RESUMO
CONTEXT: Strabismus surgery is one of the most common ophthalmic surgical procedures in children and is associated with significant postoperative nausea and vomiting (PONV). OBJECTIVE: We evaluated the effect of intravenous paracetamol on PONV in children after strabismus surgery. DESIGN: Prospective, placebo-controlled, randomised double-blind study. SETTING: University hospital. PATIENTS: Ninety children, between 2 and 14 years scheduled for strabismus surgery, were recruited. Eighty-six completed the study. INTERVENTIONS: After induction of anaesthesia, intravenous dexamethasone 0.1âmgâkg was administered to all. The patients were enrolled to receive either intravenous physiological saline (group S) or paracetamol 15âmgâkg (group P). MAIN OUTCOME MEASURE: Incidence of PONV in the first 24âh postoperatively. RESULTS: General and clinical characteristics of the children were similar in both groups. PONV during the first 24âh was significantly higher in group S in comparison with group P (group S vs. group P, 33 vs. 14.6%, respectively, Pâ=â0.038 for nausea; 24.4 vs. 7.3%, respectively, Pâ=â0.030 for vomiting). The number of analgesic administrations during the first 24âh was higher in group S compared with group P (1.31â±â0.85 and 0.73â±â0.6, respectively, Pâ=â0.001). The repeat number of postoperative analgesic administrations was significantly different between groups during the first 24âh (Pâ=â0.005), but during 24-48âh was not significant. CONCLUSION: Intraoperative administration of intravenous paracetamol decreases the incidence of PONV during the first 24âh in children after strabismus surgery.
Assuntos
Acetaminofen/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Estrabismo/cirurgia , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Cuidados Intraoperatórios/métodos , Masculino , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/fisiopatologia , Estudos Prospectivos , Estrabismo/fisiopatologia , Fatores de Tempo , Resultado do TratamentoAssuntos
Proteínas do Citoesqueleto/genética , Neuropatia Axonal Gigante/genética , Neuropatia Axonal Gigante/patologia , Dissomia Uniparental/genética , Sequência de Bases , Exoma/genética , Feminino , Homozigoto , Humanos , Imageamento por Ressonância Magnética , Dados de Sequência Molecular , Condução Nervosa/genética , Condução Nervosa/fisiologia , Análise de Sequência de DNARESUMO
BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.
Assuntos
Tronco Encefálico/anormalidades , Veias Cerebrais/anormalidades , Síndrome de Walker-Warburg/diagnóstico por imagem , Adolescente , Tronco Encefálico/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation. METHODS: Ki67 (clone, MIB-1) liver parenchyma expression was measured by immunohistochemical staining of samples from living donors and patients with biliary atresia to assess its value in predicting outcomes after KP. RESULTS: Of 35 children with biliary atresia, 13 were native liver survivors (NLS), 17 were non-NLS, and five had primary LT. The median proportion of Ki67 immunostained areas in donors and patients with biliary atresia at KP was 0·06 and 0·99 per cent respectively. Univariable analysis identified a high proportion of Ki67 areas, high Ki67 cell numbers and high Ki67-positive/leucocyte common antigen-positive cell numbers at KP as significant predictors of poor native liver survival after KP (hazard ratio 9·29, 3·37 and 12·17 respectively). The proportion of Ki67 areas in the non-NLS group was significantly higher than that in the NLS group (1·29 versus 0·72 per cent respectively; P = 0·001), and then decreased at LT (0·32 per cent versus 1·29 per cent at KP; P < 0·001). CONCLUSION: This study has demonstrated the clinical data and time course of Ki67 expression in patients with biliary atresia. High Ki67 expression at KP may be an important predictor of native liver survival following the procedure.
