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1.
J Physiol Pharmacol ; 62(5): 513-20, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22204798

RESUMO

Local inflammation and respiratory burst of polymorphonuclear leukocytes generate reactive oxygen species (ROS). The aim of our study was to analyze the effects of peritoneal neutrophils on changes of the muscle tension of isolated aorta and compare their effects with those of different ROS. While native neutrophils did not influence muscle tension, the N-formyl-methionyl-leucyl-phenylalanine activated ones evoked a biphasic response on the KCl-precontracted aorta. The effects of activated neutrophils were in both respects similar to those evoked by xanthine/xanthine oxidase (X/XO) and differed from the effects evoked by H(2)O(2) and Fe(2)SO(4)/H(2)O(2). Using H(2)O(2) we demonstrated that the effects of ROS were dependent on the KCl induced initial tension. To exclude the effect of extensive depolarization the action of different ROS was studied also on tissues precontracted by phenylephrine. Under such condition activated neutrophils caused a marked contraction similar to that evoked by X/XO. Their effects differed however, from those of H(2)O(2) and Fe(2)SO(4)/ascorbic acid. These findings and elimination of activated neutrophil-induced contractions as well as the chemiluminiscence by superoxide dismutase suggest that the primarily activated neutrophil-released ROS was superoxide, which can be transformed to peroxynitrite, and other ROS including H(2)O(2). Reduction of all followed-up contractions caused by nordihydroguaiaretic acid, indicate that 5-lipoxygenase metabolites unselectively reduce contractions. In contrast, selective inhibition of activated neutrophil-evoked contraction by indomethacin suggests that cyclooxygenase metabolites are involved mainly in their action on vascular smooth muscle.


Assuntos
Aorta Torácica/fisiologia , Tono Muscular/fisiologia , Músculo Liso Vascular/fisiologia , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Aorta Torácica/efeitos dos fármacos , Cobaias , Técnicas In Vitro , Masculino , Tono Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Fenilefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Xantina/metabolismo , Xantina Oxidase/metabolismo
2.
Rehabilitation (Stuttg) ; 48(5): 312-20, 2009 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-19847728

RESUMO

BACKGROUND: Between 50 and 90% of patients in psychosomatic rehabilitation are affected by occupational problems and misdirected stress. The patients often find themselves in a vicious circle in which occupational problems lead to the development of mental illnesses before a background of lacking compensation possibilities and positive resources. Besides, mobbing can be understood as a special form of occupational stress, whereas in former studies, no differences in the magnitude of mental strain were discovered in comparison with rehabilitants who were in a psychosomatic remedial treatment. PURPOSE: Patients who are in psychosomatic remedial treatment and are norm-aberrantly limited in their occupational efficiency and patients who are affected by mobbing in the job show a higher psychosocial strain than other patients in treatment whose occupational efficiency is not limited. Do mobbing victims more frequently receive a recommendation that measures to strengthen their working life participation be considered? METHOD: A total of 189 patients were handed out a questionnaire at the beginning of their remedial treatment comprised of questions regarding their mobbing experiences, the IRES-3, the SCL-27, the Fatigue-Scale, the Incongruity questionnaire and the VDS-scale. The sample was split up into a group whose occupational efficiency was limited, a group affected by mobbing, and a group who had no efficiency limitations. RESULTS: 72.6% were clearly limited in their occupational efficiency. 27.4% felt neither affected in their occupational efficiency nor due to mobbing. 21% of the sample as a whole were affected by mobbing. Patients limited in their occupational efficiency differed neither from patients whose efficiency was unlimited, nor from those who were affected by mobbing. On the other hand, mobbing victims differed in all symptom scales evaluated from patients who had no occupational efficiency limitations. Also the scales on personality styles were substantially increased compared to this group. With mobbing victims it was recommended more often that the possibilities for working life participation measures should be checked. CONCLUSIONS: Patients in psychosomatic rehabilitation are strongly affected by occupational limitations and have a huge need for counselling and support. Therapy concepts should pick up the occupational problems at hand in a differentiated manner, with job-oriented linked-up rehabilitation being recommended. The increased mental strain of mobbing victims must always be borne in mind.


