RESUMO
PURPOSE: To understand the characteristics of DNA damage induced by Auger effect in DNA by ultrasoft X-irradiation. In situ electron paramagnetic resonance (EPR) spectroscopy as well as biochemical analysis has been applied to examine the DNA damage induction in both viewpoints of intermediate species and final products. MATERIALS AND METHODS: Unpaired electron species induced in a calf thymus DNA film irradiated with monochromatic ultrasoft X-rays (270-580 eV) was observed using an X-band EPR spectrometer installed in a synchrotron beamline. To determine the yield of single strand break (SSB), pUC18 plasmid DNA was irradiated and then analyzed by agarose gel electrophoresis. To analyze molecular change in a single strand DNA, a new technique using DNA-denaturation-treatment has been applied to quantify multiple SSB arising in both DNA strands. RESULTS: Short-lived EPR spectra were observed during irradiation. The intensity of transient EPR spectrum shows the similar energy dependence with that of the SSB yield around oxygen K-edge in particular. The fraction of the single-strand plasmid DNA (SS-DNA) after irradiation could be determined using a low-temperature-denaturation condition. The obtained slope of the dose-response for SS-DNA shows half of that of closed circular DNA as expected under the diluted solution condition. CONCLUSION: The availability of an EPR apparatus installed in a synchrotron beamline is demonstrated by detecting very short-lived unpaired electron species. Transient EPR spectra of DNA show the similar energy dependence to that of the SSB yield. The proposed DNA-denaturation assay works as expected using the low-temperature-denaturation condition.
Assuntos
Dano ao DNA , DNA/efeitos da radiação , DNA de Cadeia Simples/química , DNA de Cadeia Simples/efeitos da radiação , Espectroscopia de Ressonância de Spin Eletrônica , Eletroforese em Gel de Ágar , Conformação de Ácido Nucleico , Raios XRESUMO
PURPOSE: Hot flash (HF) is a common side effect in prostate cancer patient undergoing androgen-deprivation therapy (ADT). In this study, we evaluated the efficacy of paroxetine (selective serotonin reuptake inhibitors (SSRIs)) for HF. PATIENTS AND METHODS: In total, 10 men with prostate cancer under ADH who were suffering with HF entered this study. Self-report questionnaire was used for the evaluation. RESULTS: The average rating for HF frequency decreased (P=0.009) and HF severity decreased (P=0.0332) also, reported QOL score increased (P=0.0218). CONCLUSION: These preliminary data suggest that low dose (10 mg/day) of antidepressant paroxetine can be helpful in the treatment of HFs in patients under ADT for prostate cancer. Further controlled studies are needed to more fully evaluate the efficacy of the SSRIs.
Assuntos
Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Carcinoma/tratamento farmacológico , Fogachos/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Relação Dose-Resposta a Droga , Fogachos/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Paroxetina/administração & dosagem , Paroxetina/efeitos adversos , Paroxetina/uso terapêutico , Projetos PilotoRESUMO
We investigate edge state transmission in quantum point contacts (QPCs) in the fractional quantum-Hall regime, finding behavior reminiscent of a metal-insulator transition. The transition is suggested by an unusual behavior of the differential conductance in the fractional-quantum-Hall regime, and by the presence of a fixed point and universal scaling in the temperature dependence of the linear conductance. Noting that the 0.7 feature evolves continuously into a last fractional plateau at high magnetic fields, we suggest that this still unresolved feature may itself be viewed as a manifestation of a local, microscopic, metal-insulator transition.
RESUMO
A gene for prokaryotic pyruvate carboxylase (PC) was cloned from Bacillus stearothermophilus. It has an open reading frame of 3441 base pairs which can code for a protein of 128,353 Da. Not only the molecular size and domain organization but also the deduced amino acid sequence of B. stearothermophilus PC are similar to those of eukaryotic PCs.