ANTECEDENTES: La atresia biliar (biliary atresia, BA) es una enfermedad pediátrica rara que consiste en una obstrucción biliar de etiología desconocida, y es la indicación pediátrica más frecuente de trasplante hepático (liver transplantation, LT). Sin embargo, no existe consenso para predecir los resultados de la portoenterostomía de Kasai (Kasai portoenterostomy, KP) en base a los hallazgos histológicos hepáticos. El Ki67 es un biomarcador conocido para medir y controlar la proliferación celular. MÉTODOS: Se midieron los niveles de expresión del parénquima hepático de Ki67 (clon, MIB-1) por tinción inmunohistoquímica de las muestras de cinco donantes vivos y 35 pacientes con BA, para evaluar su valor predictivo de los resultados de la KP. RESULTADOS: Los pacientes con BA incluían 13 sobrevivientes con hígado nativo (native liver survivors, NLS), 17 no NLS y 5 pacientes que se sometieron inicialmente a LT. La proporción media de las áreas de expresión de Ki67 en donantes y pacientes con BA en KP fue de 0,06% y 0,99%, respectivamente. El análisis univariado identificó una alta proporción de áreas de Ki67, un alto número de células Ki67, un alto número de células Ki67 positivas (+)/leucocitos (LCA/CD45) + en KP como predictores significativos de una peor supervivencia del hígado nativo después de KP (cociente de riesgos instantáneos, hazard ratio, HR 9,29, 3,37 y 12,17, respectivamente). La proporción de las áreas Ki67 fueron significativamente superiores en los pacientes sin NLS que en los pacientes con NLS (P = 0,001). Entre los pacientes sin hígado nativo, los niveles de Ki67 disminuyeron posteriormente de acuerdo con la presencia de una lesión hepática irreparable, tales como son los hígados con BA en LT (en KP versus en LT = 1,29% versus 0.32%; P < 0,001). CONCLUSIÓN: Demostramos los datos clínicos y la evolución temporal de la expresión de Ki67 en los pacientes con BA. El alto nivel de expresión de Ki67 en KP puede ser un predictor importante para la supervivencia del hígado nativo después de KP.
Assuntos
Atresia Biliar/metabolismo , Atresia Biliar/cirurgia , Antígeno Ki-67/metabolismo , Transplante de Fígado/estatística & dados numéricos , Portoenterostomia Hepática , Atresia Biliar/mortalidade , Atresia Biliar/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Fígado/fisiopatologia , Fígado/cirurgia , Testes de Função Hepática , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: The present study was planned to evaluate the efficacy and safety of ultrasound-guided Pecs I and II blocks for postoperative analgesia after sub-pectoral breast augmentation. METHODS: Fifty-four adult female patients undergoing breast augmentation were randomly divided into two groups: the control group (Group C, n=27) who were not subjected to block treatment and Pecs group (Group P, n=27) who received Pecs I (bupivacain 0.25%, 10mL) and Pecs II (bupivacain 0.25%, 20mL) block. Patient-controlled fentanyl analgesia was used for postoperative pain relief in both groups, and the patients were observed for the presence of any block-related complications. RESULTS: The 24-h fentanyl consumption was smaller in Group P [mean±SD, 378.7±54.0µg and 115.7±98.1µg, respectively; P<0.001]. VAS scores in Group P were significantly lower at the time of admission to the post-anaesthetic care unit and at 1, 2, 4, 8, 12, and 24h (P<0.001). The rates of nausea and vomiting were higher in Group C than in Group P (9 vs 2, P=0.018). Hospital stay duration was shorter in Group P than in Group C (24.4±1.2h vs 27.0±3.1h, P<0.001). No block-related complications were recorded. CONCLUSIONS: Combine used of Pecs I and II blocks provide superior postoperative analgesia in patients undergoing breast augmentation and shortens hospital stay.
