RESUMEN
AIMS: We assessed focal adhesion kinase (FAK) response to concentric (CON) vs eccentric (ECC) resistance training (RT) at two vastus lateralis (VL) sites, and the relationships between FAK, muscle protein synthesis (MPS) and morphological remodelling. METHODS: Six young males trained both legs unilaterally 3 times/week for 8 weeks; one leg performed CON RT, the contralateral performed ECC RT. Muscle biopsies were collected after training from VL mid-belly (MID) and distal (distal) sites at 0, 4, 8 weeks. Focal adhesion kinase content and activation were evaluated by immunoblotting. MPS was assessed by deuterium oxide tracer; morphological adaptations were evaluated by ultrasound and DXA. RESULTS: pY397-FAK 8 weeks levels were ~4-fold greater after ECC at the distal site compared to CON (P < .05); pY397FAK to total FAK ratio was greater in ECC vs CON at 4 (~2.2-fold, P < .05) and 8 weeks (~9-fold, P < .001) at the distal site. Meta-vinculin was found transiently increased at 4 weeks at the distal site only after ECC RT. ECC presented greater fascicle length (Lf) increases (10.5% vs 4%), whereas CON showed greater in pennation angle (PA) changes (12.3% vs 2.1%). MPS did not differ between exercise types or muscle sites at all time points. distal pY397-FAK and pY397-FAK/FAK values correlated to changes in Lf at 8 weeks (r = .76, P < .01 and r = .66, P < .05 respectively). CONCLUSION: Focal adhesion kinase phosphorylation was greater at 8 weeks after ECC RT and was muscle region-specific. FAK activity correlated to contraction-dependent architectural remodelling, suggesting a potential role of FAK in orienting muscle structural changes in response to distinct mechanical stimuli.
Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Proteínas Musculares/biosíntesis , Músculo Cuádriceps/enzimología , Entrenamiento de Fuerza , Adolescente , Adulto , Humanos , Masculino , Miosinas del Músculo Esquelético/metabolismo , Vinculina/metabolismo , Adulto JovenRESUMEN
Skeletal muscle responds to endurance exercise with an improvement of biochemical pathways that support substrate supply and oxygen-dependent metabolism. This is reflected by enhanced expression of associated factors after exercise and is specifically modulated by tissue perfusion and oxygenation. We hypothesized that transcript expression of pro-angiogenic factors (VEGF, tenascin-C, Angpt1, Angpt1R) and oxygen metabolism (COX4I1, COX4I2, HIF-1α) in human muscle after an endurance stimulus depends on vasoconstriction, and would be modulated through angiotensin-converting enzyme inhibition by intake of lisinopril. Fourteen non-specifically trained, male Caucasians subjects, carried out a single bout of standardized one-legged bicycle exercise. Seven of the participants consumed lisinopril in the 3 days before exercise. Biopsies were collected pre- and 3 h post-exercise from the m. vastus lateralis. COX4I1 (P = 0.03), COX4I2 (P = 0.04) mRNA and HIF-1α (P = 0.05) mRNA and protein levels (P = 0.01) showed an exercise-induced increase in the group not consuming the ACE inhibitor. Conversely, there was a specific exercise-induced increase in VEGF transcript (P = 0.04) and protein levels (P = 0.03) and a trend for increased tenascin-c transcript levels (P = 0.09) for subjects consuming lisinopril. The observations indicate that exercise-induced expression of transcripts involved in angiogenesis and mitochondrial energy metabolism are to some extent regulated via a hypoxia-related ACE-dependent mechanism.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Ejercicio Físico/fisiología , Lisinopril/farmacología , Mitocondrias/genética , ARN/metabolismo , Transcripción Genética/efectos de los fármacos , Adulto , Angiopoyetina 1/genética , Angiopoyetina 1/metabolismo , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Metabolismo Energético/efectos de los fármacos , Prueba de Esfuerzo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Mitocondrias/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Músculo Cuádriceps/fisiología , ARN Mitocondrial , Tenascina/genética , Tenascina/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
We report a case study of a 22-year-old woman with mitochondrial thymidine kinase 2 deficiency and chronic respiratory failure due to severe neuromuscular weakness requiring noninvasive positive pressure ventilation (NIPPV) since 12 years of age. During pregnancy and cesarean delivery, she was successfully supported with NIPPV. A multidisciplinary team approach should be used in pregnant patients with these disorders with specific attention to management of pulmonary complications, selection of route of delivery, anesthesia, and analgesia.