Assuntos
Geobacillus stearothermophilus/enzimologia , Piruvato Carboxilase/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , DNA Bacteriano , Geobacillus stearothermophilus/classificação , Dados de Sequência Molecular , FilogeniaRESUMO
Recordings of noxious intra-arterial bradykinin (BK)-induced chemonociceptive and spontaneous activity from 30 single spinal lamina V neurones of the dorsal horns in non-anaesthetized and decerebrated rabbits, were performed with tungsten microelectrodes. Intravenous injection of midazolam (0.2 mg/kg; 7 neurones) depressed BK-induced neural discharges by 55.0 +/- 6.2% (P less than 0.05) and 57.9 +/- 8.4% (P less than 0.05) 5 and 25 min after administration, respectively. Treatment with flumazenil (0.2 mg/kg, i.v.; 7 neurones), administered 20 min after midazolam, completely reversed the inhibition by midazolam of the BK-induced spinal lamina V neural responses and spontaneous neuronal activity. In contrast, a large dose of naloxone (1.0 mg/kg, i.v.; 6 neurones), administered 20 min after midazolam, failed to alter the midazolam-induced depressant effects on the nociceptive responses, at the spinal dorsal horn. Treatments with flumazenil (5 neurones) and naloxone (5 neurones) did not influence either the spontaneous or the BK-induced neuronal discharges, recorded in spinal lamina V cells. Midazolam depressed the nociceptive responses probably through its agonistic activity on the binding to the GABA-benzodiazepine-barbiturate system in the spinal dorsal horn.
Assuntos
Midazolam/farmacologia , Neurônios/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Animais , Bradicinina/farmacologia , Estado de Descerebração , Flunitrazepam/farmacologia , Microeletrodos , Naloxona/farmacologia , Dor/induzido quimicamente , Coelhos , Medula Espinal/citologiaRESUMO
The distribution, ontogeny and fiber projections of cholecystokinin-8, vasoactive intestinal polypeptide and gamma-aminobutyrate-containing neuronal systems in the rat spinal cord were investigated by means of immunocytochemistry. Immunoreactive fibers to cholecystokinin-8, vasoactive intestinal polypeptide and glutamate decarboxylase (gamma-aminobutyrate-synthesizing enzyme, used as a marker of gamma-aminobutyrate) were widely distributed in the spinal cord, being particularly concentrated in the superficial dorsal horn, suggesting a close relationship to the pain transmission system. Cholecystokinin-8-containing neurons were mostly distributed in the dorsal laminae and glutamate decarboxylase-containing neurons were distributed in both the dorsal and ventral horns. Vasoactive intestinal polypeptide-containing neurons were detected in the lateral spinal nucleus and the lamina X. Cholecystokinin-8 and vasoactive intestinal polypeptide immunoreactive structures first appeared on gestational day 17-18. Although no substantial change in immunoreactive structures was observed during the fetal period, they increased markedly after birth. On the other hand, glutamate decarboxylase-positive structures appeared at gestational day 16 and those in the grey matter reached a maximum content at birth; both groups were present in adult animals. Transection of the upper cervical cord resulted in accumulations of cholecystokinin-8 and glutamate decarboxylase rostral to the lesion, revealing the presence of supraspinal projections of cholecystokinin-8 and glutamate decarboxylase to the spinal cord. The same experimental procedure demonstrated the existence of vasoactive intestinal polypeptide-mediating neuronal projections to the supraspinal level, as the accumulating fibers occurred in the area caudal to the lesion.
Assuntos
Sincalida/metabolismo , Medula Espinal/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Feminino , Imunofluorescência , Glutamato Descarboxilase/metabolismo , Masculino , Vias Neurais/anatomia & histologia , Ratos , Medula Espinal/anatomia & histologia , Medula Espinal/crescimento & desenvolvimentoRESUMO
[figure: see text] Configurationally defined optically active octinaphthalenes were synthesized using the oxidative coupling of optically active quaternaphthalenes with a 2-hydroxynaphthol moiety as a key reaction. The absolute configuration was determined by comparison with products of [6 + 2] coupling.