Assuntos
Analgesia/métodos , Mamoplastia/métodos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/terapia , Nervos Torácicos , Ultrassonografia de Intervenção , Adulto , Analgesia Controlada pelo Paciente , Analgésicos Opioides/administração & dosagem , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Feminino , Fentanila/administração & dosagem , Humanos , Incidência , Tempo de Internação , Mamoplastia/efeitos adversos , Pessoa de Meia-Idade , Bloqueio Nervoso/efeitos adversos , Manejo da Dor/métodos , Medição da Dor , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Prospectivos , Adulto JovemRESUMO
Obstructive sleep apnea (OSA) is a disorder characterized by breathing cessation caused by obstruction of the upper airway during sleep. It is associated with multiorgan comorbidities such as obesity, hypertension, heart failure, arrhythmias, diabetes mellitus, and stroke. Patients with OSA have an increased prevalence of ophthalmic disorders such as cataract, glaucoma, central serous retinopathy (detachment of retina, macular hole), eyelid laxity, keratoconus, and nonarteritic anterior ischemic optic neuropathy; and some might require surgery. Given that OSA is associated with a high incidence of perioperative complications and more than 80% of surgical patients with OSA are unrecognized, all surgical patients should be screened for OSA (eg, STOP-Bang questionnaire) with comorbidities identified. Patients suspected or diagnosed with OSA scheduled for ophthalmic surgery should have their comorbid conditions optimized. This article includes a review of the literature and highlights best perioperative anesthesia practices in the management of ophthalmic surgical patients with OSA.
Assuntos
Anestesia/métodos , Gerenciamento Clínico , Oftalmopatias/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Assistência Perioperatória/métodos , Apneia Obstrutiva do Sono/complicações , Oftalmopatias/complicações , HumanosRESUMO
OBJECTIVE: To compare the effects of fentanyl or remifentanil in combination with midazolam on hemodynamic parameters, pain, and satisfaction profile in cataract surgery. METHODS: This randomized, double blind, prospective study was conducted between 10 and 20th July 2005 at Kudret Eye Hospital, Ankara, Turkey. Patients scheduled for cataract surgery by the phacoemulsification technique were randomly enrolled to receive sedation with midazolam 1 mg intravenous iv either with fentanyl 25 microgram group 1, n=54 or remifentanil 0.3 microgram/kg group 2, n= 46. Heart rate, systolic and diastolic arterial pressure values were recorded as baseline, after retrobulbar injection, and during the operation. We evaluated recall of retrobulbar block, pain during injection and operation, satisfaction of patient and surgeon, and the adverse effects. RESULTS: There were statistically significant alterations in systolic and diastolic arterial pressure measurements within and between groups, whereas all kept in the clinically normal range. Twenty-four percent of patients in group 1 and 15.2% in group 2 did not even remember the retrobulbar injection. The pain scores during retrobulbar injection and operation were similar in both groups. Also, satisfaction of patients and surgeon was high and comparable between groups. CONCLUSION: Remifentanil and fentanyl are both efficient and comparable opioid adjuncts to midazolam providing low injection pain and high satisfaction level with hemodynamic stability in cataract surgery under retrobulbar injection.
Assuntos
Anestésicos Intravenosos/administração & dosagem , Fentanila/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Facoemulsificação/métodos , Piperidinas/administração & dosagem , Idoso , Método Duplo-Cego , Feminino , Humanos , Injeções , Masculino , Estudos Prospectivos , RemifentanilRESUMO
INTRODUCTION: Donor safety is one of the most important factors in living-donor liver transplantation. Duodenal ulcer (DU) is a common postoperative complication. Here we aimed to reveal the risk factors associated with postoperative DU in the donors. METHODS: Between April 2007 and March 2017, 318 cases underwent donor hepatectomy for liver transplantation at Kumamoto University Hospital. We classified the donors into two groups: a DU group and a non-DU group. DU was defined as mucosal break with unequivocal depth requiring an endoscopic procedure. The characteristics and clinical factors of the donors were retrospectively analyzed. RESULTS: Postoperative DU occurred in 17 donors during the study period. The mean interval after donor hepatectomy to occurrence of DU was 124.8 ± 185.4 days. The two groups were comparable in terms of age at time of the donor hepatectomy (P = .45). The male-to-female ratio (P = .03) was significantly different between the two groups and left-side hepatectomy was performed more often in the DU group (P = .003). Multivariable logistic regression revealed that left-side hepatectomy was independently associated with postoperative DU in the donors. CONCLUSIONS: These findings indicated that left-side hepatectomy is a risk factor for postoperative DU in the donors.
