Temperature evolution in tissues embedded with large blood vessels during photo-thermal heating

During laser-assisted photo-thermal therapy, the temperature of the heated tissue region must rise to the therapeutic value (e.g., 43 °C) for complete ablation of the target cells. Large blood vessels (larger than 500 micron in diameter) at or near the irradiated tissues have a considerable impact on the transient temperature distribution in the tissue. In this study, the cooling effects of large blood vessels on temperature distribution in tissues during laser irradiation are predicted using finite element based simulation. A uniform flow is assumed at the entrance and three-dimensional conjugate heat transfer equations in the tissue region and the blood region are simultaneously solved for different vascular models. A volumetric heat source term based on Beer–Lambert law is introduced into the energy equation to account for laser heating. The heating pattern is taken to depend on the absorption and scattering coefficients of the tissue medium. Experiments are also conducted on tissue mimics in the presence and absence of simulated blood vessels to validate the numerical model. The coupled heat transfer between thermally significant blood vessels and their surrounding tissue for three different tissue-vascular networks are analyzed keeping the laser irradiation constant. A surface temperature map is obtained for different vascular models and for the bare tissue (without blood vessels). The transient temperature distribution is seen to differ according to the nature of the vascular network, blood vessel size, flow rate, laser spot size, laser power and tissue blood perfusion rate. The simulations suggest that the blood flow through large blood vessels in the vicinity of the photothermally heated tissue can lead to inefficient heating of the target.     

Laser-induced hyperthermia of nanoshell mediated vascularized tissue – A numerical study

Laser-induced hyperthermia treatment of tumor in a 2-D axisymmetric tissue embedded with moderate size (100–150 µm) blood vessels is studied. Laser absorption is enhanced by embedding gold–silica nanoshells in the tumor. Heat transfer in the tissue is modeled using Weinbaum–Jiji bioheat transfer equation. With laser irradiation, the volumetric radiation is accounted in the governing bioheat equation. Radiative information needed in the bioheat equation is calculated using the discrete ordinate method, and the coupled bioheat-radiation equation is solved using the finite volume method. Effects of power density, laser exposure time, beam radius, diameter of blood vessel and volume fractions of nanoshells on temperature spread in the tissue are analyzed.     

热疗对SW1990 胰腺癌细胞上皮间质转化（EMT）的影响及其作用机制

目的：探讨热疗对化疗诱导的人胰腺癌细胞株SW1990 细胞上皮间质转化（EMT）的影响及其可能的作用机制。方法：分别 用不同浓度吉西他滨(0, 5, 10, 20,30 滋M)作用于SW1990 细胞不同时间(24, 48, 72 小时)及30 滋M 吉西他滨作用24h 联合热疗 43℃ 1h,观察细胞的形态学变化,通过四甲基偶氮唑蓝(MTT) 法检测细胞的增殖情况。采用Western blot 方法检测细胞内 E-cadherin 蛋白和剪切的Notch1 蛋白的表达。结果：①吉西他滨在一定浓度范围内可明显抑制SW1990细胞的增殖（P<0.05）,并 呈浓度和时间依赖性。吉西他滨作用前24 h 给予43℃ 1h热疗预处理可显著增强吉西他滨对SW1990细胞的抑制作用（P<0.05） ②吉西他滨作用SW1990 细胞24 小时后,细胞数目减少,细胞形态变大,细胞呈梭形,且细胞间连接减少;而热疗预处理的联合 能够逆转此种形态学变化。③吉西他滨作用24 小时后,细胞内E-cadherin蛋白的表达下调、Cleaved Notch1 的蛋白表达上调,热 疗预处理可明显上调吉西他滨诱导的E-cadherin 蛋白表达下调、并下调Cleaved Notch1 蛋白表达的上调。结论：热疗预处理显著 逆转吉西他滨所诱导的人胰腺癌细胞株SW1990 细胞的EMT 现象,其机制可能与Notch 信号通路有关。     

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.     

