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1.
Artigo em Russo | MEDLINE | ID: mdl-35758948

RESUMO

OBJECTIVE: Determination of the dose-dependent effect of the Teraligen for various nosological forms of disorders in psychiatric practice and general medicine. MATERIAL AND METHODS: Analysis of 98 publications included in the database of the RISC (2012-2021) with the identification of disorders (according to ICD-10) in which Teraligen is prescribed or can be used (in adults and children from the age of 7). RESULTS: Despite a rather long and successful history use, research work on the study drug Teraligen continues. Currently Teraligen is widely and actively used by doctors of various specialties in the psychiatry, neurology, pediatrics, gerontology, internal medicine, gastroenterology, gynecology, cardiology, endocrinology and other disciplines. The drug is presented in several release forms: Teraligen 5 mg tablets; Teraligen retard 20 mg; Teraligen solution for intravenous injections. Teraligen is characterized by the following psychotropic effects: anxiolytic (++ - a distinct, moderately pronounced effect); sedative (++); hypnotic (++); antidepressant (+ - the effect is distinct, but expressed slightly and does not determine the drug main prescriptions spectrum); antipsychotic (± - the effect is weakly expressed and clinically insignificant when using conventional (5-80 mg/day) drug dosages). CONCLUSION: According to the authors, the main effect of the «small¼ neuroleptic/antipsychotic Alimemazine (Teraligen ) is primarily aimed at pathological anxiety and affective instability. Its use is possible in various age groups, as it has a fairly high safety. In addition, like other «small¼ neuroleptics/antipsychotics with a predominantly sedative effect, the drug can be used to correct neuroleptics-prolongs side effects with dominant manifestations in the form of anxiety, irritability and insomnia.


Assuntos
Ansiolíticos , Antipsicóticos , Adulto , Ansiolíticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Criança , Humanos , Hipnóticos e Sedativos/uso terapêutico , Psicotrópicos/uso terapêutico , Trimeprazina/uso terapêutico
2.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(6. Vyp. 2): 68-76, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32729693

RESUMO

OBJECTIVE: An analysis of the efficacy and safety of additional therapy of excitement with the injectable form of alimemazine during exacerbations of schizophrenia with psychomotor agitation, impulsivity, including dangerous behavior, irritability, conflict, hostility, aggressiveness, anxiety, sleep disturbances (insomnia). MATERIAL AND METHODS: Thirty patients, aged 18 to 65 years, with a diagnosis of «paranoid schizophrenia¼, established in accordance with the ICD-10 criteria, were studied. The patients received treatment with a second-generation antipsychotic and alimemazine (intramuscular injection solution) in daily dose from 25 mg to 150 mg during no more than 9 days. The patients were assessed with psychometric scales (PANSS, ABS, HARS and VAS) four times during the observation period. RESULTS AND CONCLUSION: During therapy with a combination of second-generation antipsychotics and alimemazine solution for intramuscular injection, a reliable (p<0.001) reduction in the severity of psychotic symptoms assessed with PANSS was achieved by 8-9 days (the average total score decreased by 30% relative to the initial level) that indicated the improvement in all manifestations of schizophrenia exacerbation. A decrease of 34.8% (p=0.007) in the risk of aggression (PANSS points S1-S3) was established. The level of excitation on the agitation scale (ABS) decreased by 3.6% (p<0.001). In 50% of patients, manifestations of anxiety disappeared, and the average HARS score decreased by 2.2 times compared with the initial level (p<0.001). Almost half of the patients noted the normalization of sleep, and the average value of sleep disturbance on a visual analogue scale decreased threefold compared with the initial level (p<0.001). The observed adverse events were moderate or mild. Alimemazine shows the highest efficacy in the treatment of anxiety arousal in patients with schizophrenia with affective-delusional attacks.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Ansiedade , Humanos , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Agitação Psicomotora/tratamento farmacológico , Resultado do Tratamento , Trimeprazina/uso terapêutico , Adulto Jovem
3.
Cell Death Dis ; 11(4): 283, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32332706

