13 research outputs found
Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia
To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles
Synergetic Insulin Sensitizing Effect of Rimonabant and BGP-15 in Zucker-Obes Rats
Abdominal obesity is referred for as a common pathogenic root of
multiple risk factors, which include insulin resistance,
dyslipidemia, hypertension, and a pro-atherogenic and pro-
inflammatory state. Irrespective of its psychiatric side
effects, rimonabant through blocking cannabinoid-1 receptor
(CB1R) induces an increase in whole body insulin sensitivity.
The aim of this work was to study the effect of selected doses
of another insulin sensitizer compound BGP-15, and rimonabant on
insulin resistance in Zucker obese rats with a promise of
inducing insulin sensitization together at lower doses than
would have been expected by rimonabant alone. We found that BGP-
15 potentiates the insulin sensitizing effect of rimonabant. The
combination at doses, which do not induce insulin sensitization
by themselves, improved insulin signaling. Furthermore our
results suggest that capsaicin-induced signal may play a role in
insulin sensitizing effect of both molecules. Our data might
indicate that a lower dose of rimonabant in the treatment of
insulin resistance and type 2 diabetes is sufficient to
administer, thus a lower incidence of the unfavorable
psychiatric side effects of rimonabant are to be expected
Hydroximic Acid Derivatives: Pleiotrophic Hsp Co-Inducers Restoring Homeostasis and Robustness
According to the "membrane sensor" hypothesis, the membranes physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy