Bioenergetics and biomechanics of cycling: the role of ‘internal work’

The ‘dissection’ of energy expenditure of cycling into the metabolic equivalent of the different forms of mechanical work done, inaugurated 30 years ago by di Prampero and collaborators, has been much debated in the last few decades. The mechanical internal work, particularly, which is currently associated to the movement of the lower limbs, has been approached, estimated and discussed in several different ways and there is no agreed consensus on its role in cycling. This paper, through re-processing previously published data of oxygen consumption during pedalling at different frequency, external load and limb mass, proposes a model equation and a multiple non-linear regression as the method to assess the internal work of cycling. With that tool a very consistent metabolic equivalent of the internal work is obtained. However, a software simulation of pedalling limbs showed, as suggested in the literature, that the link with the chain ring allows the system to passively revolve forever, after an initial push. This result challenges the very existence of the ‘kinematic internal work’ of cycling. We conclude and suggest that the ‘viscous internal work’, an often neglected and almost unmeasurable portion of the internal work that could be proportional to the ‘kinematic’ form, is responsible for the extra metabolic expenditure as measured when the pedalling frequency of cycling increases.     

Cancer procoagulant in acute lymphoblastic leukemia

In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype.     

Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype

It recently was reported that Duchenne muscular dystrophy (DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscle. However, it remains unknown whether increased caveolin-3 levels in DMD patients contribute to the pathogenesis of DMD. Here, using a genetic approach, we test this hypothesis directly by overexpressing wild-type caveolin-3 as a transgene in mice. Analysis of skeletal muscle tissue from caveolin-3- overexpressing transgenic mice reveals: (i) a dramatic increase in the number of sarcolemmal muscle cell caveolae; (ii) a preponderance of hypertrophic, necrotic, and immature/regenerating skeletal muscle fibers with characteristic central nuclei; and (iii) down-regulation of dystrophin and beta-dystroglycan protein expression. In addition, these mice show elevated serum creatine kinase levels, consistent with the myo-necrosis observed morphologically. The Duchenne-like phenotype of caveolin-3 transgenic mice will provide an important mouse model for understanding the pathogenesis of DMD in humans.     

Mannan and oligomers of N-acetylglucosamine protect intestinal mucosa of celiac patients with active disease from in vitro toxicity of gliadin peptides

Wheat flour and other cereals toxic for celiac patients contain an alcohol-soluble protein fraction that, under experimental conditions simulating in vivo protein digestion, yields peptides that agglutinate undifferentiated K 562(S) cells. In contrast, cereals well tolerated in celiac disease (i.e., rice and maize) do not. Furthermore, purified A-gliadin peptides that damage in vitro-cultured flat celiac mucosa are powerful agglutinins for K 562(S) cells, whereas A-gliadin peptides that do not show any adverse in vitro effect on celiac intestine lack agglutinating activity. Mannan, acetylglucosamine, and its oligomers (N,N'-diacetylchitobiose and N,N',N"-triacetylchitotriose) were able to prevent and reverse cell agglutination induced by peptides from all the toxic cereals. Moreover, mannan and N,N',N"-triacetylchitotriose exhibited a protective effect on intestinal mucosa specimens of patients with active celiac disease cultured with wheat protein-derived peptides. These data are consistent with the hypothesis that the agglutinating and toxic peptides are bound by carbohydrates.