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for progression of steatohepatitis, liver cirrhosis, and liver cancer. Although pathological condition of NAFLD, which arises from an excessive accumulation of triglyceride in the liver, is accompanied by elevated sterol regulatory element-binding protein 1c (SREBP1c) level, it is largely unknown which factors are involved in the modification of SREBP1c. In this study, we discovered that neddylation of SREBP1c competes with its ubiquitination and stabilizes SREBP1c protein level, and eventually promotes hepatic steatosis. We also demonstrated that human homolog of mouse double minute 2 (HDM2) acts as an E3 neddylation ligase of SREBP1c. Further, treatment with the neddylation inhibitor, MLN4924, attenuates high-fat diet-induced hepatic steatosis by reducing the levels of SREBP1c protein and hepatic triglyceride. Our results indicate that the blockade of SREBP1c neddylation could be a novel approach in the defense against NAFLD.


Assuntos
Proteína NEDD8/genética , Hepatopatia Gordurosa não Alcoólica/terapia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Humanos , Proteína NEDD8/metabolismo , Fatores de Risco , Transfecção , Trimeprazina
4.
Artigo em Russo | MEDLINE | ID: mdl-31626168

RESUMO

AIM: To evaluate the efficacy of alimemazine in the form of a solution for intramuscular injections in the treatment of anxiety and depressive disorders. MATERIAL AND METHODS: Twenty patients, who met ICD-10 criteria for anxiety and depressive disorders, participated in the clinical observation. Alimemazine was used in the form of a solution for intramuscular injection (5 mg/ml) along with SSRIs and SNRIs. RESULTS: The significant positive dynamics in the reduction of anxiety-depressive disorders, sleep disorders and vegetative symptoms was observed in patients treated with alimemazine (solution) and antidepressants from the group of SSRIs and SSRIs. CONCLUSION: The drug has demonstrated efficacy and a favorable tolerability profile.


Assuntos
Antidepressivos , Transtorno Depressivo , Trimeprazina , Antidepressivos/administração & dosagem , Ansiedade , Transtorno Depressivo/tratamento farmacológico , Humanos , Injeções Intramusculares , Inibidores de Captação de Serotonina/uso terapêutico , Trimeprazina/administração & dosagem
5.
Sud Med Ekspert ; 62(1): 31-35, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30724891

RESUMO

There is the present-day tendency toward prescribing atypical neuroleptics for the management of neurologic and psychic disorders. Alimemazine appears to be very frequently used for this purpose due to the broad spectrum of its actions. At the same time, cases of alimemazine poisoning with the fatal outcome have been described. The objective of the present study was determine alimemazine in the biological fluids from the laboratory animals under the acute poisoning conditions. The experiments were carried with the use of the Wistar rats having 200 g body weight. Alimemazine was isolated from their biological fluids (blood plasma and urine) using the liquid-liquid extraction techniques developed specially for the purpose of this study. Alimemazine was extracted and quantitatively determined by HPLC and HPLC/MS. The method for the isolation of alimemazine from the urine and blood plasma is described. The results of the study give evidence that the maximum amount of the substance of interest can be extracted from the blood plasma within 1 hour after the administration of the toxic dose of alimemazine and within 2 hours after the administration of its therapeutic dose. The maximum amount of alimemazine in the urine is found within 3 hours after the administration of its therapeutic dose to the laboratory animals. It is concluded that the proposed methods for the extraction of alimemazine from the biological fluids can be included in the scheme of the chemical toxicological analysis of this substance.


