Nursing a canine with presumptive tremorgenic mycotoxicosis following ingestion of mouldy dog food – a case report

A one-year-old neutered female Labrador Retriever presented with twitches and subsequent generalised tonic–clonic seizure activity following ingestion of mouldy dog food. Further complicating factors were hyperthermia and metabolic acidosis. Initial emergency treatment involved seizure management, blood analysis, intravenous fluid therapy, active cooling and decontamination via gastric lavage, administration of activated charcoal and an intralipid infusion. The patient was maintained under general anaesthesia to manage the seizure activity. Post-anaesthetic management included treatment of aspiration pneumonia, physiotherapy, intravenous fluid therapy and management of an indwelling urinary catheter. The patient was discharged 48 h post-admission without further complication.     

Repeated social defeat stress induces chronic hyperthermia in rats

Psychological stressors are known to increase core body temperature (T_c) in laboratory animals. Such single stress-induced hyperthermic responses are typically monophasic, as T_c returns to baseline within several hours. However, studies on the effects of repeated psychological stress on T_c are limited. Therefore, we measured T_c changes in male Wistar rats after they were subjected to 4 social defeat periods (each period consisting of 7 daily 1 h stress exposures during the light cycle followed by a stress-free day). We also assessed affective-like behavioral changes by elevated plus maze and forced swim tests.In the stressed rats, the first social defeat experience induced a robust increase in T_c (+ 1.3 °C). However, the T_c of these rats was not different from control animals during the subsequent dark period. In comparison, after 4 periods of social defeat, stressed rats showed a small but significantly higher (+ 0.2-0.3 °C) T_c versus control rats during both light and dark periods. Stressed rats did not show increased anxiety-like behavior versus control rats as assessed by the elevated plus maze test. However, in the forced swim test, the immobility time of stressed rats was significantly longer versus control rats, suggesting an increase in depression-like behavior. Furthermore, hyperthermia and depression-like behavior were still observed 8 days after cessation of the final social defeat session. These results suggest that repeated social defeat stress induces a chronic hyperthermia in rats that is associated with behavior resembling depression but not anxiety.     

Temperature dependence of NR1/NR2B NMDA receptor channels

N-methyl-D-aspartate (NMDA) receptors are highly expressed in the CNS, mediate the slow component of excitatory transmission and play key roles in synaptic plasticity and excitotoxicity. These ligand-gated ion channels are heteromultimers composed of NR1 and NR2 subunits activated by glycine and glutamate. In this study, patch-clamp recordings were used to study the temperature sensitivity of recombinant NR1/NR2B receptors expressed in human embryonic kidney (HEK) 293 cells. Rate constants were assessed by fitting a six-state kinetic scheme to time courses of transient macroscopic currents induced by glutamate at 21.9-46.5 degrees C. Arrhenius transformation of the rate constants characterizing NMDA receptor channel activity indicates that the most sensitive were the rate constants of desensitization (temperature coefficient Q(10)=10.3), resensitization (Q(10)=4.6) and unbinding (Q(10)=3.6). Other rate constants and the amplitude of single-channel currents were less temperature sensitive. Deactivation of responses mediated by NR1/NR2B receptors after a brief application of glutamate was best fit by a double exponential function (tau(fast): Q(10)=3.7; tau(slow): Q(10)=2.7). From these data, we conclude that desensitization/resensitization of the NMDA receptor and glutamate unbinding are especially temperature sensitive and imply that at physiological temperatures the channel kinetics play an important role in determining amplitude and time course of NMDA receptor-mediated postsynaptic currents and these receptors mediated synaptic plasticity.     

Cooling the neck region during exercise in the heat

Context:

Cooling the neck region can improve the ability to exercise in a hot environment. It might improve performance by dampening the perceived level of thermal strain, allowing individuals to override inhibitory signals.

Objective:

To investigate whether the enhanced ability to exercise in a hot environment observed when cooling the neck region occurs because of dampening the perceived level of thermal strain experienced and the subsequent overriding of inhibitory signals.

Design:

Crossover study.

Setting:

Walk-in environmental chamber.

Patients or Other Participants:

Eight endurance-trained, nonacclimated men (age  =  26 ± 2 years, height  =  1.79 ± 0.04 m, mass  =  77.0 ± 6.2 kg, maximal oxygen uptake [V̇O_2max]  =  56.2 ± 9.2 mL·kg⁻¹·min⁻¹) participated.

Intervention(s):

Participants completed 4 running tests at approximately 70% V̇O_2max to volitional exhaustion: 2 familiarization trials followed by 2 experimental trials (cooling collar [CC] and no collar [NC]). Trials were separated by 7 days. Familiarization and NC trials were performed without a collar and used to assess the test variability.

Main Outcome Measure(s):

Time to volitional exhaustion, heart rate, rectal temperature, neck skin temperature, rating of perceived exertion, thermal sensation, and feeling scale (pleasure/displeasure) were measured.

Results:

Time to volitional exhaustion was increased by 13.5% ± 3.8% (CC  =  43.15 ± 12.82 minutes, NC  =  38.20 ± 11.70 minutes; t₇  =  9.923, P < .001) with the CC, which reduced mean neck skin temperature throughout the test (P < .001). Participants terminated exercise at identical levels of perceived exertion, thermal sensation, and feeling scale, but the CC enabled participants to tolerate higher rectal temperatures (CC  =  39.61°C ± 0.45°C, NC  =  39.18°C ± 0.7°C; t₇  =  −3.217, P  =  .02) and heart rates (CC  =  181 ± 6 beats/min, NC  =  178 ± 9 beats/min; t₇  =  −2.664, P  =  .03) at the point of termination.

