A two-state cell damage model under hyperthermic conditions: theory and in vitro experiments

The ultimate goal of cancer treatment utilizing thermotherapy is to eradicate tumors and minimize damage to surrounding host tissues. To achieve this goal, it is important to develop an accurate cell damage model to characterize the population of cell death under various thermal conditions. The traditional Arrhenius model is often used to characterize the damaged cell population under the assumption that the rate of cell damage is proportional to exp(-EaRT), where Ea is the activation energy, R is the universal gas constant, and T is the absolute temperature. However, this model is unable to capture transition phenomena over the entire hyperthermia and ablation temperature range, particularly during the initial stage of heating. Inspired by classical statistical thermodynamic principles, we propose a general two-state model to characterize the entire cell population with two distinct and measurable subpopulations of cells, in which each cell is in one of the two microstates, viable (live) and damaged (dead), respectively. The resulting cell viability can be expressed as C(tau,T)=exp(-Phi(tau,T)kT)(1+exp(-Phi(tau,T)kT)), where k is a constant. The in vitro cell viability experiments revealed that the function Phi(tau,T) can be defined as a function that is linear in exposure time tau when the temperature T is fixed, and linear as well in terms of the reciprocal of temperature T when the variable tau is held as constant. To determine parameters in the function Phi(tau,T), we use in vitro cell viability data from the experiments conducted with human prostate cancerous (PC3) and normal (RWPE-1) cells exposed to thermotherapeutic protocols to correlate with the proposed cell damage model. Very good agreement between experimental data and the derived damage model is obtained. In addition, the new two-state model has the advantage that is less sensitive and more robust due to its well behaved model parameters.     

Response of preosteoblasts to thermal stress conditioning and osteoinductive growth factors

Conditioning protocols involving mechanical stress independently or with chemical cues such as growth factors (GFs) possess significant potential to enhance bone regeneration. However, utilization of thermal stress conditioning alone or with GFs for bone therapy has been under-investigated. In this study, a preosteoblast cell line (MC3T3-E1) was exposed to treatment with water bath heating (44°C, 4 and 8 min) and osteoinductive GFs (bone morphogenetic protein-2 and transforming growth factor-β1) individually or in combination to investigate whether these stimuli could promote induction of bone-related markers, an angiogenic factor, and heat shock proteins (HSPs). Cells remained viable when heating durations were less than 20 min at 40oC, 16 min at 42oC, and 10 min at 44oC. Increasing heating duration at 44°C, promoted gene expression of HSPs, osteocalcin (OCN), and osteopontin (OPN) at 8 h post-heating (PH). Heating in combination with GFs caused the greatest gene induction of osteoprotegerin (OPG; 6.9- and 1.6-fold induction compared to sham-treated and GF only treated groups, respectively) and vascular endothelial growth factor (VEGF; 16.0- and 1.6-fold compared to sham and GF-only treated groups, respectively) at 8 h PH. Both heating and GFs independently suppressed the matrix metalloproteinase-9 (MMP-9) gene. GF treatment caused a more significant decrease in MMP-9 protein secretion to non-detectable levels compared to heating alone at 72 h PH. Secretion of OCN, OPN, and OPG increased with the addition of GFs but diminished with heating as measured by ELISA at 72 h PH. These results suggest that conditioning protocols utilizing heating and GFs individually or in combination can induce HSPs, bone-related proteins, and VEGF while also causing downregulation of osteoclastic activity, potentially providing a promising bone therapeutic strategy.     

Correlation of HSP70 expression and cell viability following thermal stimulation of bovine aortic endothelial cells

Thermal preconditioning protocols for cardiac cells were identified which produce elevated HSP70 levels while maintaining high cell viability. Bovine aortic endothelial cells were heated with a water bath at temperatures ranging from 44 to 50 degrees C for periods of 1-30 min. Thermal stimulation protocols were determined which induce HSP70 expression levels ranging from 2.3 to 3.6 times the control while maintaining cell viabilities greater than 90%. An Arrhenius injury model fit to the cell damage data yielded values of A = 1.4 X 10(66) s(-1) and Ea = 4.1 X 10(5) J/mol. Knowledge of the injury parameters and HSP70 kinetics will enhance dosimetry guideline development for thermal stimulation of heat shock proteins expression in cardiac tissue.     

