Background: (Papers I and II) The objectives were to first determine incidence and contributing factors to cold-related injuries in northern Sweden, both those that led to hospitalization and those that led to fatality.  (Papers III and IV) A further aim was to assess post-cooling hand-rewarming responses and effects of training in a cold environment, both on fingertip rewarming and on function of the autonomic nervous system, to evaluate if there was adaptation related to prolonged occupational cold exposure. Methods:  In a retrospective analysis, cases of accidental cold-related injury with hospital admission in northern Sweden during 2000-2007 were analyzed (Paper I).  Cases of fatal hypothermia in the same region during 1992-2008 were analyzed (Paper II).  A cohort of volunteers was studied before and after many months of occupational cold exposure. Subject hand rewarming response was measured after a cold hand immersion provocation and categorized as slow, moderate or normal in rewarming speed.  This cold provocation and rewarming assessment was performed before and after their winter training.  (Paper III).  Heart rate variability (HRV) was analyzed from the same cold provocation/recovery sequences (Paper IV). Results:  (Paper I) For the 379 cases of hospitalization for cold-related injury, annual incidences for hypothermia, frostbite, and drowning were 3.4/100,000, 1.5/100,000, and 1.0/100,000 inhabitants, respectively.  Male gender was more frequent for all categories.  Annual frequencies for hypothermia hospitalizations increased during the study period.  Hypothermia degree and distribution of cases were 20 % mild (between 32 and 35ºC), 40% moderate (31.9 to 28ºC), and 24% severe (< 28ºC), while 12% had temperatures over 35.0ºC.  (Paper II) The 207 cases of fatal hypothermia showed an annual incidence of 1.35 per 100,000 inhabitants, 72% in rural areas, 93% outdoors, 40% found within 100 meters of a building.  Paradoxical undressing was documented in 30%.  Ethanol was detected in femoral vein blood in 43%. Contributing co-morbidity was common including heart disease, previous stroke, dementia, psychiatric disease, alcoholism, and recent trauma.  (Paper III) Post-training, baseline fingertip temperatures and cold recovery variables in terms of final rewarming fingertip temperature and vasodilation time increased significantly in moderate and slow rewarmers.  Cold-related injury (frostbite) during winter training occured disproportionately more often in slow rewarmers (4 of the 5 injuries).  (Paper IV) At ‘pre- winter-training’, normal rewarmers had higher power for low frequency and high frequency heart rate variability.  After cold acclimatization (post-training), normal rewarmers showed lower resting power values for the low frequency and high frequency heart rate variability components.  Conclusions: Hypothermia and cold injury continues to cause injury and hospitalization in the northern region of Sweden.  Assessment and management is not standardized across hospitals.  With the identification of groups at high risk for fatal hypothermia, it should be possible to reduce the incidence, particularly for highest risk subjects; rural, living alone, alcohol-imbibing, and psychiatric diagnosis-carrying citizens.  Long-term cold-weather training may affect hand rewarming patters after a cold provocation, and a warmer baseline hand temperature with faster rewarming after a cold provocation may be associated with less general risk for frostbite.  Heart rate variability results support the conclusion that cold adaptation in the autonomic nervous system occurred in both groups, though the biological significance of this is not yet clear.

Vibrio vulnificus is a model environmental organism exhibiting a classical starvation response during nutrient limitation as well as a non-culturable state when exposed to low temperatures. In addition to these classic global responses, this organism is an opportunistic pathogen that exhibits numerous virulence factors. This organism was chosen as the model organism for the identification of regulators of the viable but nonculturable response (VBNC) and the starvation-induced maintenance of culturability (SIMC) that occurs when cells are starved prior to low temperature incubation. In order to accomplish this, three indirect approaches were used; proteomics, investigation of intercellular signalling pathways and genetic analysis of regulators involved in these responses. Two-dimensional gel electrophoresis was used to identify proteins expressed under conditions that induced SIMC. It was determined that carbon and long-term phosphorus starvation were important in the SIMC response. V. vulnificus was shown to possess genes, luxS and smcR, that are homologues of genes involved in signalling system system 2 in Vibrio harveyi. Signal molecules were produced upon starvation and the entry to stationary phase in V. vulnificus. Furthermore, a null mutation in smcR, a transcriptional regulator was shown to have pleiotropic effects in V. vulnificus, including up-regulation of numerous virulence factors and a defect in starvation survival and development of the SIMC response. We propose that V. vulnificus possesses a signalling system analogous to that of system 2 in V. harveyi, and that this system is involved in the regulation of stationary phase and starvation adaptation in this organism.

