as new mechanisms particular to these devices, which challenges that the tobacco industry's claims. The present study provides significant evidence to suggest that these devices are an emerging public health problem and that they should be regulated or avoided.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Indústria do Tabaco , Produtos do Tabaco , Adolescente , Humanos , Pulmão , MarketingRESUMO
Studies of serotonin in animal husbandry has received growing interest. However, there is limited information about serotonin manipulation using 5-HTP administered postruminally and its residual effects in cattle. The objective of this study was to evaluate the effectiveness of 5-HTP infused into the abomasum for enhancing circulating serotonin in cattle. Four Holstein steers (487 ± 7.6 kg) fitted with ruminal cannulas were used in a 4 × 4 Latin Square design experiment. The treatments were intra-abomasal infusion of 5-HTP at 0, 0.25, 0.5, and 1 mg/kg BW. Blood was collected from the jugular vein of each steer at -60, -30, 0, 30, 60, 120, 240, and 480 min from 5-HTP infusion for basal and short term evaluation and, at 1, 2, 4, and 7 d after 5-HTP infusion for long term evaluation. Dry matter intake was not affected (P > 0.05) by intra-abomasal infusions. The half-life of 5-HTP was dose-independent (128 min). The serum 5-HTP, serotonin, and 5-hydroxyindoleacetic acid area under the curve increased (P < 0.05) linearly with an increased dose of 5-HTP. Serum 5-HTP reached peak concentration in approximately 30 min after dosing while serum and plasma serotonin peaked after 240 min postinfusion. Serotonin was greater than control for all 5-HTP doses 1 d and 2 d after infusion in serum and plasma, respectively. Intra-abomasal infusion of 5-HTP at doses up to 1 mg/ kg BW increases circulating serotonin for up 2 days.
Assuntos
5-Hidroxitriptofano , Abomaso , 5-Hidroxitriptofano/farmacologia , Abomaso/metabolismo , Animais , Bovinos , SerotoninaRESUMO
Although serotonin has been extensively studied in many species, there is a lack of information in ruminants, and no research has been evaluated if its precursor, 5-hydroxytryptophan (5-HTP), administered into the abomasum may be used as a means to manipulate serotonin metabolism. Thus, the objective of this study was to evaluate if intra-abomasal infusion of 5-HTP increases circulating serotonin in the steer. Eight Holstein steers (471 ± 8.9 kg) were used in a replicated 4 × 4 Latin Square design experiment. The treatments were intra-abomasal infusion of 5-HTP at 0.5, 1, 2.5, and 5 mg/kg BW. Blood was collected at 0, 2, 4, 6, 8, and 24 h after infusion. The serum concentration of 5-HTP increased quadratically (P = 0.005) with a peak at 2 h after administration. The 5-HTP administration increased (P < 0.05) serum serotonin in comparison with baseline with no difference (P > 0.05) between the doses of 5-HTP. When 5-HTP was dosed at 2.5 mg/kg BW or higher, intake decreased, and there was an altered manure consistency. The serum 5-hydroxyindole acetic acid concentrations followed the same pattern as 5-HTP. Plasma glucose content was not affected (P > 0.05) by 5-HTP dosing. However, free fatty acids concentration in the plasma was lower (P > 0.05) compared with baseline for the infusion levels of 0.5 and 1 mg/kg BW. Intra-abomasal infusion of 5-HTP efficiently increases serum serotonin cattle.
Assuntos
5-Hidroxitriptofano/farmacologia , Antidepressivos de Segunda Geração/farmacologia , Bovinos/fisiologia , Serotonina/biossíntese , Animais , Glicemia , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , MasculinoRESUMO
Resumen Se describen 21 casos con hallazgo incidental de várices esofágicas superiores (Downhill varices) en endoscopia de las vías digestivas altas. Además, se detallan algunos datos relevantes de la historia clínica y de los hallazgos endoscópicos. La relación hombres/mujeres fue 1:1 y la edad promedio fue de 67,9 años. La comorbilidad más frecuente fue la enfermedad pulmonar obstructiva crónica (EPOC), seguida de las neumoconiosis, la obesidad y el síndrome de apnea-hipopnea, todas con hipertensión pulmonar (HTP) asociada. Las tres últimas causas no han sido descritas previamente en la literatura sobre várices esofágicas superiores. Ningún paciente tenía antecedente de hemorragia variceal.