Asunto(s)
Cesárea , Miopatías Mitocondriales , Complicaciones del Embarazo , Insuficiencia Respiratoria/terapia , Adulto , Femenino , Humanos , Respiración con Presión Positiva , EmbarazoAsunto(s)
Celulosa , Granuloma de Cuerpo Extraño/diagnóstico por imagen , Aumento de la Imagen , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Acetaminofén/efectos adversos , Adulto , Diagnóstico Diferencial , Combinación de Medicamentos , Granuloma de Cuerpo Extraño/patología , Humanos , Hidrocodona/efectos adversos , Masculino , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Nódulo Pulmonar Solitario/patología , Abuso de Sustancias por Vía Intravenosa/complicacionesAsunto(s)
Aspergilosis Broncopulmonar Alérgica/diagnóstico , Aspergilosis Broncopulmonar Alérgica/terapia , Enfermedades Pulmonares Fúngicas/diagnóstico , Enfermedades Pulmonares Fúngicas/terapia , Enfermedades Pulmonares/fisiopatología , Enfermedades Nasales/fisiopatología , Hipersensibilidad Respiratoria/diagnóstico , Hipersensibilidad Respiratoria/terapia , Sinusitis/diagnóstico , Sinusitis/terapia , Aspergilosis Broncopulmonar Alérgica/complicaciones , Diagnóstico Diferencial , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Hipersensibilidad Respiratoria/complicaciones , Sinusitis/complicacionesAsunto(s)
Alveolitis Alérgica Extrínseca/inducido químicamente , Alveolitis Alérgica Extrínseca/diagnóstico por imagen , Antineoplásicos Fitogénicos/efectos adversos , Paclitaxel/efectos adversos , Tomografía Computarizada por Rayos X , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Factores de TiempoRESUMEN
STUDY OBJECTIVES: To investigate the hypothesis that an increase in circulating vascular endothelial growth factor (VEGF) occurs in mountaineers at high altitude, particularly in association with acute mountain sickness (AMS) and/or low hemoglobin oxygen saturation. DESIGN: : Collection of medical histories, AMS scores, plasma samples, and arterial oxygen saturation (SaO(2)) measurements from mountaineers at 1,500 feet (sea level) and at 14,200 feet. SETTING: Mount McKinley ("Denali"), AK. PARTICIPANTS: Sixty-six mountaineers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Plasma VEGF at 14,200 feet was not increased in any group. In fact, plasma VEGF was significantly lower in subjects who did not develop AMS (53 +/- 7.9 pg/mL; mean +/- SEM; n = 47) compared to control subjects at sea level (98.4 +/- 14.3 pg/mL; n = 7; p = 0.005). Plasma VEGF at 14, 200 feet for subjects with AMS (62 +/- 12 pg/mL; n = 15) did not differ significantly from subjects at 14,200 feet without AMS, or from control subjects at sea level. Of a small number of subjects with paired specimens at sea level and at base camp (n = 5), subjects who exhibited a decrease in plasma VEGF at 14,200 feet were those who did not develop AMS. Neither SaO(2), prior AMS, AMS symptom scores, or acetazolamide use were correlated with plasma VEGF. CONCLUSIONS: Subjects at high altitude who do not develop AMS have lower plasma VEGF levels compared to control subjects at sea level. Plasma VEGF at high altitude is not elevated in association with AMS or hypoxia. Sustained plasma VEGF at altitude may reflect a phenotype more susceptible to AMS.
Asunto(s)
Mal de Altura/sangre , Factores de Crecimiento Endotelial/sangre , Linfocinas/sangre , Isoformas de Proteínas/sangre , Adulto , Mal de Altura/genética , Femenino , Humanos , Hipoxia/sangre , Masculino , Oximetría , Fenotipo , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularAsunto(s)
Linfangiectasia/diagnóstico , Linfangioma/diagnóstico , Linfedema/diagnóstico , Neoplasias Torácicas/diagnóstico , Diagnóstico Diferencial , Humanos , Linfangiectasia/patología , Linfangiectasia/terapia , Linfangioma/patología , Linfangioma/terapia , Sistema Linfático/patología , Linfedema/patología , Linfedema/terapia , Pronóstico , Síndrome , Neoplasias Torácicas/patología , Neoplasias Torácicas/terapiaRESUMEN
Anthrax, a disease of great historical interest, is once again making headlines as an agent of biological warfare. Bacillus anthracis, a rod-shaped, spore-forming bacterium, primarily infects herbivores. Humans can acquire anthrax by agricultural or industrial exposure to infected animals or animal products. More recently, the potential for intentional release of anthrax spores in the environment has caused much concern. The common clinical manifestations of anthrax are cutaneous disease, pulmonary disease from inhalation of anthrax spores, and GI disease. The course of inhalational anthrax is dramatic, from the insidious onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension, and hemorrhage within days of exposure. A rapid decline, culminating in septic shock, respiratory distress, and death within 24 h is not uncommon. The high mortality seen in inhalational anthrax is in part due to delays in diagnosis. Classic findings on the chest radiograph include widening of the mediastinum as well as pleural effusions. Pneumonia is less common; key pathologic manifestations include severe hemorrhagic mediastinitis, diffuse hemorrhagic lymphadenitis, and edema. Diagnosis requires a high index of suspicion. Treatment involves supportive care in an intensive care facility and high doses of penicillin. Resistance to third-generation cephalosporins has been noted. Vaccines are currently available and have been shown to be effective against aerosolized exposure in animal studies.