Pathophysiology of muscle dysfunction in COPD

Muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD) and may involve both respiratory and locomotor (peripheral) muscles. The loss of strength and/or endurance in the former can lead to ventilatory insufficiency, whereas in the latter it limits exercise capacity and activities of daily life. Muscle dysfunction is the consequence of complex interactions between local and systemic factors, frequently coexisting in COPD patients. Pulmonary hyperinflation along with the increase in work of breathing that occur in COPD appear as the main contributing factors to respiratory muscle dysfunction. By contrast, deconditioning seems to play a key role in peripheral muscle dysfunction. However, additional systemic factors, including tobacco smoking, systemic inflammation, exercise, exacerbations, nutritional and gas exchange abnormalities, anabolic insufficiency, comorbidities and drugs, can also influence the function of both respiratory and peripheral muscles, by inducing modifications in their local microenvironment. Under all these circumstances, protein metabolism imbalance, oxidative stress, inflammatory events, as well as muscle injury may occur, determining the final structure and modulating the function of different muscle groups. Respiratory muscles show signs of injury as well as an increase in several elements involved in aerobic metabolism (proportion of type I fibers, capillary density, and aerobic enzyme activity) whereas limb muscles exhibit a loss of the same elements, injury, and a reduction in fiber size. In the present review we examine the current state of the art of the pathophysiology of muscle dysfunction in COPD.

Armazenamento de abacaxi 'smooth cayenne' minimamente processado sob refrigeração e atmosfera modificada

Estudou-se a influência de diferentes atmosferas modificadas durante o armazenamento de abacaxis da cv. Smooth Cayenne minimamente processados, por um período de oito dias, a 5º C e 85% UR. Foram realizadas as análises de acidez total titulável (ATT), sólidos solúveis totais (SST), pH, líquido drenado (LD), pectina total (PT), pectina solúvel (PS), firmeza e determinou-se a atividade das enzimas polifenoloxidase (PFO) e poligalacturonase (PG) da polpa dos frutos, a cada 2 dias. Os tratamentos utilizados foram: atmosferas modificadas com a injeção de 5% de O2 e 5% de CO2, com 2% de O2 e 10% de CO2 e o Controle (atmosfera modificada passivamente). As atmosferas modificadas ativas apresentaram ação injuriosa sobre os tecidos do abacaxi minimamente processado, estimulando a atividade da PFO. O uso de atmosferas modificadas proporcionou menor atividade da PG e, conseqüentemente, menor solubilização de substâncias pécticas. O abacaxi cv. Smooth Cayenne, minimamente processado, apresentou uma vida útil de 6 dias, pois, embora suas principais características físicas e físico-químicas não tenham sido comprometidas, as alterações químicas e bioquímicas não permitiram que o produto atingisse os 8 dias de armazenamento previstos.

Qualidade do abacaxi cv Smooth Cayenne minimamente processado

O objetivo deste trabalho foi verificar a qualidade e o tempo de conservação de abacaxis minimamente processados, sob armazenamento a 8ºC e 85% U.R., influenciados pelo tipo de corte, o uso ou não de sanificação com hipoclorito de sódio e o tipo de embalagem. Foram analisados os seguintes parâmetros: acidez titulável total, sólidos solúveis totais, pH, aparência, fungos e leveduras, coliformes totais e fecais. Concluiu-se que: a) o tipo de corte não influenciou nas características físico-químicas e químicas do abacaxi durante o armazenamento; b) o baixo pH, a sanificação e o uso de Boas Práticas de Fabricação inibiram o crescimento de bactérias do grupo coliforme; c) a sanificação com hipoclorito não foi eficiente no controle de fungos e leveduras; d) os produtos tiveram uma vida útil de prateleira de 6 dias, sob as condições oferecidas.

Épocas de indução floral e soma térmica do período do florescimento à colheita de abacaxi 'Smooth Cayenne'

Na produção do abacaxi, é importante conhecer o efeito do clima no ciclo da cultura. O objetivo do trabalho foi estudar as somas térmicas do período da indução floral à colheita de abacaxi 'Smooth Cayenne' para diferentes épocas de indução floral no Norte do Paraná e sua influência na produção e qualidade dos frutos. Os tratamentos foram indução floral artificial com ethephon, nos meses de abril, maio, junho e julho, além da testemunha, induzida naturalmente. A inflorescência surgiu aos 115,5; 107,3; 77,3 e 48,3 dias após a indução floral, respectivamente, para os tratamentos de abril, maio, junho e julho. O período entre o surgimento da inflorescência e a colheita foi de 163 dias para a indução de abril, maior do que o observado para os demais tratamentos (144 a 151 dias). O tratamento de abril proporcionou frutos menores do que o de julho, mas a acidez titulável, o teor de sólidos solúveis e o "ratio" não foram influenciados pelas épocas de aplicação do indutor. A soma térmica média do período entre o florescimento e a colheita foi de 1.090 graus-dia, sem diferenças estatísticas entre as épocas de indução floral.

Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice

Background: Aging results in a progressive loss of skeletal muscle, a condition known as sarcopenia. Mitochondrial DNA (mtDNA) mutations accumulate with aging in skeletal muscle and correlate with muscle loss, although no causal relationship has been established. Methodology/Principal Findings: We investigated the relationship between mtDNA mutations and sarcopenia at the gene expression and biochemical levels using a mouse model that expresses a proofreading-deficient version (D257A) of the mitochondrial DNA Polymerase c, resulting in increased spontaneous mtDNA mutation rates. Gene expression profiling of D257A mice followed by Parametric Analysis of Gene Set Enrichment (PAGE) indicates that the D257A mutation is associated with a profound downregulation of gene sets associated with mitochondrial function. At the biochemical level, sarcopenia in D257A mice is associated with a marked reduction (35–50%) in the content of electron transport chain (ETC) complexes I, III and IV, all of which are partly encoded by mtDNA. D257A mice display impaired mitochondrial bioenergetics associated with compromised state-3 respiration, lower ATP content and a resulting decrease in mitochondrial membrane potential (Dym). Surprisingly, mitochondrial dysfunction was not accompanied by an increase in mitochondrial reactive oxygen species (ROS) production or oxidative damage. Conclusions/Significance: These findings demonstrate that mutations in mtDNA can be causal in sarcopenia by affecting the assembly of functional ETC complexes, the lack of which provokes a decrease in oxidative phosphorylation, without an increase in oxidative stress, and ultimately, skeletal muscle apoptosis and sarcopenia.

Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits

BACKGROUND: Selection for increasing intramuscular fat content would definitively improve the palatability and juiciness of pig meat as well as the sensorial and organoleptic properties of cured products. However, evidences obtained in human and model organisms suggest that high levels of intramuscular fat might alter muscle lipid and carbohydrate metabolism. We have analysed this issue by determining the transcriptomic profiles of Duroc pigs with divergent phenotypes for 13 fatness traits. The strong aptitude of Duroc pigs to have high levels of intramuscular fat makes them a valuable model to analyse the mechanisms that regulate muscle lipid metabolism, an issue with evident implications in the elucidation of the genetic basis of human metabolic diseases such as obesity and insulin resistance. RESULTS: Muscle gene expression profiles of 68 Duroc pigs belonging to two groups (HIGH and LOW) with extreme phenotypes for lipid deposition and composition traits have been analysed. Microarray and quantitative PCR analysis showed that genes related to fatty acid uptake, lipogenesis and triacylglycerol synthesis were upregulated in the muscle tissue of HIGH pigs, which are fatter and have higher amounts of intramuscular fat than their LOW counterparts. Paradoxically, lipolytic genes also showed increased mRNA levels in the HIGH group suggesting the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Several genes related to the insulin-signalling pathway, that is usually impaired in obese humans, were also upregulated. Finally, genes related to antigen-processing and presentation were downregulated in the HIGH group. CONCLUSION: Our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to to elucidate the effects of lipid deposition on muscle metabolism in pigs.

Correlations of glycogen synthase and phosphorylase activities with glycogen concentration in human muscle biopsies. Evidence for a double-feedback mechanism regulating glycogen synthesis and breakdown.

The purpose of this study was to verify in man the relationships of muscle glycogen synthase and phosphorylase activities with glycogen concentration that were reported in animal studies. The upper level of glycogen concentration in muscle is known to be tightly controlled, and glycogen concentration was reported to have an inhibitory effect on synthase activity and a stimulatory effect on phosphorylase activity. Glycogen synthase and phosphorylase activity and glycogen concentration were measured in muscle biopsies in a group of nine normal subjects after stimulating an increase of their muscle glycogen concentration through either an intravenous glucose-insulin infusion to stimulate glycogen synthesis, or an Intralipid (Vitrum, Stockholm, Sweden) infusion in the basal state to inhibit glycogen mobilization by favoring lipid oxidation at the expense of glucose oxidation. Phosphorylase activity increased from 71.3 +/- 21.0 to 152.8 +/- 20.0 nmol/min/mg protein (P < .005) after the glucose-insulin infusion. Phosphorylase activity was positively correlated with glycogen concentration (P = .005 and P = .0001) after the glucose-insulin and Intralipid infusions, respectively. Insulin-stimulated glycogen synthase activity was significantly negatively correlated with glycogen concentration at the end of the Intralipid infusion (P < .005). In conclusion, by demonstrating a negative correlation of glycogen concentration with glycogen synthase and a positive correlation with phosphorylase, this study might confirm in man the double-feedback mechanism by which changes in glycogen concentration regulate glycogen synthase and phosphorylase activities. It suggests that this mechanism might play an important role in the regulation of glucose storage.

Results of Anterior Tucking of the Superior Oblique Muscle Tendon in Bilateral Fourth Nerve Palsy.

