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1.
Int J Cosmet Sci ; 42(4): 388-398, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32453870

RESUMO

OBJECTIVE: As skin ages, impaired extracellular matrix (ECM) protein synthesis and increased action of degradative enzymes manifest as atrophy, wrinkling and laxity. There is mounting evidence for the functional role of exogenous peptides across many areas, including in offsetting the effects of cutaneous ageing. Here, using an artificial intelligence (AI) approach, we identified peptide RTE62G (pep_RTE62G), a naturally occurring, unmodified peptide with ECM stimulatory properties. The AI-predicted anti-ageing properties of pep_RTE62G were then validated through in vitro, ex vivo and proof of concept clinical testing. METHODS: A deep learning approach was applied to unlock pep_RTE62G from a plant source, Pisum sativum (pea). Cell culture assays of human dermal fibroblasts (HDFs) and keratinocytes (HaCaTs) were subsequently used to evaluate the in vitro effect of pep_RTE62G. Distinct activities such as cell proliferation and ECM protein production properties were determined by ELISA assays. Cell migration was assessed using a wound healing assay, while ECM protein synthesis and gene expression were analysed, respectively, by immunofluorescence microscopy and PCR. Immunohistochemistry of human skin explants was employed to further investigate the induction of ECM proteins by pep_RTE62G ex vivo. Finally, the clinical effect of pep_RTE626 was evaluated in a proof of concept 28-day pilot study. RESULTS: In vitro testing confirmed that pep_RTE62G is an effective multi-functional anti-ageing ingredient. In HaCaTs, pep_RTE62G treatment significantly increases both cellular proliferation and migration. Similarly, in HDFs, pep_RTE62G consistently induced the neosynthesis of ECM protein elastin and collagen, effects that are upheld in human skin explants. Lastly, in our proof of concept clinical study, application of pep_RTE626 over 28 days demonstrated anti-wrinkle and collagen stimulatory potential. CONCLUSION: pep_RTE62G represents a natural, unmodified peptide with AI-predicted and experimentally validated anti-ageing properties. Our results affirm the utility of AI in the discovery of novel, functional topical ingredients.


OBJECTIF: À mesure que la peau vieillit, une altération de la synthèse des protéines de la matrice extracellulaire (ECM) et une action accrue des enzymes dégradantes se manifestent par une atrophie, des rides et un laxisme. Il existe de plus en plus de preuves du rôle fonctionnel des peptides exogènes dans de nombreux domaines, y compris pour compenser les effets du vieillissement cutané. Ici, en utilisant une approche d'intelligence artificielle (AI), nous avons identifié le peptide RTE62G (pep_RTE62G), un peptide naturel non modifié avec des propriétés de stimulation ECM. Les propriétés anti-âge prédites par l'IA de pep_RTE62G ont ensuite été validées par des tests cliniques in vitro, ex vivo et de validation de principe. LES MÉTHODES: Une approche d'apprentissage en profondeur a été appliquée pour déverrouiller pep_RTE62G à partir d'une source végétale, Pisum sativum (pois). Des tests de culture cellulaire de fibroblastes dermiques humains (HDF) et de kératinocytes (HaCaTs) ont ensuite été utilisés pour évaluer l'effet in vitro de pep_RTE62G. Des activités distinctes telles que la prolifération cellulaire et les propriétés de production de protéines ECM ont été déterminées par des tests ELISA. La migration cellulaire a été évaluée à l'aide d'un test de cicatrisation des plaies, tandis que la synthèse des protéines ECM et l'expression des gènes ont été analysées, respectivement, par microscopie à immunofluorescence et PCR. L'immunohistochimie des explants de peau humaine a été utilisée pour approfondir l'induction des protéines ECM par pep_RTE62G ex vivo. Enfin, l'effet clinique de pep_RTE626 a été évalué dans une étude pilote de 28 jours de validation de principe. RÉSULTATS: Les tests in vitro ont confirmé que pep_RTE62G est un ingrédient anti-âge multifonctionnel efficace. Dans HaCaTs, le traitement pep_RTE62G augmente de manière significative à la fois la prolifération et la migration cellulaire. De même, dans les HDF, pep_RTE62G a induit de manière cohérente la néosynthèse de la protéine ECM élastine et collagène, effets qui sont maintenus dans les explants de peau humaine. Enfin, dans notre étude clinique de preuve de concept, l'application de pep_RTE626 sur 28 jours a démontré un potentiel stimulant anti-rides et collagène. CONCLUSION: pep_RTE62G représente un peptide naturel, non modifié avec des propriétés anti-âge prédites par l'IA et validées expérimentalement. Nos résultats confirment l'utilité de l'IA dans la découverte de nouveaux ingrédients topiques fonctionnels.