Assuntos
Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/reabilitação , Comportamento Social , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/epidemiologia
3.
Arch Pediatr ; 15(6): 1068-75, 2008 Jun.
Artigo em Francês | MEDLINE | ID: mdl-18434108

RESUMO

UNLABELLED: Link between maternal body mass index (BMI) and pregnancy outcome is not clear. OBJECTIVE: To appreciate the impact of prepregnancy maternal BMI on very preterm birth (22-32 gestation's weeks). SECONDARY OBJECTIVE: To assess how maternal BMI does explain the mechanism of very preterm birth among live births. METHODS: Population-based study, including each mother with a live or stillborn baby was included in a geographically defined (Poitou-Charentes and Franche-comté, France) case-control study in 2004 to 2006. Leanness (BMI<18.5kg/m(2)) and overweight and obesity (BMI> or =25kg/m(2)) were defined according to World Health Organization's standards. Statistical analysis consisted in a polynomial regression on 832 mothers of very preterm babies and 431 mothers of full-term babies, taking account for confounders as maternal age, birth country, educational level, maternal work and smoking during the pregnancy. RESULTS: Leanness is a risk factor for very preterm live birth (aOR=1.73 [1.12-2.68]), overweight is a risk factor for stillbirth. (aOR=1.71 [1.03-2.84]). Among mothers of live born babies, leanness is a risk factor for spontaneous preterm birth (aOR=2.12 [1.20-3.74]), whereas overweight is a risk factor for very preterm birth on medical decision due to gestational hypertension (aOR=2.85 [1.80-4.52]). CONCLUSION: Morbid maternal stoutness before pregnancy is a complex risk factor for very preterm delivery. Women and couples should be informed and practitioners should be aware in order to prevent and manage this pathological status.


Assuntos
Índice de Massa Corporal , Mães , Nascimento Prematuro , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Sobrepeso/complicações , Gravidez , Fatores de Risco , Natimorto , Magreza/complicações
4.
Clin Neurophysiol ; 118(11): 2332-43, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17889601

RESUMO

OBJECTIVE: A robust and fast algorithm for the offline detection of epileptic seizures in scalp EEG is described. It is aimed for seizure detection with high sensitivity and low number of false detections in long-term EEG data without a priori information. METHODS: To capture the characteristic electrographic changes of seizures, we developed an efficient method based on power spectral analysis techniques. The integrated power is calculated in two frequency bands for three multi-channel seizure detection montages (referenced against the average of Fz-Cz-Pz, common average, bipolar) using the same parameters for all montages and all patients taking into account an appropriate artifact rejection. RESULTS: A total of 3248 h of scalp recordings containing 148 seizures from 19 patients were examined. The averaged sensitivity was 90.9% and selectivity (false-positive errors/h, FPH) was 0.29/h of the Fz-Cz-Pz montage; the other montages yielded lower sensitivities but even better selectivity values. CONCLUSIONS: Taking into account that the method has been performed in a standardized way with fixed parameters for all patients and montages the obtained values for sensitivity are quite high while the selectivity is acceptably low. The parameters can additionally be tuned to patient specific seizures. It is assumed that this may further improve the seizure detection performance. SIGNIFICANCE: The proposed method may enhance the clinical use for the detection of seizures in scalp EEG long-term monitoring during presurgical evaluation.


