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1.
Muscle Nerve ; 24(3): 428-32, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11353432

RESUMO

The purpose of this study was to assess the impact of prednisone treatment for 8 weeks on the level of transforming growth factor-beta 1 (TGF-beta1), hydroxyproline (HYP) concentrations, and level of the mature, nonreducible collagen cross-link hydroxylysylpyridinoline (HP) in diaphragm muscle from 12-week-old mdx mice. Diaphragm muscle from untreated mdx mice had a significantly higher level of TGF-beta1, HYP, and HP cross-link compared with normal C57BL/10J (control) mice. Prednisone treatment significantly reduced the level of TGF-beta1 and HYP in diaphragm from mdx mice to values similar to control mice, but resulted in a higher level of the HP cross-link compared with untreated mdx mice. These findings indicate that short-term treatment of mdx mice with prednisone can attenuate the fibrotic response in diaphragm muscle, possibly by mediating the level of TGF-beta. Although prednisone was beneficial in preventing collagen accumulation, it resulted in a higher level of the HP cross-link, presumably by decreasing collagen turnover


Assuntos
Colágeno/análise , Diafragma/química , Glucocorticoides/farmacologia , Prednisona/farmacologia , Fator de Crescimento Transformador beta/análise , Animais , Reagentes de Ligações Cruzadas/análise , Diafragma/efeitos dos fármacos , Hidroxiprolina/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Fator de Crescimento Transformador beta1
2.
Neuromuscul Disord ; 10(4-5): 235-9, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10838248

RESUMO

The genetically dystrophin-deficient mdx mouse, with its characteristic and regular exercise-induced loss of strength, is a useful experimental platform on which to screen potential drug therapies in the treatment of some dystrophic diseases. Pharmacological agents of several chemical and functional classes were examined in their ability to reduce the loss of muscular strength in young exercised mdx mice. Therapeutic intervention over the period 4-10 weeks of age was evaluated in weekly tests of whole-body strength. This age period represents the most severe manifestation of disease in these animals. Significant improvements in whole-body strength were brought about by treatment with the immunosuppressive and anti-inflammatory drugs prednisone (at low dose only, 1 mg/kg body weight), pentoxifylline (100 mg/kg) and tinset (100 mg/kg). The anabolic hormone insulin-like growth factor-1 (5 mg/kg), as well as the amino acids/metabolites glutamine (10 mg/kg), glutamine plus alanine (each 10 mg/kg), and creatinine (10 mg/kg) all improved strength test performance. The mdx mouse is a responsive system for the screening of potential therapeutic treatments for the muscular dystrophies.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Distrofia Muscular de Duchenne/fisiopatologia
3.
Res Commun Mol Pathol Pharmacol ; 91(3): 287-96, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8829768

RESUMO

Exercised mdx mice were used to evaluate the efficacy of two pharmacologic entities, cromolyn and compound 48/80. Beginning at 2 weeks of age, mdx mice were treated with either cromolyn (50 mg/kg/day), prednisone (2mg/kg/day), compound 48/80 (1mg/kg/day), or diluent vehicle. At 4 weeks of age, treated mice were subjected to twice weekly, forced treadmill running which has previously been shown to cause expressed weakness in mdx mice (Hudecki, Pollina et al., 1993). Strength was evaluated weekly through 6 weeks of age using a previously described "pull-test" procedure (Hudecki, Pollina et al., 1993). Serum creatine kinase (CK) and mast cell tryptase activities were evaluated from 6 week blood samples. There was a significant increase in strength in mdx mice treated with cromolyn (p < or = 0.05), while no significant increase in strength was found in mice treated with compound 48/80, or prednisone compared to vehicle controls. While no significant change in tryptase activity was found between treatments, CK activity was significantly increased in the cromolyn group compared to vehicle controls. However, when tryptase and CK were expressed as a combined factor (Tryp x CK), the cromolyn treated group was significantly different from all other groups. The results of this study suggest a possible use for cromolyn-like compounds in the treatment of Duchenne muscular dystrophy.