Assuntos
Envelhecimento/efeitos dos fármacos , Cosméticos , Aprendizado Profundo , Queratinócitos/efeitos dos fármacos , Peptídeos/farmacologia , Idoso , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Método Duplo-Cego , Proteínas da Matriz Extracelular/biossíntese , Feminino , Humanos , Queratinócitos/citologia , Pessoa de Meia-Idade , Pisum sativum/química , Projetos Piloto , Placebos , Proteínas de Plantas/química , Estudo de Prova de Conceito , Reprodutibilidade dos Testes
2.
J Dairy Sci ; 102(9): 8027-8039, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279544

RESUMO

Two experiments were carried out to evaluate different dietary buffers and their influence on (1) rumen pH in dairy cows and (2) milk production in dairy cows. The supplements included were calcareous marine algae (CMA; Lithothamnion calcareum), with or without marine magnesium oxide (MM; precipitated magnesia derived from seawater), and sodium bicarbonate (SB). Dietary treatments in experiment 1 consisted of the control [32.9% starch and sugar, and 19.9% neutral detergent fiber from forage per kg of dry matter (DM)] including no dietary buffer (CON); the control plus 0.45% DM CMA (CMA); the control plus 0.45% DM CMA and 0.11% DM MM (CMA+MM); the control plus 0.9% DM SB (SB). Diets were formulated to a dry matter intake (DMI) of 18 kg per cow/d. Dietary treatments in experiment 2 also consisted of CON (28.3% starch and sugar, and 23% neutral detergent fiber from forage per kg of DM), CMA, CMA+MM, and SB and were formulated to achieve identical intakes of experimental ingredients (80 g of CMA, 80 g of CMA plus 20 g MM, and 160 g of SB per cow/d) with a DMI of 22.6 kg per cow/d. Experiment 1 used 4 rumen-cannulated dairy cows in a 4 × 4 Latin square design. Rumen pH was measured over five 2-h periods, following feeding, using rumen pH probes. In experiment 2, 52 multiparous and 4 primiparous cows (62.7 ± 3.4 d in milk) were assigned to 4 experimental treatments for 80 d. Both CMA treatments maintained a greater mean rumen pH than the CON during 4 of the 5 periods following feeding and the CON had a greater number of hours below rumen pH 5.5 compared with all other treatments. Dry matter intakes tended to be higher on the SB compared with CON. The CMA treatment increased the production of milk fat and protein yield (kg/d) compared with all other treatments. Both CMA and CMA+MM increased milk fat yield compared with CON but were similar to each other and SB. Protein yield was highest in the CMA treatment compared with CON, CMA+MM, and SB. All 3 buffer treatments increased milk fat concentration compared with CON but did not differ from each other. The SB treatment reduced milk protein concentration and milk production efficiency, energy-corrected milk per kilogram of DMI. Results indicate that the addition of CMA can benefit milk fat and protein production when included in diets based on typical feedstuffs of the northern European region. The use of CMA when compared with SB, in such diets, can increase milk protein production and milk production efficiency.