Assuntos
Eletroencefalografia , Couro Cabeludo/fisiopatologia , Convulsões/diagnóstico , Adolescente , Adulto , Algoritmos , Epilepsia/complicações , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Convulsões/etiologia , Sensibilidade e Especificidade , Fatores de Tempo
5.
Fundam Clin Pharmacol ; 19(1): 73-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15660962

RESUMO

Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)-diabetic rats in a 8-month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ-diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (D,L-alpha-tocopheryl acetate, 400-500 IU/kg/day) or ST plus vitamin E through an intra-oral catheter for a 8-month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1-64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline-induced contractions to basal levels. The tension induced by 120 mm KCl was not statistically different among the experimental groups. In normal rats, EFS-induced contractions were significantly inhibited by pyrogallol (10(-4) m), a free-radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)-induced contractions in ring sections was 48 +/- 5.8 in control, 75 +/- 5.5 in untreated-diabetic, 54 +/- 2.7 in ST-treated diabetic, and 58 +/- 4.7 in vitamin E-treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 +/- 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Norepinefrina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sistema Nervoso Simpático/fisiologia , Ducto Deferente/fisiopatologia , Vasoconstritores/farmacologia , Animais , Glicemia/metabolismo , Carbolinas/farmacologia , Doença Crônica , Diabetes Mellitus Experimental/metabolismo , Estimulação Elétrica , Hemoglobinas Glicadas/metabolismo , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiopatologia , Pirogalol/farmacologia , Ratos , Ratos Wistar , Transmissão Sináptica , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/inervação , Vitamina E/farmacologia
7.
J Diabetes Complications ; 18(2): 129-40, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15120709

RESUMO

Cataract--opacification of the lens--is closely related to diabetes as one of its major late complications. This review deals with three molecular mechanisms that may be involved in the development of diabetic cataract: nonenzymatic glycation of eye lens proteins, oxidative stress, and activated polyol pathway in glucose disposition. Implications resulting from these mechanisms for possible pharmacological interventions to prevent diabetic cataract are discussed. The article reviews research on potential anticataract agents, including glycation inhibitors, antioxidants, and aldose reductase inhibitors. Information on possible benefits of putative anticataract agents comes from a variety of approaches, ranging from laboratory experiments, both in vitro and in vivo, to epidemiological studies in patients.


Assuntos
Catarata/prevenção & controle , Retinopatia Diabética/prevenção & controle , Antioxidantes/uso terapêutico , Cegueira/prevenção & controle , Catarata/fisiopatologia , Retinopatia Diabética/fisiopatologia , Humanos , Estresse Oxidativo
8.
Gen Physiol Biophys ; 22(2): 151-66, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-14661728

RESUMO

The effects of H2O2 on electrical and mechanical activity of the longitudinal layer from the guinea-pig ileum were studied using sucrose-gap technique and the influence of H2O2 on ionic current was investigated in single smooth muscle cells by the patch-clamp method. In most of the preparations tested, the spontaneous activity observed was composed of slow waves with superimposed action potentials (APs). Both were resistant to tetrodotoxin and atropine. H2O2 (1 mmol/l) evoked sustained 3-5 mV membrane depolarisation, doubled the amplitude of the slow waves and increased their frequency, augmented the APs and reduced their splitting. These changes were accompanied with significant contraction, which had an amplitude comparable to that of the tonic component of 50 mmol/l K+-induced contraction. Calcium-free solution caused membrane depolarisation, reduction of the slow wave amplitude and frequency, disappearance of APs and decreased the mechanical tension of the preparations. Application of H2O2 (1 mmol/l) into the zero-calcium bath solution recovered the APs, which was accompanied by a low amplitude contraction. H2O2 (up to 1 mmol/l) increased the L-type calcium current (I(Ca)) both under conventional whole-cell patch-clamp configuration and under amphotericin-perforated patches by 16 +/- 3%. These data demonstrated that contractile response of the ileum longitudinal smooth muscle preparation evoked by H2O2 was mainly due to the enhanced electrical activity.


