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1.
Bone Joint J ; 101-B(2): 147-153, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30700113

RESUMO

AIMS: The aim of this study was to investigate the effects of preoperative bisphosphonate treatment on the intra- and postoperative outcomes of arthroplasty of the shoulder. The hypothesis was that previous bisphosphonate treatment would adversely affect both intra- and postoperative outcomes. PATIENTS AND METHODS: A retrospective cohort study was conducted involving patients undergoing arthroplasty of the shoulder, at a single institution. Two patients with no previous bisphosphonate treatment were matched to each patient who had received this treatment preoperatively by gender, age, race, ethnicity, body mass index (BMI), and type of arthroplasty. Previous bisphosphonate treatment was defined as treatment occurring during the three-year period before the arthroplasty. The primary outcome measure was the incidence of intraoperative complications and those occurring at one and two years postoperatively. A total of 87 patients were included: 29 in the bisphosphonates-exposed (BP+) group and 58 in the non-exposed (BP-) group. In the BP+ group, there were 26 female and three male patients, with a mean age of 71.4 years (51 to 87). In the BP- group, there were 52 female and six male patients, with a mean age of 72.1 years (53 to 88). RESULTS: Previous treatment with bisphosphonates was positively associated with intraoperative complications (fracture; odds ratio (OR) 39.40, 95% confidence interval (CI) 2.42 to 6305.70) and one-year postoperative complications (OR 7.83, 95% CI 1.11 to 128.82), but did not achieve statistical significance for complications two years postoperatively (OR 3.45, 95% CI 0.65 to 25.28). The power was 63% for complications at one year. CONCLUSION: Patients who are treated with bisphosphonates during the three-year period before shoulder arthroplasty have a greater risk of intraoperative and one-year postoperative complications compared with those without this previous treatment.


Assuntos
Artroplastia do Ombro/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Difosfonatos/efeitos adversos , Difosfonatos/farmacologia , Articulação do Ombro/efeitos dos fármacos , Articulação do Ombro/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Ombro/métodos , Doenças Ósseas Metabólicas/tratamento farmacológico , Remoção de Dispositivo , Difosfonatos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Falha de Prótese , Reoperação , Estudos Retrospectivos , Fatores de Risco
2.
Bone Joint J ; 100-B(3): 324-330, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29589497

RESUMO

Aims: The factors that predispose to recurrent instability and revision stabilization procedures after arthroscopic Bankart repair for anterior glenohumeral instability remain unclear. We sought to determine the rate and risk factors associated with ongoing instability in patients undergoing arthroscopic Bankart repair for instability of the shoulder. Materials and Methods: We used the Statewide Planning and Research Cooperative System (SPARCS) database to identify patients with a diagnosis of anterior instability of the shoulder undergoing arthroscopic Bankart repair between 2003 and 2011. Patients were followed for a minimum of three years. Baseline demographics and subsequent further surgery to the ipsilateral shoulder were analyzed. Multivariate analysis was used to identify independent risk factors for recurrent instability. Results: A total of 5719 patients were analyzed. Their mean age was 24.9 years (sd 9.3); 4013 (70.2%) were male. A total of 461 (8.1%) underwent a further procedure involving the ipsilateral shoulder at a mean of 31.5 months (sd 23.8) postoperatively; 117 (2.1%) had a closed reduction and 344 (6.0%) had further surgery. Revision arthroscopic Bankart repair was the most common subsequent surgical procedure (223; 65.4%). Independent risk factors for recurrent instability were: age < 19 years (odds ratio 1.86), Caucasian ethnicity (hazard ratio 1.42), bilateral instability of the shoulder (hazard ratio 2.17), and a history of closed reduction(s) prior to the initial repair (hazard ratio 2.45). Revision arthroscopic Bankart repair was associated with significantly higher rates of ongoing persistent instability than revision open stabilization (12.4% vs 5.1%, p = 0.041). Conclusion: The incidence of a further procedure being required in patients undergoing arthroscopic Bankart repair for anterior glenohumeral instability was 8.1%. Younger age, Caucasian race, bilateral instability, and closed reduction prior to the initial repair were independent risk factors for recurrent instability, while subsequent revision arthroscopic Bankart repair had significantly higher rates of persistent instability than subsequent open revision procedures. Cite this article: Bone Joint J 2018;100-B:324-30.