Assuntos
Ração Animal , Bovinos/metabolismo , Óxido de Magnésio/administração & dosagem , Rodófitas , Rúmen/metabolismo , Animais , Soluções Tampão , Indústria de Laticínios , Dieta/veterinária , Suplementos Nutricionais , Feminino , Concentração de Íons de Hidrogênio , Lactação , Óxido de Magnésio/farmacologia , Distribuição Aleatória , Bicarbonato de Sódio/administração & dosagem
4.
Front Genet ; 13: 945296, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186440

RESUMO

A uniparental disomy (UPD) screen using whole genome sequencing (WGS) data from 164 trios with rare disorders in the Irish population was performed to identify large runs of homozygosity of uniparental origin that may harbour deleterious recessive variants. Three instances of whole chromosome uniparental isodisomy (UPiD) were identified: one case of maternal isodisomy of chromosome 1 and two cases of paternal isodisomy of chromosome 2. We identified deleterious homozygous variants on isodisomic chromosomes in two probands: a novel p (Glu59ValfsTer20) variant in TMCO1, and a p (Pro222Leu) variant in PRKRA, respectively. The overall prevalence of whole chromosome UPiD in our cohort was 1 in 55 births, compared to 1 in ∼7,500 births in the general population, suggesting a higher frequency of UPiD in rare disease cohorts. As a distinct mechanism underlying homozygosity compared to biallelic inheritance, the identification of UPiD has important implications for family planning and cascade testing. Our study demonstrates that UPD screening may improve diagnostic yields by prioritising UPiD chromosomes during WGS analysis.

5.
Cardiol Young ; 20(5): 532-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20519053

RESUMO

OBJECTIVES: To assess the general health and activity levels of 4- and 5-year-old children after intervention for congenital cardiac disease. METHODS: Health behaviour outcomes were assessed in 91 children who had surgery or catheter intervention for congenital cardiac disease. The children were classified into four groups according to severity. The main parameters of classification were the presence of residual symptoms, frequency of visits to general practitioner or the Accident and Emergency Department, and ability to participate in physical activity according to a calculated "activity score". RESULTS: Children had very few residual symptoms after "corrective surgery". Those with complex congenital cardiac disease post-Fontan-type repair still had symptoms on average 18.2 days per month. Surprisingly, the complex group had fewer days "sick" from non-cardiac causes and had fewer visits to general practitioner or Accident and Emergency Departments. Regression analysis indicates that three variables had significant relevance to the general practitioner or Accident and Emergency visits: complex congenital cardiac disease, fewer visits; Townsend score - more deprivation - more visits; and maternal worry - higher maternal worry score - more visits. Regression analysis indicates that lower activity score is significantly related to complex cardiac disease and higher maternal worry score. CONCLUSIONS: The majority of this group of 4- and 5-year-old children had few residual symptoms and had good exercise tolerance. Maternal worry is a significant factor in influencing both activity levels and frequency of unscheduled health service demands - general practitioner or Accident and Emergency visits.


Assuntos
Tolerância ao Exercício/fisiologia , Comportamentos Relacionados com a Saúde , Cardiopatias Congênitas/psicologia , Atividade Motora/fisiologia , Pré-Escolar , Feminino , Seguimentos , Cardiopatias Congênitas/fisiopatologia , Humanos , Masculino , Cuidados Pré-Operatórios , Prognóstico
6.
Child Care Health Dev ; 36(1): 110-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19961494

RESUMO

Abstract Background Congenital heart disease can have a negative impact on both infant development and maternal adjustment. This study considered the impact of a new programme of early psychosocial interventions on such outcomes, following the birth of a child with severe congenital heart disease. Methods Seventy infants and their mothers were assigned to an intervention or control group based on order of presentation to the unit. Interventions aimed at bolstering mother-infant transactions, through psychoeducation, parent skills training and narrative therapy techniques were implemented. Results Clinically and statistically significant gains were observed at 6-month follow-up on the mental (but not the psychomotor) scale of the Bayleys-II. Positive gains were also manifested on feeding practices, maternal anxiety, worry and appraisal of their situation. Conclusions A programme of generalizable psychosocial interventions is shown to have a positive impact on the infant with severe congenital heart disease and the mother.


