RESUMO
The symptoms of attention-deficit/hyperactivity disorder (ADHD) are characterized by inattention and hyperactivity-impulsivity. It is a common childhood neurodevelopmental disorder that often persists into adulthood. Improvements in ADHD symptoms using psychostimulants have been recognized as a paradoxical calming effect. The psychostimulant methylphenidate (MPH) is currently used as the first-line medication for the management of ADHD. Recent studies have drawn attention to altered dopamine-mediated neurotransmission in ADHD, particularly reuptake by the dopamine transporter (DAT). This hypothesis is supported by the observation that DAT knockout mice exhibit marked hyperactivity that is responsive to acute MPH treatment. However, other behaviors relevant to ADHD have not been fully clarified. In the present study, we observed learning impairment in shuttle-box avoidance behavior together with hyperactivity in a novel environment in DAT knockout mice. Methylphenidate normalized these behaviors and enhanced escape activity in the tail suspension test. Interestingly, the effective dose of MPH increased extracellular dopamine in the prefrontal cortex but not striatum, suggesting an important role for changes in prefrontal dopamine in ADHD. Research that uses rodent models such as DAT knockout mice may be useful for elucidating the pathophysiology of ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Inibidores da Captação de Dopamina/farmacologia , Dopamina/metabolismo , Metilfenidato/farmacologia , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Aprendizagem da Esquiva , Corpo Estriado/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora , Córtex Pré-Frontal/metabolismoRESUMO
Bipolar and major depressive disorders are essentially relapsing and remitting disorders of affect with nearly full recovery between episodes. Although the underlying molecular mechanisms remain unclear, myelin-related abnormalities have long been suspected. Here, using novel statistical analysis, we show that subtle but significant abnormalities exist in the composition of fatty acids (FAs), including docosapentaenoic acid (22:5n-3), one of the omega-3 polyunsaturated FAs, found in the post-mortem frontopolar cortex (FPC) of subjects with bipolar or major depressive disorders, although not in those with schizophrenia. These abnormalities were all aggravated in a myelin level-dependent manner, suggesting their close relationship with myelination. Animal studies have further revealed that chronic antidepressant treatment induces robust changes in brain FA metabolism, but contributes only part of the abnormalities found in the affective disorder brains. These findings indicate that the pathophysiology of affective disorders involves an unknown type of perturbed myelination in the FPC that may serve as a novel diagnostic and therapeutic target.
Assuntos
Ácidos Graxos/análise , Lobo Frontal/química , Transtornos do Humor/metabolismo , Adulto , Idoso , Animais , Transtorno Bipolar/metabolismo , Transtorno Depressivo Maior/metabolismo , Ácidos Graxos Insaturados/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/metabolismo , Mudanças Depois da Morte , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Esquizofrenia/metabolismoAssuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Próstata/metabolismo , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Idoso , Humanos , Infusões Intravenosas , Masculino , Meropeném , Estudos Prospectivos , Próstata/cirurgia , Tienamicinas/sangue , Ressecção Transuretral da PróstataRESUMO
We investigated the effects of a Chinese herbal medicine, Gosha-jinki-gan (GJG), on the regulation of insulin levels in rats fed a sucrose-rich diet (SRD). Normal Wistar rats in the SRD group were fed an SRD for 4 weeks. Increased dietary sucrose did not alter plasma glucose levels but it increased plasma insulin levels at 2 and 4 weeks in the SRD-fed rats relative to control rats that were fed standard chow. GJG treatment significantly suppressed the SRD-induced elevation in plasma insulin levels. These results suggest that GJG improves hyperinsulinemia caused by an SRD.