Assuntos
Artroscopia/métodos , Instabilidade Articular/cirurgia , Reoperação/estatística & dados numéricos , Lesões do Ombro/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Resultado do Tratamento
3.
Bone Joint J ; 98-B(6): 818-24, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27235526

RESUMO

AIMS: Depression can significantly affect quality of life and is associated with higher rates of medical comorbidities and increased mortality following surgery. Although depression has been linked to poorer outcomes following orthopaedic trauma, total joint arthroplasty and spinal surgery, we wished to examine the impact of depression in elective total shoulder arthroplasty (TSA) as this has not been previously explored. PATIENTS AND METHODS: The United States Nationwide Inpatient Sample (NIS) was used to identify patients undergoing elective TSA over a ten-year period. Between 2002 and 2012, 224 060 patients underwent elective TSA. RESULTS: Among the identified patients who had undergone TSA, 12.4% had a diagnosis of a history of depression. A diagnosis of depression was twice as common in women compared with men (16.0% vs 8.0%, p < 0.001), and more frequent in those with low income and Medicaid insurance (p < 0.001). A diagnosis of depression was an independent risk factor for post-operative delirium (odds ratio (OR) 2.29, p < 0.001), anaemia (OR 1.65, p < 0.001), infection (2.09, p = 0.045) and hospital discharge to a placement other than home (OR 1.52, p < 0.001) CONCLUSION: A history of clinical depression is present in 12.4% of patients undergoing elective TSA and the disease burden is projected to increase further in the future. Depression is often underdiagnosed and pre-operative screening and appropriate peri-operative management of patients is encouraged. TAKE HOME MESSAGE: The awareness that clinical depression is associated with increased complications following total shoulder arthroplasty provides physicians an opportunity for early intervention in this at-risk population. Cite this article: Bone Joint J 2016;98-B:818-24.


Assuntos
Artroplastia do Ombro , Depressão/epidemiologia , Injúria Renal Aguda/epidemiologia , Anemia/epidemiologia , Comorbidade , Bases de Dados Factuais , Delírio/epidemiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Renda , Tempo de Internação/estatística & dados numéricos , Masculino , Medicaid/estatística & dados numéricos , Alta do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Estados Unidos/epidemiologia
4.
J Int Med Res ; 40(6): 2327-35, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23321190

RESUMO

OBJECTIVE: To evaluate the effects of alcohol consumption and cigarette smoking on sperm quality using transmission electron microscopy and light microscopy. METHODS: Semen samples were collected from 62 healthy men. The subjects were classified according to alcohol consumption and smoking status. Semen analysis was performed according to World Health Organization criteria. Transmission electron microscopy was used to examine sperm ultrastructure. RESULTS: Heavy smoking (> 20 cigarettes/day) was associated with a decreased sperm count. Moderate/high alcohol consumption (≥ 15.4 g/day) was associated with an increase in morphologically abnormal sperm. Transmission electron microscopy revealed no effect of smoking on sperm ultrastructure. Alcohol consumption resulted in significant increases in morphologically abnormal nuclei and plasma membranes. CONCLUSIONS: Heavy smoking was associated with decreased sperm counts and alcohol consumption was associated with increased numbers of morphologically abnormal sperm.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Análise do Sêmen , Fumar/efeitos adversos , Contagem de Espermatozoides , Espermatozoides/ultraestrutura , Adulto , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Motilidade dos Espermatozoides
5.
J Nanosci Nanotechnol ; 11(7): 6157-61, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22121677