Assuntos
Adaptação Psicológica , Cardiopatias/congênito , Comportamento Materno/psicologia , Mães/psicologia , Psicoterapia/métodos , Ansiedade/psicologia , Ansiedade/terapia , Criança , Desenvolvimento Infantil , Feminino , Seguimentos , Pesar , Culpa , Humanos , Relações Mãe-Filho , Avaliação de Resultados em Cuidados de Saúde , Poder Familiar/psicologia , Gravidez , Reino Unido
7.
Rev Esp Quimioter ; 31(2): 136-145, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29532655

RESUMO

OBJECTIVE: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum ß-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI). METHODS: Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010. ESBLs were phenotypically detected. RESULTS: Escherichia coli, the most common isolate, significantly decreased in community acquired IAI (60.9% 2002-2010 vs. 56.1% 2011-2015, P=0.0003). It was followed in prevalence by Klebsiella pneumoniae that increased both in the community (8.9% vs. 10.8%, P=0.016) and nosocomial (9.2% vs. 10.8%, P=0.029) IAI and P. aeruginosa, which significantly increased in community acquired IAI (5.6% vs. 8.0%, P=0.0003). ESBLs were more prevalent in K. pneumoniae (16.3%) than in E. coli (9.5%) of nosocomial origin and were more frequently isolated from elderly patients (>60 years). Considering all Enterobacteriaceae, ertapenem (92.3-100%) and amikacin (95.5%-100%) were the most active antimicrobials. Ertapenem activity, unlike amoxicillin-clavulanate or piperacillin-tazobactam, remained virtually unchanged in ESBL (100%) and non-ESBL (98.8%) E. coli producers. Its activity decreased in ESBL-K. pneumoniae (74.7%) but was higher than that of amoxicillin-clavulanate (14.0%) and piperacillin-tazobactam (24.0%). Interestingly, ertapenem susceptibility was maintained in >60% of ESBL isolates that were resistant to amoxicillin-clavulanate, piperacillin-tazobactam or fluoroquinolones. CONCLUSIONS: SMART-Spain results support current guidelines which include ertapenem as empiric treatment in mild-moderate community-acquired IAI, particularly with ESBL producers. These recommendations will need to be updated with the recently introduction of new antimicrobials.


Assuntos
Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , beta-Lactamases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecção Hospitalar/microbiologia , Combinação de Medicamentos , Ertapenem , Escherichia coli/efeitos dos fármacos , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Espanha/epidemiologia , beta-Lactamases/análise , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico
8.
J Med Chem ; 18(3): 304-7, 1975 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1133822

RESUMO

Norepinephrine N-methyltransferase (NMT) from rabbit adrenal glands was inhibited by benzylamine and phenethylamine analogs in which the nitrogen was replaced by an amidino or guanidino group. Mono and dichloro derivatives of benzamidines, phenylacetamidines, benzylguanidines, and phenethylguanidines were studied. The two most potent NMT inhibitors among the compounds examined were 2,3-dichlorobenzamidine and 3,4-dichlorophenylacetamidine, with pI50 values of 5.55 and 5.36, respectively. These inhibitors were reversible and were competitive with norepinephrine as the variable substrate. They inhibited NMT from human, rat, and bovine adrenal glands but were slightly less effective against those enzymes than against the rabbit adrenal enzyme. In exercised rats, 2, 3-dichlorobenzamidine had no significant effect on adrenal catecholamine levels. 3,4-Dichlorophenylacetamidine slightly reduced epinephrine levels in the adrenal glands of exercised rats, but the effect may have been due to release rather than inhibition of synthesis, since heart norepinephrine levels were also reduced significantly by that agent (which is from a chemical series known to release catecholamines). Thus, whereas these compounds are reasonably potent inhibitors of NMT in vitro, they apparently are not effective in blocking enzyme activity in vivo.


