Fitness as a determinant of oxygen uptake response to constant-load exercise

Exercise performed above the lactate threshold (OLa) produces a slowly-developing phase of oxygen uptake (VO2) kinetics which elevates VO2 above that predicted from the sub-OLa VO2-work rate relationship. This phenomenon has only been demonstrated, to date, in subjects who were relatively homogeneous with respect to fitness. This investigation therefore examined whether this behaviour occurred at a given absolute VO2 or whether it was a characteristic of supra-OLa exercise in a group of subjects with over a threefold range of OLa (990-3000 ml O2.min-1) and peak VO2 (1600-5260 ml O2.min-1). Twelve healthy subjects performed: 1) exhausting incremental cycle ergometer exercise for estimation of OLa (OLa) and peak VO2, and 11) a series of constant-load tests above and below OLa for determination of the VO2 profile and efficiency of work. During all tests expired ventilation, VO2 and carbon dioxide production were monitored breath-by-breath. The efficiency of work determined during incremental exercise (28.1 +/- 0.7%, means +/- SE, n = 12) did not differ from that determined during sub-OLa constant-load exercise (27.4 +/- 0.5%, p greater than 0.05). For constant-load exercise, VO2 rose above that predicted, from the sub-OLa VO2-work rate relationship, for all supra-OLa work rates. This was evident above 990 ml O2.min-1 in the least fit subject but only above 3000 ml O2.min-1 in the fittest subject. As a consequence the efficiency of work was reduced from 27.4 +/- 0.5% for sub-OLa exercise to 22.6 +/- 0.4% (p less than 0.05) at the lowest supra-OLa work rate (i.e. OLa + 20 W, on average).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mitochondrial function as a determinant of recovery or death in cell response to injury

Many pathological conditions can be the cause or the consequence of mitochondrial dysfunction. For instance anoxia, which is initiated by a critical reduction of oxygen availability for mitochondrial oxidations, is followed by a wide variety of mitochondrial alterations. A crucial role in the evolution of cell injury is to be attributed to the direction of operation of the F₀F₁ ATPase, which may turn mitochondria into the major consumers of cellular ATP in the futile attempt to restore the proton electrochemical gradient. On the other hand, functional mitochondria can paradoxically accelerate or exacerbate cell damage. This concept is particularly relevant for the ischemic myocardium. Indeed, inhibition of the respiratory chain or addition of uncouplers of oxidative phosphorylation can both limit the extent of enzyme release in the intact heart and prevent the onset of irreversible morphological changes in isolated myocytes. From studies on different tissues in a variety of pathological conditions a general consensus emerges on the role of intracellular Ca²⁺ overload as a pivotal link between cellular alterations and mitochondrial dysfunction. Oxidative phosphorylation is reduced by a massive mitochondrial uptake of Ca²⁺, resulting in a vicious cycle whereby the reduced ATP availability is followed by a failure of the mechanisms which extrude Ca²⁺ from the sarcoplasm. In addition, the rise in [Ca²⁺]_i could promote opening of the cyclosporin-sensitive mitochondrial permeability transition pore, leading to a sudden _m dissipation. Here, we review the changes in intracellular and intramitochondrial ionic homeostasis occurring during ischemia and reperfusion. In particular, we evaluate the potential contribution of the permeability transition pore to cellular damage and discuss the mechanisms which can determine the cellular fate from a mitochondrial point of view.     

Relation between insufficient response to antihypertensive treatment and poor compliance with treatment: a prospective case-control study

ObjectivesTo prospectively compare compliance with treatment in patients with hypertension responsive to treatment versus patients with treatment resistant hypertension.DesignProspective case-control study.SettingOutpatient department in a large city hospital in Switzerland, providing primary, secondary, and tertiary care.Participants110 consecutive medical outpatients with hypertension and taking stable treatment with at least two antihypertensive drugs for at least four weeks.ResultsComplete data were available for 103 patients, of whom 86 took ⩾80% of their prescribed doses (“compliant”) and 17 took <80% (“non-compliant”). Of the 49 patients with treatment resistant hypertension, 40 (82%) were compliant, while 46 (85%) of the 54 patients responsive to treatment were compliant.ConclusionNon-compliance with treatment was not more prevalent in patients with treatment resistant hypertension than in treatment responsive patients.

What is already known on this topic

For many patients with arterial hypertension, blood pressure cannot be adequately controlled despite treatment with antihypertensive drugsPatients'' poor compliance with treatment is often suggested as the reason for lack of response to antihypertensive drugs

What this study adds

When treatment compliance was monitored in hypertensive patients following stable treatment regimens, no difference in compliance was found between those with treatment resistant hypertension and those responsive to treatmentFactors other than patients'' compliance with treatment regimens should be examined to explain lack of response to antihypertensive drugs     

Reasons for failure of antihypertensive treatment.