RESUMO

We synthesized the vertical-structured LED (VLED) using nano-scaled Pt between p-type GaN and Ag-based reflector. The metallization scheme on p-type GaN for high reflectance and low was the nano-scaled Pt/Ag/Ni/Au. Nano-scaled Pt (5 A) on Ag/Ni/Au exhibited reasonably high reflectance of 86.2% at the wavelength of 460 nm due to high transmittance of light through nano-scaled Pt (5 A) onto Ag layer. Ohmic behavior of contact metal, Pt/Ag/Ni/Au, to p-type GaN was achieved using surface treatments of p-type GaN prior to the deposition of contact metals and the specific contact resistance was observed with decreasing Pt thickness of 5 A, resulting in 1.5 x 10(-4) ohms cm2. Forward voltages of Pt (5 A)/Ag/Ni contact to p-type GaN showed 4.19 V with the current injection of 350 mA. Output voltages with various thickness of Pt showed the highest value at the smallest thickness of Pt due to its high transmittance of light onto Ag, leading to high reflectance. Our results propose that nano-scaled Pt/Ag/Ni could act as a promising contact metal to p-type GaN for improving the performance of VLEDs.

6.
J Nanosci Nanotechnol ; 11(7): 6271-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22121700

RESUMO

We report on the vertical-structure light emitting diodes (VLEDs) fabricated with wafer bonding method using Al-alloyed graphite and Si supporter. VLEDs with Al-alloyed graphite produced no crack during/after laser lift-off (LLO) techniques while the wafer crack took place using Si supporter because of the difference of thermal expansion coefficients between Si and sapphire. The performance of VLEDs with wafer bonding method using Al-alloyed graphite supporter was compared to those fabricated by Cu plating methods. The output power of the chips with wafer bonding method was nearly same as the one with Cu-plating method. However, the forward voltage of VLEDs with wafer bonding method was higher than those with Cu-plating method. In the terms of reliabilities the wafer bonding process is more preferable to Cu-plating and our report proposes that Al-alloyed graphite could be one of promising candidates for the supporters in wafer bonding process.

10.
J Nanosci Nanotechnol ; 5(5): 703-12, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-16010925

RESUMO

Using eigenvalue analysis of mass and stiffness matrices directly computed from atomistic simulations, natural frequencies and mode shapes of various carbon nanotubes are studied. The stiffness matrix was developed from the Tersoff-Brenner potential for carbon-carbon interactions. The computed frequencies of the radial breathing modes of a variety of armchair (n, n) nanotubes agree well with results obtained by others using different techniques. In addition, the study reveals diverse mode shapes such as accordion-like axial modes, lateral bending modes, torsional modes, axial shear modes, and radial breathing modes for a variety of single-wall, multi-wall, and bamboo-type carbon nanotubes. The effects of different constraints on the carbon nanotube ends on the computed frequencies and mode shapes have been investigated for possible applications in vibration sensors or electromechanical resonators.


Assuntos
Modelos Químicos , Nanotecnologia/instrumentação , Nanotubos de Carbono/química , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de Materiais/métodos , Movimento (Física) , Nanotecnologia/métodos , Nanotubos de Carbono/análise , Vibração
11.
Acta Physiol Scand ; 179(2): 167-72, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14510780

RESUMO

AIM: Effects of prolonged habitual cold-water immersion on fibre size and capillarity in vastus lateralis muscle were studied in human beings. The hypothesis tested in the present study was that cold acclimatized human skeletal muscle would have reduced muscle fibre size and higher capillarity, favouring the idea of efficacy of recruitment under cold environment. METHODS: Ten women breath-hold divers (BHDs) and 10 active women (controls CONs) participated in this study. Muscle biopsy was obtained from vastus lateralis and determined fibre type composition and capillary density. RESULTS: A major finding was that all BHDs revealed a markedly smaller cross-sectional area (CSA) in all fibre types than the CONs, or even than any other morphological data reported in previous investigations. Furthermore, mean CSA of type II fibre (range 1205-2766 microm2) was much smaller than type I fibre (2343-4327 microm2). The number of capillaries per fibre in different fibre types in the BHDs was higher than in the CONs (P < 0.001), and diffusional area was smaller in type II fibres than in type I fibres (P < 0.001). The BHDs and the CONs have similarity in the percentage of type I fibres, but type II fibre was predominant in both groups. Interestingly the proportion of type IIx fibre in the BHDs was higher (31%) than in the CONs (22%). No significant difference was found in the thigh circumference between the groups. CONCLUSION: The present study demonstrates that prolonged habitual cold-water immersion may induce a decrease in fibre size and an increase in capillarity in human skeletal muscle.