Assuntos
Amidinas/farmacologia , Guanidinas/farmacologia , Metiltransferases/antagonistas & inibidores , Feniletanolamina N-Metiltransferase/antagonistas & inibidores , Acetamidas/farmacologia , Glândulas Suprarrenais/análise , Glândulas Suprarrenais/enzimologia , Animais , Bovinos , Epinefrina/análise , Humanos , Técnicas In Vitro , Cinética , Miocárdio/análise , Norepinefrina/análise , Coelhos , Ratos , Relação Estrutura-Atividade
9.
Thromb Haemost ; 61(2): 243-5, 1989 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-2749598

RESUMO

A panel of haemostatic tests was performed on 400 primiparous women at 28 weeks to test whether one or more could predict the development of pregnancy complications. Fifteen women subsequently developed pre-eclampsia with significant proteinuria and 13 delivered growth retarded infants. There were no significant differences between mothers in the pre-eclampsia group and 22 randomly selected controls. A stepwise logistic discriminant analysis of the data did not produce a significant model. In the growth retarded group only beta thromboglobulin levels were significantly lower than in the controls (p less than 0.05), although in the logistic discriminant analysis the inclusion of both beta thromboglobulin and fibrin degradation products led to a borderline significant improvement in fit of the model. We conclude that the haemostatic variables studied are not significantly changed at 28 weeks nor clinically useful predictors of either pre-eclampsia or fetal growth retardation.


Assuntos
Retardo do Crescimento Fetal/diagnóstico , Hemostasia , Pré-Eclâmpsia/diagnóstico , Valor Preditivo dos Testes , Feminino , Humanos , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Fatores de Risco
10.
Biochem Pharmacol ; 32(7): 1243-9, 1983 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-6847714

RESUMO

The effects of N-[2-(o-iodophenoxy)ethyl]cyclopropylamine hydrochloride (LY121768) on types A and B monoamine oxidase (MAO) assayed with radiocarbon-labeled serotonin and phenylethylamine, respectively, were studied in vitro and in vivo. Type A MAO from rat brain was inhibited in vitro by LY121768 with an IC50 of 4 x 10(-10) M, whereas 2500 times higher concentrations of LY121768 (IC50 = 1 x 10(-6) M) were required to inhibit type B MAO. The inhibition of type A MAO increased with time of incubation of LY121768 with enzyme prior to substrate addition and persisted after dialysis, indicative of irreversible inhibition. The irreversible inactivation was prevented by harmaline, a reversible, competitive inhibitor of type A MAO, indicating a requirement for catalytic activity of MAO in the time-dependent inactivation by LY121768. In rats, LY121768 selectively inhibited type A MAO in brain and in liver at low doses. The inhibition of type A MAO persisted for several days after a single 10 mg/kg i.p. dose of LY121768 and was associated with a significant increase in brain dopamine, norepinephrine and epinephrine concentrations and a significant decrease in the concentration of the dopamine metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid. The inactivation of type A MAO by LY121768 in vivo was prevented by co-administration of harmaline, indicating a similar mechanism for the in vivo inactivation as for the in vitro inactivation of MAO by LY121768. A reasonable inference from these data and from previous literature is that LY121768 acts as a "suicide substrate" for MAO and inactivates the enzyme by formation of a reactive intermediate which binds covalently to the enzyme. The presence of iodine in the LY121768 molecule not only confers high selectivity for type A MAO but offers a site for radionuclide introduction that might be a useful means of labeling type A MAO in vitro or in vivo for various purposes.


Assuntos
Ciclopropanos/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Animais , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Harmalina/farmacologia , Cinética , Masculino , Mitocôndrias/enzimologia , Mitocôndrias Hepáticas/enzimologia , Monoaminoxidase/metabolismo , Miocárdio/enzimologia , Ratos , Ratos Endogâmicos
11.
Brain Res ; 112(1): 113-26, 1976 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-181116

RESUMO

The concentration of cyclic AMP (cAMP) and cyclic GMP (cGMP) in slices of rat cerebellum was increased markedly in the presence of 100 muM kainic acid, a cyclic analogue of glutamic acid. No acitvity was detected in other brain areas at various dosed or incubation times. Ksainic acid was significantly more potent than glutamic acid and other glutamate-like compounds. The increases in cAMP and cGMP could be differentially inhibited with theophylline or cocaine respectively, but both systems required calcium. Compounds similar in structure to kainic acid or glutamate did not block the effects of kainic acid.