Assuntos
Trimeprazina/análise , Animais , Animais de Laboratório , Antipsicóticos , Análise Química do Sangue , Cromatografia Líquida de Alta Pressão , Toxicologia Forense , Extração Líquido-Líquido , Espectrometria de Massas , Ratos , Ratos Wistar , Urinálise
6.
Rev. lab. clín ; 11(3): 153-155, jul.-sept. 2018.
Artigo em Espanhol | IBECS | ID: ibc-176910

RESUMO

La alimemazina (Variargil(R)) es un antihistamínico anti-H1 reversible inespecífico que atraviesa la barrera hematoencefálica. Actúa como anticolinérgico. Su forma de presentación es en gotas en suspensión oral. Su uso clínico está extendido a rinitis alérgica estacional, angioedema y urticaria leve a partir de los 2 años de edad, conjuntivitis alérgica e insomnio de conciliación en la infancia. Presenta una farmacocinética muy variable, somnolencia excesiva conocida como «heavy hangover» y efecto de rebote tras su retirada. No está autorizado su uso en menores de 2 años. Presentamos el caso de un paciente de 19 meses que acude a Urgencias por referir somnolencia y falta de respuesta a estímulos tras la administración de alimemazina por dificultad para conciliar el sueño


Alimemazine (Variargil(R)) is a non-specific reversible anti-H1 antihistamine that crosses the blood-brain barrier. It acts as anticholinergic drug. It is marketed in drop form (oral suspension). It is used to relieve seasonal allergic rhinitis, angioedema, mild urticaria, allergic conjunctivitis, and for difficulty in falling asleep in children. It has a very variable pharmacokinetic, excessive "heavy hangover drowsiness" and rebound effect after withdrawal. It is not authorised for children under 2 years of age. The case is presented of a patient seen in the emergency room due to drowsiness and lack of response to stimuli after administration of alimemazine due to difficulties in falling asleep


Assuntos
Humanos , Masculino , Lactente , Morfina/urina , Detecção do Abuso de Substâncias/normas , Trimeprazina/farmacocinética , Antidepressivos Tricíclicos/farmacocinética , Reações Falso-Positivas , Sensibilidade e Especificidade , Reações Cruzadas , Antagonistas dos Receptores Histamínicos H1/farmacocinética
7.
Water Res ; 141: 57-64, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29775773

RESUMO

A great number of available pharmaceuticals are chiral compounds. Although they are usually manufactured as racemic mixtures, they can be enantioselectively biodegraded as a result of microbial processes. In this paper, a biodegradability assay in similar conditions to those recommended in OECD tests of enantiomers of trimeprazine (a phenothiazine employed as a racemate) is carried out. Experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant, WWTP) and supplemented with the racemate. The concentration of the enantiomers of trimeprazine were monitored by means of a chiral HPLC method using a cellulose-based chiral stationary phase and 0.5 M NaClO4/acetonitrile (60:40, v/v) mobile phases. Experiments were performed at three concentration levels of the racemate. In parallel, the optical density at 600 nm (OD600) was measured to control the biomass growth and to connect it with enantioselectivity. The calculated enantiomeric fractions (EF) offer the first evidence of enantioselective biodegradation of trimeprazine. A simplified Monod equation was used as a curve fitting approach for concentration (S), biodegradation (BD), and for the first time, EF experimental data in order to expand the usefulness of the results. Precision studies on S (repeatability conditions) and, for the first time, EF (intermediate precision conditions) were also performed.


Assuntos
Antipruriginosos/metabolismo , Trimeprazina/metabolismo , Poluentes Químicos da Água/metabolismo , Antipruriginosos/química , Biodegradação Ambiental , Cromatografia Líquida de Alta Pressão , Esgotos , Estereoisomerismo , Trimeprazina/química , Poluentes Químicos da Água/química
8.
Zh Nevrol Psikhiatr Im S S Korsakova ; 118(1. Vyp. 2): 39-44, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29658503

RESUMO

AIM: To assess the efficacy of monotherapy of anxiety in alcoholism with alimemazine (teraligen). MATERIAL AND METHODS: Thirty-six patients with alcohol addiction were treated with alimemazine in dose 15 mg during 9 month. In control group (11 patients) teraligen was no used. RESULTS AND CONCLUSION: A significant positive effect of treatment with teraligen was observed. There were the improvement in alcohol addiction course, decrease in scores on the Addiction Severity Index (ASI) from severe to mild level and decrease in trait and state anxiety measured with the Spielberger-Khanin scale from high to low levels. The reduction on symptoms of depression from moderate (at baseline) to subdepressive levels on the Beck Depression Inventory was noted in the end of treatment.