Assuntos
Úlcera Duodenal/etiologia , Hepatectomia/métodos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Complicações Pós-Operatórias/etiologia , Adulto , Feminino , Hepatectomia/efeitos adversos , Humanos , Fígado/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Coleta de Tecidos e Órgãos/efeitos adversos , Coleta de Tecidos e Órgãos/métodosRESUMO
Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.
Assuntos
Dantroleno/uso terapêutico , Heterozigoto , Proteínas de Membrana/genética , Proteínas Musculares/genética , Distrofias Musculares/genética , Mutação , Irmãos , Adolescente , Povo Asiático/genética , Disferlina , Feminino , Humanos , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/genética , Distrofias Musculares/diagnóstico , Distrofias Musculares/tratamento farmacológico , LinhagemRESUMO
BACKGROUND: Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an inherited disease characterized by cholestatic features. We report two patients with PFIC1 who underwent liver retransplantation. CASE REPORT: One patient was a 3-year-old female who underwent liver transplantation for PFIC1. She presented with severe diarrhea and fatty liver, and went into liver failure. She therefore underwent liver retransplantation and external biliary diversion 8 years after the initial liver transplantation. The explanted liver was histologically diagnosed with chronic rejection. Her intractable diarrhea stopped after the retransplantation. She was diagnosed with a fatty liver 8 months after the retransplantation and died 4 years after retransplantation due to bleeding from an ileostomy. The other patient was a 3-year-old male. This patient underwent liver retransplantation due to liver cirrhosis caused by steatohepatitis 9 years after the initial liver transplantation. The biliary tract was not diverted. He also experienced severe diarrhea after the retransplantation and requires home parenteral nutrition due to an eating disorder. CONCLUSIONS: Liver transplantation is the only treatment to resolve life-threatening issues due to PFIC1, but requires further improvement as a therapeutic modality.
Assuntos
Colestase Intra-Hepática/cirurgia , Transplante de Fígado/mortalidade , Doadores Vivos , Reoperação/mortalidade , Pré-Escolar , Fígado Gorduroso/etiologia , Feminino , Rejeição de Enxerto , Humanos , Cirrose Hepática/etiologia , Falência Hepática/etiologia , Transplante de Fígado/efeitos adversos , Masculino , Reoperação/efeitos adversosRESUMO
Patients with isolated peripheral branch neuralgia of trigeminal nerve usually receive traditional treatment such as medical therapy and interventional procedures targeting the entire trigeminal nerve or related ganglions. However, if the intractable pain is limited to a certain branch, the patient may also benefit from a peripheral and nerve-targeted interventional approach. Here, we report the management of a patient with isolated infraorbital neuralgia by ultrasound-guided infraorbital nerve block with steroid and local anesthetic combination. 48years-old male patient diagnosed with trigeminal neuralgia was resistant to medical therapy for 3years. The pain site was isolated to the area of the right nasal wing, right lateral incisor, the upper right canine and the first premolar teeth. His pain was an electric shock-like, throbbing and stabbing with a pain score of 8-9 according to numeric rating scale (NRS) and 18 according to the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS). Following a diagnostic ultrasound-guided infraorbital nerve block with 1% lidocaine, the block was repeated twice with 15mg lidocaine and 1.5mg dexamethasone in a total volume of 1.5mL in a month. The patient's NRS and LANSS scores decreased to 2 and 8, for approximately 21months until this report was written. We suggest that ultrasound-guided infraorbital nerve block with dexamethasone and lidocaine combination may present as an initial interventional treatment option in patients with isolated infraorbital neuralgia.