Assuntos
Potenciais de Ação/fisiologia , Peróxido de Hidrogênio/farmacologia , Íleo/efeitos dos fármacos , Íleo/fisiologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Potenciais de Ação/efeitos dos fármacos , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Cobaias , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia
9.
Dtsch Med Wochenschr ; 128(43): 2242-7, 2003 Oct 24.
Artigo em Alemão | MEDLINE | ID: mdl-14574637

RESUMO

BACKGROUND AND OBJECTIVE: The gate-keeping role of general practitioners (GPs) is currently the topic of much debate in Germany. Currently it is possible for patients in Germany to see a specialist either through referral by their GP or directly through self-referral. To determine whether the gate-keeping role of GPs has a filtering effect, we compared patients referred by their GPs with self-referred patients presenting with suspected chronic venous insufficiency (CVI) to a specialist practice. PATIENTS AND METHODS: From September to December 2001, we prospectively recruited 316 patients seen for suspected CVI in a specialist practice for vascular surgery and phlebology. Symptoms and clinical findings were recorded using a standardized form. RESULTS: 58.2 % of patients were referred by their GPs. These patients were on average 6 years older and presented at a more advanced stage of disease than self-referred patients. No difference was found between patients with and without referral with respect to the symptoms reported or the therapy recommended by the specialist. CVI was excluded in 7.1 % of patients with a referral and in 6.8 % of those without a referral. CONCLUSIONS: The majority of patients consulting a specialist were referred by their GP. The more advanced disease stage of these patients indicates that a filtering process occurs in referral by GPs. However, the share of patients without referrals in whom CVI could be excluded was low and not significantly different from that of patients with referrals. This indicates that misdiagnosis due to self-referral is relatively modest. A cost reduction effect in a gate-keeper system could therefore only be small.


Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Médicos de Família , Encaminhamento e Consulta/estatística & dados numéricos , Insuficiência Venosa/terapia , Adulto , Fatores Etários , Doença Crônica , Feminino , Controle de Acesso/economia , Controle de Acesso/estatística & dados numéricos , Alemanha/epidemiologia , Pesquisa sobre Serviços de Saúde , Hematologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Encaminhamento e Consulta/classificação , Encaminhamento e Consulta/economia , Índice de Gravidade de Doença , Procedimentos Cirúrgicos Vasculares , Insuficiência Venosa/economia , Insuficiência Venosa/epidemiologia
10.
Methods Find Exp Clin Pharmacol ; 25(4): 287-96, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12808474

RESUMO

The aim of this study was to investigate the effect of reactive oxygen species (ROS), generated by electrolysis of Krebs-Henseleit solution (GE-KHS), on isolated guinea pig trachea and to assess the possible involvement of nitric oxide (NO) in the observed effects. The isolated trachea was superfused in GE-KHS, generating H2O2 and hypochlorous acid (HOCl), both of which slowly increased in the organ bath and reached final stable concentrations of 42 and 63 microM, respectively, at the rate of 20 ml/min(-1), and 261 and 245 microM, respectively, at the rate of 5 ml/min(-1). ROS GE-KHS-induced relaxation of tracheal rings was preceded by a small transient contraction in 40% and 65% of experiments when tracheal rings were superfused at the rate of 20 ml/min(-1) and 5 ml/min(-1), respectively. Removal of tracheal epithelium abolished the relaxation of the trachea induced by ROS GE-KHS and unmasked or potentiated trachealis contraction. The ROS GE-KHS-induced changes in trachealis tension were accompanied by an increase in thiobarbituric acid reactive substances (TBARS) and a decrease in nonprotein (NP) thiols in the trachea. These changes were inhibited by treatment with the antioxidant N-acetylcysteine (100 microM). Pretreatment of tracheal rings with the inhibitor of NO synthase (NOS) N(omega)-nitro-L-arginine (L-NOARG; 100 microM) for 20 min prior to exposure to ROS GE-KHS decreased the ROS GE-KHS-induced relaxation. When L-NOARG (100 microM) was present in the superfusing solution, not only 20 min before but also during superfusion with ROS GE-KHS, the evoked trachealis relaxation was reduced in the first 15 min but was enhanced in the 30th min. This late enhancement of relaxation was accompanied by a 12-fold increase in nitric oxide metabolites (NO(x)). ROS GE-KHS-induced elevation of TBARS levels in the trachea was decreased to 63% by pretreatment with L-NOARG (100 microM). Elevation of TBARS levels induced by incubation of brain liposomes with a hydroxyl radical generating system was decreased to 90% by L-NOARG (10, 100 microM), while the antioxidant stobadine (100 microM) nearly completely inhibited the evoked lipid peroxidation. In comparison with Trolox, L-NOARG exerted a slight scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl radical. The presence of L-arginine and D-arginine in the superfusion fluid for 15-20 min before and during exposure of the trachea to ROS GE-KHS inhibited trachealis relaxation. Results indicate that epithelium derived NO may participate in the response of guinea pig trachea to ROS GE-KHS. The presence of L-NOARG in the bathing fluid during superfusion with ROS GE-KHS gave rise to NO(x), with relaxing activity. L- and D-arginine induced an inhibition of the relaxatory response to ROS GE-KHS and partially prevented a ROS-induced decrease in NP thiols. The involvement of the small antioxidant effects of L-NOARG and L- and D-arginine in the above mentioned actions of L-NOARG and L-arginine requires additional investigation.