Assuntos
Alcoolismo , Ansiolíticos , Trimeprazina , Alcoolismo/complicações , Alcoolismo/psicologia , Ansiolíticos/uso terapêutico , Ansiedade , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/tratamento farmacológico , Depressão , Humanos , Trimeprazina/uso terapêutico
9.
Ticks Tick Borne Dis ; 8(6): 895-906, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28784308

RESUMO

Tick-borne encephalitis virus (TBEV) is the causative agent of tick-borne encephalitis (TBE), a vector-borne zoonotic neuroinfection. For successful circulation in natural foci the virus has to survive in the vector for a long period of time. Information about the effect of long-term infection of ticks on properties of the viral population is of great importance. In recent years, changes in the eco-epidemiology of TBEV due to changes in distribution of ixodid ticks have been observed. These changes in TBEV-endemic areas could result in a shift of the main tick vector species, which in turn may lead to changes in properties of the virus. In the present study we evaluated the selective pressure on the TBEV population during persistent infection of various species of ticks and tick cell lines. TBEV effectively replicated and formed persistent infection in ticks and tick cell lines of the vector species (Ixodes spp.), potential vectors (Dermacentor spp.) and non-vector ticks (Hyalomma spp.). During TBEV persistence in Ixodes and Dermacentor ticks, properties of the viral population remained virtually unchanged. In contrast, persistent TBEV infection of tick cell lines from both vector and non-vector ticks favoured selection of viral variants with low neuroinvasiveness for laboratory mice and substitutions in the E protein that increased local positive charge of the virion. Thus, selective pressure on viral population may differ in ticks and tick cell lines during persistent infection. Nevertheless, virus variants with properties of the original strain adapted to mouse CNS were not eliminated from the viral population during long-term persistence of TBEV in ticks and tick cell lines.


Assuntos
Vetores Aracnídeos/virologia , Vírus da Encefalite Transmitidos por Carrapatos/genética , Vírus da Encefalite Transmitidos por Carrapatos/patogenicidade , Ixodidae/virologia , Animais , Linhagem Celular , Dermacentor/virologia , Ixodes/virologia , Camundongos , Trimeprazina/análogos & derivados , Virulência
11.
Arch Dis Child ; 102(1): 56-60, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27335428

RESUMO

BACKGROUND AND AIMS: During the last decades, much attention has been paid to off-label and unlicensed prescriptions in paediatrics. However, on-label prescribing can also cause health issues. In this paper, the case of first-generation H1-antihistamines is investigated, notably the range of indications for which products are licensed in different European countries and the evidence base (or lack thereof) for each indication, as well as reported adverse drug reactions. METHODS: Review of the Summary of Product Characteristics of first-generation H1-antihistamines with a focus on paediatric use. This is plotted against the evidence available in the literature. RESULTS: This investigation shows a large variability in labelled indications and licensing ages when compared in five different European countries. Moreover, most of the indications are not based on clinical trials evaluating efficacy and safety of these drugs in children. CONCLUSIONS: Many of the licensed indications of first-generation antihistamines do not appear to be evidence based.