RESUMO
[structure: see text] A hybrid molecule 1 consisting of phenolphthalein and two crown ether moieties can be used to discriminate the length of linear triamines strictly by color development. The purple color is developed most deeply at -10 degrees C and fades with either an increase or decrease in temperature.
RESUMO
[structure: see text] Optically active artificial host molecules 2-5 based on a phenolphthalein skeleton have been prepared for visual enantiomeric recognition of alanine derivatives 8 and 9. The receptor 3 discriminates (R)-8 and (R)-9 from (S)-8 and (S)-9, respectively, to develop a purple color.
RESUMO
[reaction: see text] alpha-Methylation of 3 gave 5 as a major product whereas 4 gave 6 predominantly, although both 3 and 4 have an (S)-chiral center at C(3). This indicates that chirality at C(2) in 3 and 4 was memorized in the corresponding intermediate enolates and the induced chirality made a major contribution in the stereochemical course of the reaction, while chirality at the adjacent chiral center C(3) had little effect.
Assuntos
Isoleucina/análogos & derivados , Isoleucina/química , Alquilação , Cristalografia por Raios X , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , EstereoisomerismoRESUMO
The degeneration of cholinergic neurons may be responsible for cognitive impairment in patients with Alzheimer's disease (AD). Since nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system, this factor may have some beneficial effects on the cognitive impairment observed in patients with AD. However, since NGF does not cross the blood-brain barrier and is easily metabolized when administered peripherally, it can only be used when directly injected into the brain. In this review, we show that repeated oral administration of the NGF synthesis stimulators, idebenone and propentofylline, partially restored the age-associated decrease of NGF in the frontal and parietal cortices. Furthermore, this treatment attenuated the impairment of performance in the water maze, passive avoidance, and habituation tasks in rats with bilateral forebrain lesions, and in rats which had received continuous infusion of anti-NGF antibody into the septum. The behavioral improvement induced by idebenone and propentofylline was accompanied by recovery of both the reduced activity of choline acetyltransferase and the changes in [3H]QNB binding. These results suggest that the use of NGF synthesis stimulators may provide a novel therapeutic approach to cholinergic dysfunction.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Benzoquinonas/uso terapêutico , Fatores de Crescimento Neural/antagonistas & inibidores , Fatores de Crescimento Neural/biossíntese , Nootrópicos/uso terapêutico , Xantinas/uso terapêutico , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Benzoquinonas/farmacologia , Humanos , Nootrópicos/farmacologia , Ratos , Ubiquinona/análogos & derivados , Xantinas/farmacologiaRESUMO
The effects of repeated propentofylline administration on impairments of learning and memory in rats with basal forebrain lesions were investigated in several behavioral tasks (water maze, habituation and passive avoidance tasks). Rats were subjected to all the tasks in sequence. Basal forebrain lesions produced by bilateral injections of ibotenic acid (approximately 6 micrograms on each side) severely impaired performance in water maze, habituation and passive avoidance tasks. Repeated administration of propentofylline (10 and 25 mg/kg per day for 14 days, p.o.) improved the deficits of performance in a water maze task, even when administration began one week after the basal forebrain lesions were produced. The impaired performance in habituation and passive avoidance tasks was also markedly ameliorated after repeated administration (24 and 26 days) of propentofylline. The rats with basal forebrain lesions exhibited a significant decrease in choline acetyltransferase activity in the cortex. Propentofylline significantly increased hippocampal choline acetyltransferase activity in basal forebrain-lesioned rats compared with that in vehicle-treated basal forebrain-lesioned rats. However, cortical choline acetyltransferase activity in basal forebrain-lesioned animals was not affected by repeated propentofylline administration. These results indicate that repeated administration of this agent ameliorated the impaired performance of basal forebrain-lesioned rats in part by increasing hippocampal choline acetyltransferase activity. Propentofylline might be useful for the treatment of amnesia and dementia.