Assuntos
Antiasmáticos/farmacologia , Cromolina Sódica/farmacologia , Esforço Físico/efeitos dos fármacos , Envelhecimento/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Quimases , Creatina Quinase/sangue , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/enzimologia , Camundongos , Camundongos Endogâmicos mdx , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Prednisona/farmacologia , Serina Endopeptidases/sangue , Triptases , p-Metoxi-N-metilfenetilamina/farmacologia
4.
J Neurol Sci ; 131(1): 1-7, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7561939

RESUMO

Dystrophin-deficient female mdx mice were bred with male Tsk+/+ pa mice to examine the role played by mast cells in the pathophysiology of dystrophin deficiency. Resultant mdx/Tsk double-mutant mice were then examined functionally, biochemically, and histologically. While mdx mice remained as strong as their normal counterparts, mdx/Tsk double-mutant mice became progressively weak with age. Serum creatine kinase activity was significantly elevated in both mdx and mdx/Tsk double-mutant mice over normal controls. However, mast cell-derived plasma tryptase activity was consistently higher in the double-mutant than in mdx mice. In addition, histological examination of gastrocnemius muscle revealed that while necrosis was persistent in both strains of mdx mice from 2 to 8 weeks of age, regeneration was significantly reduced in the double-mutant mice. Of particular interest was the fact that necrosis in the mdx/Tsk double mutant exceeded mdx values at 8 weeks of age, corresponding approximately with a second peak in tryptase activity. Therefore, heightened mast cell activity appears to elicit in the dystrophin-deficient mdx mouse a myopathy not unlike the human Duchenne disease.


Assuntos
Mastócitos/fisiologia , Distrofia Muscular Animal/genética , Mutação , Animais , Quimases , Creatina Quinase/sangue , Distrofina/deficiência , Distrofina/genética , Feminino , Masculino , Mastócitos/metabolismo , Camundongos , Camundongos Mutantes , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patologia , Necrose/patologia , Fenótipo , Serina Endopeptidases/sangue , Pele/patologia , Triptases
5.
J Appl Physiol (1985) ; 78(6): 2014-9, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7665393

RESUMO

Autosomal-recessive dystrophic chickens were treated in three experimental groups with an intraperitoneal multicomponent drug mixture (50 mg/kg Ep475, 20 mg/kg Cinanserin, 10 mg/kg stanazolol, 100 mg/kg leucine, 0.1 mg/kg insulin, 100 mg/kg glucose, and 50 mg/kg carnitine), percutaneous high-frequency electrostimulation of the pectoralis muscle, or a combination of both drug and electrostimulation treatments. Therapeutic efficacy was determined in each group by measurements of strength, righting ability, and histomorphometric analyses of the pectoralis musculature. Drug treatment alone was found to significantly improve muscular strength, function, and relative myofiber necrosis compared with sham-injected controls. The efficacy of drug treatment was found to be equal to or better than singular electrostimulation treatment; there was no apparent additive effect of electrostimulation. As a result, these findings support the use of drug treatment as a useful nongenetic approach to the management of human muscular dystrophy where there is the potential risk of injury from exercise usage.


Assuntos
Terapia por Estimulação Elétrica , Distrofia Muscular Animal/tratamento farmacológico , Distrofia Muscular Animal/terapia , Fatores Etários , Animais , Carnitina/uso terapêutico , Galinhas , Cinanserina/uso terapêutico , Combinação de Medicamentos , Glucose/uso terapêutico , Injeções Intraperitoneais , Insulina/uso terapêutico , Leucina/uso terapêutico , Estanozolol/uso terapêutico
6.
Res Commun Chem Pathol Pharmacol ; 84(3): 351-62, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7938907

RESUMO

Species-specific differences in the inflammatory response, specifically with regard to mast cells, have been proposed to explain the phenotypic variation among dystrophin-deficient humans, and mdx mice (Gorospe et al., 1994). To test this hypothesis we have intramuscularly injected a mast cell secretogogue into both dystrophin-negative mdx and dystrophin-positive normal mice. Mast cell activity was determined by measuring the activity of mast cell tryptase, while creatine kinase activity was used to determine the course of muscle damage in vivo. Area of damage around the injection site was measured at autopsy, and used as an indication of relative sensitivity to the secretogogue effect of compound 48/80. Mdx mice exhibited more damage in response to intramuscular injection than normal control mice. In addition, mdx mice showed a substantial increase in plasma tryptase activity, followed by a large increase in muscle creatine kinase activity. On the other hand, dystrophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity. These results are consistent with the hypothesis that species-specific differences in mast cell activity, or sensitivity to mast cell products could account for the variation in pathology seen in dystrophin-deficient animals.