Assuntos
Arginina/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traqueia/fisiologia , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Arginina/química , Arginina/farmacologia , Eletrólise , Glucose , Cobaias , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/metabolismo , Nitroarginina/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Estereoisomerismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/metabolismo , Trometamina
11.
Rev. méd. Chile ; 131(1): 46-54, 2003. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: lil-342222

RESUMO

Background: Mutations in type II 3ß hydroxysteroid Dehydrogenase (3ßHSD) are found in male children with severe undervirilized genitalia. Mild undervirilization (isolated micropenis or with distal hypospadia) can be associated with a partial deficit in 3ßHSD activity. Aim: To assess the frequency of abnormal adrenal response to ACTH, suggesting a deficit in adrenal enzymatic activity, in children with mild undervirilization. Patients and methods : We studied 26 male children with micropenis, aged one to eight years. Children with evidences of puberal development or in treatment with drugs that affect steroidal metabolism were excluded from the study. Serum levels of androstenedione (A), dehydroepiandrosterone (DHEA), progesterone (P), 17 hydroxyprogesterone (17 P) and the ratios DHEA/A, P/17 P, 17 P/DHEA were measured after an adrenal stimulation with 0.25 mg/m2 intramuscular ACTH. Results: Two children had DHEA y DHEA/A values suggesting a defective 3ßHSD activity. Other two children had high levels of 17 P, suggesting a deficiency of cytochrome p450c21. A CYP 21 gene mutation was found in one of the later children. Conclusions: A low proportion of children with micropenis have a deficient 3ßHSD activity


Assuntos
Humanos , Masculino , Pré-Escolar , Lactente , Criança , Pênis , Glândulas Suprarrenais/fisiopatologia , Hormônios Esteroides Gonadais/deficiência , Antropometria , Hormônio Adrenocorticotrópico , Criptorquidismo , Hipospadia
12.
Brain Res ; 918(1-2): 96-100, 2001 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-11684046

RESUMO

We have recently shown that six of seven totally blind people (who had free-running circadian rhythms with periods longer than 24 h) could be entrained (synchronized) to a nightly dose of 10 mg melatonin. After treatment discontinuation and re-entrainment to the 10 mg dose, we further found in three of these subjects that the dose could be gradually reduced to 0.5 mg without loss of effect. The question then arose: can a de novo (starting) dose of 0.5 mg initially capture free-running rhythms? Following withdrawal of the stepped-down 0.5 mg dose and consequent release into a free-run, the same three individuals were given 0.5 mg of melatonin de novo. All entrained within a few weeks.