Assuntos
Amnésia/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Ácido Ibotênico/toxicidade , Prosencéfalo/efeitos dos fármacos , Xantinas/farmacologia , Amnésia/induzido quimicamente , Análise de Variância , Animais , Encéfalo/enzimologia , Colina O-Acetiltransferase/metabolismo , Masculino , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Wistar , Xantinas/administração & dosagemRESUMO
The effects of naftidrofuryl oxalate (LS-121) on 5-HT2 receptors in the brain were assessed in mice on the basis of quantitative autoradiography and head-twitch responses. LS-121 inhibited [3H]ketanserin (2 nM) binding in all brain areas assayed in which there were 5-HT2 receptors, such as the frontal cortex, cingulate cortex, parietal cortex, occipital cortex, temporal cortex, nucleus accumbens, caudate-putamen, olfactory tubercle and hippocampus. In the frontal cortex, which has the highest density of 5-HT2 receptors, the Ki value of LS-121 was 6.08 x 10(-8) M. The inhibitory potencies of methysergide and ritanserin for 5-HT2 receptors were about 16- and 60-fold stronger, respectively, than that of LS-121. Moreover, in behavioral studies, LS-121 (12.5-50 mg/kg i.p.) produced dose-dependent and significant inhibitory effects on head twitches induced by 5-hydroxytryptophan (5-HTP) plus pargyline, which is a 5-HT2 receptor-dependent behavior in mice. These results suggest that LS-121 inhibits 5-HTP plus pargyline-induced head twitches by blocking 5-HT2 receptors.
Assuntos
Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Ketanserina/metabolismo , Nafronil/farmacologia , Receptores de Serotonina/efeitos dos fármacos , 5-Hidroxitriptofano/farmacologia , Animais , Autorradiografia , Sítios de Ligação , Relação Dose-Resposta a Droga , Masculino , Metisergida/farmacologia , Camundongos , Pargilina/farmacologia , Receptores de Serotonina/metabolismo , Ritanserina/farmacologia , Distribuição TecidualRESUMO
Acute intrastriatal injection of quinolinic acid (QA) caused a significant reduction of choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities as well as a decrease of the specific binding of [3H]hemicholinium-3. Pretreatment with MK-801 completely blocked the QA-induced neurotoxicity. Continuous infusion of QA into the lateral ventricle resulted in a reduction of hippocampal and cortical ChAT activities while GAD activities were unchanged. These results suggest that continuous infusion of QA into the lateral ventricle could be a useful technique for the study of chronic neurodegenerative diseases including Alzheimer's disease.
Assuntos
Doenças do Sistema Nervoso/induzido quimicamente , Ácidos Quinolínicos/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Colina O-Acetiltransferase/metabolismo , Corpo Estriado , Maleato de Dizocilpina/farmacologia , Glutamato Descarboxilase/metabolismo , Hemicolínio 3/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Injeções , Injeções Intraventriculares , Masculino , Doenças do Sistema Nervoso/fisiopatologia , Ácido Quinolínico , Ácidos Quinolínicos/administração & dosagem , Ratos , Ratos EndogâmicosRESUMO
The distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactive structures in the rat spinal cord and their projections were investigated by means of an immunofluorescent method. In the normal rat, a small number of VIP-positive fibers were observed in the superficial layer of the dorsal horn and in the lateral funiculus. With colchicine pretreatment, VIP-positive neurons were demonstrated in the lateral spinal nucleus (lsn) and in the lamina X (Rexed). Transections of the spinal cord at various levels revealed that some of the VIP neurons in the lsn might project to supraspinal areas via lateral funiculus.
Assuntos
Hormônios Gastrointestinais/análise , Neurônios/análise , Ratos/fisiologia , Medula Espinal/análise , Transmissão Sináptica , Peptídeo Intestinal Vasoativo/análise , Animais , Imunofluorescência , Histocitoquímica , Masculino , Radioimunoensaio , Medula Espinal/citologiaRESUMO
Basal forebrain (BF) lesions induced by ibotenic acid produced increases in the Bmax and Kd values of [3H]QNB binding sites in the frontal cortex, parietal cortex, and hippocampus. Twenty-eight-day successive administration of propentofylline (10 and 25 mg/kg, p.o.) significantly reduced the Kd values of [3H]QNB binding sites, to the levels of those in a sham group, in a dose-dependent manner. Moreover, propentofylline (25 mg/kg, p.o.) significantly reduced the Bmax value of [3H]QNB binding sites compared with that in a vehicle-treated BF-lesioned group. These results suggest that successive administration of propentofylline ameliorates changes in muscarinic cholinergic receptors through improving presynaptic cholinergic dysfunction.