Assuntos
Anestésicos Locais/uso terapêutico , Glucocorticoides/uso terapêutico , Bloqueio Nervoso/métodos , Doenças Orbitárias/terapia , Manejo da Dor/métodos , Dor Intratável/terapia , Neuralgia do Trigêmeo/terapia , Anestésicos Locais/administração & dosagem , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Humanos , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Orbitárias/tratamento farmacológico , Doenças Orbitárias/cirurgia , Medição da Dor , Dor Intratável/tratamento farmacológico , Dor Intratável/cirurgia , Neuralgia do Trigêmeo/tratamento farmacológico , Neuralgia do Trigêmeo/cirurgia , Ultrassonografia de IntervençãoRESUMO
After several experimental campaigns in the Kyushu University Experiment with Steady-state Spherical Tokamak (QUEST), the originally stainless steel plasma-facing wall (PFW) becomes completely covered with a deposited film composed of mixture materials, such as iron, chromium, carbon, and tungsten. In this work, an innovative colorimetry-based method was developed to measure the thickness of the deposited film on the actual QUEST wall. Because the optical constants of the deposited film on the PFW were position-dependent and the extinction coefficient k1 was about 1.0-2.0, which made the probing light not penetrate through some thick deposited films, the colorimetry method developed can only provide a rough value range of thickness of the metal-containing film deposited on the actual PFW in QUEST. However, the use of colorimetry is of great benefit to large-area inspections and to radioactive materials in future fusion devices that will be strictly prohibited from being taken out of the limited area.
RESUMO
BACKGROUND: Distal myopathy with rimmed vacuoles (DMRV) is an autosomal-recessive disorder with preferential involvement of the tibialis anterior muscle that starts in young adulthood and spares quadriceps muscles. The disease locus has been mapped to chromosome 9p1-q1, the same region as the hereditary inclusion body myopathy (HIBM) locus. HIBM was originally described as rimmed vacuole myopathy sparing the quadriceps; therefore, the two diseases have been suspected to be allelic. Recently, HIBM was shown to be associated with the mutations in the gene encoding the bifunctional enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). OBJECTIVE: To determine whether DMRV and HIBM are allelic. METHODS: The GNE gene was sequenced in 34 patients with DMRV. The epimerase activity in lymphocytes from eight DMRV patients was also measured. RESULTS: The authors identified 27 unrelated DMRV patients with homozygous or compound-heterozygous mutations in the GNE gene. DMRV patients had markedly decreased epimerase activity. CONCLUSIONS: DMRV is allelic to HIBM. Various mutations are associated with DMRV in Japan. The loss-of-function mutations in the GNE gene appear to cause DMRV/HIBM.
Assuntos
Carboidratos Epimerases/genética , Proteínas de Escherichia coli , Músculo Esquelético/patologia , Doenças Musculares/genética , Doenças Musculares/patologia , Miosite de Corpos de Inclusão/genética , Miosite de Corpos de Inclusão/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Alelos , DNA/genética , DNA/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Ligação Genética/genética , Testes Genéticos , Humanos , Leucócitos/enzimologia , Músculo Esquelético/enzimologia , Músculo Esquelético/ultraestrutura , Doenças Musculares/enzimologia , Mutação/genética , Miosite de Corpos de Inclusão/enzimologia , Vacúolos/ultraestruturaRESUMO
Oxidant carcinogens interact with multiple cellular targets including membranes, proteins, and nucleic acids. They cause structural damage to DNA and have the potential to mutate cancer-related genes. At the same time, oxidants activate signal transduction pathways and alter the expression of growth- and differentiation-related genes. Indeed, the carcinogenic action of oxidants results from the superposition of these genetic and epigenetic effects. All cells possess elaborate antioxidant defense systems that consist of interacting low and high molecular weight components. Among them, superoxide dismutases (SOD), glutathione peroxidases (GPx), and catalase (CAT) play a central role. Our studies with mouse epidermal cells demonstrate that the balance between several antioxidant enzymes rather than the activity of a single component determines the degree of protection. Unexpectedly, increased levels of Cu,Zn-SOD alone in stable transfectants resulted in sensitization to oxidative chromosomal aberrations and DNA strand breaks. However, a concomitant