Heparin Prevents Intracellular Hyaluronan Synthesis and Autophagy Responses in Hyperglycemic Dividing Mesangial Cells and Activates Synthesis of an Extensive Extracellular Monocyte-adhesive Hyaluronan Matrix after Completing Cell Division

Growth-arrested rat mesangial cells (RMCs) at a G₀/G₁ interphase stimulated to divide in hyperglycemic medium initiate intracellular hyaluronan synthesis that induces autophagy/cyclin D3-induced formation of a monocyte-adhesive extracellular hyaluronan matrix after completing cell division. This study shows that heparin inhibits the intracellular hyaluronan synthesis and autophagy responses, but at the end of cell division it induces synthesis of a much larger extracellular monocyte-adhesive hyaluronan matrix. Heparin bound to RMC surfaces by 1 h, internalizes into the Golgi/endoplasmic reticulum region by 2 h, and was nearly gone by 4 h. Treatment by heparin for only the first 4 h was sufficient for its function. Streptozotocin diabetic rats treated daily with heparin showed similar results. Glomeruli in sections of diabetic kidneys showed extensive accumulation of autophagic RMCs, increased hyaluronan matrix, and influx of macrophages over 6 weeks. Hyaluronan staining in the glomeruli of heparin-treated diabetic rats was very high at week 1 and decreased to near control level by 6 weeks without any RMC autophagy. However, the influx of macrophages by 6 weeks was as pronounced as in diabetic glomeruli. The results are as follows: 1) heparin blocks synthesis of hyaluronan in intracellular compartments, which prevents the autophagy and cyclin D3 responses thereby allowing RMCs to complete cell division and sustain function; 2) interaction of heparin with RMCs in early G₁ phase is sufficient to induce signaling pathway(s) for its functions; and 3) influxed macrophages effectively remove the hyaluronan matrix without inducing pro-fibrotic responses that lead to nephropathy and proteinurea in diabetic kidneys.     

Apparent involvement of opioid peptides in stress-induced enhancement of tumor growth

Exposure to stress has been associated with alterations in both immune function and tumor development in man and laboratory animals. In the present study, we investigated the effect of a particular type of inescapable footshock stress, known to cause an opioid mediated form of analgesia, on survival time of female Fischer 344 rats injected with a mammary ascites tumor. Rats subjected to inescapable footshock manifested an enhanced tumor growth indicated by a decreased survival time and decreased percent survival. This tumor enhancing effect of stress was prevented by the opiate antagonist, naltrexone, suggesting a role for endogenous opioid peptides in this process. In the absence of stress, naltrexone did not affect tumor growth.     

Resistance to thermal stress in adult Drosophila buzzatii: acclimation and variation among populations

Survival after heat stress was examined in adult Drosophila buzzatii from seven localities. Males and females were conditioned by a non-lethal high temperature before exposure to a severe thermal stress. Variable times elapsed between conditioning, either as adults or pupae, and exposure to the stress were used, and experimental times to the stress ranged from 2 to 96 hours. Survival after stress varied among populations, and differences generally were consistent across conditioning treatments and across experiments. Resistance to thermal stress was much higher following one conditioning bout 2–4 hours before exposure to a severe stress than when the time elapsed between conditioning and exposure was increased to 24 or more hours. Significantly more adults survived the stress if conditioned 4 days before exposure to the thermal stress, either as adults or as pupae, than if not conditioned. The rank order of resistance roughly followed that predicted from the climatic conditions of the localities of origin.     

Heat induced liver cell proliferation in the livebearing fish Poeciliopsis

Synopsis Liver regeneration is induced by heat stress in the small viviparous fish, Poeciliopsis. Acute exposure to sublethal temperatures, one to two degrees below their killing temperature, damages tissue and initiates liver cell proliferation in P. lucida, P. monacha, and P. monacha-lucida hybrid clones, SYN-4 and SYN-5. Regeneration of liver cells began within 1–2 days following heat stress and proceeded over 5 days. Peak cell proliferation occurred 2–3 days after treatment in fish of all four genotypes. Cell proliferation was induced in the two all-female clones, SYN-4 and SYN-5, by exposure to 40.5° C for 60 minutes. This treatment imposed mortalities of 17.9% and 16.7%, respectively, whereas reduction of the temperature to 39.5°C and reduction of the time to 30 minutes resulted in no mortalities without significantly lowering the level of cell proliferation (p > 0.05). Liver cell proliferation induced by both heat treatments was significantly higher (p < 0.05) in the SYN-5 hybrids than in SYN-4. The induction of liver cell proliferation with sublethal temperature exposures is discussed as it may relate to chemical carcinogenesis in both feral and laboratory fish. Acute heat exposure may be used experimentally in fish as an independent stimulus for liver cell proliferation in carcinogenesis studies. In poikilothermic animals-heat exposure offers an alternative to surgical removal of approximately two-thirds of the liver, the method most frequently used in rodents to study the process of liver regeneration.     

应激模型的生理学基础及其比较研究进展

各种外界因素如创伤、手术、感染、缺氧、强光、噪音等通过一定强度作用于机体可以引起机体特异性和非特异性反应,非特异性反应与刺激因素性质无直接关系,称为应激(stress)。近年来,随着社会的发展,生活节奏的加快、自然环境和生活环境的恶化,应激已经成为威胁人类健康的重要因素,有关应激影响机体健康的研究备受国内外学者的重视,而合适的应激动物模型的建立对应激研究的顺利开展有着重要意义。本文就目前应激动物模型的病理生理特点、种类、制作和评价方法等进行综述,旨在为应激研究提供参考。     

Stress relaxation behaviors of articular cartilages in porcine temporomandibular joint

In this study, we tested the compressive stress relaxation behaviors of the mandibular condylar and temporal cartilages in the porcine temporomandibular joint (TMJ). The aim was to determine the quantitative and qualitative similarities and differences of compressive stress relaxation behaviors between the two cartilages. Ten porcine TMJs were used; the articular surface was divided into 5 regions: anterior, central, posterior, lateral and medial. Compressive relaxation test was carried out at a strain level of 5% in each region of the two cartilages. The stress relaxation was monitored over a period of 5 min. In all the regions of the two cartilages, the time-dependent stress relaxation curves showed a marked drop in stress within the initial 10 s, which can be fitted by a standard linear viscoelastic model. The instantaneous moduli in the temporal cartilage were dominantly larger than those in the condylar cartilage, while the condylar cartilage had slightly larger relaxation moduli than the temporal cartilage except for the medial region. The both cartilages showed the regional differences in the compressive stress relaxation behavior, and in the temporal cartilage the lateral and medial regions revealed the largest values for the instantaneous and relaxation moduli. The present results demonstrate that the viscoelastic properties of compressive stress relaxation in both cartilages are region-specific, which might have an important implication for stress distribution and transmission along with the TMJ disc.