Hypothermia improves ventricular myocyte contractility under conditions of normal perfusion and after an interval of ischemia

Aim

Recent investigations have reported improved myocardial function during hypothermia following resuscitation from cardiac arrest. The effects of hypothermia on myocyte contractility were investigated under conditions of normal perfusion and after a 10 min interval of ischemia.

Methods

Ventricular myocytes were obtained from 10 male Sprague-Dawley rats weighing 400 ± 50 g. The myocytes were randomized to be perfused at: 37 °C, 34 °C, 32 °C, or 30 °C. A subsequent set of myocytes was subjected to 10 min of ischemia at 37 °C, prior to being randomized to reperfusion at: 37 °C, 34 °C, 32 °C or 30 °C. Myocyte contractility was expressed as length-shortening percentage. Intracellular Ca²⁺ transients were assessed in a separate group of myocytes preloaded with Fura-2/AM. Sensitivity to Ca²⁺ was tested by increasing perfusate Ca²⁺ content, i.e. 0.5 mM, 1 mM and 2 mM.

Results

During normal perfusion and following reperfusion after 10 min of ischemia, myocyte contractility increased at 34 °C compared to 37 °C (P < 0.01). When the perfusion temperature was decreased to 32 °C and 30 °C, contractility further increased (P < 0.001). Intracellular Ca²⁺ transients were greater during perfusion at 34 °C compared to those at 37 °C (P < 0.001) and further increased at 30 °C (P < 0.001). Increases in extracellular Ca²⁺ concentration from 0.5 mM to 2 mM resulted in greater myocyte contractility during perfusion at 30 °C compared to that observed at 37 °C (P < 0.001). Effects of hypothermia on intracellular Ca²⁺ transients and sensitivity to Ca²⁺ persisted after ischemia.

Conclusions

Hypothermia improved myocyte contractility, intracellular Ca²⁺ transients and sensitivity to Ca²⁺ under conditions of normal perfusion and following reperfusion after 10 min of ischemia.     

链霉素缓释复合降解膜植入损伤肌腱局部腱周结缔组织的变化

背景:国内外学者曾用生物、非生物及药物等方法,诸如生物膜、透明质酸钠、纤维素密封胶等材料进行大量肌腱修复防粘连研究,但到目前为止尚未取得突破性进展。目的:观察肌腱损伤局部植入链霉素复合降解膜后腱周结缔组织的增生。方法:切断SD大鼠跟腱后,随机数字表法分为3组,分别在肌腱断端缝合处植入链霉素复合缓释降解膜、维生素C复合缓释降解膜、空白缓释降解膜。术后90d行肌腱损伤局部组织学观察、羟脯氨酸含量和生物力学指标检测。结果与结论:链霉素复合缓释降解膜组肌腱缝合处内部的成纤维细胞、胶原纤维均较其腱周围、维生素C复合缓释降解膜组、空白缓释降解膜组多;腱缝合处肌腱周围多为正常结构的疏松结缔组织,很少有增生的结缔组织长入肌腱内部;肌腱与周围组织分界清晰,最大抗拉强度、羟脯氨酸含量明显优于其他两组。表明链霉素复合缓释降解膜通过抑制腱周结缔组织增生,防止腱周结缔组织增生长入腱内,从而减轻或防止粘连形成。     

An Approach for Predicting the Low-Cycle-Fatigue Crack Initiation Life of Ultrafine-Grained Aluminum Alloy Considering Inhomogeneous Deformation and Microscale Multiaxial Strain

In this paper, a low-cycle-fatigue (LCF) crack initiation life prediction approach that explicitly distinguishes nucleation and small crack propagation regimes is presented for ultrafine-grained (UFG) aluminum alloy by introducing two fatigue indicator parameters (FIPs) at the grain level. These two characterization parameters, the deformation inhomogeneity measured by the standard deviation of the dot product of normal stress and longitudinal strain and the microscale multiaxial strain considering the non-proportional cyclic additional hardening and mean strain effect, were proposed and respectively regarded as the driving forces for fatigue nucleation and small crack propagation. Then, the nucleation and small crack propagation lives were predicted by correlating these FIPs with statistical variables and cyclic J-integrals, respectively. By constructing a microstructure-based 3D polycrystalline finite element model with a free surface, a crystal plasticity finite element-based numerical simulation was carried out to quantify FIPs and clarify the role of crystallographic anisotropy in fatigue crack initiation. The numerical results reveal the following: (1) Nucleation is prone to occur on the surface of a material as a result of it having a higher inhomogeneous deformation than the interior of the material. (2) Compared with the experimental data, the LCF initiation life of UFG 6061 aluminum alloy could be predicted using the new parameters as FIPs. (3) The predicted results confirm the importance of considering the fatigue behavior of nucleation and small crack propagation with different deformation mechanisms for improving the fatigue crack initiation life prediction accuracy.     