RESUMO
Hachimi-jio-gan (HJ) is a Chinese medicine that has been widely used for the treatment of nephrotic syndromes, hypertension, and diabetes mellitus. We reported that HJ lowers plasma glucose in type 1 diabetic rats. We investigated the effects of HJ on diabetic hyperglycemia and insulin secretion in type 2 diabetic Goto-Kakizaki (GK) rats. Eight-week-old diabetic GK rats were given free access to pellets containing 1% HJ extract powder for 14 weeks. HJ consumption increased the food intake and body weight of these rats in comparison to control rats. HJ may control the body weight loss observed in GK rats. HJ also reduced hyperglycemia in diabetic GK rats, and it significantly increased insulin secretion in non-fasting GK rats over the experimental period. In oral glucose tolerance tests, HJ significantly improved the insulin response at 30 min and reduced the plasma glucose level at 60 min after glucose administration (p < 0.05). Ten weeks after administration, the plasma leptin levels significantly increased in the HJ group rats. These results demonstrate that in diabetic GK rats, HJ decreased the level of postprandial glucose via enhanced insulin secretion coupled with the regulation of food intake by leptin.
Assuntos
Diabetes Mellitus Experimental , Medicina Herbária , Animais , Glicemia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2 , Insulina/sangue , Ratos , Ratos WistarRESUMO
BACKGROUND AND STUDY AIMS: Hot saline may be potentially useful for inducing necrosis of pancreatic tissue. However, the local and systemic effects are largely unknown. This pilot study aimed to evaluate the feasibility and safety of EUS-guided injection of hot saline into the pancreas in the porcine model. METHODS: Boiling hot saline was injected into the tail of normal porcine pancreas under EUS guidance in six pigs via a transgastric approach. Three pigs were killed 4 hours later to study the acute effect of the hot saline injection (acute study). The remaining three pigs were killed after 7 days of clinical observation (survival study). RESULT: Injection of 5 mL, 2 mL and 1 mL of hot saline produced localized necrosis (7 - 10 mm) of pancreatic tissue in the acute study. However, there was pooling of hot saline on the surface of the pancreas when 5mL was injected. On the basis of the results of the acute study, the volume of hot saline injected in the survival study was 1 mL. One milliliter of hot saline produced localized or sporadic necrosis of pancreatic tissue without any signs of pancreatitis in all three pigs in the survival study; hot saline was observed to pool on the pancreatic surface of one pig. There was no histological evidence of necrosis in the pancreatic tissue adjacent to the pooled hot saline in either the acute or the survival study. CONCLUSION: EUS-guided hot saline injection of pancreatic tissue in the porcine model was technically successful and led to localized necrosis of pancreatic tissue without any sign of pancreatitis.
Assuntos
Endossonografia , Hipertermia Induzida/métodos , Pâncreas/patologia , Cloreto de Sódio/administração & dosagem , Animais , Estudos de Viabilidade , Injeções Intralesionais , Necrose/etiologia , Necrose/patologia , Projetos Piloto , SuínosRESUMO
The autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by diverse mutations in one allele of the gene that encodes the arginine vasopressin (AVP) precursor protein, AVP-neurophysin II (AVP-NP II). Most of the mutations identified so far are located in either the signal peptide or NP II moiety. Two recently published mutations in the AVP gene identified in kindreds with adFNDI predict a substitution of histidine for tyrosine at position 2 and a deletion of phenylalanine at position 3 in AVP. They are unique among adFNDI mutations in that they are the only adFNDI mutations that affect amino acid residues in the AVP moiety of the pro-hormone. Here, we report a novel heterozygous missense mutation in the AVP moiety of the AVP-NP II gene in a Japanese person with neurohypophyseal diabetes insipidus (DI). This mutation occurs at position 2 in AVP and predicts a substitution of serine for tyrosine (Y21S). It is expected to interfere with normal binding of AVP with NP II, and thus result in misfolding of the precursor proteins. The data of this study support the notion that mutations affecting the AVP moiety can result in the initiation of the pathological processes.