Assuntos
Mastócitos/fisiologia , Músculos/patologia , Distrofia Muscular Animal/patologia , p-Metoxi-N-metilfenetilamina/administração & dosagem , Animais , Quimases , Creatina Quinase/sangue , Distrofina/deficiência , Fibrose , Processamento de Imagem Assistida por Computador , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Músculos/efeitos dos fármacos , Distrofia Muscular Animal/sangue , Distrofia Muscular Animal/fisiopatologia , Serina Endopeptidases/sangue , Triptases
7.
Res Commun Chem Pathol Pharmacol ; 79(1): 45-60, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8434132

RESUMO

The dystrophin-deficient, X-linked dystrophic mouse (mdx) was used to evaluate the efficacy of prednisolone treatment. A test protocol was used to take advantage of the quantifiable weakness and disability as well as molecular genetic defect shared with the X-linked Duchenne muscular dystrophy (DMD). Whole-body weakness and fatigue were determined by non-invasive force-transducer physiographic and variable-speed treadmill techniques, respectively. Other measurements included hind-limb muscle protein, calcium, and histomorphology. Subcutaneously-administered prednisolone elicited significant improvements in whole body strength throughout a two-month test period. Increases in strength were also accompanied by measurable increments in running endurance. In fact, prednisolone treatment appeared to protect mdx mice from the stressful effect of continuous running as determined by strength and muscle fiber diameter. Test results from this study support the limited therapeutic benefit observed previously in DMD patients treated with the glucocorticoid.


Assuntos
Distrofia Muscular Animal/tratamento farmacológico , Prednisolona/uso terapêutico , Animais , Cálcio/metabolismo , Fadiga/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/metabolismo , Músculos/patologia , Músculos/fisiopatologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/fisiopatologia , Resistência Física/fisiologia
9.
Res Commun Chem Pathol Pharmacol ; 63(3): 439-50, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2727393

RESUMO

The dystrophic chicken line 413 (University of California, Davis) and its genetically related normal line 412 were investigated for possible differences in serum blood chemistry indices and hepatic cytochrome P-450 content at two and three different ages ex ovo, respectively. There were statistical differences in the serum levels of creatine kinase, SGOT, uric acid, and phosphorus between normal and dystrophic animals at 34 and 48 days ex ovo. In the dystrophic animals, the elevations in uric acid and phosphorus levels may be suggestive of renal dysfunction, while the elevations in SGOT levels may indicate the presence of hepatic abnormalities. The hepatic concentrations of cytochrome P-450 and cytochrome b5 were not different between normal and dystrophic animals at 34, 48, and 70 days ex ovo.


Assuntos
Fígado/metabolismo , Distrofia Muscular Animal/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Galinhas , Técnicas In Vitro , Rim/efeitos dos fármacos , Testes de Função Renal , Fígado/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Distrofia Muscular Animal/sangue , Tamanho do Órgão/efeitos dos fármacos
10.
Biochemistry ; 27(19): 7519-24, 1988 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-2974724