One hundred patients whose hypertension was originally well controlled were carefully screened when a routine clinic visit showed that their blood pressure was above 170/100 mm Hg. Simple misconceptions accounted for 75 failures: 38 did not know they had to continue their drugs, 14 thought they should not take antihypertensive drugs if they had not had a meal, 13 did not know which drugs controlled their blood pressure, and 10 believed it was better not to take their drugs on clinic days. Eleven patients were using racemic alpha-methyldopa, which was ineffective; 11 others said they could not afford the drugs; only three intentionally stopped their drugs because of unpleasant side effects. Patients need to be thoroughly informed about their treatment and the number of drugs kept to a minimum.     

SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess

Mineralocorticoids modify salt balance by both stimulating salt intake and inhibiting salt loss. Renal salt retention is accomplished by upregulation of reabsorption, an effect partially mediated by serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the contribution of SGK1 to the regulation of renal function, salt intake, and blood pressure during mineralocorticoid excess. DOCA/1% NaCl treatment increased blood pressure and creatinine clearance to a similar extent in SGK1-deficient sgk1(-/-) and wild-type sgk1(+/+) mice but led to more pronounced increase of proteinuria in sgk1(+/+) mice (by 474 +/- 89%) than in sgk1(-/-) mice (by 154 +/- 31%). DOCA/1% NaCl treatment led to significant increase of kidney weight (by 24%) and to hypokalemia (from 3.9 +/- 0.1 to 2.7 +/- 0.1 mmol/l) only in sgk1(+/+) mice. The treatment enhanced renal Na(+) excretion significantly more in sgk1(+/+) mice (from 3 +/- 1 to 134 +/- 32 micromol.24 h(-1).g body wt(-1)) than in sgk1(-/-) mice (from 4 +/- 1 to 49 +/- 8 micromol.24 h(-1).g body wt(-1)), pointing to SGK1-dependent stimulation of salt intake. With access to two drinking bottles containing 1% NaCl or water, DOCA treatment did not significantly affect water intake in either genotype but increased 1% NaCl intake in sgk1(+/+) mice (within 9 days from 3.5 +/- 0.9 to 16.5 +/- 2.4 ml/day) consistent with DOCA-induced salt appetite. This response was significantly attenuated in sgk1(-/-) mice (from 2.6 +/- 0.6 to 5.9 +/- 0.9 ml/day). Thus SGK1 contributes to the stimulation of salt intake, kidney growth, proteinuria, and renal K(+) excretion during mineralocorticoid excess.     

Receptor noise as a determinant of colour thresholds.

Inferences about mechanisms at one particular stage of a visual pathway may be made from psychophysical thresholds only if the noise at the stage in question dominates that in the others. Spectral sensitivities, measured under bright conditions, for di-, tri-, and tetrachromatic eyes from a range of animals can be modelled by assuming that thresholds are set by colour opponency mechanisms whose performance is limited by photoreceptor noise, the achromatic signal being disregarded. Noise in the opponency channels themselves is therefore not statistically independent, and it is not possible to infer anything more about the channels from psychophysical thresholds. As well as giving insight into mechanisms of vision, the model predicts the performance of colour vision in animals where physiological and anatomical data on the eye are available, but there are no direct measurements of perceptual thresholds. The model, therefore, is widely applicable to comparative studies of eye design and visual ecology.     

Confinement as a determinant of macromolecular structure and reactivity.

The confinement of macromolecules within enclosures or "pores" of comparable dimensions results in significant size- and shape-dependent alterations of macromolecular chemical potential and reactivity. Calculations of the magnitude of this effect for model particles of different shapes in model enclosures of different shapes were carried out using hard particle partition theory developed by Giddings et al. (J. Phys. Chem. 1968. 72:4397-4408). Results obtained indicate that the equilibrium constants of reactions, such as isomerization, self-association, and site binding, that result in significant change in macromolecular size, shape, and/or mobility may be altered within pores by as much as several orders of magnitude relative to the value in the unbounded or bulk phase. Confinement also produces a substantial size-dependent outward force on the walls of an enclosure. These results are likely to be important within the fluid phase of biological media, such as the cytoplasm of eukaryotic cells, containing significant volume fractions of large fibrous structures (e.g., the cytomatrix).     