Assuntos
Mergulho/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/anatomia & histologia , Tecido Adiposo/fisiologia , Adulto , Idoso , Anaerobiose/fisiologia , Peso Corporal/fisiologia , Capilares/fisiologia , Temperatura Baixa/efeitos adversos , Ergometria/métodos , Feminino , Humanos , Imersão , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Respiração , Coxa da Perna/anatomia & histologia , Água
12.
Biochem Biophys Res Commun ; 278(2): 312-7, 2000 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-11097836

RESUMO

IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6. Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly. To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB. Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento Insulin-Like II/farmacologia , Interleucina-6/genética , NF-kappa B/metabolismo , Psoríase/genética , Sequência de Bases , Linhagem Celular , DNA/metabolismo , Primers do DNA , Humanos , Proteínas I-kappa B/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Regiões Promotoras Genéticas , Psoríase/metabolismo , Psoríase/patologia , RNA Mensageiro/genética
13.
Electromyogr Clin Neurophysiol ; 38(5): 279-84, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9741005

RESUMO

This study was designed to determine the optimal sites for the active electrode in a nerve conduction study of each branch of the facial nerve. Twenty healthy male and female volunteers between 20 and 40 years old were investigated. Our criteria for the optimal site of the active electrode were initial negative deflection and maximal amplitude of the response and the most synchronized response. Optimal sites were found to be as follows: 1. Frontalis (temporal branch): a point midway between the hairline and the eyebrow along a line passing vertically through the pupil. 2. Orbicularis oculi (zygomatic branch): the medial quarter between the medial and lateral canthus. 3. Nasalis (buccal branch): muscle belly. 4. Triangularis (mandibular branch): 15 mm lateral and 25 mm below the corner of the mouth. 5. Orbicularis oris (zygomatic, mandibular and buccal branches): 2 mm below the lower lip midway between the midline and the corner of the mouth.


Assuntos
Eletrodos , Eletrodiagnóstico/instrumentação , Nervo Facial/fisiologia , Condução Nervosa/fisiologia , Adulto , Estimulação Elétrica , Músculos Faciais/inervação , Feminino , Humanos , Masculino , Valores de Referência
14.
Biochem Biophys Res Commun ; 243(1): 158-62, 1998 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-9473498

RESUMO

In order to identify genes differentially expressed under hypoxia (1% O2, 5% CO2, balance N2), we performed mRNA differential display analysis using total RNA extracted from hypoxic and normoxic HepG2, human hepatocellular carcinoma (HCC) cells. Of the differentially expressed genes by hypoxia, some of cDNA fragments were cloned and sequenced. The expression patterns of these clones by hypoxia were confirmed by Northern blot analysis and the quantitative RT-PCR. Down-regulated genes by hypoxia have homology to cDNA sequences encoding cytochrome oxidase subunit II and ADP/ATP translocase, respectively. Up-regulated gene by hypoxia was identified as Homo sapiens oscillin. Moreover, novel genes induced by hypoxia represent partial sequences of cDNAs that have not been reported or functionally identified. Up- or down-regulated expression of these genes in response to hypoxia may contribute to human hepatocarcinogenesis.


Assuntos
Carcinoma Hepatocelular/genética , Hipóxia Celular/genética , Neoplasias Hepáticas/genética , Oncogenes , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Ligação ao Cálcio , Clonagem Molecular , DNA Complementar/genética , DNA de Neoplasias/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Translocases Mitocondriais de ADP e ATP/genética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , Ratos , Homologia de Sequência de Aminoácidos , Células Tumorais Cultivadas
15.
J Neurobiol ; 29(4): 503-16, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8656214

RESUMO

A general feature of the developing nervous system is the activity-dependent rearrangement of genetically defined, synaptic connections. A parallel process occurs at the developing neuromuscular junction as activity-dependent synapse withdrawal reduces the initial polyneuronal innervation of individual muscle fibers to a mononeuronal innervation within the first few weeks after birth. Because members of the neurotrophin gene family influence motor neuron differentiation and survival, we examined whether or not they also influence synaptic rearrangements in neonatal muscles. We found that treatment with brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) causes the transient retention of multiple synaptic contacts on neonatal myofibers. However, the combination of both electrophysiological and histological assays revealed that the majority of such supernumerary synaptic contacts are functionally inactive or "silent." There also occurs an increase in the number of retracting axons. Because BDNF mRNA is expressed in developing muscle and the trkB tyrosine kinase receptor for BDNF is expressed by neonatal motor neurons, our results suggest that BDNF may play an endogenous role in the refinement of synaptic connectivity that occurs in skeletal muscles after birth.