RESUMO

A skeletal muscle membrane fraction enriched in sarcoplasmic reticulum (SR) contained Ca2+-ATPase activity which was stimulated in vitro in normal chickens (line 412) by 6 nM purified bovine calmodulin (33% increase over control, P less than 0.001). In contrast, striated muscle from chickens (line 413) affected with an inherited form of muscular dystrophy, but otherwise genetically similar to line 412, contained SR-enriched Ca2+-ATPase activity which was resistant to stimulation in vitro by calmodulin. Basal levels of Ca2+-ATPase activity (no added calmodulin) were comparable in muscles of unaffected and affected animals, and the Ca2+ optima of the enzymes in normal and dystrophic muscle were identical. Purified SR vesicles, obtained by calcium phosphate loading and sucrose density gradient centrifugation, showed the same resistance of dystrophic Ca2+-ATPase to exogenous calmodulin as the SR-enriched muscle membrane fraction. Dystrophic muscle had increased Ca2+ content compared to that of normal animals (P less than 0.04) and has been previously shown to contain increased levels of immuno- and bioactive calmodulin and of calmodulin mRNA. The calmodulin resistance of the Ca2+-ATPase in dystrophic muscle reflects a defect in regulation of cell Ca2+ metabolism associated with elevated cellular Ca2+ and calmodulin concentrations.


Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Calmodulina/farmacologia , Músculos/enzimologia , Distrofia Muscular Animal/enzimologia , Animais , Soluções Tampão , Cálcio/metabolismo , Fosfatos de Cálcio , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Bovinos , Membrana Celular/enzimologia , Centrifugação com Gradiente de Concentração , Galinhas , Concentração de Íons de Hidrogênio , Músculos/metabolismo , Retículo Sarcoplasmático/enzimologia
11.
Neuron ; 1(5): 411-20, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3078411

RESUMO

Duchenne muscular dystrophy is the result of dystrophin deficiency. We have determined the cell types likely to express the pathogenic effects of this neuromuscular disease by determining the pattern of dystrophin expression in normal cells. We find that all physiological types of muscle cells express dystrophin at similar levels, and that the dystrophin content of various tissues correlates with the myogenic cell population of each tissue. The dystrophin content of brain and spinal cord, however, is found not to correlate with any type of muscle cell, and it is suggested that neurons express dystrophin. The potential involvement of striated muscle fibers, the vasculature, and the nervous system in the etiology of Duchenne muscular dystrophy makes it likely that the disease is a complex disorder of combined pathogenesis. We also find that the dystrophic chicken does not represent an animal model for dystrophin deficiency.


Assuntos
Química Encefálica , Córtex Cerebral/análise , Proteínas Musculares/análise , Músculos/análise , Medula Espinal/análise , Animais , Especificidade de Anticorpos , Complexo Antígeno-Anticorpo/análise , Western Blotting , Células Cultivadas , Galinhas , Cromatografia de Afinidade , Distrofina , Camundongos , Proteínas Musculares/fisiologia , Músculo Liso/análise , Distrofia Muscular Animal/metabolismo , Neuroglia/análise , Neurônios/análise , Especificidade de Órgãos , Ratos
12.
Muscle Nerve ; 11(4): 372-9, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2456462

RESUMO

The effect of denervation on avian muscle alpha-spectrin was examined in fast and slow muscles. Using immunofluorescence, the surgically denervated fast-twitch posterior latissimus dorsi (PLD) exhibited a significant increase in spectrin antigen associated with the sarcolemma and within the sarcoplasm compared with the contralateral innervated control muscle. Using gel electrophoresis followed by immunoblotting, we found a two- to three-fold increase in the levels of spectrin in the denervated PLD over that found in the innervated PLD. These levels were comparable to those found previously in slow and dystrophic muscle. The intrafiber distribution of spectrin is similar between the denervated PLD and the slow-tonic anterior latissimus dorsi (ALD). When spectrin was examined in dystrophic PLD muscle, denervation was found to have no effect. These results support our hypothesis that the concentration of spectrin within muscle fibers reflects the physiological state of those fibers. Changes in spectrin concentration may be a useful probe to study the various alterations in physical parameters found among fast, slow, dystrophic, and denervated fibers.