Assuntos
Relógios Biológicos/efeitos dos fármacos , Cegueira/complicações , Ritmo Circadiano/efeitos dos fármacos , Melatonina/administração & dosagem , Transtornos do Sono do Ritmo Circadiano/tratamento farmacológico , Transtornos do Sono do Ritmo Circadiano/etiologia , Adulto , Relógios Biológicos/fisiologia , Cegueira/metabolismo , Cegueira/fisiopatologia , Ritmo Circadiano/fisiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Melatonina/efeitos adversos , Melatonina/sangue , Pessoa de Meia-Idade , Glândula Pineal/metabolismo , Glândula Pineal/fisiopatologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Núcleo Supraquiasmático/efeitos dos fármacos , Núcleo Supraquiasmático/metabolismo , Vias Visuais/lesões , Vias Visuais/fisiopatologia
13.
Am J Physiol Regul Integr Comp Physiol ; 281(4): R1186-92, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11557627

RESUMO

Hibernating mammals can survive several months without feeding by limiting their carbohydrate catabolism and using triacylglycerols stored in white adipose tissue (WAT) as their primary source of fuel. Here we show that a lipolytic enzyme normally found in the gut, pancreatic triacylglycerol lipase (PTL), is expressed in WAT of hibernating 13-lined ground squirrels (Spermophilus tridecemlineatus). PTL expressed in WAT is encoded by an unusual chimeric retroviral-PTL mRNA approximately 500 bases longer than the predominant PTL message found in other ground squirrel tissues. Seasonal measurements detect the chimeric mRNA and PTL enzymatic activity in WAT before and during hibernation, with both showing their lowest observed levels 1 wk after hibernation concludes in mid-March. PTL is expressed in addition to hormone-sensitive lipase, the enzyme typically responsible for hydrolysis of triacylglycerols in WAT. Because of the distinct catalytic and regulatory properties of both enzymes, this dual-triacylglycerol lipase system provides a means by which the fuel requirements of hibernating 13-lined ground squirrels can be met without interruption.


Assuntos
Hibernação/fisiologia , Lipase/metabolismo , Lipólise/fisiologia , RNA Mensageiro/biossíntese , Retroelementos/genética , Tecido Adiposo/metabolismo , Animais , Northern Blotting , Clonagem Molecular , Regulação da Expressão Gênica , Lipase/genética , Dados de Sequência Molecular , RNA Mensageiro/genética , Sciuridae , Estações do Ano , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Esterol Esterase/genética , Esterol Esterase/metabolismo
15.
Methods Find Exp Clin Pharmacol ; 23(3): 121-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11523310

RESUMO

We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on the reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month hyperglycemia were studied. Hyperglycemia was induced by streptozotocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated under isometric conditions. The first changes in aortic reactivity started after 1 month of hyperglycemia and were exhibited by significantly increased NA-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 months did not cause any additional significant changes in responsiveness to NA. Decreased ACh-induced relaxation and increased contractile responses to H2O2 were observed in month 4. The functional responses were not substantially deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic rats resulted in the protection of aortic function as well as its ultrastructure. These results suggest that abnormalities occurring in the aorta of diabetic rats might result from the damaging effects of oxygen free radicals.


Assuntos
Antioxidantes/farmacologia , Carbolinas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Aorta Torácica/ultraestrutura , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Carbolinas/administração & dosagem , Técnicas de Cultura , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/patologia , Angiopatias Diabéticas/fisiopatologia , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Endotélio Vascular/ultraestrutura , Masculino , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Fatores de Tempo , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia
16.
Bratisl Lek Listy ; 101(6): 331-9, 2000.
Artigo em Eslovaco | MEDLINE | ID: mdl-11039206

RESUMO

The activation of smooth muscle muscarinic receptors leads to its contraction. Electrophysiological and biochemical methods have gradually, over the time span of roughly 30-40 past years, helped to reveal this phenomenon's underlying processes. One element of this cascade of processes is the influx of cations into the smooth muscle cell--non-selective cationic current--causing depolarisation of the cell membrane and subsequent opening of voltage-operated calcium channels. This mini-review provides the reader with up-to-date knowledge on non-selective cationic current, supplemented with information on muscarinic receptors of smooth muscle, their coupling with effectors via G proteins, as well as on muscarinic modulation of calcium and potassium channels of smooth muscle. The conclusion is dedicated to pointing out the future trends of research in this area. (Tab. 2, Fig. 2, Ref. 82.)