Investigations of the relationship betw een disease and airborne (1-->3)-beta-D-glucan in buildings

Studies on the relationship between symptoms in indoor air and the amount of airborne (1-->3)-beta-D-glucan were reviewed. Relationships were found for symptoms and objective tests of airways inflammation. The data suggest that (1-->3)-beta-D-glucan could be a causative agent.     

Investigation of the transduction mechanism of infrared detection in Melanophila acuminata: photo-thermal-mechanical hypothesis

Differential phase optical low coherence reflectometry (OLCR) was used to detect sub-wavelength displacements in the infrared-sensitive thoracic pit organ of Melanophila acuminata (Coleoptera: Buprestidae) upon absorption of infrared radiation at 3.39 microm. The displacement had more complex morphology but similar amplitude ( approximately 100 nm at 1 W cm(-2)) when compared to the displacement measured from the exocuticle in an alternate region on the beetle's body. In addition, a simplified finite difference model was developed to predict the temperature distribution and resultant thermal expansion in the pit organ tissue. The experimental and model results were interpreted to help clarify the mechanism by which the sensilla in the pit organ convert infrared radiation to neural signals. The results of this paper are discussed in relation to the photo-thermal-mechanical transduction hypothesis. This is the first experimental examination of the transduction mechanism in Melanophila acuminata.     

Effects of nighttime low frequency noise on the cortisol response to awakening and subjective sleep quality

The effects of night-time exposure to traffic noise (TN) or low frequency noise (LFN) on the cortisol awakening response and subjective sleep quality were determined. Twelve male subjects slept for five consecutive nights in a noise-sleep laboratory. After one night of acclimatisation and one reference night, subjects were exposed to either TN (35dB L(Aeq), 50dB L(Amax)) or LFN (40dB L(Aeq)) on alternating nights (with an additional reference night in between). Salivary free cortisol concentration was determined in saliva samples taken immediately at awakening and at three 15-minute intervals after awakening. The subjects completed questionnaires on mood and sleep quality. The awakening cortisol response on the reference nights showed a normal cortisol pattern. A significant interaction between night time exposure and time was found for the cortisol response upon awakening. The awakening cortisol response following exposure to LFN was attenuated at 30 minutes after awakening. Subjects took longer to fall asleep during exposure to LFN. Exposure to TN induced greater irritation. Cortisol levels at 30 minutes after awakening were related to "activity" and "pleasantness" in the morning after exposure to LFN. Cortisol levels 30 minutes after awakening were related to sleep quality after exposure to TN. This study thus showed that night time exposure to LFN may affect the cortisol response upon wake up and that lower cortisol levels after awakening were associated with subjective reports of lower sleep quality and mood.     

Homologies of the adductor mandibulae muscles in Tetraodontiformes as indicated by nerve branching patterns

Homologies of the adductor mandibulae muscles in eight families of Tetraodontiformes were hypothesized from the branching patterns of ramus mandibularis trigeminus. Insertions of the muscles to the upper or lower jaw were weak indicators of homology, migrations of the sites occurring frequently in A1, A2, A2, and A3. In monacanthids, tetraodontids, and diodontids, A1 tended to be split into numerous subsections, whereas in aracanids and ostraciids, A3 was highly developed, comprising three or four subsections. In tetraodontids, A2 was found to be a composite of A1 subsection and A2. The methods of and limits to applying nerve branching patterns to muscle homology are discussed. A new naming system that reflects both muscle homologies and insertions is proposed.     

Endotoxins from Cyanobacteria and Gram-negative Bacteria as the Cause of an Acute Influenza-like Reaction after Inhalation of Aerosols

Endotoxins (lipopolysaccharides) in aerosols, originating from cyanobacteria and gram-negative bacteria, were the likely etiological agent behind outbreaks of a transient, flu-like syndrome, described from four Scandinavian towns and Harare, Zimbabwe. The syndrome with fever, malaise, muscle pains, tightness of the chest and respiratory-tract symptoms, also known as toxic pneumonitis, occurred 1.5–6 hours after taking a bath or shower. The outbreaks were associated with mass developments of cyanobacteria in the drinking water reservoirs. Cyanobacterial cells and elevated levels of endotoxins were detected in the Harare tap water when human subjects reported symptoms. In a field study of 21 water bodies, the concentrations of endotoxins were much higher in water dominated by cyanobacteria, compared to water with dominance of eukaryotic algae. This observation may partially be explained by the fact that cyanobacteria possess endotoxins and partially by our findings that endotoxin-possessing bacteria inhabit the mucilage of several mass developing cyanobacterial taxa.