Assuntos
Galinhas/fisiologia , Denervação Muscular , Músculos/metabolismo , Espectrina/metabolismo , Animais , Autorradiografia , Galinhas/metabolismo , Feminino , Imunofluorescência , Técnicas Imunológicas , Masculino , Concentração Osmolar , Coloração e Rotulagem , Fatores de Tempo
13.
Biochem Biophys Res Commun ; 151(3): 1434-40, 1988 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-2965585

RESUMO

We have reported previously that the pectoralis muscle from three month-old dystrophic chickens with signs of myopathy exhibits increased calmodulin content, elevated calmodulin-specific mRNA (Biochem. Biophys. Res. Commun. 137:507-512, 1986), and reduced sarcoplasmic reticulum (SR) Ca2+-ATPase activity in response to calmodulin exposure in vitro (Clin. Res. 34: 725A, 1986). To determine the early time sequence for development of these abnormalities, we have studied muscle from embryos and post-hatched chickens at various ages. Quantitated by dot blot analysis, there was an approximate two-fold increase in calmodulin-specific mRNA in dystrophic muscle as early as 13 days ex ovo which was maintained throughout development up to three months ex ovo. Similarly, Ca2+-ATPase activity measured in SR membranes from chickens as early as 13 days post-hatch was also found to be resistant to stimulation in vitro by exogenous calmodulin, whereas the enzyme from normal muscle was calmodulin-stimulable. These findings suggest that the genetic lesion expressed in the avian dystrophic animal model involves the loss of normal control of intracellular calcium metabolism early in the maturation of the affected musculature and prior to appearance of disease signs.


Assuntos
ATPases Transportadoras de Cálcio/metabolismo , Calmodulina/genética , Regulação da Expressão Gênica , Distrofia Muscular Animal/enzimologia , Animais , Bovinos , Galinhas , Hibridização de Ácido Nucleico , RNA Mensageiro/metabolismo , Retículo Sarcoplasmático/enzimologia
14.
Biochem Biophys Res Commun ; 137(1): 507-12, 1986 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-3718517

RESUMO

Compared to that of genetically-related normal chickens, pectoralis muscle from the dystrophic chicken contained increased calmodulin measured by radioimmunoassay. Determined by the dot blot procedure, expression of the calmodulin gene was enhanced in muscle from affected animals. The bioactivity of the gene product was normal. Together with previous studies reporting increased cell Ca2+ content in dystrophic muscle, the current findings of increased sarcoplasmic calmodulin suggest the latter is a cellular response to defective Ca2+ transport at the level of cell efflux or intracellular organelle (sarcoplasmic reticulum) uptake.


Assuntos
Calmodulina/genética , Distrofia Muscular Animal/genética , Animais , Galinhas , Regulação da Expressão Gênica , Músculos/fisiologia , Hibridização de Ácido Nucleico , RNA Mensageiro/genética
15.
Proc Natl Acad Sci U S A ; 83(3): 802-6, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2935877

RESUMO

A significant increase in the concentration of spectrin has been observed in dystrophic chicken pectoralis major muscle when compared to normal fast-twitch muscle. In normal muscle, alpha-spectrin-specific immunofluorescence delineates each myofiber with a network pattern of staining at the sarcolemma with little staining within the cytoplasm. In dystrophic fibers, numerous intensely stained areas occur within the cytoplasm and staining at the sarcolemma is increased, thereby obscuring or eliminating the highly regular network arrangement of spectrin usually seen in this region. When immunofluorescence experiments are performed on microsomal vesicles isolated from normal and dystrophic tissues, only a small fraction of normal vesicles are stained, whereas most of the dystrophic vesicles are associated with spectrin. An increase in spectrin concentration is observed using immunoautoradiography of whole muscle and isolated microsomes, thus supporting the immunofluorescent observations described above. The early-age post-hatching when increases in spectrin concentration can be detected and the simplicity of the immunofluorescent technique make this observation useful as a new diagnostic parameter. This observation also shows that the distribution of spectrin and its concentration within nonerythroid cells can be modified by abnormal physiological states; this modification may contribute to subsequent symptoms, such as increased rigidity and abnormal calcium metabolism, that are observed in dystrophy.