空肠弯曲菌慢性感染诱致自身免疫反应的机理初探

用空肠弯曲菌CJ—S131株感染昆明种小鼠3个月,观察到:(1)感染鼠血清中,出现高滴度的抗ds—DNA和ss—DNA抗体;(2)Con A诱导的抑制细胞功能降低和TH/Ts细胞比值增加;(3)PFC形成和LPS诱致的淋巴细胞转化作用增强:(4)DTH和Con A及PHA诱致的淋巴细胞转化作用增强。提示,CJ—S131感染小鼠使其T_S细胞功能降低,导致T_H细胞功能偏亢,B细胞功能亢进,这可能与自身免疫反应的产生有关。     

Identification of the nuclear localization signal of human papillomavirus type 16 L1 protein.

Human papillomavirus type 16(HPV16) L1 and L2 capsid proteins can be detected only in the nucleus of infected cells. For other nuclear proteins, specific sequences of basic amino acids(aa) termed nuclear localization signals (NLS) direct the protein from the cytoplasm to the nucleus. We used a series of deletion and substitution mutations of the HPV16 L1 protein, produced by recombinant vaccinia virus (rVV), to identify NLS within HPV16 L1 and showed that HPV16 L1 contains two NLS sequences, each containing basic aa clusters. One NLS consisted of 6 basic amino acids (KRKKRK from aa 525 to 530) at the carboxy terminal end of L1. The other NLS contained 2 basic aa clusters(KRK from aa 510 to 512 and KR at aa 525, 526) separated by 12 amino acids. Mutations in either NLS did not alter nuclear localization of L1 when the other remained intact, but mutations to both prevented nuclear localization of L1. The L1 NLS could be overridden by introduction of a membrane binding sequence at the amino terminal end of the protein. A databases search showed that all sequenced papillomaviruses are predicted to have L1 and L2 capsid proteins with sequences of basic amino acids homologous with one or both NLS of HPV16 L1.     

Cord blood contains cells secreting antibodies to nervous system components.

Umbilical cord blood of newborns and peripheral blood of healthy adults were investigated by an immunospot assay for cells secreting IgG, IgA and IgM antibodies against myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG) which represent putative antigens for an autoimmune attack in multiple sclerosis (MS) and against acetylcholine receptor (AChR) which is considered an important autoantigen in myasthenia gravis. Cells secreting antibodies against one or more of these autoantigens were detected in 18 out of 24 newborns, and in eight out of 20 adults. Eight of the cord blood samples contained cells secreting antibodies of IgG, IgA and/or IgM isotypes to one antigen, five to two antigens, two to three antigens, two to four antigens, and one to five antigens. Most prominent were anti-MBP IgG antibody secreting cells which were detected in 13 newborns at a mean number of 1/20,000 cord blood cells, and in six adults at a mean number of 1/10(5) peripheral blood cells. Anti-AChR IgG antibody secreting cells were detected in four out of 12 newborns versus four out of 14 peripheral blood specimens, at mean values of 1/10(5) cells in both instances. Cells secreting autoantibodies of IgA and IgM isotypes were less frequent both in cord blood and peripheral blood. The occurrence of nervous tissue autoantibody secreting cells in newborns must be related to a possible primary role of such autoantibodies in MS and myasthenia gravis.     

Effect of ursodeoxycholic acid on experimental hepatic porphyria induced by griseofulvin.

Griseofulvin(GF) has become the drug of choice as an antifungal agent for patients who suffer from many kinds of fungal infection. In order to clarify hepatic injury by griseofulvin(GF) overload and the effect of UDCA on GF-induced hepatic injury, the authors carried out biochemical, histologic, and ultrastructural studies of liver following treatment with griseofulvin and ursodeoxycholic acid(UDCA) in mice. Urine porphobilinogen excretion in the group treated with GF alone was significantly increased and reached the highest level in the 4th week and declined thereafter. Biochemical studies of the liver function showed no remarkable changes of serum bilirubin levels throughout the experimental period in all groups, except for SGPT and alkaline phosphatase activities which were significantly elevated and reached the highest level in the second week. Then they slightly decreased in GF treated groups(GF alone and GF plus UDCA) in comparison with the control group. Pathologic findings in the group treated with GF alone include focal liver cell necrosis(esp, zone 3), Mallory bodies in hepatocytes(esp, zone 1), Kupffer cell activation, and brown protoporphyrin pigments in the hepatocytes, bile canaliculi and interlobular bile ducts with a marked inflammatory cell infiltration in the portal tracts. Under the polarizing light microscope, bile ductular and canalicular thrombi showed a "Maltese cross" birefringence in mice treated with GF alone. There is no definite finding of fatty change in hepatocyte. Under the microscope, the liver appeared normal with an intact lobular architecture in the GF plus UDCA treated group. Electron microscopically, GF-induced changes include swelling of mitochondria, globular protoporphyrin crystals in the hepatocyte cytoplasm, markedly dilated bile cannaliculi and bile ducts and the formation of a Mallory hyaline bodies in the hepatocytes. There were no noticeable structural changes in the GF plus UDCA-treated group. Therefore the results suggest that GF causes hepatic injury, namely porphyria and cholestasis, and the treatment of UDCA may have cytoprotective and choleretic effects on GF-induced hepatic injuries.