吐温80合并温热诱导BGC-823胃癌细胞凋亡及对Hsp70,Bcl-2和Bax表达的影响

目的　观察膜活化剂吐温 80合并温热作用对BGC 82 3人胃癌细胞生长、凋亡及对Hsp70、Bcl 2、Bax表达的影响。方法　应用MTT法、荧光染色及DNA琼脂糖凝胶电泳 ,测定 0 1%吐温 80与 4 2℃ 10 0min合并作用对BGC 82 3细胞的抑制效应和诱导细胞凋亡的影响 ;应用免疫细胞化学染色 ,观察合并作用后不同时间 (0h、 8h、 16h、 2 4h)BGC 82 3细胞Hsp70、Bcl 2、Bax的表达改变。结果　①吐温 80合并 4 2℃温热作用对细胞具有明显的抑制效应 (P <0 0 0 1)。②合并作用后 2 4h ,可见大量肿瘤细胞凋亡。③合并作用可明显抑制BGC 82 3细胞Hsp70的表达 ;Bcl 2、Bax的表达均增加 ,且Bax的表达强于Bcl 2 ,并全部分布在胞浆。结论　吐温 80合并 4 2℃温热可通过诱导细胞凋亡来抑制肿瘤细胞生长 ,其对细胞Hsp70表达的抑制和对Bcl 2、Bax表达及分布的影响可能与凋亡的发生有关     

Ca2+ Influx via the Na+/Ca2+ Exchanger Is Enhanced in Malignant Hyperthermia Skeletal Muscle

Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca²⁺ dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca²⁺ depending on cellular activity. Resting intracellular calcium ([Ca²⁺]_r) and sodium ([Na⁺]_r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na⁺]_e elevates [Ca²⁺]_r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca²⁺ or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca²⁺]_r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca²⁺]_r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca²⁺]_r in MHS muscle fibers and decreases the amplitude of [Ca²⁺]_r rise triggered by halothane, but had no effect on [Ca²⁺]_r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca²⁺ transient elicited by high [K⁺]_e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca²⁺]_r and the Ca²⁺ transient area induced by high [K⁺]_e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca²⁺ transients associated with K⁺-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers.     

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.     

Expression of NADPH-diaphorase in nucleus tractus solitarius after peripheral injection of E. coli endotoxin in rats

1. The possibility that peripheral exogenous pyrogens can activate brainstem nuclei by abdominal viscera afferents was studied using the NADPH-diaphorase method in E. coli lipopolysaccharide treated rats with and without ibuprofen pre-treatment.

2. NADPH-d staining revealed: (i) a significant increase in the number of NADPH-d labeled neurons in the subpostremal area of the nucleus tractus solitarius lipopolysaccharide treated rats compared with control animals (p<0.05), and (ii) an almost similar number of NADPH-d positive neurons in both control and ibuprofen pre-treated rats (p=0.091).

3. These data indicate that peripheral administration of an exogenous pyrogen stimulates the synthesis of nitric oxide in the nucleus tractus solitarius, and are consistent with the hypothesis of a direct neural link between the periphery and the hypothalamus.

Transient receptor potential vanilloid 1-mediated expression and secretion of endothelial cell-derived calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP), the principal transmitter in sensory nerves, could also be expressed in vascular endothelium. Transient receptor potential vanilloid 1(TRPV1), which modulates the synthesis and release of CGRP in sensory nerves, is also present in endothelial cells. The present study tested whether TRPV1 modulates the release and synthesis of CGRP in endothelial cells, and evaluated the protective effect of endothelial cell-derived CGRP. Human umbilical vein endothelial cells (HUVECs) were treated with capsaicin or hyperthermia. The level of CGRP mRNA was detected by RT-PCR, and protein level was measured by radioimmunoassay. Endothelial cell injury was induced by lysophosphatidylcholine, and evaluated by cell viability and lactate dehydrogenase activity. HUVECs expressed CGRP, both alpha- and beta-subtype. Capsaicin increased the level of CGRP in the culture medium, and up-regulated the expression of CGRP in endothelial cells. Hyperthermia also increased the level of CGRP mRNA. These effects were abolished by capsazepine, a competitive antagonist of TRPV1. Capsaicin significantly attenuated the endothelial cell damage induced by LPC, which was prevented and aggravated by capsazepine or CGRP(8-37,) antagonist of CGRP receptor. These results indicate that TRPV1 also regulates the expression and secretion of endothelial cell-derived CGRP, which affords protective effects on endothelial cells.