Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

2 121例老年急性冠脉综合征患者血清脂类浓度的分析

目的分析60岁以上老年人血清脂类水平的参考值,并探讨急性冠脉综合征与血脂指标的相关性.方法将3 766例健康成人分为≤60岁和＞60岁的两个年龄段,采用生物化学的方法测量他们的血脂水平,找出60岁以上老年人的脂类参考值.同时分析2 121例老年急性冠脉综合征病人的脂类指标.结果 60岁以上老年人血脂参考值为:TC 4.65±1.96×1.05mmol/L;TG 1.02±1.96×0.45mmol/L;HDL-C 1.47±1.96×0.40mmol/L;LDL-C 2.98±1.96×0.56mmol/L;ApoA1 1.32±1.96×0.25g/L;ApoB 0.99±1.96×0.35g/L,并且急性心肌梗死和不稳定性心绞痛病人血清脂类各项指标之间没有显著性差异.结论血清LDL-C/HDL-C＞5和TG ≥1.9mmol/L这两项联合指标比其他单独指标与老年人急性冠脉综合征关系更密切.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

Reactive oxygen species and human spermatozoa: physiology and pathology

The role of reactive oxygen species (ROS) in the pathophysiology of human sperm function has been emphasized in recent years. ROS production in semen has been associated with loss of sperm motility, decreased capacity for sperm–oocyte fusion and loss of fertility. There is a current presumption that the most prolific source of ROS in sperm suspensions is an NADPH oxidase located in leukocytes or in spermatozoa which produces superoxide which is further converted to peroxide by the action of superoxide dismutase. Hydrogen peroxide has been recognized as the most toxic oxidizing species for human spermatozoa, which are very sensitive to lipid peroxidation owing to the high content of polyunsaturated fatty acids in their plasma membrane, though this is not the sole mechanism by which sperm function might be impaired by ROS. Although the excessive production of ROS is detrimental to human spermatozoa, there is a growing body of evidence which suggests that ROS are also involved in the physiological control of some sperm functions. This review focuses on the nature and source of the ROS generated by human spermataozoa as well as their operational mechanisms and their effects, which may be detrimental or beneficial.     

Lipid extract from completely sporoderm‐broken germinating Ganoderma sinensis spores elicits potent antitumor immune responses in human macrophages

Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.     

Conjugated linoleic acid evokes de-lipidation through the regulation of genes controlling lipid metabolism in adipose and liver tissue

Conjugated linoleic acid (CLA) is a unique lipid that elicits dramatic reductions in adiposity in several animal models when included at < or = 1% of the diet. Despite a flurry of investigations, the precise mechanisms by which conjugated linoleic acid elicits its dramatic effects in adipose tissue and liver are still largely unknown. In vivo and in vitro analyses of physiological modifications imparted by conjugated linoleic acid on protein and gene expression suggest that conjugated linoleic acid exerts its de-lipidating effects by modulating energy expenditure, apoptosis, fatty acid oxidation, lipolysis, stromal vascular cell differentiation and lipogenesis. The purpose of this review shall be to examine the recent advances and insights into conjugated linoleic acid's effects on obesity and lipid metabolism, specifically focused on changes in gene expression and physiology of liver and adipose tissue.     

外加磁场对半乳糖化白蛋白磁性阿霉素纳米粒在大鼠体内分布影响的研究

目的观察半乳糖化白蛋白磁性阿霉素纳米粒(ADR-GHMN)在正常肝脏中的靶向性,并观察ADR-GHMN在全身各脏器的分布特征及外加磁场对其分布的影响.方法大鼠正中开腹,肝动脉插管并固定,肝动脉注射125I-ADR-GHMN(相当于阿霉素0.5 mg/kg),左外叶加磁场,磁场应用30 min,移去磁场后,动物立即处死;对照组:肝动脉注射ADR-GHMN,左外叶不加磁场,30min后,移去磁场后,动物立即处死,立即取靶区肝、非靶区肝、肾、心、肺、小肠、脾及周围血作γ计数.肝组织作病理切片.结果注入的纳米粒75～85%分布于肝脏,其它脏器极少.病理切片显示磁区小动脉见大量纳米粒存在,对照组及非磁区肝中纳米粒很少见.结论ADR-GHMN在正常肝组织中有明显的磁靶向性;在磁场作用下,ADR-GHMN主要分布于肝脏,其它脏器含量很少;试验组肾、心、肺、小肠、脾及外周血于对照组的放射活性比较明显降低,表明磁性物质的存在使这些脏器的相对药物暴露明显减少.     

The effect of seamustard on blood lipid profiles and glucose level of rats fed diet with different energy composition

Recently, Korean people are consuming seaweeds almost 3.5 times more now than three decades ago. It is well known that seaweeds contain lots of soluble dietary fiber in addition to micronutrients such as β-carotene, iodine and some bioactive components. Seaweeds are considered to be effective for preventing chronic diseases including obesity, diabetes mellitus, atherosclerosis, cancer or constipation. This study was conducted to investigate the effect of seamustard intake on body weight gain, blood glucose level and lipid profiles in rats fed diets with different energy nutrient composition. Male Sprague-Dawley rats (average initial weight 103.7 g) were divided into groups for two experiments as follows; Control, M2.5 & M5 groups (Exp. I) and M5, M10, HCM5, HCM10, HFM5 & HFM10 groups (Exp. II). The rats were fed diet and water ad libitum for 4 weeks. In general, there was no significant difference in blood glucose and triglyceride concentration among groups. In Exp. I, serum LDL-cholesterol level of rats fed diet with 5% seamustard powder (M5) was significantly lower than that of control group, while HDL-cholesterol level, TC/LDL ratio and weight of adrenal gland were higher. In Exp. II, food intake, body weight gain and EER of high fat diet with 10% seamustard group (HFM10) were the lowest among groups. Except gastrocnemius muscle, all organ weights of HFM10 group were the lowest. Fecal cholesterol excretion and serum LDL-cholesterol concentration of HFM10 group were the highest, while serum HDL-cholesterol level was the lowest among groups. Interestingly, HDL-cholesterol concentration was the highest in HCM5 group among groups. From these results, it was suggested that seamustard intake might be more effective for body weight control, but not for improving blood lipid profiles in high fat diet than in high carbohydrate diet.     

Effect of ozonized normal saline on biochemical parameters of the liver in malignant growth

Injection of ozonized normal saline to animals with transplanted sarcoma-45 normalized energy metabolism in the liver, which is important for this organ's function under conditions of malignant growth. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 207–209, August, 1998     

Correlation between the parameters of free-radical lipid peroxidation and antioxidant system in children living in the north

A comparative study of the parameters of free-radical lipid peroxidation and antioxidant system was performed in children living in the North for various time periods. Intense lipid peroxidation was shown to be the key factor in the pathogeneses of several diseases caused by disturbances in the cellular membrane. Decreased resistance of red blood cells to peroxidative hemolysis is a phenomenon characterizing the adaptation-violating processes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 342–344, September, 1998