Assuntos
Arginina Vasopressina/genética , Diabetes Insípido Neurogênico/genética , Heterozigoto , Mutação de Sentido Incorreto , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Arginina Vasopressina/química , Sequência de Bases , Diabetes Insípido Neurogênico/patologia , Humanos , Hipotálamo/patologia , Japão , Imageamento por Ressonância Magnética , Masculino , Neurofisinas/genética , Linhagem , Hipófise/patologia , Precursores de Proteínas/genética , Vasopressinas/genéticaRESUMO
Barrett's oesophagus is considered to increase the risk of cancer 30-fold. Helical microwave antennas have been developed for ablative treatment of Barrett's. A microwave balloon applicator was tested in an initial animal study using adult white pigs. For treatment, a balloon filled with tissue-equivalent material encapsulated the antenna. A range of different treatment temperatures and durations was used to investigate a range of thermal ablations of the oesophageal epithelium. Eight animals were investigated, five non-survival and three with a 1-week survival period. The balloon was fitted with an array of temperature sensors, which gave an indication of the treatment in situ and allowed modifications to be performed in real time. Temperature data were recorded from all four quadrants of the balloon throughout and test sites were collected and analysed histologically. All experiments were successfully completed without perforation, serious adverse effects or death. Sites of discrete ulceration were induced in the survival tests, whereas the non-survival tests yielded little reproducible tissue modification. Results suggested that an activation temperature of approximately 55 degrees C needed to be reached during the treatment for tissue damage to be induced. Once damage had been triggered the severity was related to the mean temperature attained during the treatment period. A mean temperature of 52 degrees C or more resulted in substantial damage, whilst a mean temperature of approximately 50 degrees C resulted in the desired surface damage with sparing of subjacent tissues.
Assuntos
Esôfago de Barrett/fisiopatologia , Esôfago/patologia , Hipertermia Induzida , Animais , Técnicas Biossensoriais , Suínos , Úlcera/patologiaRESUMO
OBJECTIVES: To compare dietary habits and percent compositions of omega (omega)-3 fatty acid (FA) in plasma phospholipids and to examine if there is any association between fish intake and selected coronary disease risk (CHD) factors in this population. DESIGN: Cross sectional population study. SETTING: Three areas in Tanzania: urban Dar es Salaam (D), rural Handeni (H) and pastoralist population of Maasai in Moduli (Mo). SUBJECTS: One hundred and five participants (Dar 36, Handeni 37 and Monduli 32) aged 47-57 years. MAIN OUTCOME MEASURES: Fatty acids composition in plasma phospholipids. RESULTS: The frequency of intake of fish, meat, coconut milk and fruits was higher in Dar than in Handeni or Monduli (all p< 0.0001). The Maasai from Monduli had the highest percentage consumption of milk in a week (p<0.0001) and lowest intake of fish (p<0.0001). Participants from Handeni had the highest prevalence of consumption of green vegetables (p<0.0001). Percent compositions of arachidonic acid (AA; C20: 4omega-6) and docosahexaenoic acid (DHA; C22: 6omega-3) in plasma phospholipids were the lowest in Monduli (p<0.0001). Selected coronary disease risk factors were higher in the urban area Dar. The frequency of intake of fish per week correlated negatively with total cholesterol (TC) and LDL-C and HBA1c percent but not with blood pressure. The percent composition of omega-3 FA in plasma phospholipids was positively correlated with the frequency of intake of fish a week. CONCLUSION: Our results indicate that, there are significant differences in dietary patterns among the three study areas, and that the intake of fish is inversely associated with selected risk factors for coronary heart disease.
Assuntos
Doença das Coronárias/prevenção & controle , Ácidos Graxos Ômega-3/sangue , Comportamento Alimentar , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TanzâniaRESUMO
The purpose of this study is to investigate the diagnostic value of evoked spinal cord potentials (ESCPs) and choline acetyltransferase (CAT) activity during exploration of injuries to the brachial plexus. We assessed 25 spinal roots in 19 patients. The results of the two investigations were consistent in all except two roots. Although assessment of ESCPs is easy and quick, it mainly records the nerve potentials along the sensory pathway. Although measurement of CAT activity needs a specimen of the nerve and the availability of a radioisotope laboratory, it gives direct information regarding the motor function of ventral spinal roots. These two techniques should be complementary to each other in order to achieve a more accurate diagnosis.