Background: Bilateral fourth nerve palsy is characterised by excyclotorsion, which can be corrected by reinforcement of the anterior tendon fibres of the superior oblique muscle. Patients and Methods: A retrospective study of 40 consecutive patients with bilateral acquired fourth nerve palsy operated by a selective tuck of the anterior portion of the superior oblique tendon between 1994 and 2012 was undertaken. Horizontal, vertical and torsional deviations were measured in 9 diagnostic positions of gaze and the field of binocular single vision was evaluated with the Harms tangent screen. Postoperative follow-ups took place at 1 week, 6 months, and ≥ 3 years. Results: Preoperative mean excyclotorsion was 9° in the primary position and 15° in downgaze. These values decreased to 2° and 5° 6 months after surgery, and 2.5° and 6° at ≥ 3 years. Immediate post-operative incyclotorsion in upgaze (28 patients) and Brown syndrome (15 patients) regressed spontaneously. The median score of field of binocular single vision improved from 4 % preoperatively to 76 % postoperatively. Conclusions: The selective tuck of the anterior tendon fibers of the superior oblique tendon enables an efficient and long-lasting correction of the ocular torsion induced by bilateral trochlear palsy.

Resposta à adubação com uréia, cloreto de potássio e ácido bórico em mudas abacaxizeiro'Smooth Cayenne'

Mudas do abacaxizeiro (Ananas comosus L.), cultivar Smooth Cayenne, obtidas por seccionamento de caule, foram submetidas à adubação foliar com soluções em diferentes concentrações de uréia, KCl e H3BO3. O delineamento utilizado foi fatorial fracionado do tipo (1/5)5³, com três tipos de adubo e cinco concentrações, num total de 25 tratamentos, que consistiram de combinações de concentrações de 0; 2,5; 5,0; 7,5 e 10 g L-1 de uréia e KCl, e 0; 0,5; 1,0; 1,5 e 2,0 g L-1 de H3BO3. Os tratamentos foram iniciados nove semanas após o plantio das seções do caule, com 26 pulverizações semanais para a uréia e KCl e 4 pulverizações mensais para o H3BO3. Verificou-se crescimento linear positivo para as características: altura das brotações, número de folhas, área foliar, massa seca e fresca das mudas, em resposta a níveis crescentes de uréia. Não foi observado efeito do KCl e H3BO3 para nenhuma das características de crescimento avaliadas. As mudas adubadas com 10 g L-1 de uréia atingiram altura de 40 cm e massa fresca de 242 g no 9º mês após o plantio das seções.

Efeito do Paclobutrazol no controle da diferenciação floral natural do abacaxizeiro cv. Smooth Cayenne

O abacaxizeiro é uma planta de grande importância econômica, porém seu florescimento natural causa sérios problemas, tornando seu manejo difícil devido à desuniformidade de frutos e colheitas, elevando o custo de produção. O objetivo deste trabalho foi manipular o florescimento do abacaxizeiro, contribuindo para uma produção uniforme colocada no mercado, nos meses de menor oferta. Utilizou-se o Paclobutrazol (PBZ) nas concentrações de 100; 150 e 200 mg L-1, em 2; 3 ou 4 aplicações via foliar, em plantas de abacaxi cv. Smooth Cayenne, no município de Presidente Alves-SP. O delineamento empregado foi em blocos ao acaso, com 10 tratamentos e três repetições, com 40 plantas por parcela experimental. No período de 100 a 150 dias após a primeira aplicação dos tratamentos, efetuaram-se as contagens de inflorescências presentes no centro da roseta foliar das plantas. Todos os tratamentos com Paclobutrazol inibiram a diferenciação floral natural do abacaxizeiro, recomendando-se a concentração de 150 mg L-1 em duas aplicações, com início em abril, a intervalo de 15 dias.

Interplay between connexin40 and nitric oxide signaling during hypertension.

Connexins (Cxs) and endothelial nitric oxide synthase (eNOS) contribute to the adaptation of endothelial and smooth muscle cells to hemodynamic changes. To decipher the in vivo interplay between these proteins, we studied Cx40-null mice, a model of renin-dependent hypertension which displays an altered endothelium-dependent relaxation of the aorta because of reduced eNOS levels. These mice, which were either untreated or subjected to the 1-kidney, 1-clip (1K1C) procedure, a model of volume-dependent hypertension, were compared with control mice submitted to either the 1K1C or the 2-kidney, 1-clip (2K1C) procedure, a model of renin-dependent hypertension. All operated mice became hypertensive and featured hypertrophy and altered Cx expression of the aorta. The combination of volume- and renin-dependent hypertension in Cx40-/- 1K1C mice raised blood pressure and cardiac weight index. Under these conditions, all aortas showed increased levels of Cx40 in endothelial cells and of both Cx37 and Cx45 in smooth muscle cells. In the wild-type 1K1C mice, the interactions between Cx40 and Cx37 with eNOS were enhanced, resulting in increased NO release. The Cx40-eNOS interaction could not be observed in mice lacking Cx40, which also featured decreased levels of eNOS. In these animals, the volume overload caused by the 1K1C procedure resulted in increased phosphorylation of eNOS and in a higher NO release. The findings provide evidence that Cx40 and Cx37 play an in vivo role in the regulation of eNOS.