Assuntos
Fatores de Crescimento Neural/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Junção Neuromuscular/embriologia , Sinapses/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Axônios/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo , Eletrofisiologia , Feminino , Camundongos , Camundongos Endogâmicos ICR , Denervação Muscular , Músculo Esquelético/inervação , Músculo Esquelético/ultraestrutura , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/crescimento & desenvolvimento , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurotrofina 3 , Gravidez , Sinapses/fisiologia
16.
J Neurobiol ; 28(1): 35-50, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8586964

RESUMO

We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.


Assuntos
Inibidores do Crescimento/fisiologia , Interleucina-6 , Linfocinas/fisiologia , Junção Neuromuscular/fisiologia , Sinapses/fisiologia , Animais , Animais Recém-Nascidos , Sequência de Bases , Fator Neurotrófico Ciliar , Citocinas/fisiologia , Desenvolvimento Embrionário e Fetal/fisiologia , Inibidores do Crescimento/genética , Fator Inibidor de Leucemia , Linfocinas/genética , Camundongos , Camundongos Endogâmicos ICR , Dados de Sequência Molecular , Placa Motora , Desenvolvimento Muscular , Músculo Esquelético/embriologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Fatores de Crescimento Neural/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Oncostatina M , Peptídeos/fisiologia , RNA Mensageiro/biossíntese , Fatores de Tempo
17.
Mol Cell Neurosci ; 6(4): 349-62, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8846004

RESUMO

The mutation gly93-->ala of Cu,Zn superoxide dismutase (SOD) is found in patients with familial amyotrophic lateral sclerosis and causes motor neuron disease when expressed in transgenic mice. The progression of clinical and pathological disease was studied in a line of mice designated G1H. Clinical disease started at 91 +/- 14 days of age with fine shaking of the limbs, followed by paralysis and death by 136 +/- 7 days of age. Pathological changes begin by 37 days of age with vacuoles derived from swollen mitochondria accumulating in motor neurons. At the onset of clinical disease (90 days), significant death of somatic motor neurons innervating limb muscles has occurred; mice at end-stage disease (136 days) show up to 50% loss of cervical and lumbar motor neurons. However, neither thoracic nor cranial motor neurons show appreciable loss despite vacuolar changes. Autonomic motor neurons also are not affected. Mice that express wild-type human Cu,Zn SOD remain free of disease, indicating that mutations cause neuron loss by a gain-of-function. Thus, the age-dependent penetrance of motor neuron disease in this transgenic model is due to the gradual accumulation of pathological damage in select populations of cholinergic neurons.


Assuntos
Envelhecimento/fisiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Morte Celular , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Mutação , Degeneração Neural , Regeneração Nervosa , Superóxido Dismutase/genética , Vacúolos/ultraestrutura
18.
Science ; 264(5166): 1772-5, 1994 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-8209258

RESUMO

Mutations of human Cu,Zn superoxide dismutase (SOD) are found in about 20 percent of patients with familial amyotrophic lateral sclerosis (ALS). Expression of high levels of human SOD containing a substitution of glycine to alanine at position 93--a change that has little effect on enzyme activity--caused motor neuron disease in transgenic mice. The mice became paralyzed in one or more limbs as a result of motor neuron loss from the spinal cord and died by 5 to 6 months of age. The results show that dominant, gain-of-function mutations in SOD contribute to the pathogenesis of familial ALS.