Assuntos
Plexo Braquial/lesões , Colina O-Acetiltransferase/metabolismo , Adolescente , Adulto , Plexo Braquial/enzimologia , Criança , Pré-Escolar , Potenciais Evocados , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Research and development of the adenosine A2A receptor selective antagonist KW6002 have focused on developing a novel nondopaminergic therapy for Parkinson's disease (PD). Salient pharmacologic features of KW6002 were investigated in several animal models of PD. In rodent and primate models, KW6002 provides symptomatic relief from parkinsonian motor deficits without provoking dyskinesia or exacerbating existing dyskinesias. The major target neurons of the A2A receptor antagonist were identified as GABAergic striatopallidal medium spiny neurons. A possible mechanism of A2A receptor antagonist action in PD has been proposed based on the involvement of striatal and pallidal presynaptic A2A receptors in the "dual" modulation of GABAergic synaptic transmission. Experiments with dopamine D2 receptor knockout mice showed that A2A receptors can function and anti-PD activities of A2A antagonists can occur independent of the dopaminergic system. Clinical studies of KW6002 in patients with advanced PD with L-dopa-related motor complications yielded promising results with regard to motor symptom relief without motor side effects. The development of KW6002 represents the first time that a concept gleaned from A2A biologic research has been applied successfully to "proof of concept" clinical studies. The selective A2A antagonist should provide a novel nondopaminergic approach to PD therapy.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Transtornos Parkinsonianos/tratamento farmacológico , Purinas/uso terapêutico , Animais , Antiparkinsonianos/efeitos adversos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Corpo Estriado/citologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Discinesia Induzida por Medicamentos/prevenção & controle , Globo Pálido/citologia , Globo Pálido/efeitos dos fármacos , Globo Pálido/metabolismo , Humanos , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Primatas , Ratos , Receptor A2A de Adenosina/metabolismo , Receptores de Dopamina D2/deficiência , Receptores de Dopamina D2/genética , Ácido gama-Aminobutírico/metabolismoRESUMO
Trimethyltin (TMT) preferentially induces neuronal changes in the hippocampus and pyriform cortex. In the present study we investigated the time course of microglial and astroglial responses associated with neurodegeneration after the administration of TMT (i.p. 9 mg/kg or 12 mg/kg body weight) in the rat. At a dosage of 9 mg/kg TMT, neurodegeneration was clearly demonstrated in the CA1 and CA3 regions of the hippocampus as argyrophilic (dark) neurons by day 4 using the Gallyas-Braak (G-B) impregnation method that has been shown to be sensitive and specific for neurodegeneration. Early microglial response was immunohistochemically shown with anti-microglial response factor-1 (MRF-1) antibody in the CA3 by day 1, preceding neurodegeneration morphologically detected by the G-B method. Activation of astrocytes was revealed by immunohistochemical staining for glial fibrillary acidic protein (GFAP) by day 2. In parallel with the maximal neurodegeneration, large numbers of hypertrophied microglia and astrocytes were observed in the CA1 and CA3 by day 7. Numbers of degenerative neurons appeared to be closely associated with adjacent microglia by the double staining of G-B impregnation and MRF-1 immunohistochemistry. The number of reactive microglia considerably decreased to the resting state by day 14, while hypertrophied astrocytes were still prominent in the CA3 up to day 21. With the high dose of TMT, granule cells in the dentate gyrus and CA1 and CA3 pyramidal cells were significantly impregnated. After TMT treatment, accompaning neurodegeneration we observed early response of microglia and prolonged activation of astrocytes, suggesting an individual role of glial cells in maintenance and repair of damaged neurons following brain injury.
