Hyperthermia Induces the Synthesis of a Heat Shock Protein by Polysomes Isolated from the Fetal and Neonatal Mammalian Brain

Abstract: Analysis of the cell-free translation products of polysomes isolated from fetal brain and other organs indicates that elevation of maternal body temperature induces the synthesis of a heat shock protein of molecular weight 74,000 (74K). The newborn mammal is particularly sensitive to induction of the 74K protein. As early postnatal development proceeds, higher body temperatures are required to induce synthesis of the 74K heat shock protein.     

Enhancement of hyperthermic killing cultured mammalian cells by treatment with anisotonic NaCl or medium solutions

The exposure of cultured Chinese hamster cells (CHO) to anisotonic medium increased the cellular sensitivity to heat treatment at 42.3°C. A greater potentiation of heat killing is observed when the anisotonic solution consists of pure NaCl in water compared to growth medium made anisoltonic by dilution or by addition of NaCl. Hypertonic treatment caused greater heat sensitization than hypotonic treatment. Thermal tolerance observed in the control cells after 4–6 hours of heating in medium was also observed for cells exposed to anisotonic media during heating if the heating period was greater than 4 h. The exposure of cells to anisotonic media during heating if the heating period was greater than 4 h. The exposure of cells to anisotonic NaCl solutions during heating removed the shoulder from the heat survival curve, while the curves for cells heated in medium made anisotonic retained their shoulders. These studies suggest: (1) that either the plasma membrane is a primary target for heat inactivation of mammalian cells, or (2) that changes in intracellular ion concentrations enhance thermal damage occurring in critical intracellular structures.     

A study on thermal damage during hyperthermia treatment based on DPL model for multilayer tissues using finite element Legendre wavelet Galerkin approach

Hyperthermia is a process that uses heat from the spatial heat source to kill cancerous cells without damaging the surrounding healthy tissues. Efficacy of hyperthermia technique is related to achieve temperature at the infected cells during the treatment process. A mathematical model on heat transfer in multilayer tissues in finite domain is proposed to predict the control temperature profile at hyperthermia position. The treatment technique uses dual-phase-lag model of heat transfer in multilayer tissues with modified Gaussian distribution heat source subjected to the most generalized boundary condition and interface at the adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved using finite element Legendre wavelet Galerkin approach. The present solution has been verified with exact solution in a specific case and provides a good accuracy. The effect of the variability of different parameters such as lagging times, external heat source, metabolic heat source and the most generalized boundary condition on temperature profile in multilayer tissues is analyzed and also discussed the effective approach of hyperthermia treatment. Furthermore, we studied the modified thermal damage model with regeneration of healthy tissues as well. For viewpoint of thermal damage, the least thermal damage has been observed in boundary condition of second kind. The article concludes with a discussion of better opportunities for future clinical application of hyperthermia treatment.     

Deep body and surface temperature responses to hot and cold environments in the zebra finch

Global warming increasingly challenges thermoregulation in endothermic animals, particularly in hot and dry environments where low water availability and high temperature increase the risk of hyperthermia. In birds, un-feathered body parts such as the head and bill work as ‘thermal windows’, because heat flux is higher compared to more insulated body regions. We studied how such structures were used in different thermal environments, and if heat flux properties change with time in a given temperature. We acclimated zebra finches (Taeniopygia guttata) to two different ambient temperatures, ‘cold’ (5 °C) and ‘hot’ (35 °C), and measured the response in core body temperature using a thermometer, and head surface temperature using thermal imaging. Birds in the hot treatment had 10.3 °C higher head temperature than those in the cold treatment. Thermal acclimation also resulted in heat storage in the hot group: core body temperature was 1.1 °C higher in the 35 °C group compared to the 5 °C group. Hence, the thermal gradient from core to shell was 9.03 °C smaller in the hot treatment. Dry heat transfer rate from the head was significantly lower in the hot compared to the cold treatment after four weeks of thermal acclimation. This reflects constraints on changes to peripheral circulation and maximum body temperature. Heat dissipation capacity from the head region increased with acclimation time in the hot treatment, perhaps because angiogenesis was required to reach peak heat transfer rate. We have shown that zebra finches meet high environmental temperature by heat storage, which saves water and energy, and by peripheral vasodilation in the head, which facilitates dry heat loss. These responses will not exclude the need for evaporative cooling, but will lessen the amount of energy expend on body temperature reduction in hot environments.     

Activation of transgene expression in skeletal muscle by focused ultrasound

To correlate thermal dose from focused ultrasound (FUS) with gene expression and tissue injury, a temperature plateau strategy was employed. Plasmids encoding luciferase gene under the control of hsp70B promoter were transfected into the right gastrocnemius muscle in a rat via electroporation. One day after transfection, hind limbs were treated with 3.3-MHz focused ultrasound, using one of four different temperature plateaus with spatial-peak time-average focal temperatures (T_SPTA) of 46 °C, 48 °C, 51 °C and 62 °C. The treatment duration at the plateau temperature was varied from 0 to 30 s. Gene expression was analyzed in vivo one day following FUS treatment, and H&E staining was employed to assess tissue injury. Gene activation and tissue damage correlated closely with thermal dose. The highest level of gene activation was induced by FUS at T_SPTA = 51 °C for 20 s, which was found to be statistically equivalent to that produced by water-bath hyperthermia.     