Abstract We describe 21 cases with incidental endoscopic findings of upper esophageal varices (downhill varices) and relevant data from patients' clinical histories and endoscopic findings. The male/female ratio was 1:1 and patients' average age was 67.9 years. The most frequent comorbidity was chronic obstructive pulmonary disease, followed by pneumoconiosis, obesity and apnea-hypopnea syndrome. All comorbidities had associated pulmonary hypertension. The last three causes have not been previously described in the literature on upper esophageal varices. None of the patients had histories of variceal hemorrhaging.
Assuntos
Humanos , Animais , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Varizes Esofágicas e Gástricas , Endoscopia , Pneumoconiose , Doença Pulmonar Obstrutiva Crônica , Hipertensão PulmonarRESUMO
5-Hydroxy-L-tryptophan (5-HTP) is a serotonin pathway metabolite of L-tryptophan in the brain. In the knowledge that the biological properties of some compounds can be modified upon metal complexation, a new solid metal complex, [Cu(5-hydroxytryptophan)2].H2O (Cu5HTP), has been synthesized and characterized to analyze the modification of some biological properties. The conformational investigations (optimized in gas phase at B3LYP/6-311G** theory level) suggest the coexistence of two conformers of Cu5HTP with cis- and trans- arrangements of the amino acids in the equatorial plane. The trans- Cu5HTP1 complex is the most stable conformer. The complexation led to an enhancement of the antioxidant properties of the ligand. The metal complex also improved the anticancer behavior of the ligand (tested in cancer cell lines derived from human lung (A549), cervix (HeLa) and colon (HCT-116)). It did not show toxicity against either the non-malignant human lung fibroblast (MRC-5) cell line or Artemia salina and did not behave as mutagenic agent (Ames test). Cellular reactive oxygen species production may be one of the possible mechanisms of action. Besides, the metal complex exerted neuroprotective action on cortical neurons from embryonic 18 days rats exposed to glutamate.
Assuntos
5-Hidroxitriptofano/síntese química , Antineoplásicos/síntese química , Antioxidantes/síntese química , Cobre/química , Citotoxinas/síntese química , Fármacos Neuroprotetores/síntese química , 5-Hidroxitriptofano/farmacologia , Células A549 , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cobre/farmacologia , Citotoxinas/farmacologia , Relação Dose-Resposta a Droga , Células HCT116 , Células HeLa , Humanos , Fármacos Neuroprotetores/farmacologiaRESUMO
Este estudo tem como objetivo verificar as principais características psicológicasem pacientes com diagnóstico de recidiva de câncer, por meio do teste HTP. Participamquatro mulheres diagnosticadas com recidiva de câncer e que fazem parte do grupoterapêutico de uma instituição de combate ao câncer. Para o desenvolvimento destapesquisa, utiliza-se a entrevista Semi-estruturada e o Teste HTP (Casa-Árvore-Pessoa).Os dados são analisados pelo método qualitativo, verificando a prevalência dos conteúdoseliciados pelo teste e entrevista. Dentre os resultados destacam-se a Ansiedade,Organicidade, Regressão, Retraimento, Insegurança, Preocupações e Conflitos sexuais,Inadequação, Satisfação na fantasia, Dependência, Impulsividade, Rigidez, ObsessividadeCompulsiva e Imaturidade. Tais resultados confirmam a hipótese relativa à prevalênciade aspectos de funcionamento de personalidade nesta população, que diante dodiagnóstico de recidiva de câncer e o tratamento, pode ocorrer um impacto emocional/afetivo, afetando de alguma forma o funcionamento psicológico. As análises do HTPpermitem aprofundar o estudo da dinâmica de personalidade de mulheres acometidascom câncer e enfatizam a importância de um olhar atento às questões psicossomáticas.Esta pesquisa também é relevante, pois remete aos sintomas e mecanismos de defesainconscientes associados ao adoecer e ao enfrentamento do tratamento. E, taisinformações são essenciais para o psicólogo que trabalha nesse contexto(AU)