Assuntos
Músculos/metabolismo , Distrofia Muscular Animal/metabolismo , Espectrina/metabolismo , Animais , Autorradiografia , ATPases Transportadoras de Cálcio/metabolismo , Galinhas , Imunofluorescência , Distrofia Muscular Animal/genética
16.
Exp Neurol ; 90(1): 53-72, 1985 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3876237

RESUMO

The breast musculature of genetically dystrophic Line 413 and genetically related normal Line 412 chickens were treated in three separate trials with high-frequency electrical stimulation (ES). Beginning on days 7 or 14 ex ovo, each bird received three ES treatments per week. Each stimulation cycle repeated five times per day consisted of 15 s "on" followed by 50 s "off". In the third trial only, the birds were additionally treated beginning day 3 ex ovo with either leucine (100 mg/kg) or the proteinase inhibitor Ep475 (10 mg/kg). ES significantly delayed the onset of righting disability in the dystrophic chickens. However, this improvement was temporary and could be masked by single treatments of either leucine or Ep475. Plasma creatine kinase activities were increased generally in both the stimulated normal and dystrophic birds. In two trials ES increased the relative muscle mass, and in one trial increased protein. ES had little effect on normal muscle mass or protein. However, ES treatment together with either leucine or Ep475 appeared to improve both normal and dystrophic muscle mass and protein. Furthermore ES decreased dystrophic muscle calcium but not acetylcholinesterase activity. On the other hand, ES had no effect on the total normal muscle calcium but increased normal acetylcholinesterase values. In both normal and dystrophic muscle samples, ES treatment in combination with leucine appeared to increase the mean muscle fiber diameters and number of myonuclei, and in the case of the dystrophic muscle, appeared to decrease the relative proportion of vacuolated, degenerating, and intensely oxidative histochemical fibers. In general, stimulation (especially in combination with leucine) appears to alter in varying degrees the phenotypic expression of the muscle disease exhibited in the dystrophic chicken.


Assuntos
Terapia por Estimulação Elétrica , Distrofias Musculares/terapia , Acetilcolinesterase/análise , Animais , Cálcio/análise , Galinhas/genética , Creatina Quinase/sangue , Movimento , Proteínas Musculares/análise , Distrofias Musculares/metabolismo , Distrofias Musculares/fisiopatologia
17.
J Interferon Res ; 5(2): 279-88, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-2409190

RESUMO

Lymphocytes from thymus and spleen of normal (Line 412) and genetically dystrophic (Line 413) chickens produce two types of interferons (IFNs) with different host cell specificities. The first type, referred to as ChIFN-alpha, demonstrates antiviral activity on primary normal chicken embryo (CE) cells. This activity is stable at 60 degrees C for 1 h and, in this respect, ChIFN-alpha is similar to the standard ChIFN-beta. In contrast, the second type, referred to as ChIFN-alpha 1, demonstrates antiviral activity in human and simian cells but not in primary CE cells. This activity is labile at 60 degrees C for 1 h. The amount of these two types of IFNs produced in lymphocytes from the spleen of dystrophic chickens was fourfold greater than that produced from normal chickens under similar experimental conditions. In contrast to the lymphocytes from thymus and spleen, the lymphocytes from the bursa of both the normal and dystrophic chickens produced only one type of IFN, namely ChIFN-alpha 1. The development of antiviral state in human cells by ChIFN-alpha 1 requires host RNA synthesis. Although ChIFN-alpha 1 has antiviral properties similar to HuIFN-alpha in human cells, the two IFNs are not antigenically related.


Assuntos
Interferon Tipo I/biossíntese , Linfócitos/metabolismo , Distrofia Muscular Animal/metabolismo , Animais , Galinhas , Chlorocebus aethiops , Humanos , Interferon Tipo I/farmacologia , Camundongos , Distrofia Muscular Animal/etiologia , RNA/biossíntese , Especificidade da Espécie , Temperatura , Vírus/efeitos dos fármacos
18.
Exp Neurol ; 84(3): 512-23, 1984 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6723877