Assuntos
Cerebelo/efeitos dos fármacos , AMP Cíclico/biossíntese , GMP Cíclico/biossíntese , Glutamatos/farmacologia , Animais , Tronco Encefálico/efeitos dos fármacos , Cálcio/metabolismo , Cerebelo/metabolismo , Cocaína/farmacologia , Técnicas In Vitro , Masculino , Norepinefrina/farmacologia , Potássio/farmacologia , Ratos , Estimulação Química , Relação Estrutura-Atividade , Teofilina/farmacologia , Fatores de Tempo , Ácido gama-Aminobutírico/farmacologia
12.
Eur J Pharmacol ; 33(1): 119-24, 1975 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-126166

RESUMO

Pretreatment of rats with an agent that inhibits uptake into serotoninergic neurons [Lilly 110140: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine hydrochloride] prevented the depletion of brain serotonin by 4-chloroamphetamine, presumably by preventing the entry of 4-chloroamphetamine into the serotonin neuron. When the uptake inhibitor was given after 4-chloroamphetamine, the lowering of both serotonin and tryptophan hydroxylase levels in brain was reversed. Serotonin levels returned to normal after 110140 administration to 4-chloroamphetamine-treated rats at a rate similar to the calculated rate of serotonin turnover in rats treated with 110140 alone. Progressively less reversibility of the 4-chloroamphetamine effect occurred when 110140 was injected at 8, 16 and 24 hr after 4-chloroamphetamine, and no reversibility was observed when 110140 was injected at 32 or 48 hr after 4-chloroamphetamine. These findings indicate that the depletion of brain serotonin by 4-chloroamphetamine is initially reversible but that there is a gradual transition into an irreversible effect between 24 and 48 hr after 4-chloroamphetamine injection. Apparently the prolonged presence of 4-chloroamphetamine inside the serotonin neuron produced by continual reuptake of 4-chloroamphetamine is required for the semi-permanent depletion of brain serotonin stores.


Assuntos
Anfetaminas/farmacologia , Propilaminas/farmacologia , Serotonina/metabolismo , p-Cloroanfetamina/farmacologia , Animais , Encéfalo/enzimologia , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Fenclonina/farmacologia , Masculino , Éteres Fenílicos/farmacologia , Ratos , Fatores de Tempo , Triptofano Hidroxilase/metabolismo
13.
Eur J Pharmacol ; 52(1): 11-6, 1978 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-720384

RESUMO

1-(m-Trifluoromethylphenyl)-piperazine inhibited the specific binding of tritiated serotonin to membranes from rat brain in vitro at lower concentrations than did quipazine or MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine). In rats 1-(m-trifluoromethylphenyl)-piperazine decreased the concentration of 5-hydroxyindoleacetic acid (5-HIAA) without altering the concentration of serotonin in whole brain. The decrease in 5-HIAA was apparently due to a decrease in serotonin turnover, since 1-(m-trifluoromethylphenyl)-piperazine caused a slower decline in serotonin concentration after synthesis inhibition by alpha-propyldopacetamide and a slower accumulation of 5-HIAA after probenecid injection to block its efflux from brain. The decrease in serotonin turnover is an expected result of stimulating serotonin receptors in brain and has earlier been reported to occur with quipazine. Thus all of the results are compatible with the idea that 1-(m-trifluoromethylphenyl)-piperazine acts as a serotonin receptor agonist in rat brain.


Assuntos
Encéfalo/efeitos dos fármacos , Piperazinas/farmacologia , Serotonina/metabolismo , Membranas Sinápticas/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Ratos , Receptores de Serotonina/efeitos dos fármacos , Membranas Sinápticas/metabolismo , p-Cloroanfetamina/antagonistas & inibidores
14.
Fertil Steril ; 43(1): 26-33, 1985 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3917407