increase in CAT or GPx in double transfectants corrected or overcorrected the hypersensitivity of the SOD clones depending on the ratios of activities CAT/SOD or GPx/SOD. The cellular antioxidant capacity also affected oxidant induction of the growth-related immediate early protooncogene c-fos. Increases in CAT or SOD reduced the accumulation of c-fos message, albeit for different reasons. The cellular antioxidant defense also affects the action of UVB light (290-320 nm) that represents the most potent carcinogenic wavelength range of the solar spectrum. UVB light is known to exert its action in part through oxidative mechanisms. Increases in CAT and GPx protected mouse epidermal cells from UVB-induced DNA breakage.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Neoplasias Experimentais/induzido quimicamente , Oxirredutases/fisiologia , Espécies Reativas de Oxigênio , Animais , Dano ao DNA , Regulação da Expressão Gênica , Humanos , Proto-Oncogenes , Raios UltravioletaRESUMO
An enhancing effect of L-histidine (L-His) was detected on the induction by hydrogen peroxide (H2O2) of chromosomal aberrations of both the chromosome type and the chromatid type, in human embryonic fibroblasts. The maximum efficiency of induction was about 8-fold higher in the presence of L-His than in the presence of H2O2 alone, at a concentration of L-His of 50 microM. D-His and DL-His showed lower enhancing effects than L-His, with approximately 2-fold and 5-fold enhancement of induction of chromosomal aberrations, respectively. L-Histidinol and L-His-methyl ester, among various derivatives of L-His tested, also enhanced this process. However, the effects of these derivatives were smaller than those of L-His in a range of concentrations equivalent to that of the most effective dose of L-His (50 microM), while they produced greater enhancement than L-His at concentrations higher than 200 microM. Other derivatives of L-His, such as L-carnosine, urocanic acid, imidazolepyruvic acid, 1-methyl-L-His, imidazolelactic acid, imidazoleacetic acid and histamine and imidazole itself did not enhance the frequency of chromosomal aberrations induced by H2O2. These results indicate that at least both the imidazole ring and the amino group are essential components of the chemical structure of L-His required for the enhancing effect. Moreover, in order to cause such an enhancing effect, L-His had to be applied together with H2O2 to cells, because the enhancing effect of L-His was not observed with cells which were washed after pretreatment with L-His. The preliminary study suggested that this enhancing effect depends on the His-peroxide adduct derived from L-His and H2O2. None of the amino acids tested other than His produced any enhancing effect on the induction of chromosomal aberrations by H2O2.
Assuntos
Aberrações Cromossômicas , Fibroblastos/efeitos dos fármacos , Histidina/farmacologia , Peróxido de Hidrogênio/farmacologia , Aminoácidos/farmacologia , Sinergismo Farmacológico , Embrião de Mamíferos , Embrião não Mamífero , Fibroblastos/ultraestrutura , Histidina/análogos & derivados , Histidinol/farmacologia , Relação Estrutura-Atividade , Fatores de TempoRESUMO
The cytogenetic effect of hydrogen peroxide (H2O2) was investigated in human embryonic fibroblasts. Chromosome-type aberrations were found together with chromatid-type aberrations in metaphase cells harvested 24 h after a single 10-min treatment with 10(-5)-10(-3) M H2O2 in 0.9% NaCl solution. The chromosome-type aberrations were observed to be predominantly dicentrics and deletions. Both types of aberration showed a dose-response relationship to the dose of H2O2 over the range of 10(-5)-1.5 X 10(-4) M H2O2. The intercellular distribution of dicentrics showed a Poisson distribution. Centric and acentric rings and abnormal monocentrics were a minor fraction of the chromosome-type aberrations. The chromatid-type aberrations observed, such as breaks, exchanges and gaps, showed no dose-response relationship. The frequency of isochromatid breaks was higher than that of chromatid breaks and approximately 70% of the isochromatid breaks were found in the centromeric or pericentromeric region. The intercellular distribution of chromatid exchanges showed an over-dispersed distribution. The generation of aberrations by H2O2 was effectively suppressed by catalase and several scavengers of hydroxyl radicals (.OH) such as ethanol, dimethyl sulfoxide (DMSO) and mannitol. This result suggest that .OH plays an essential role in the generation of the chromosome aberrations by H2O2.