Conclusions:

Cooling the neck increased the time taken to reach volitional exhaustion by dampening the perceived levels of thermal strain.     

高温与阿霉素对兔VX-2细胞的协同作用

以体外长期培养的兔ＶＸ－２细胞为靶细胞,采用水浴加法进行体外细胞毒试验,（ＭＴＴ法）,观察了热疗,化疗及热化疗对兔ＶＸ－２细胞的生长抑制规律的影响,结果表明：（１）温热和阿纱对ＶＸ－２均有一定的抑制和杀伤作用两者一定方式的联合具有协同或相加作用。（２）热化疗加热温度以４２～４３℃为柱,加热时间以３０ｍｉｎ以上为佳。     

加温诱导人神经母细胞瘤SK-H-SN细胞凋亡的研究

目的：探讨加温对诱导神经母细胞瘤SK－H－SN细胞凋亡的作用及其意义。方法：用三种温度41．5℃、43℃、45℃诱导SK－H－SN细胞凋亡。采用形态学观察，原位缺口末端标记（TUNEL）的方法检测细胞凋亡的结果。结果：加温至41．5℃、43℃均可诱导SK－H－SN细胞凋亡，且凋亡率随温度的升高而升高。45℃时凋亡率下降，但出现大量的坏死细胞，结论：加温可诱导SK－H－SN细胞凋亡，在一定范围内，凋亡率和温度呈正相关，热疗可能为神经母细胞瘤的治疗提供新的手段。     

头颈部鳞状细胞癌细胞热疗后HSP70/HSP90的表达规律及其抑制对热疗疗效的影响

目的探讨口腔鳞状细胞癌（简称鳞癌）CA9-22细胞系热疗后HSP70/HSP90的表达规律及抑制HSP70/HSP90表达对头颈部鳞癌热疗的影响。方法①对体外培养的口腔鳞癌CA9-22细胞,恒温水浴42℃热休克2h,荧光定量PCR检测HSP70/HSP90的基因表达规律,采用Western-blot检测蛋白表达量的变化;②流式细胞术检测热休克前、后2、4、6、8、12、24h细胞的凋亡情况,观察在热疗前应用槲皮素、格尔德霉素及联合对HSP70/HSP90的抑制后对热疗的增敏效果。结果①42℃热疗后CA9-22细胞HSP70/HSP90表达在基因及蛋白水平上均有明显升高,4h达到高峰,8h后开始回落,24h接近正常;②热疗前使用槲皮素及格尔德霉素处理,凋亡细胞比例明显增加,联合处理组增加更为明显。结论 HSP70/HSP90在CA9-22细胞内的表达在热疗后迅速升高,在热疗前联合抑制HSP70/HSP90的活性,可以有效增加热疗敏感性。     

Genotype–Phenotype Correlations of Malignant Hyperthermia and Central Core Disease Mutations in the Central Region of the RYR1 Channel

Type 1 ryanodine receptor (RYR1) is a Ca²⁺ release channel in the sarcoplasmic reticulum of skeletal muscle and is mutated in some muscle diseases, including malignant hyperthermia (MH) and central core disease (CCD). Over 200 mutations associated with these diseases have been identified, and most mutations accelerate Ca²⁺‐induced Ca²⁺ release (CICR), resulting in abnormal Ca²⁺ homeostasis in skeletal muscle. However, it remains largely unknown how specific mutations cause different phenotypes. In this study, we investigated the CICR activity of 14 mutations at 10 different positions in the central region of RYR1 (10 MH and four MH/CCD mutations) using a heterologous expression system in HEK293 cells. In live‐cell Ca²⁺ imaging, the mutant channels exhibited an enhanced sensitivity to caffeine, a reduced endoplasmic reticulum Ca²⁺ content, and an increased resting cytoplasmic Ca²⁺ level. The three parameters for CICR (Ca²⁺ sensitivity for activation, Ca²⁺ sensitivity for inactivation, and attainable maximum activity, i.e., gain) were obtained by [³H]ryanodine binding and fitting analysis. The mutant channels showed increased gain and Ca²⁺ sensitivity for activation in a site‐specific manner. Genotype–phenotype correlations were explained well by the near‐atomic structure of RYR1. Our data suggest that divergent CICR activity may cause various disease phenotypes by specific mutations.     

应用银染mRNA差异显示法寻找高温致神经管畸形差异表达基因

目的 :寻找高温致神经管畸形的差异表达基因。方法 :在高温致神经管畸形的动物模型上 ,分别于高温处理后 2 4、48和 72小时 ,提取鼠胚神经管组织总RNA和正常对照组鼠胚相应时间的神经管组织总RNA ,反转录合成cDNA第一链后进行差异显示PCR扩增 ,采用PAGE和银染技术显示差异条带 ,回收差异条带并经PCR二次扩增后 ,用点杂交方法筛除假阳性条带 ,再用Northern印迹杂交进一步鉴定。结果 :在高温致畸的鼠胚神经管组织中筛选到一个特别明显的差示cDNA片段N3 2 ,该片段所在基因在高温致畸的胚胎神经管组织中的表达远低于正常同龄胚的神经管组织。结论 :N3 2片段所在基因的低表达与高温致神经管畸形相关。     

Influence of hyperthermal regimes on experimental teratoma development in vitro

We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ? .0001) and enhanced differentiation of both myotubes (P ? .01) and cylindrical epithelium (P ? .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ? .01) and diminished cell proliferation (P ? .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ? .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ? .0001), overall growth (P ? .01) and cartilage differentiation (P ? .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.