RESUMO

Seventy-three treatment courses of pulsatile gonadotropin-releasing hormone (GnRH) were given to 19 patients with clomiphene nonresponsive anovulatory infertility. Fifty cycles were given by the subcutaneous route, and 23 were given intravenously. Doses varied between 1 and 40 micrograms per pulse given at 60- or 90-minute intervals. Luteal support was either by continuation of the pulsatile GnRH or by human chorionic gonadotropin injections. In 16 cycles, potentially fertile ovulation occurred, and three pregnancies resulted, of which one continues normally. Only one of the three pregnancies occurred during intravenous GnRH treatment, and it is likely that this patient would have responded to subcutaneous treatment. The optimum dosage to induce ovulation ranged between 10 and 20 micrograms per pulse at a frequency of 60 to 90 minutes. Those patients who responded to treatment were all of normal or low body weight for their age and frame. Conversely, those who failed to respond to pulsatile GnRH with ovulation were obese except for one patient with the polycystic ovary syndrome. Because pulsatile GnRH treatment is simple and potentially safe to administer, a therapeutic trial is indicated in patients of low to normal body weight who fail to respond to clomiphene. Where patients are responsive to pulsatile GnRH, the ovulations produced are likely to be fertile, possibly because of the endogenous nature of the ovulatory luteinizing hormone surge.


Assuntos
Infertilidade Feminina/tratamento farmacológico , Hormônios Liberadores de Hormônios Hipofisários/administração & dosagem , Adulto , Anovulação/etiologia , Gonadotropina Coriônica/uso terapêutico , Clomifeno/uso terapêutico , Corpo Lúteo/efeitos dos fármacos , Resistência a Medicamentos , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Feminina/etiologia , Infusões Parenterais , Injeções Subcutâneas , Hormônio Luteinizante/sangue , Indução da Ovulação , Hormônios Liberadores de Hormônios Hipofisários/uso terapêutico
15.
J Epidemiol Community Health ; 51(3): 299-303, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9229060

RESUMO

STUDY OBJECTIVE: To see whether the community mothers' programme, using lay volunteer mothers to deliver a childhood development programme, could be extended successfully to the travelling community in Ireland. DESIGN: This was a prospective study of the travelling community; comparisons were made with results of a previous randomised trial of settled mothers. SETTING: A regional health authority in Ireland. PARTICIPANTS: These comprised 39 traveller and 127 settled intervention mother/ infant pairs (randomised controlled trial (RCT) intervention); settled community mothers; 105 settled control pairs (RCT control). All mothers received standard support; traveller and RCT intervention groups also received the services of a community mother. MAIN RESULTS: The travellers' sociodemographic profile differed significantly from the other groups. At the end of the study, traveller and intervention children were exposed to more cognitive games and nursery rhymes. There were significant differences in the proportions who received all three shots of their primary immunisation schedule before 12 months of age and who received "three in one" vaccination, with traveller children doing least well. The diet of traveller children surpassed that of RCT controls in all food groups except fruit; they were less likely to begin cows' milk before 26 weeks of age. Traveller mothers' diet was superior to that of RCT control and similar to RCT intervention mothers. Traveller and RCT intervention mothers were less likely to feel tired, feel miserable, and want to stay indoors than RCT control mothers. CONCLUSIONS: The results of the community mothers' programme in the travelling community are encouraging; poor immunisation uptake remains a challenge.


Assuntos
Desenvolvimento Infantil , Redes Comunitárias , Mães/educação , Migrantes , Acidentes , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Feminino , Nível de Saúde , Hospitalização , Humanos , Imunização , Lactente , Recém-Nascido , Irlanda , Mães/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Desenvolvimento de Programas , Estudos Prospectivos , Fatores Socioeconômicos
16.
J Pharm Sci ; 66(2): 271-2, 1977 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-839428

RESUMO

Tissue levels of amphetamine and of amphetamine analogs with a rigid conformation (2-aminoindan, 2-aminotetralin, and 2-aminobenzocycloheptene) were measured in rats by a spectrofluorometric method involving the reaction of the primary amine group with fluorescamine. All drugs were concentrated in tissues, the order of distribution being lungs greater than kidneys greater than liver=spleen=brain greater than muscle greater than fat=heart greater than blood. In brain, amphetamine and 2-aminoindan were present mostly in the supernatant fraction after high speed centrifugation onbrain homogenates; the two higher molecular weight drugs were present at slightly greater concentrations in the particulate fraction. All four drugs disappeared from rat brain with half-lives of 1-2 hr. Iprindole pretreatment increased drug levels in brain and prolonged the half-lives by two- to threefold. The data suggest that the biological disposition of the rigid analogs resembles generally that of amphetamine and that all of the drugs are probably metabolized by ring hydroxilation in the rat.