This study aims to verify the main psychological features of patients diagnosedwith relapsing cancer, using the HTP test. Four women diagnosed with relapsing cancer,as part of a group therapy from a cancer institution participate on the study. A semistructuredinterview is used for data collection, as well as the HTP test (House-TreePerson).Data are analyzed using a qualitative method, checking the prevalence ofcontent elicited by both the test and the interview. Main results were anxiety, organicity,regression, withdrawal, insecurity, sexual concerns and conflicts, inadequacy,gratification fantasy, dependency, impulsivity, rigidity, compulsive obsessiveness, andimmaturity. Those results confirm the hypothesis of the prevalence of personalityaspects in this populations behavior, where there may be emotional/affective impactdue to the diagnosis of cancer relapse and treatment, affecting somehow theirpsychological functioning. HTP analyses allow deepen studies of the personalitydynamics of women with cancer, emphasizing the importance of a closer look topsychosomatic issues. The relevance of this research is related to symptoms andunconscious defense mechanisms associated to becoming ill and facing treatment.Such information is essential for the psychologist working in that context(AU)
Este estudio tiene como objetivo determinar las principales característicaspsicológicas en pacientes con diagnóstico de recurrencia del cáncer a través de laprueba del HTP. Participaron de este estudio cuatro mujeres con diagnóstico derecurrencia del cáncer, que al mismo tiempo forman parte del grupo terapéutico de unainstitución para combatir el cáncer. Para el desarrollo de esta investigación, se utilizala entrevista semi-estructurada y el Test HTP (Casa-Árbol-Persona). Los datos seanalizaron por medio del método cualitativo a través de la comprobación de la prevalenciadel contenido provocado por la prueba y la entrevista. Entre los resultados destacan laansiedad, organicidad, regresión, retraimiento, inseguridad, preocupaciones y conflictossexuales, inadecuación, satisfacción en la fantasía, dependencia, impulsividad, rigidez,obsesión compulsiva e inmadurez. Estos resultados confirman la hipótesis sobre laprevalencia de los aspectos de funcionamiento de la personalidad de esta población,que ante el diagnóstico de recurrencia de cáncer y el tratamiento, puede experimentarun impacto emocional / afectivo, lo que afecta de alguna forma el funcionamientopsicológico. Los análisis del HTP permiten profundizar en el estudio de la dinámica dela personalidad de las mujeres afectadas con el cáncer y enfatizar en la importanciade una mirada más enfocada a las cuestiones psicosomáticas. Esta investigacióntambién es relevante ya que se refiere a los síntomas y mecanismos de defensainconscientes asociados a la enfermedad y al afrontamiento del tratamiento. Talinformación es esencial para el psicólogo que trabaja en este contexto(AU)
RESUMO
O artigo discutiu, a partir de um estudo de caso, a expressão do mundo interno de um dependente de heroína internado por seis meses em um centro de recuperação e tratamento na França. O paciente cumpriu as tarefas propostas pelos testes projetivos de Zulliger, Pirâmides Coloridas de Pfister e Casa-Árvore-Pessoa em dois momentos distintos, na primeira semana de internação e após seis meses de tratamento. O método fenômeno-estrutural foi utilizado como referencial teórico para compreender as respostas dadas aos três testes de personalidade. Os resultados foram coerentes com a realidade vivida pelo paciente tanto na primeira semana de internação, marcada por intenso sofrimento relacionado ao consumo abusivo da heroína, quanto após seis meses, período marcado por significativa reorganização psíquica e boas perspectivas no prognóstico. Conclui-se que o uso das técnicas projetivas no contexto da toxicomania se mostrou eficaz para conhecer as dificuldades dessa pessoa no tratamento da dependência química.