RESUMO

Genetically homozygous Line 413 dystrophic chickens were given in separate trials daily i.p. injections of aqueous solutions of the calcium blocker drugs, diltiazem, verapamil, or nifedipine. At a dosage of 20 mg/kg/day, drug therapy in each case significantly prolonged the functional ability of the dystrophic chickens as quantitated regularly by a standardized test for righting ability. Enhanced functional ability, however, was not generally accompanied by a decrease in the usually high plasma creatine kinase activity. In addition, there was no change in the pectoralis muscle mass or protein with any of the drug treatments. Moreover, no significant reduction in the abnormally high total muscle calcium was found with calcium blocker treatment. Also, there was no marked change in the histopathology of muscle from the drug-treated dystrophic chickens. We concluded that drugs with calcium entry blocker activity offer only limited benefit in retarding dystrophic symptoms expressed in the chicken (viz., short-term enhancement in righting ability).


Assuntos
Benzazepinas/uso terapêutico , Diltiazem/uso terapêutico , Distrofias Musculares/genética , Nifedipino/uso terapêutico , Verapamil/uso terapêutico , Animais , Cálcio/análise , Galinhas/genética , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Músculos/análise , Distrofias Musculares/tratamento farmacológico , Distrofias Musculares/enzimologia , Distrofias Musculares/patologia
19.
Biochim Biophys Acta ; 803(1-2): 106-14, 1984 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-6696951

RESUMO

Rates of protein degradation and synthesis were determined in myofibrillar and non-myofibrillar fractions and in myofibrillar subunits of cultured muscle cells from normal and dystrophic chick embryos of genetically closely related lines. Growth characteristics of normal and dystrophic cells were identical as measured by DNA, RNA and protein accumulation. Degradation rates of myofibrillar and non-myofibrillar protein determined from label-chase experiments were the same in normal and dystrophic cultures. In similar experiments in which degradation rates of eight different components of the myofibrillar fraction were measured, a spectrum of degradation rates was obtained indicating that myofibril components turn over individually or in groups, rather than as an intact unit. Myosin heavy chain was the slowest turning over component of those measured, while actin was among the most rapid. No differences were found between normals and dystrophics in the turnover of any of the components. Fractional rates of protein synthesis were also determined for the myofibrillar and non-myofibrillar fractions of cultured cells. The rates obtained with normal and dystrophic cells were indistinguishable and were the same for the myofibrillar and non-myofibrillar fractions. Initial amino acid incorporation rates into 17 separate components of the myofibrillar fractions were compared in normal and dystrophic cells. No significant differences were found.


Assuntos
Proteínas Musculares/metabolismo , Distrofia Muscular Animal/metabolismo , Miofibrilas/metabolismo , Animais , Células Cultivadas , Embrião de Galinha , Proteínas Musculares/biossíntese
20.
J Neurol Sci ; 60(1): 55-66, 1983 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6875613

RESUMO

Chickens with inherited muscular dystrophy (Line 413) were treated in two separate trials with daily intraperitoneal injections of 10% DMSO-water solutions containing the proteinase inhibitors, Ep475 and E64. Drug therapy in each case significantly prolonged the functional ability of the treated chickens. Diluent control chickens around day 35 ex ovo characteristically reached a maximum ability to right from the supine position in a standardized functional test for muscle weakness. Subsequently, the control chickens were found to decline progressively in their ability to right. Treatment with the proteinase inhibitors had no effect on the typically elevated levels of plasma creatine kinase activity. In a histological analysis of the affected pectoralis major muscle, drug treatment had no effect on the relative distribution of degenerating, and vacuolated fibers, inflammatory cells, and abnormal fiber diameters. An exception was seen in decreased necrotic fibers of chickens treated with high doses of Ep475. Moreover, both inhibitors had positive effects on two biochemical abnormalities common to the dystrophic pectoralis muscle: increase in noncollagen protein, and reduction in total calcium.


Assuntos
Galinhas/genética , Leucina/análogos & derivados , Distrofia Muscular Animal/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Animais , Cálcio/análise , Creatina Quinase/sangue , Leucina/uso terapêutico , Atividade Motora/efeitos dos fármacos , Proteínas Musculares/análise , Músculos/análise , Distrofia Muscular Animal/sangue , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/patologia , Músculos Peitorais/patologia
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