Assuntos
Antagonistas dos Receptores Histamínicos/uso terapêutico , Criança , Ciproeptadina/uso terapêutico , Dimetideno/uso terapêutico , Aprovação de Drogas , Rotulagem de Medicamentos , Medicina Baseada em Evidências , Humanos , Uso Off-Label , Resultado do Tratamento , Trimeprazina/uso terapêutico
12.
Forensic Sci Int ; 266: e18-e22, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27567044

RESUMO

Munchausen syndrome by proxy (MSBP), also known as fabricated or induced illness in a child by a caretaker, is a form of abuse where a caregiver deliberately produces or feigns illness in a person under his or her care, so that the proxy will receive medical care that gratifies the caregiver. The affected children are often hospitalized for long periods and endure repetitive, painful and expensive diagnostic attempts. We present an analytically confirmed case of MSBP by alimemazine. A 3-year-old boy was brought repetitively to a Pediatric Emergency Department by his mother because he presented limb tremors, dysarthria, obnubilation, and ataxia and generalized tonic-clonic seizures coinciding with intermittent fever. Neither the rest of the physical examination nor the complementary tests showed any significant alterations. MSBP was suspected and a routine systematic toxicological analysis in urine and blood was requested. Alimemazine was detected in all biological samples. The administration of this drug was never mentioned by the mother and the subsequent interview with her corroborated the suspicion of MSBP. Clinically, after separation from the mother, the child's neurological symptoms gradually improved until the complete disappearance of the cerebellar symptoms. Alimemazine was quantified in serum, urine, gastric content and cerebrospinal fluid samples by gas chromatography-mass spectrometry (maximum serum level was 0.42µg/ml). Hair quantification of alimemazine was performed by ultra-performance liquid chromatography-tandem mass spectrometry in different segments of hair. The results confirmed regular substance use during the at least eight last months (8.8, 14.7, 19.7 and 4.6ng/mg hair starting from most proximal segment). This patient represents the first case published with analytical data of alimemazine in blood, urine, gastric content, cerebrospinal fluid and hair, which allowed us to prove an acute and repetitive poisoning with alimemazine as evidence of MSBP.


Assuntos
Antipruriginosos/envenenamento , Síndrome de Munchausen Causada por Terceiro/diagnóstico , Trimeprazina/envenenamento , Antipruriginosos/análise , Maus-Tratos Infantis/diagnóstico , Pré-Escolar , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Conteúdo Gastrointestinal/química , Cabelo/química , Humanos , Masculino , Trimeprazina/análise
13.
Artigo em Russo | MEDLINE | ID: mdl-26356157

RESUMO

AIM: To develop a new instrument able to identify pathological states and assess their changes during medication treatment. We aimed to study the typical practice of using alimemazine (teraligen) in patients with the diagnosis of autonomic nervous system disorder and to test the Russian version of @The Four-Dimensional Symptom Questionnaire@ (4DSQ) for measuring distress, depression, anxiety and somatization. MATERIAL AND METHODS: We examined 3053 patients (mean age 42.09 ± 11.71 years) who received teraligen in doses gradually increasing from 5 to 15 mg per day. The observational program was carried out in over 600 outpatient clinics of the Russian Federation. The 4DSQ was administered before treatment and 4 weeks after treatment. The Clinical Global Impression (CGI) scale was used before, during (after 2 weeks) and after (4 weeks) treatment with teraligen. RESULTS AND CONCLUSION: There was a significant improvement of patient's state assessed both by physicians (CGI scale) and by patients (96 and 98%, respectively). The 4DSQ was sensitive to the parameters of response to treatment with teraligen: parameters obtained at baseline and 4 weeks after the beginning of treatment differed significantly demonstrating a significant decrease in distress, anxiety and somatization.