Assuntos
Astrócitos/efeitos dos fármacos , Gliose/induzido quimicamente , Hipocampo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Degeneração Neural/induzido quimicamente , Regeneração Nervosa/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Compostos de Trimetilestanho/toxicidade , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Proteínas de Ligação ao Cálcio , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Gliose/fisiopatologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Imuno-Histoquímica , Masculino , Proteínas dos Microfilamentos , Microglia/metabolismo , Microglia/patologia , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-DawleyRESUMO
We previously reported that vascularized bone allograft using immunosuppressants, such as cyclosporine A (CsA), is one approach for reconstruction of large bone defects in both experimental animals (Microsurgery 15:663; 1994) and clinically in humans (Lancet 347:970, 1996). Because immunosuppressive agents such as CsA induce significant side effects, including bone loss, other therapeutic agents supporting successful vascularized bone allografts have been sought after. We investigated the effects of 22-oxa-1,25-dihydroxyvitamin D(3) (OCT) on vascularized bone allograft, and compared its effects with CsA. Twelve-week-old DA rats with the major histocompatibility antigen (MHC) RT-1(a) were used as donors and age-matched Lewis rats with MHC RT-1(l) used as recipients. Allografted bones in rats treated with vehicle were rejected completely. Soft X-ray examination demonstrated that administration of OCT (0.5 microg/kg per day) for 12 weeks after bone graft induced bone union as effective as treatment for 12 weeks with CsA (10 mg/kg per day). Transplanted bones in OCT-treated rats showed higher bone mineral density than that in CsA-treated rats. Histologically, transplanted bones in OCT-treated rats at 12 weeks were nonvital, but these bones united with recipient vital bones. After cessation of 12 week treatment with OCT, new bone formation occurred around the grafted nonvital bones during a 9 month period. Transplanted bones in CsA-treated rats were vital and formed union with recipient bones, whereas cortical bones became thin when compared with nonvital bones in OCT-treated rats. Urinary deoxypyridinoline levels in rats treated with CsA were significantly higher than levels in rats treated with OCT, suggesting accelerated bone resorption in CsA-treated rats. These results suggest that OCT exerts an anabolic action on bone reconstruction by allogeneic bone transplantation.
Assuntos
Antineoplásicos/farmacologia , Transplante Ósseo , Calcitriol/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Tíbia/transplante , Aminoácidos/urina , Animais , Fios Ortopédicos , Calcitriol/análogos & derivados , Cálcio/sangue , Ciclosporina/farmacologia , Fíbula/irrigação sanguínea , Fíbula/patologia , Fíbula/transplante , Imunossupressores/farmacologia , Masculino , Fósforo/sangue , Ratos , Ratos Endogâmicos Lew , Tíbia/irrigação sanguínea , Tíbia/patologia , Transplante HomólogoRESUMO
We investigated the inhibitory effect of Magnolia obovata Thunb. bark ethanol extracts on human fibrosarcoma HT-1080 cells invasion in a reconstituted basement membrane [Matrigel (MG)]. We found that the effective components of the bark ethanol extracts were magnolol and honokiol, two biphenyl compounds. The extracts, magnolol and honokiol, did not affect HT-1080 cells adhesion to MG, but did inhibit HT-1080 cells migration at a high concentration (100 microM). HT-1080 cells secrete matrix metalloproteinase (MMP)-9, which degrades the extracellular matrix as a part of the invasive process. Magnolol and honokiol inhibited the activity of MMP-9, which may have been responsible, in part, for the inhibition of tumor cell invasiveness.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Fibrossarcoma/tratamento farmacológico , Lignanas , Magnoliaceae , Compostos de Bifenilo/química , Humanos , Magnoliaceae/química , Inibidores de Metaloproteinases de Matriz , Invasividade Neoplásica , Fitoterapia , Casca de Planta/química , Células Tumorais CultivadasRESUMO
A variety of intracranial self-stimulation (ICSS) paradigms have been utilized for investigations of reward. Among them, nose-poking and spatial-preference paradigms are known to be relatively more resistant to the effects of drug-induced motor-deficits in rat studies, although these two ICSS paradigms have not been directly compared in previous studies. In the present study, head-dipping and place-learning (forms of nose-poking and spatial-preference tasks, respectively) paradigms with lateral hypothalamus stimulation were systematically analyzed using C57BL/6 mice in the presence and absence of two motor-deficit-inducing drugs: tolperisone and harmaline. Rapid acquisition and rapid extinction patterns of ICSS responding were observed in the head-dipping and place-learning paradigms. In contrast to these pre-drug similarities in responding, dramatic differences were noted after drug administration. Tolperisone significantly reduced head-dipping but not place-learning ICSS responding. Similarly, reduction of ICSS responding after harmaline was more pronounced in the head-dipping task. Therefore, the place-learning paradigm may be superior for the assessment of reward values under motor-deficit-inducing conditions in C57BL/6 mice. The relative benefits and disadvantages of both ICSS paradigms are discussed. Combinations of complementary ICSS paradigms using mice may be useful for further investigations of the molecular bases of reward.
Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Clássico/fisiologia , Atividade Motora/fisiologia , Autoestimulação/fisiologia , Meio Social , Comportamento Estereotipado/fisiologia , Animais , Aprendizagem por Associação/fisiologia , Mapeamento Encefálico , Estimulação Elétrica , Hipotálamo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MotivaçãoRESUMO
New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.
Assuntos
Alcaloides/isolamento & purificação , Bombyx/química , Glicosídeo Hidrolases/antagonistas & inibidores , Folhas de Planta/química , Animais , Bombyx/enzimologia , Cromatografia por Troca Iônica , Diabetes Mellitus/tratamento farmacológico , Glicosídeo Hidrolases/metabolismo , Humanos , Hidroxilação , Fitoterapia , Folhas de Planta/metabolismo , Plantas Medicinais/uso terapêuticoRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic variceal ligation (EVL) is an alternative to sclerotherapy for the treatment of esophageal varices, but is associated with higher rates of recurrence and subsequent bleeding than sclerotherapy. To prevent recurrence of varices after EVL, we have developed a low-dose diode laser therapy combined with the injection of indocyanine green, which allows enhanced tissue absorption of the laser beam selectively around varices. In this study we investigated the efficacy and safety of this technique. PATIENTS AND METHODS: Eight patients with F2 or F3 esophageal varices were enrolled. At 1 week after EVL, indocyanine green solution (1 mg/ml) was injected submucosally around the remaining varices. A diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. The spot size was kept to 5 mm in diameter. RESULTS: Laser irradiation was performed safely, without bleeding from the varices, or perforation. There were no major complications. Endoscopy 1 month later showed F0 forms in seven patients, F1 in one patient, and no red color sign in any patient. No recurrence of varices has been observed in any of the patients during the follow-up period of at least 12 months. CONCLUSION: This technique may provide a simple, safe and effective procedure, as an additional treatment to EVL, for the prevention of recurrence of esophageal varices.
Assuntos
Corantes/administração & dosagem , Varizes Esofágicas e Gástricas/radioterapia , Verde de Indocianina/administração & dosagem , Terapia com Luz de Baixa Intensidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Animais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Regulação da Expressão Gênica , Humanos , Expectativa de Vida , Masculino , Inquéritos Nutricionais , Estado Nutricional , Estresse Oxidativo , Fenótipo , Ratos , Ratos Endogâmicos SHR , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/efeitos adversosRESUMO
Ultrapremature babies accompanied by intrauterine growth retardation may require supplemental calcium and phosphorus far above the recommended doses.
Assuntos
Compostos de Cálcio/administração & dosagem , Desenvolvimento Infantil/fisiologia , Suplementos Nutricionais , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Fósforo/administração & dosagem , Adulto , Osso e Ossos/efeitos dos fármacos , Cesárea , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Seguimentos , Humanos , Recém-Nascido , Gravidez , Resultado do Tratamento , Ultrassonografia Pré-Natal/métodos , Aumento de PesoRESUMO
In mammals, lipoate-activating enzyme (LAE) catalyzes the activation of lipoate to lipoyl-nucleoside monophosphate. The lipoyl moiety is then transferred to the specific lysine residue of lipoate-dependent enzymes by the action of lipoyltransferase. We purified LAE from bovine liver mitochondria to apparent homogeneity. LAE activated lipoate with GTP at a 1000-fold higher rate than with ATP. The reaction absolutely required lipoate, GTP, and Mg(2+) ion, and the reaction product was lipoyl-GMP. LAE activated both (R)- and (S)-lipoate to the respective lipoyl-GMP, although a preference for (R)-lipoate was observed. Similarly, lipoyltransferase equally transferred both the (R)- and (S)-lipoyl moieties from the respectively activated lipoates to apoH-protein. Interestingly, however, only H-protein carrying (R)-lipoate was active in the glycine cleavage reaction. cDNA clones encoding a precursor LAE with a mitochondrial presequence were isolated. The predicted amino acid sequence of LAE is identical with that of xenobiotic-metabolizing/medium-chain fatty acid:CoA ligase-III, but an amino acid substitution due to a single nucleotide polymorphism was found. These results indicate that the medium-chain acyl-CoA synthetase in mitochondria has a novel function, the activation of lipoate with GTP.