Assuntos
Anfetaminas/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Ciclização , Interações Medicamentosas , Fluorescamina , Meia-Vida , Hidroxilação , Iprindol/farmacologia , Cinética , Masculino , Ratos , Frações Subcelulares/metabolismo
17.
J Antibiot (Tokyo) ; 31(1): 27-32, 1978 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-627520

RESUMO

An inhibitor of dopamine-beta-hydroxylase, designated A32390A, was isolated from the culture broth of a Pyrenochaeta species. The inhibitor showed antimicrobial activity against fungi and gram-positive bacteria. Spectroscopic analysis and chemical degradation studies indicated that the structure was 1,6-di-O-(2-isocyano-3-methylcrotonyl)-D-mannitol.


Assuntos
Antibacterianos/isolamento & purificação , Manitol/análogos & derivados , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Resistência Microbiana a Medicamentos , Fungos/efeitos dos fármacos , Masculino , Manitol/isolamento & purificação , Camundongos , Miocárdio/análise , Nitrilas/isolamento & purificação , Norepinefrina/análise , Ratos
18.
Transplant Proc ; 25(4 Suppl 3): 38-40, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8351714

RESUMO

Ethics aims to achieve optimal human behavior. However, applied ethics depend on the cultural environment. In medicine, ethics could allow an amoral operation in a fetus or in chronically ill patients because it is new and rich in prospects for acquiring knowledge and could improve the quality of life of the patient or at least save the life. The operation itself must not be ill natured or unethical and the patient must not be misled or given false hope over the outcome. Ethics would allow us to offend the dignity of man, such as by xenotransplantation, because the wish for well being is often greater than the desire to retain dignity. Ethics in xenotransplantation must be based on the interests of the poor and unlucky patient and must aim for the good of everyone, but especially meet the patient's demands.


Assuntos
Ética Médica , Transplante Heterólogo/psicologia , Direitos dos Animais , Animais , Diversidade Cultural , Revelação , Humanos , Obrigações Morais , Seleção de Pacientes , Medição de Risco , Controle Social Formal , Valor da Vida
19.
Int J Gynaecol Obstet ; 23(2): 135-6, 1985 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2862075

RESUMO

Ectopic pregnancy is a well-recognized complication of tubal reanastomosis (Young PE, Egan JE, Barlow JJ: Reconstructive surgery for infertility at the Boston Hospital for Women. Am J Obstet Gynecol 108: 1092, 1970 and Hodari AA, Vibhasiri A, Isaac AY: Reconstructive tubal surgery for midtubal obstruction. Fertil Steril 28: 620, 1977). We describe here, however, a case of tubal pregnancy occurring in a tubal remnant on the opposite side to a successful tubocornual reanastomosis.


Assuntos
Gravidez Tubária , Reversão da Esterilização/efeitos adversos , Esterilização Tubária , Adulto , Feminino , Humanos , Gravidez
20.
Int J Gynaecol Obstet ; 22(3): 243-9, 1984 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6148285

RESUMO

Venous blood samples were taken daily from 21 regularly menstruating Sudanese women throughout one complete menstrual cycle. FSH, LH, estradiol-17 beta and progesterone were assayed in all plasma samples and normal reference ranges were thus established. Fifteen subjects had a luteal phase of more than 12 days whilst in 3 subjects it was shorter. Two subjects were found to be hyperprolactinemic and one had an anovulatory cycle with an elevated LH. The plasma concentrations of estradiol-17 beta in the follicular phase and progesterone in the luteal phase were significantly lower in subjects with short luteal phase than in those with a luteal phase of more than 12 days. The hormonal profile of FSH, LH, estradiol-17 beta and progesterone throughout a normal menstrual cycle in regularly menstruating Sudanese women was similar to what has been reported in the literature for other ethnic groups.


Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Ciclo Menstrual , Progesterona/sangue , Adulto , Feminino , Humanos , Valores de Referência , Sudão
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