RESUMEN
This study describes an evaluation of a community-based psychoeducational intervention, called The Family Series Workshop, for caregivers of community-dwelling persons with Alzheimer's disease or related dementias (ADRD). In a one-group pretest-posttest design, participants (n = 35) attended six weekly sessions. Caregiver stress, coping, and caregiving competence were evaluated along with demographic characteristics of participants. There was a significant improvement found for caregiving competence, and a marginally significant increase in coping with humor. Using regression analysis we also found that coping with humor, along with stress, were significant predictors of caregiving competence. These findings indicate that it is possible to increase caregiving competence utilizing a "grassroots" approach and that it is feasible to hold educational, group discussions on a plethora of challenging caregiving topics.
Asunto(s)
Enfermedad de Alzheimer/enfermería , Cuidadores/psicología , Demencia/enfermería , Conocimientos, Actitudes y Práctica en Salud , Educación del Paciente como Asunto/métodos , Anciano , Educación/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Striated muscle contraction is powered by actin-activated myosin ATPase. This process is regulated by Ca(2+) via the troponin complex. Slow- and fast-twitch fibers of vertebrate skeletal muscle express type I and type II myosin, respectively, and these myosin isoenzymes confer different ATPase activities, contractile velocities, and force. Skeletal muscle troponin has also diverged into fast and slow isoforms, but their functional significance is not fully understood. To investigate the expression of troponin isoforms in mammalian skeletal muscle and their functional relationship to that of the myosin isoforms, we concomitantly studied myosin, troponin T (TnT), and troponin I (TnI) isoform contents and isometric contractile properties in single fibers of rat skeletal muscle. We characterized a large number of Triton X-100-skinned single fibers from soleus, diaphragm, gastrocnemius, and extensor digitorum longus muscles and selected fibers with combinations of a single myosin isoform and a single class (slow or fast) of the TnT and TnI isoforms to investigate their role in determining contractility. Types IIa, IIx, and IIb myosin fibers produced higher isometric force than that of type I fibers. Despite the polyploidy of adult skeletal muscle fibers, the expression of fast or slow isoforms of TnT and TnI is tightly coupled. Fibers containing slow troponin had higher Ca(2+) sensitivity than that of the fast troponin fibers, whereas fibers containing fast troponin showed a higher cooperativity of Ca(2+) activation than that of the slow troponin fibers. These results demonstrate distinct but coordinated regulation of troponin and myosin isoform expression in skeletal muscle and their contribution to the contractile properties of muscle.
Asunto(s)
Contracción Muscular/fisiología , Fibras Musculares Esqueléticas , Músculo Esquelético , Isoformas de Proteínas/metabolismo , Troponina I/metabolismo , Troponina T/metabolismo , Citoesqueleto de Actina/metabolismo , Animales , Calcio/metabolismo , Masculino , Fibras Musculares Esqueléticas/citología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Isoformas de Proteínas/genética , Ratas , Ratas Sprague-Dawley , Troponina I/genética , Troponina T/genéticaRESUMEN
Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue. Triton-skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver-enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by approximately 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
Asunto(s)
Contracción Isométrica , Malaria/fisiopatología , Fatiga Muscular , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/fisiopatología , Animales , Células Cultivadas , Masculino , Ratones , Músculo Esquelético/patologíaRESUMEN
Mitsugumin 29 (MG29) is a transmembrane protein that is normally found in the triad junction of skeletal muscle. Our previous studies have shown that targeted deletion of mg29 from the skeletal muscle resulted in abnormality of the triad junction structure, and also increased susceptibility to muscle fatigue. To elucidate the basis of these effects, we investigated the properties of Ca2+-uptake and -release in toxin-skinned Extensor Digitorium Longus (EDL) muscle fibers from control and mg29 knockout mice. Compared with the control muscle, submaximal Ca2+-uptake into the sarcoplasmic reticulum (SR) was slower and the storage of Ca2+ inside the SR was less in the mutant muscle, due to increased leakage process of Ca2+ movement across the SR. The leakage pathway is associated with the increased sensitivity of Ca2+/caffeine -induced Ca2+ release to myoplasmic Ca2+. Therefore, the increased fatigability of mutant EDL muscles can result from a combination of a slowing of Ca2+ uptake, modification of Ca2+-induced Ca2+ release (CICR), and a reduction in total SR Ca2+ content.