Assuntos
Aberrações Cromossômicas , Fibroblastos/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Antioxidantes/farmacologia , Catalase/farmacologia , Células Cultivadas , Cromátides/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Embrião de Mamíferos , Humanos , PeleRESUMO
Crystals were prepared from a mixture of L-histidine (L-His) and hydrogen peroxide (H2O2) and tested for biological activity in human embryonic fibroblasts. The crystal structure was determined by X-ray diffraction to be that of an adduct, in which the H2O2 molecule forms a OH-N hydrogen bond with N delta of the side chain of L-His. A 10-min treatment with this adduct in solution (25-150 microM) induced more marked chromosomal aberrations and more single-strand breaks (SSB) in DNA than H2O2 itself, and these effects were generated in a dose-dependent manner. With respect to the induction of dicentric and ring chromosomes (Dic and Ring), a maximum frequency of 1.3 per cell was obtained at 75 microM. This maximum level of induction by the adduct was 6-7 times higher than that by H2O2 and was comparable to that by the mixture of L-His and H2O2 which we observed in our previous studies. The most effective dose for such induction by the adduct was also similar to that of L-His in the mixture. Cell growth was inhibited more strongly by the adduct than by H2O2 alone after a 60-min treatment at 75 microM, although there was not much difference between their effects after a 10-min treatment at 75 microM. The reactive factors derived from the adduct were the same as those in the mixture, and are suggested to be derivatives of H2O2, hydroxyl radicals (.OH) and/or singlet oxygen (1O2). Thus the patterns of induction and kinetics of the biological activities of the adduct were very similar to those of the mixture, but not to those of H2O2. These results suggest that the formation of the adduct plays an important role in the enhancement of the expression of the biological activity of H2O2 by the coadministration of L-His and H2O2, which we observed in our previous study.
Assuntos
Histidina/toxicidade , Peróxido de Hidrogênio/toxicidade , Catalase/farmacologia , Aberrações Cromossômicas , Cristalização , Dano ao DNA , DNA de Cadeia Simples/efeitos dos fármacos , Sinergismo Farmacológico , Sequestradores de Radicais Livres , Histidina/química , Difração de Raios XRESUMO
We report the outcome of trial of clenbuterol in four adult muscular dystrophy patients. One patient with Becker type, one with Miyoshi type, and two with facioscapulohumeral type were given clenbuterol (30 or 40 micrograms/day) for 6 to 18 months. We evaluated muscle strength of isometric contraction, grip and pinch power, compound muscle action potentials of intrinsic muscles, vital capacity, urinary creatinine excretion, and muscle CT. Power and volume of well preserved muscles increased mostly, while those of atrophic muscles did not improve. Vital capacity increased in two patients. No improvement of ADL was observed presumably because ADL was mainly determined by the most atrophic and weak muscles. Irrespective of type of muscular dystrophy, administration of clenbuterol may be beneficial in early stage of the disease.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Clembuterol/uso terapêutico , Distrofias Musculares/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/fisiopatologiaRESUMO
A 54-year-old patient with myotonic dystrophy presented unilateral painful gynecomastia, which occurred 3 months after aggravation of diabetes mellitus. Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were slightly high. LH was elevated than 2 years before. Breast pain and gynecomastia disappeared by daily administration of 10 mg tamoxifen. He could not have intramuscular injection therapy because of marked muscle atrophy. Painful gynecomastia may be one of the endocrine complications in myotonic dystrophy.