Assuntos
Lobo Frontal/metabolismo , Hipocampo/metabolismo , Lobo Parietal/metabolismo , Prosencéfalo/fisiologia , Receptores Muscarínicos/metabolismo , Xantinas/farmacologia , Animais , Autorradiografia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Ácido Ibotênico , Cinética , Masculino , Fatores de Crescimento Neural/biossíntese , Lobo Parietal/efeitos dos fármacos , Quinuclidinil Benzilato/metabolismo , Ratos , Ratos Wistar , Receptores Muscarínicos/efeitos dos fármacos , TrítioRESUMO
We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.
Assuntos
Alcaloides/uso terapêutico , Amnésia/prevenção & controle , Doenças do Sistema Nervoso Autônomo/prevenção & controle , Lesões Encefálicas/complicações , Neurônios/efeitos dos fármacos , Sistema Nervoso Parassimpático , Proteína Quinase C/antagonistas & inibidores , Animais , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Encéfalo/anatomia & histologia , Encéfalo/enzimologia , Lesões Encefálicas/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Colina O-Acetiltransferase/metabolismo , Feminino , Ácido Ibotênico/farmacologia , Ratos , Ratos Endogâmicos , EstaurosporinaRESUMO
In an in vitro bioassay system for adrenocorticotropic hormone using isolated rat adrenal cells, kaurenol, a diterpene alcohol, stimulated corticosterone production and augmented the steroidogenic effect of adrenocorticotropin or forskolin, dose-dependently. Kaurenol had no effect on cyclic AMP production by the cells. The diterpene also had no stimulatory effect on the adrenal adenylate cyclase activity in a cell free system. The results suggest that this particular diterpene exerts a steroidogenic effect through a mechanism independent of cyclic AMP generation.
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Diterpenos/farmacologia , Adenilil Ciclases/metabolismo , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Toxina da Cólera/farmacologia , Colforsina/farmacologia , AMP Cíclico/biossíntese , Relação Dose-Resposta a Droga , RatosRESUMO
The long-term effects of Lipiodol-transcatheter arterial embolization (Lp-TAE) combined with cisplatin (CDDP) or doxorubicin (ADM) on unresectable hepatocellular carcinoma (HCC) were analyzed. Eighty-four consecutive patients with unresectable HCC were treated with TAE. Of the 84, 38 patients were treated with CDDP-Lp-TAE (CDDP group), whereas the remaining 46 patients were treated with ADM-Lp-TAE (ADM group). No significant difference in characteristics of patients and tumors was noted between the groups. CDDP (50 mg) or ADM (20-50 mg) was administered with Lp followed by embolization of the feeding arteries using gelatin sponge particles. The mean number of TAE treatments was 3.3 in the CDDP group and 1.9 in the ADM group (p < 0.01). The 5-year overall survival rates of the CDDP group and the ADM group were 19% and 6%, respectively. The overall survival rate of the CDDP group was significantly higher than that of the ADM group (p < 0.05). No serious side effects were observed in either group. CDDP-Lp-TAE improved the prognosis of unresectable HCC compared with ADM-Lp-TAE, which may be attributable to the fact that CDDP-Lp-TAE treatment could be repeated more times than ADM-Lp-TAE.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Óleo Iodado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
New methods for asymmetric reactions developed by the author's group are outlined. They include asymmetric nitroolefination through an addition-elimination process, asymmetric synthesis utilizing 2,2'-disubstituted and 8,8'-disubstituted binaphthyl derivatives, and enantioselective alpha-alkylation of carbonyl compounds under conditions with absolutely no external chiral environmental factors.