Heart rate as a determinant of the decay rate of the cardiac inotropic response to sympathetic nervous activity

The cardiac responses to sympathetic nerve stimulation were measured in a series of open-chest, anesthetized dogs. In half the animals, the hearts were in a sinus rhythm; in the remaining animals, the hearts were in an atrioventricular (AV) junctional rhythm. Cocaine markedly prolonged the decay times of the chronotropic responses after cessation of sympathetic stimulation, regardless of the type of rhythm. The decay times of the inotropic responses were only slightly prolonged by cocaine in animals with a sinus rhythm, but the prolongations were pronounced in animals with an AV junctional rhythm. The lower basal heart rate appeared to be more responsible for the greater decay times of the inotropic responses in the animals with an AV junctional rhythm than in those with a sinus rhythm. In a second series of dogs, complete heart block was produced, cocaine was given, AND the hearts were paced at four different frequencies. The mean decay time of the inotropic response to sympathetic stimulation varied inversely AND substantially with the pacing frequency. The change in contraction frequency probably affects the rate of neurotransmitter dissipation from the ventricular myocardium, by altering either the coronary blood flow or the massaging action of the cardiac contractions.     

Climate as a determinant of dung beetle response to native forest replacement by cattle pastures in South America

Anthropogenic disturbance in natural ecosystems reduces the number of species in biological communities and homogenizes their composition across different regions. Climate is one of the main abiotic determinants of species distributions and different factors were proposed as the main climatic drivers. Here we explored the role of regional climate on the local response of dung beetle assemblages to the replacement of native forest by cattle pastures in South America by simultaneously contrasting three climatic hypotheses: energy, seasonality and heterogeneity. We compiled a database by searching published studies comparing dung beetle richness and composition between both native forests and cattle pastures. We calculated the proportional difference in species richness and composition between habitat types. As explanatory variables, we used seven abiotic variables grouped into the three climatic hypotheses. Energy/Productivity: mean annual temperature (°C/year) and total annual precipitation (mm/year). Seasonality: annual thermal amplitude (°C/year), the average coefficient of variation of monthly precipitation and the coefficient of average monthly variation in temperature. Heterogeneity: coefficient of variation of mean annual temperature, coefficient of variation of mean annual precipitation. Using regression analyses and a model selection procedure, we found differences in species richness between native forests and cattle pastures were explained by the coefficient of variation of mean annual precipitation, whereas changes in species composition were explained by total annual precipitation and the coefficient of variation of mean annual precipitation. The response of dung beetle assemblages to livestock grazing in South American forests was associated with precipitation variation. The heterogeneity hypothesis better explained changes in species richness following forest replacement by cattle pastures, while both energy/productivity and heterogeneity hypotheses explained the changes in species composition.     

Exposure to pretreatment hypothermia as a determinant of heat killing

When Chinese hamster ovary (CHO) cells were exposed to 22 degrees C for 2 hr prior to 42.4 degrees C hyperthermia, neither the shoulder region of the survival curve nor the characteristic development of thermotolerance after 3-4 hr of heating were observed. Absolute cell survival after 4 hr at 42.4 degrees C was decreased by a factor of between 10 and 100 (depending on the rate of heating of nonprecooled controls). Conditioning at 30 degrees C for 2 hr, 26 degrees C for 2 hr, or 22 degrees C for 20 min followed by heating to 42.4 degrees C over 30 min did not result in sensitization. Prolonged (16 hr) conditioning at 30 degrees C, however, increased the cytotoxicity of immediate exposure to 41.4 or 45 degrees C with maximum sensitization to 45 degrees C occurring after 6 hr at 30 degrees C. Both 3- and 18-hr pretreatments at 30 degrees C similarly increased the cytotoxicity of 45-41.5 degrees C step-down heating (D0 = 28 min in precooled versus 40 min in nonprecooled cells).     

Obesity as a culture-bound syndrome

Although the term culture-bound syndrome has been used for many years, a concise definition has not been available. The less precise synonym folk illness has implied that such syndromes exist only in other cultures. This paper provides a four-part definition to permit examination and comparison of disease categories in any system, including biomedicine.Anthropologists have tended to view biomedicine as the standard for comparison, and have not examined it in the same critical light as other systems. This may be due in part to a confusion of the biomedical classificatory system (biomedicine per se, emic level) with the biological data on which in is based (etic level). One can in fact retain use of the biological data while analyzing biomedicine, which is understood to include cultural componentsMild-to-moderate obesity in the U.S. today fits the proposed definition of a culture-bound syndrome. This paper offers a brief overview of the evidence that culture has shaped both the definition of the disease over time and its treatment.