Assuntos
Bombas de Íon/fisiologia , Músculo Liso/fisiologia , Animais , Proteínas de Ligação ao GTP/fisiologia , Humanos , Receptores Colinérgicos/fisiologia , Receptores Muscarínicos/fisiologia
17.
Biomed Chromatogr ; 14(3): 188-201, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10850624

RESUMO

This overview provides comprehensive information on the most relevant results of Stobadine preclinical disposition studies. In order to investigate pharmacokinetic processes of the drug in rats, dogs and in human volunteers, several bioanalytical assays based on radiometric, spectrofluorometric, as well as chromatographic determination methods were developed and implemented. In small laboratory animals, the drug absorption, distribution, metabolism and elimination were investigated by administering 3H-labeled Stobadine. Spectrofluorometry was used alternatively for the determination of cold/unlabeled Stobadine in extracts of biomaterials sampled from larger animal species. The chromatographic separation methods proved, however, to be the most advantageous for determining details of the drug disposition and fate in the body.


Assuntos
Antioxidantes , Carbolinas/isolamento & purificação , Carbolinas/farmacocinética , Cromatografia/métodos , Sequestradores de Radicais Livres , Animais , Encéfalo/metabolismo , Química Encefálica , Cromatografia Gasosa/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina/métodos , Cães , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Fígado/química , Fígado/metabolismo , Pulmão/química , Pulmão/metabolismo , Miocárdio/química , Miocárdio/metabolismo , Ratos , Espectrometria de Fluorescência , Trítio
18.
J Auton Nerv Syst ; 79(1): 34-44, 2000 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-10683504

RESUMO

To study the possible role of reactive oxygen species in airway hyperreactivity, we examined the effects of the superoxide anion radical (O(2)(-)) generating systems, pyrogallol and xanthine with xanthine oxidase, on muscle tone, excitatory and inhibitory neurotransmission in the cat airway. Smooth muscle contraction or non-adrenergic non-cholinergic (NANC) relaxation evoked by electrical field stimulation (EFS) were measured before or after O(2)(-) generating systems with or without diethydithiocarbamic acid (DEDTCA), an inhibitor of endogenous superoxide dismutase (SOD). Resting membrane potential or excitatory junction potential (EJP) were also measured in vitro. Both pyrogallol and xanthine/xanthine oxidase produced biphasic changes in basal and elevated (by 5-HT) muscle tone. After SOD pretreatment, both systems consistently produced a prolonged contraction, thereby indicating that O(2)(-) was converted to H(2)O(2) by the action of SOD and as a result the actions of O(2)(-) were lost but those of H(2)O(2) introduced. The O(2)(-) showed no significant effect on smooth muscle contraction or EJP evoked by EFS, however after DEDTCA pretreatment, it evoked initial enhancement followed by suppression of the contraction and EJP. DEDTCA pretreatment ameliorated the inhibitory action of pyrogallol and xanthine/xanthine oxidase on the NANC relaxation, probably because O(2)(-) could combine with endogenous NO to form peroxynitrite. These results indicate that the O(2)(-) generating systems have multiple actions, presumably due to the presence and simultaneous action of at least two different reactive oxygen species (O(2)(-) and H(2)O(2)). While H(2)O(2) seems to be responsible for elevation of muscle tone and augmentation of smooth muscle contraction by EFS, O(2)(-) inhibits muscle tone, cholinergic and NANC neurotransmission.