Thesis (M.S.)--Springfield College, 2003. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--Carleton University, 1997. / Also available in electronic format on the Internet.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2003. / Bibliography: leaves 160-171.

Thesis (M.S.)--Springfield College, 2003. / Includes bibliographical references.

Maintaining energy homeostasis at reduced temperatures is essential for the survival of the organisms. In this diploma thesis, we determined the impact of cold stress and cold adaptation on the rat immune system. A number of different factors participate at the process of thermoregulation, but the adrenergic signalling plays a crucial role. The binding of norepinephrine to β-adrenergic receptors leads to the formation of brown adipose tissue, which is necessary for non-shivering thermogenesis, as well as for energy balance. Bioactive products of adipocytes subsequently modulate the immune system, this process is significantly influenced by signalling of nerve cells. In order to understand neuro-immune interaction during the cold adaptation, we monitored changes in immune cell populations and the production of soluble products in rats treated with specific inhibitors of β-adrenergic receptors. Relationship between the immune and nervous system seems to be very important in many biological processes. Deciphering basic mechanisms of the influence of cold adaptation on immune cells can therefore explain other clinically relevant topics, such as treatment of obesity. Key words: immune system, cold adaptation, norepinephrine, adrenergic receptor, cytokines, brown adipose tissue, non-shivering thermogenesis

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Despite advances in research and therapy, cardiovascular diseases are still the leading cause of death worldwide. A closer understanding of the endogenous protective mechanism may improve pharmacological interventions for the treatment of heart diseases. Cold acclimation or hardening has strong potential for reducing cardiovascular risk and the literature shows that it stimulates the β-adrenergic and thyroid systems in tissues. At the same time, the adrenergic system in the heart is one of the main regulators of cardiac activity. However, these signaling pathways have surprisingly not been studied at the protein level in the heart yet, and no studies can be found on the subject matter in current literature. Our results show a reduced infarct size induced by ischemic injury in cold-acclimated rats (CA) at 8 ř C for 5 weeks and then returning to normothermic conditions for 2 weeks (CAR). The aim of this dissertation is to determine, the degree of involvement of the adrenergic system in the myocardium during acclimation after 3 days, 10 days, 5 weeks of CA and subsequent CAR at the level of all three β-adrenergic receptor isoforms (β-ARs) and their signaling pathways. The results show unchanged signaling of β1-AR-Gs-adenylyl cyclase-protein kinase A in the cardioprotective regimes CA and CAR, whose...

Beneficial effect of hardening or cold adaptation for human health has been known for many decades. Beneficial or detrimental effect depends on the regimen and intensity of the adaptation and thus it is very important to pay attention to them. It has been shown in previous studies that cold adaptation of animals at a low temperature 0-4 žC is accompanied by dehydration and the damage of kidneys. As our best knowledge, the effect of mild cold adaptation on the molecular mechanisms in the heart has not been studied until now. The first aim of this study was to set up a new model of cold adaptation without any negative effects on the organism. The second aim was to assess mRNA levels of selected genes related to the important mechanisms associated with energy metabolism and cardio-protective signaling pathways in the left ventricle. Results obtained using the new model for cold adaptation at 102 řC did not show any negative changes in the blood or urine parameters and body fluid balance was maintained. Screening of mRNAs showed that chronic adaptation might affect the phenotype of the heart, transcriptional activity of the antioxidant system and of the pro-apoptotic genes, lowers adrenergic signaling and moderate glucose metabolism in cardiomyocytes. Key words: cold adaptation, heart, gene...