Assuntos
Esclerose Lateral Amiotrófica/genética , Doença dos Neurônios Motores/genética , Superóxido Dismutase/genética , Esclerose Lateral Amiotrófica/enzimologia , Esclerose Lateral Amiotrófica/patologia , Animais , Encéfalo/enzimologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Placa Motora/patologia , Doença dos Neurônios Motores/enzimologia , Doença dos Neurônios Motores/patologia , Neurônios Motores/enzimologia , Neurônios Motores/patologia , Músculos/inervação , Músculos/patologia , Mutação , Linhagem , Medula Espinal/patologia , Superóxido Dismutase/metabolismo
19.
Neuroreport ; 5(7): 789-92, 1994 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-8018851

RESUMO

The ability of ciliary neurotrophic factor (CNTF) to induce sprouting by undamaged adult motor neurons was studied in gluteal muscles of adult ICR mice. Low doses of CNTF (0.02 mg kg-1 day-1) only induced sprouting in gluteus muscles that were beneath the site of injection, whereas high doses of CNTF (0.4-1.2 mg kg-1 day-1) acted systemically to induce motor neuron sprouting. We found little difference between the type or quality of sprouting induced by CNTF compared with muscle paralysis. Both stimuli induced sprouts of the same length, although muscle paralysis tended to induce more sprouts per end-plate. Paralysis also induced more nodal sprouting than did CNTF, but both were weaker stimuli for nodal sprouting than was partial denervation. In addition to its effects on motor neuron sprouting, high doses of CNTF induced loss of up to 36% of the body weight of treated mice. The substantial wasting caused by CNTF indicates that the factor has potent cachectic activity.


Assuntos
Neurônios Motores/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Proteínas do Tecido Nervoso/farmacologia , Animais , Caquexia/induzido quimicamente , Fator Neurotrófico Ciliar , Relação Dose-Resposta a Droga , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Músculos/efeitos dos fármacos , Músculos/inervação , Músculos/fisiopatologia , Fatores de Crescimento Neural/farmacologia , Paralisia/fisiopatologia
20.
J Cardiovasc Pharmacol ; 22(4): 600-8, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7505363

RESUMO

Continuous nitroglycerin (NTG) administration causes pharmacologic tolerance in humans and animals, whereas intermittent dosing is capable of avoiding or reducing tolerance development. The mechanism of NTG-induced hemodynamic tolerance may involve specific vascular desensitization and/or neurohormonal compensation. We compared effects of long-term (10 days) NTG administration (continuous or intermittent 12 h on/12 h off transdermal dosing, 10 micrograms/min) to rats with congestive heart failure (CHF) on radioligand binding from selected tissues. Tension responses in isolated blood vessels, plasma renin activity (PRA), plasma Na+ and K+ concentrations were also determined. The maximal binding values (Bmax) for [3H]glyburide and [3H]PN 200 110 in homogenates of left ventricle, right ventricle, and brain were not significantly different after NTG administration (continuous or intermittent), as compared with control. Intermittent, but not continuous, NTG caused significant increases in beta-adrenoceptor densities in the left ventricle, as judged by [3H]dihydroalprenolol binding (Bmax values: intermittent NTG 34.5 +/- 4.8, continuous NTG 24.4 +/- 2.6, placebo control 20.9 +/- 2.9 fmol/mg protein); Kd values for all ligands were not significantly altered by NTG administration. Both intermittent and continuous NTG increased the vascular contractile response to phenylephrine in isolated rat thoracic aorta. Slight reductions (two- to four-fold shifts in EC50 values) in thoracic aorta relaxant response to NTG were observed in both treatment groups as compared with control. Intermittent and continuous NTG administration caused selective changes in beta-adrenoceptor density and vascular response. These changes may contribute partly to the phenomenon of pharmacologic tolerance after chronic nitrate administration.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Canais Iônicos/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miocárdio/metabolismo , Nitroglicerina/farmacologia , Receptores Adrenérgicos/metabolismo , Administração Cutânea , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Sítios de Ligação , Tolerância a Medicamentos , Glibureto/metabolismo , Insuficiência Cardíaca/metabolismo , Técnicas In Vitro , Isradipino/metabolismo , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Nitroglicerina/administração & dosagem , Potássio/sangue , Ensaio Radioligante , Ratos , Renina/sangue , Sódio/sangue
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