Assuntos
Fibras Colinérgicas/fisiologia , Contração Muscular/fisiologia , Tono Muscular/fisiologia , Músculo Liso/fisiologia , Superóxidos/metabolismo , Traqueia/inervação , Traqueia/fisiologia , Animais , Gatos , Ditiocarb/farmacologia , Eletrofisiologia , Feminino , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Tono Muscular/efeitos dos fármacos , Pirogalol/farmacologia , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/farmacologia , Xantina/farmacologia , Xantina Oxidase/farmacologia
19.
Cesk Patol ; 36(4): 140-5, 2000 Oct.
Artigo em Eslovaco | MEDLINE | ID: mdl-11378905

RESUMO

The diseases of vessels, mainly of those in brain are one of the most serious problems of the medical practice. The encephalomalacia or cerebral infarctions are usually caused by transient or permanent obstruction of the brain arteries lumen. Beside local dysfunction of vessels the obstructions could be based on embolic events originating in the heart. Such an obstructions are resulting in global and focal cerebral ischaemias. Arterial occlusion results in cerebral ischaemia and the lack of oxygen (anoxia) which leads to reversible or irreversible injury of the nervous cells in the ischaemic region. The local cell injury or cell death causes attraction of macrophages invading into the devitalized tissue within 72-96 hours after the beginning of the ischaemia. The aim of this study was to find out the correlation between asymptomatic or symptomatic course regarding localisation of the ischaemic lesions in the cerebral tissue. Our anatomical findings were collected from 318 autopsies, and reports on postmortem examinations during the period between September-December 1998. The grossing of the brain was carried out by using of Virchow's method. Atherosclerosis, hypertension, and diabetes mellitus were found to be the main risk factors for the production of focal cerebral ischaemia. Of those patients with focal cerebral ischaemia atherosclerosis had 87.5%, 44.3% were suffering from hypertension, and 25% from diabetes mellitus. The focal ischaemia analysed in this study originated from arterial stenosis or thromboembolic obstructions. We divided the lesions into 3 groups according to their size. The most frequently apparent lesions (72%) were the small cysts (0-10 mm in diameter)-lacunae. The majority of them (90%) was found in the basal ganglia. The second group consisted of postmalatic pseudocysts (10-30 mm in diameter), and the third group was represented by encephalomalatic lesions which were larger than 30 mm. Cerebral ischaemic lesions were present in 27.8% of the studied cases. Nevertheless, more than the half (56.8%) of the affected brains (postmalatic pseudocysts, lacunae and malaciae) belongs to the group of patients who were clinically asymptomatic. The asymptomatic lesions, having negative results in the patient's history, and the clinical course were localised mainly in the basal ganglia of both sides and in the frontal part of the right (nondominant) hemisphere.


Assuntos
Isquemia Encefálica/patologia , Encéfalo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/patologia , Feminino , Humanos , Embolia e Trombose Intracraniana/patologia , Masculino , Pessoa de Meia-Idade
20.
Gen Pharmacol ; 35(2): 77-81, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11707313

RESUMO

(1) To verify the proposed role of reactive oxygen species (ROS) in ulcerative colitis, the effect of an antioxidant N-acetylcysteine (NAC) was studied in acetic acid (AA)-induced colonic inflammation. (2) Depending on the dose used, NAC administered intracolonically was found to reduce the extent of colonic damage, along with a decrease in myeloperoxidase (MPO) activity, colonic wet weight and wet/dry weight ratio. (3) NAC attenuated the enhanced vascular permeability and prevented the depletion of colonic reduced glutathione (GSH) caused by AA administration. (4) The findings indicate that NAC may prove beneficial in the treatment of colitis.


Assuntos
Acetilcisteína/uso terapêutico , Colite/tratamento farmacológico , Ácido Acético , Animais , Relação Dose-Resposta a Droga , Glutationa/análise , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio
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