This case study discussed the expression of the inner world of a heroin addict who was hospitalized for six months in a rehabilitation center and drugs treatment in France. The patient fulfilled the tasks proposed by the Zulliger projective tests, and Pfister Color Pyramid, House-Tree-Person at two different times, in the first week of hospitalization, and six months after treatment. The method phenomenon-structural was used to understand responses to the three personality tests. The results were consistent with the reality experienced by the patient both in the first week of hospitalization, marked by intense suffering related to abusive consumption of heroin, and after six months of treatment, period marked by significant psychic reorganization and good prospects in prognosis. It follows therefore that the use of projective techniques in the context of drug addiction is effective to meet the difficulties that affect a person decides to be hospitalized for treatment of chemical dependency.
Este trabajo resulta de una evaluación de estudio de caso del mundo interior de un adicto de heroína ingresado durante seis meses en un centro de recuperación y tratamiento en Francia. El paciente realizó las tareas propuestas por el Zulliger, pirámides coloridas de Pfister y casa-árbol-persona en la primera semana de internación y después de seis meses de tratamiento. El método fenómeno-estructural fue utilizado como referencia teórica para comprender las respuestas dadas a las tres pruebas de personalidad. Los resultados fueron coherentes con la realidad vivida por el paciente tanto en la primera semana de internación con consumo abusivo de heroína, cuanto después de seis meses, período marcado por significativa reorganización psíquica y buenas perspectivas en el pronóstico. Se concluye que el uso de técnicas proyectivas en el contexto toxicómano se mostró eficaz para conocer las dificultades que afectan una persona que decide internarse para el tratamiento de la dependencia química.
Assuntos
Humanos , Masculino , Adulto , Relatos de Casos , Dependência de Heroína/psicologia , Técnicas Projetivas , PersonalidadeRESUMO
O artigo discutiu, a partir de um estudo de caso, a expressão do mundo interno de um dependente de heroína internado por seis meses em um centro de recuperação e tratamento na França. O paciente cumpriu as tarefas propostas pelos testes projetivos de Zulliger, Pirâmides Coloridas de Pfister e Casa-Árvore-Pessoa em dois momentos distintos, na primeira semana de internação e após seis meses de tratamento. O método fenômeno-estrutural foi utilizado como referencial teórico para compreender as respostas dadas aos três testes de personalidade. Os resultados foram coerentes com a realidade vivida pelo paciente tanto na primeira semana de internação, marcada por intenso sofrimento relacionado ao consumo abusivo da heroína, quanto após seis meses, período marcado por significativa reorganização psíquica e boas perspectivas no prognóstico. Conclui-se que o uso das técnicas projetivas no contexto da toxicomania se mostrou eficaz para conhecer as dificuldades dessa pessoa no tratamento da dependência química.(AU)
This case study discussed the expression of the inner world of a heroin addict who was hospitalized for six months in a rehabilitation center and drugs treatment in France. The patient fulfilled the tasks proposed by the Zulliger projective tests, and Pfister Color Pyramid, House-Tree-Person at two different times, in the first week of hospitalization, and six months after treatment. The method phenomenon-structural was used to understand responses to the three personality tests. The results were consistent with the reality experienced by the patient both in the first week of hospitalization, marked by intense suffering related to abusive consumption of heroin, and after six months of treatment, period marked by significant psychic reorganization and good prospects in prognosis. It follows therefore that the use of projective techniques in the context of drug addiction is effective to meet the difficulties that affect a person decides to be hospitalized for treatment of chemical dependency.(AU)
Este trabajo resulta de una evaluación de estudio de caso del mundo interior de un adicto de heroína ingresado durante seis meses en un centro de recuperación y tratamiento en Francia. El paciente realizó las tareas propuestas por el Zulliger, pirámides coloridas de Pfister y casa-árbol-persona en la primera semana de internación y después de seis meses de tratamiento. El método fenómeno-estructural fue utilizado como referencia teórica para comprender las respuestas dadas a las tres pruebas de personalidad. Los resultados fueron coherentes con la realidad vivida por el paciente tanto en la primera semana de internación con consumo abusivo de heroína, cuanto después de seis meses, período marcado por significativa reorganización psíquica y buenas perspectivas en el pronóstico. Se concluye que el uso de técnicas proyectivas en el contexto toxicómano se mostró eficaz para conocer las dificultades que afectan una persona que decide internarse para el tratamiento de la dependencia química.(AU)