Asunto(s)
Calcio/metabolismo , Calcio/farmacocinética , Homeostasis/fisiología , Fatiga Muscular/fisiología , Proteínas Musculares/genética , Sinaptofisina/análogos & derivados , Sinaptofisina/genética , Animales , Cafeína/farmacología , Homeostasis/efectos de los fármacos , Ionomicina/farmacología , Ratones , Ratones Noqueados , Fatiga Muscular/efectos de los fármacos , Fatiga Muscular/genética , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/fisiología , Retículo Sarcoplasmático/efectos de los fármacos , Retículo Sarcoplasmático/fisiología , Factores de TiempoRESUMEN
Troponin T (TnT) is an essential protein in the Ca2+ regulatory system of striated of muscle. Three fiber type-specific TnT genes have evolved in higher vertebrates to encode cardiac, slow and fast skeletal muscle TnT isoforms. To understand the functional significance of TnT isoforms, we studied the effects of acidosis on the contractility of transgenic mouse cardiac muscle that expresses fast skeletal muscle TnT. Contractility analysis of intact cardiac muscle strips showed that while no differences were detected at physiological pH, the transgenic cardiac muscle had significantly greater decreases in +dF/dtmax at acidic pH than that of the wild-type control. Contractility of skinned cardiac muscles demonstrated that the presence of fast TnT resulted in significantly larger decreases in force and Ca2+ sensitivity at acidic pH than that of the wild-type control. The effect of TnT isoforms on the tolerance of muscle to acidosis may explain the higher tolerance of embryonic versus adult cardiac muscles. The results are consistent with the hypothesis that charge differences in TnT isoforms contribute to the contractility of muscle. The data further support a hypothesis that slow TnT is similar to the cardiac, but not fast, and TnT may contribute to the higher tolerance of slow muscles to stress conditions. Therefore, TnT isoform diversity may contribute to the compatibility of muscle thin filaments to cellular environments in different fiber types, during development and functional adaptation.
Asunto(s)
Acidosis , Ratones Transgénicos/metabolismo , Contracción Miocárdica/fisiología , Miocardio/metabolismo , Troponina T/metabolismo , Animales , Western Blotting , Calcio/metabolismo , Pollos , Expresión Génica , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos C57BL , Fibras Musculares de Contracción Rápida/química , Fibras Musculares de Contracción Rápida/fisiología , Músculo Esquelético/química , Músculo Esquelético/fisiología , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Especificidad de la Especie , Troponina T/genéticaRESUMEN
A lethal form of nemaline myopathy, named "Amish Nemaline Myopathy" (ANM), is linked to a nonsense mutation at codon Glu180 in the slow skeletal muscle troponin T (TnT) gene. We found that neither the intact nor the truncated slow TnT protein was present in the muscle of patients with ANM. The complete loss of slow TnT is consistent with the observed recessive pattern of inheritance of the disease and indicates a critical role of the COOH-terminal T2 domain in the integration of TnT into myofibrils. Expression of slow and fast isoforms of TnT is fiber-type specific. The lack of slow TnT results in selective atrophy of type 1 fibers. Slow TnT confers a higher Ca2+ sensitivity than does fast TnT in single fiber contractility assays. Despite the lack of slow TnT, individuals with ANM have normal muscle power at birth. The postnatal onset and infantile progression of ANM correspond to a down-regulation of cardiac and embryonic splice variants of fast TnT in normal developing human skeletal muscle, suggesting that the fetal TnT isoforms complement slow TnT. These results lay the foundation for understanding the molecular pathophysiology and the potential targeted therapy of ANM.
Asunto(s)
Codón sin Sentido , Fibras Musculares de Contracción Lenta/metabolismo , Músculo Esquelético/metabolismo , Miopatías Nemalínicas/genética , Troponina T/genética , Troponina T/fisiología , Adulto , Factores de Edad , Animales , Biopsia , Western Blotting , Calcio/metabolismo , Codón , Electroforesis en Gel de Poliacrilamida , Escherichia coli/metabolismo , Corazón/embriología , Humanos , Inmunohistoquímica , Lactante , Recién Nacido , Modelos Biológicos , Modelos Genéticos , Miocardio/metabolismo , Miopatías Nemalínicas/metabolismo , Fenotipo , Filogenia , Isoformas de Proteínas , Estructura Terciaria de Proteína , Tinción con Nitrato de Plata , Troponina T/químicaRESUMEN
We investigated the influence of ageing on the fatiguing characteristics of the mouse extensor digitorum longus (EDL) muscle as compared to those of the soleus muscle. Fatigue was produced by an intermittent stimulation protocol. We report for mature and aged animals the effects of fatigue on force produced during stimulation patterns that in non-fatigued muscle gave maximum force (T(max), high frequency stimulation) and approximately half-maximum force (1/2T(max), low frequency stimulation). In 15-month-old (mature) mice, fatiguing stimulation decreased T(max) in EDL and soleus muscle to 10.3 +/- 1.0 % and 33.4 +/- 3.0 % of control, respectively. In 30-month-old (aged) mice, the decrease in T(max) in EDL and soleus was statistically equal to that of the younger animals. Fatiguing stimulation decreased 1/2T(max) in EDL and soleus from 15-month-old animals to 22.5 +/- 2.9 % and 45.7 +/- 0.3 % of control, respectively. In 30-month-old animals, the 1/2T(max) in EDL and soleus muscle decreased to 18.2 +/- 1.3 % and 35.0 +/- 3.6 % of control, respectively. Under all conditions, the soleus fatigued significantly less. Contractile recovery from fatiguing stimulation was complete for the soleus in both age groups after 30 min, but incomplete for the EDL. The 1/2T(max)/T(max) ratio significantly increased in EDL and soleus muscle from 15-month-old animals after fatiguing stimulation. This increase was less significant in EDL, and absent in soleus muscle, from 30-month-old animals. These results indicate that fatiguing stimulation induces a leftward shift in the force-frequency relationship in the young animals; this shift is either significantly less (EDL) or absent (soleus) in the older animals. We speculate that the leftward shift of the force-frequency relationship may reflect a protective mechanism in younger animals against some of the damaging effects of fatiguing stimulation (i.e. oxidative stress).