Maximum vehicle cabin temperatures under different meteorological conditions

A variety of studies have documented the dangerously high temperatures that may occur within the passenger compartment (cabin) of cars under clear sky conditions, even at relatively low ambient air temperatures. Our study, however, is the first to examine cabin temperatures under variable weather conditions. It uses a unique maximum vehicle cabin temperature dataset in conjunction with directly comparable ambient air temperature, solar radiation, and cloud cover data collected from April through August 2007 in Athens, GA. Maximum cabin temperatures, ranging from 41–76°C, varied considerably depending on the weather conditions and the time of year. Clear days had the highest cabin temperatures, with average values of 68°C in the summer and 61°C in the spring. Cloudy days in both the spring and summer were on average approximately 10°C cooler. Our findings indicate that even on cloudy days with lower ambient air temperatures, vehicle cabin temperatures may reach deadly levels. Additionally, two predictive models of maximum daily vehicle cabin temperatures were developed using commonly available meteorological data. One model uses maximum ambient air temperature and average daily solar radiation while the other uses cloud cover percentage as a surrogate for solar radiation. From these models, two maximum vehicle cabin temperature indices were developed to assess the level of danger. The models and indices may be useful for forecasting hazardous conditions, promoting public awareness, and to estimate past cabin temperatures for use in forensic analyses.     

beta-Endorphin-induced hyperthermia in the cat

beta-Endorphin was injected into the third cerebral ventricle (ICV) of conscious, unrestrained cats. Hyperthermic response to 50 microgram of this peptide were reduced by 20-100 microgram naloxone given ICV 1 hr later. A dose of 40 microgram beta-endorphin increased body temperature at ambient temperature of 4, 22 and 34 degrees C, with the response being greater the warmer the environment. These results indicate that beta-endorphin acts on a central naloxone-sensitive receptor which is probably the v2 receptor that is activated by low doses of D-Ala2-Met-enkephalinamide to evoke a similar pattern of change in body temperature over a comparable range of ambient temperatures.     

Ocular blood flow decreases during passive heat stress in resting humans

Background

Heat stress induces various physiological changes and so could influence ocular circulation. This study examined the effect of heat stress on ocular blood flow.

Findings

Ocular blood flow, end-tidal carbon dioxide (P_ETCO₂) and blood pressure were measured for 12 healthy subjects wearing water-perfused tube-lined suits under two conditions of water circulation: (1) at 35°C (normothermia) for 30 min and (2) at 50°C for 90 min (passive heat stress). The blood-flow velocities in the superior temporal retinal arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow in the STRA and SNRA was calculated from the integral of a cross-sectional map of blood velocity. P_ETCO₂ was clamped at the normothermia level by adding 5% CO₂ to the inspired gas. Passive heat stress had no effect on the subjects’ blood pressures. The blood-flow velocity in the RCV was significantly lower after 30, 60 and 90 min of passive heat stress than the normothermic level, with a peak decrease of 18 ± 3% (mean ± SE) at 90 min. Blood flow in the STRA and SNRA decreased significantly after 90 min of passive heat stress conditions, with peak decreases of 14 ± 3% and 14 ± 4%, respectively.

Conclusion

The findings of this study suggest that passive heat stress decreases ocular blood flow irrespective of the blood pressure or arterial partial pressure of CO₂.     

N-terminal and Central Segments of the Type 1 Ryanodine Receptor Mediate Its Interaction with FK506-binding Proteins

We used site-directed labeling of the type 1 ryanodine receptor (RyR1) and fluorescence resonance energy transfer (FRET) measurements to map RyR1 sequence elements forming the binding site of the 12-kDa binding protein for the immunosuppressant drug, FK506. This protein, FKBP12, promotes the RyR1 closed state, thereby inhibiting Ca²⁺ leakage in resting muscle. Although FKBP12 function is well established, its binding determinants within the RyR1 protein sequence remain unresolved. To identify these sequence determinants using FRET, we created five single-Cys FKBP variants labeled with Alexa Fluor 488 (denoted D-FKBP) and then targeted these D-FKBPs to full-length RyR1 constructs containing decahistidine (His₁₀) “tags” placed within N-terminal (amino acid residues 76–619) or central (residues 2157–2777) regions of RyR1. The FRET acceptor Cy3NTA bound specifically and saturably to these His tags, allowing distance analysis of FRET measured from each D-FKBP variant to Cy3NTA bound to each His tag. Results indicate that D-FKBP binds proximal to both N-terminal and central domains of RyR1, thus suggesting that the FKBP binding site is composed of determinants from both regions. These findings further imply that the RyR1 N-terminal and central domains are proximal to one another, a core premise of the domain-switch hypothesis of RyR function. We observed FRET from GFP fused at position 620 within the N-terminal domain to central domain His-tagged sites, thus further supporting this hypothesis. Taken together, these results support the conclusion that N-terminal and central domain elements are closely apposed near the FKBP binding site within the RyR1 three-dimensional structure.     

Extremity cooling for heat stress mitigation in military and occupational settings

Physical work, high ambient temperature and wearing protective clothing can elevate body temperature and cardiovascular strain sufficiently to degrade performance and induce heat-related illnesses. We have recently developed an Arm Immersion Cooling System (AICS) for use in military training environments and this paper will review literature supporting such an approach and provide details regarding its construction. Extremity cooling in cool or cold water can accelerate body (core temperature) cooling from 0.2 to 1.0 °C/10 min vs. control conditions, depending on the size/surface area of the extremity immersed. Arm immersion up to the elbow results in greater heat loss than hand- or foot-only immersion and may reduce cardiovascular strain by lowering heart rate by 10–25 beats/min and increase work tolerance time by up to 60%. The findings from studies in this paper support the use of AICS prototypes, which have been incorporated as part of the heat stress mitigation procedures employed in US Army Ranger Training and may have great application for sports and occupational use.