Assuntos
Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Inquéritos e Questionários , Trimeprazina/uso terapêutico , Adulto , Ansiedade/diagnóstico , Doenças do Sistema Nervoso Autônomo/psicologia , Depressão/diagnóstico , Prescrições de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa
14.
Artigo em Russo | MEDLINE | ID: mdl-26978499

RESUMO

OBJECTIVE: To assess the efficacy and safety of teraligen in patients with psychoautonomic syndrome comorbid to brain ischemia. MATERIAL AND METHODS: Forty-five patients, aged from 42 to 65 years (mean age 56 years), diagnosed with brain ischemia, stages I and II, with the signs of psychoautonomic syndrome were examined. Thirty-five patients received teraligen in the daily dose of 15 mg. The control group comprised 10 patients who were not treated with this drug. The duration of treatment was 60 days. Neurological status, autonomic changes, cognitive functions and mental state were assessed during the treatment. Neurophysiological examination (EEG and P300 event-related potential) were performed in the first and last visits. RESULTS AND CONCLUSION: The distinct positive dynamics of the decrease of psychoautonomic symptoms, cephalgic syndrome, sleep normalization as well as the improvement of cognitive function were noted. Good tolerability and no side-effects, in particular, those related to vascular disorders, were demonstrated. Clinical results were supported by the results of neurophysiological examinations. The drug can be recommended for treatment of psychoautonomic syndrome in elderly patients with brain ischemia, stages I and II.


Assuntos
Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Trimeprazina/uso terapêutico , Adulto , Idoso , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Cognição , Potenciais Evocados P300 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Resultado do Tratamento
15.
Eur Addict Res ; 20(6): 300-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25300747

RESUMO

Used in the treatment of spasticity at low doses, baclofen is also prescribed off-label at high doses for the treatment of alcohol dependence. Several cases of baclofen intoxication have been reported, but only 1 case deals with the treatment of alcohol dependence. Thus, we report the first death in the context of baclofen off-label use of an alcohol-dependent patient with a high blood baclofen concentration after intentional drug intoxication. The safety profile of baclofen in the treatment of alcohol dependence is reviewed and discussed, underlining the obligatory caution that may support any prescription of high doses of baclofen in this off-label indication and especially in patients with concomitant psychiatric disorders.


Assuntos
Alcoolismo/tratamento farmacológico , Baclofeno/envenenamento , Overdose de Drogas , Agonistas dos Receptores de GABA-B/envenenamento , Antipruriginosos/envenenamento , Baclofeno/uso terapêutico , Depressores do Sistema Nervoso Central/envenenamento , Etanol/envenenamento , Evolução Fatal , Agonistas dos Receptores de GABA-B/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Trimeprazina/envenenamento
16.
Pediatr Dermatol ; 31(1): 76-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-22747704

RESUMO

We report a 6-year-old boy with severe atopic dermatitis and refractory pruritus. The novel use of clonidine, an adrenergic agonist, along with trimeprazine, led to dramatic improvement. This represents the first case report of clonidine's effect in relieving pruritus in atopic dermatitis.


Assuntos
Clonidina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Prurido/tratamento farmacológico , Trimeprazina/uso terapêutico , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Antipruriginosos/uso terapêutico , Criança , Dermatite Atópica/patologia , Quimioterapia Combinada , Humanos , Masculino , Uso Off-Label , Prurido/patologia , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Arch Dis Child ; 98(9): 732-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23845695

RESUMO

OBJECTIVE: To describe the dispensing of the hypnotic alimemazine to children aged 0-3 years and investigate the association between dispensing of alimemazine to children and dispensed hypnotics to their parents. DESIGN: An observational cohort study linking information from the Medical Birth Registry of Norway and the Norwegian Prescription Database. Hypnotics dispensed to parents in a 1-year period before pregnancy was associated with dispensed alimemazine for children aged 0-3 years. PATIENTS AND SETTING: All children born in Norway in 2008 (N=59 325) and their mothers and fathers were included. MAIN OUTCOME MEASURES: Dispensed alimemazine to children during the first 3 years of life. RESULTS: Three percent of children received alimemazine. Dispensed hypnotics to mothers increased the risk of the child receiving a prescription for alimemazine, OR of 2.3 (1.7-3.0) for boys and 1.7 (1.2-2.4) for girls. When both parents had been dispensed prescriptions for hypnotics, the risk increased nearly threefold. A dispensed alimemazine prescription was also associated with dispensed prescriptions for antidepressants to both mother and father, mother's smoking, the child's gender and child's prescriptions for antibiotics, respiratory drugs and dermatological steroids. CONCLUSIONS: Dispensed alimemazine to children under 3 was associated with parents' previous use of hypnotics, indicating that factors other than the child's health influence the use of hypnotic drugs in infancy and toddler years. The frequent usage of alimemazine in children below 3 years and the association with parents' use of hypnotics should concern prescribing doctors.


Assuntos
Prescrições de Medicamentos , Hipnóticos e Sedativos/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Trimeprazina/administração & dosagem , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Noruega , Pais , Gravidez , Sistema de Registros , Fatores de Risco
19.
Biochem Biophys Res Commun ; 434(4): 710-6, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23541943

RESUMO

Human embryonic stem cells (hESCs) and induced pluripotent cells have the potential to provide an unlimited source of tissues for regenerative medicine. For this purpose, development of defined/xeno-free culture systems under feeder-free conditions is essential for the expansion of hESCs. Most defined/xeno-free media for the culture of hESCs contain basic fibroblast growth factor (bFGF). Therefore, bFGF is thought to have an almost essential role for the expansion of hESCs in an undifferentiated state. Here, we report identification of small molecules, some of which were neurotransmitter antagonists (trimipramine and ethopropazine), which promote long-term hESC self-renewal without bFGF in the medium. The hESCs maintained high expression levels of pluripotency markers, had a normal karyotype after 20 passages, and could differentiate into all three germ layers.


Assuntos
Proliferação de Células/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Compostos Orgânicos/farmacologia , Bibliotecas de Moléculas Pequenas , Animais , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células-Tronco Embrionárias/metabolismo , Citometria de Fluxo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Imuno-Histoquímica , Metotrimeprazina/química , Metotrimeprazina/farmacologia , Camundongos , Camundongos SCID , Estrutura Molecular , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Compostos Orgânicos/química , Fenotiazinas/química , Fenotiazinas/farmacologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Prometazina/química , Prometazina/farmacologia , Trimeprazina/química , Trimeprazina/farmacologia , Trimipramina/química , Trimipramina/farmacologia
20.
Leg Med (Tokyo) ; 14(5): 267-71, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22546247

RESUMO

Dimemorfan was extracted from human plasma samples (100 µL) using MonoTip C(18) tips, which were packed with a C(18)-bonded monolithic silica gel attached to the inside of the tip. The samples, which contained dimemorfan and trimeprazine as an internal standard (IS), were mixed with 300 µL of distilled water and 50 µL of 1M glycine-sodium hydroxide buffer (pH 10). The mixture was extracted onto the C(18) phase of the tip by 20 sequential aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C(18) phase were then eluted with methanol by five sequential aspirating/dispensing cycles. The eluate was injected directly into a gas chromatograph and detected by a mass spectrometer with selected ion monitoring in positive electron ionization mode. An Equity-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.25 µm) gave adequate separation of the dimemorfan, IS, and impurities. The recoveries of dimemorfan and the IS spiked into plasma were ≥83%. The regression equation for dimemorfan showed excellent linearity from 0.25 to 32.0 ng/100 µL of plasma, and the limit of detection was 0.125 ng/100 µL of plasma. The maximum intra-day and inter-day relative standard deviations were 13%, while accuracy ranged from 88% to 105%. Dimemorfan was stable for at least 12 h at 4°C, 4 weeks at -80°C, and three freeze-thaw cycles in plasma. This new method is expected to have application as a pretreatment for the rapid, simple, and quantitative determination of dimemorfan in plasma samples.


Assuntos
Morfinanos/análise , Plasma/química , Extração em Fase Sólida/métodos , Trimeprazina/análise , Antipruriginosos/análise , Antitussígenos/análise , Humanos , Extração em Fase Sólida/instrumentação
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