Development of responsiveness to novel objects in the titi monkey,Callicebus moloch

Adult titi monkeys react to novelty more strongly and cautiously than other New World primates. Developmental changes in responsiveness were assessed by presenting complex novel objects to family groups consisting of 11 male-female pairs and their adult (31–33 months), subadult (20–23 months), and juvenile offspring (10–16 months). Food and a simple block were included as control conditions. Differences in attraction to novel objects were inversely related to age. Juveniles approached more objects, more quickly, and spent more time near them than older subjects. Parents, the least responsive age-group, seemed more indifferent than cautious. Age-effects were smaller with the block, and negligible with food. Even in the most responsive age-group, investigatory behavior appeared subdued as compared to other primate species. sensuHershkovitz, 1963.     

Epigenetics and atherosclerosis

The contribution of epigenetic mechanisms to cardiovascular diseases remains poorly understood. Hypomethylation of genomic DNA is present in human atherosclerotic lesions and methylation changes also occur at the promoter level of several genes involved in the pathogenesis of atherosclerosis, such as extracellular superoxide dismutase, estrogen receptor-α, endothelial nitric oxide synthase and 15-lipoxygenase. So far, no clear data is available about histone modification marks in atherosclerotic lesions. It remains unclear whether epigenetic changes are causally related to the pathogenetic features, such as clonal proliferation of lesion smooth muscle cells, lipid accumulation and modulation of immune responses in the lesions, or whether they merely represent a consequence of the ongoing pathological process. However, epigenetic changes could at least partly explain poorly understood environmental and dietary effects on atherogenesis and the rapid increases and decreases in the incidence of coronary heart disease observed in various populations. RNAi mechanisms may also contribute to the epigenetic regulation of vascular cells. Therapies directed towards modification of the epigenetic status of vascular cells might provide new tools to control atherosclerosis-related cardiovascular diseases.     

Preparation and investigation of 99m technetium-labeled low-density lipoproteins in rabbits with experimentally induced hypercholesterolemia

Low-density lipoproteins (LDL) were radiolabeled in atherosclerosis studies. The aim was to investigate the biodistribution and uptake of ^99mTc-labeled LDL by atherosclerotic plaques in experimentally induced hyperlipidemia. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate human LDL aliquots, to prepare radioactive-labeled lipoproteins and in rabbits with induced hyperlipidemia. Preparative density gradient centrifugation was applied for the simultaneous isolation of the major lipoprotein density classes, which form discrete bands of lipoproteins in the preparative tubes. The cholesterol and protein levels in the lipoprotein fractions were determined. LDL was subsequently dialysed against physiological solution and sterilized and apolipoprotein fragments and aggregates were eliminated by passage through a 0.22-micron filter. LDL was radiolabeled with ^99mTc by using sodium dithionite as a reducing agent. Radiochemical purity and in vitro stability were controlled by paper chromatography in acetone. The labelling efficiency was 85–90% for human LDL. Two months after the start of cholesterol feeding, the total cholesterol in the blood serum had increased approximately 33-fold in comparison with the basal cholesterol content of hypercholesterolemic rabbits. Investigation of LDL was performed by Schlieren analysis after adjustment of the density of serum and underlayering by salt solution in a spinning ultracentrifugation capillary band-forming cell. Quantitative results were obtained by measuring the Schlieren areas between the sample curves and the reference baseline curve by means of computerized numerical and graphic techniques. In this manner we measured the concentrations of human LDL and analyzed rabbit LDL levels in induced hyperlipidemia. Gamma scintillation camera scanning of the rabbits was performed. Overnight fasted rabbits were injected in the marginal ear vein with ^99mTc-labeled human LDL (4–10 mCi, 0.5–1.5 mg protein). The initial scintigram showing a typical blood-pool scan, gradually changing with time to an image of specific organ uptake of radioactivity by the liver, kidneys and brain and in the bladder. Gamma camera in vivo scintigraphy on rabbits revealed visible signals corresponding to atherosclerotic plaques in the aorta and carotid arteries. Our results show that ^99mTc-LDL can be used to assess the organ distribution pattern of LDL in the rabbit, and to detect and localize areas of arterial atherosclerotic lesions.     

Territorial shift in the yellow-handed titi monkey (Callicebus torquatus)

In this study, the ranging pattern of a single group of monogamous and territorial Callicebus torquatus was recorded over a 7-year period from 1974 to 1980. Data on ranging pattern were recorded by direct observation; daily movement patterns were plotted on an accurate, scaled map of the territory. Data were obtained during 1–3-month studies each year from 1974 to 1978 and in 1980, as well as during a 12-month study in 1979-1980. These studies show that the exclusive territory maintained by the group was not spatially stable over the 7-year period. The group gradually moved its territory to the northeast, to the extent that the territory used in 1980 was completely noncoincident with the territory used in 1974 by the same group. Analysis of the ranging pattern from the 12-month study indicates that the group did not exhibit seasonal preferences for different parts of its range. Seasonal ranging patterns, therefore, are not likely to account for the observed territorial shift. It is suggested that territorial shifting may be related to the need for monogamous groups to find new territories for their offspring.     

P66Shc mediates increased platelet activation and aggregation in hypercholesterolemia

Background and hypothesis

Hypercholesterolemia leads to a prothrombotic phenotype. Platelet hyperactivity associated with hypercholesterolemia has been attributed, in part, to oxidative stress. P66Shc is a well-known determinant of cellular and organismal oxidative stress. However, its role in platelet biology is not known. We hypothesized that p66Shc mediates platelet hyperactivation and hyperaggregation in hypercholesterolemia.

Methods and results

P66Shc was expressed in both human and mouse platelets, as determined by qRT-PCR and immunoblotting. Mouse platelet p66Shc expression was upregulated by hypercholesterolemia induced by high-fat diet feeding. Compared to wild-type mice, high-fat diet-induced p66Shc expression in platelets was suppressed in transgenic mice expressing a short hairpin RNA targeting p66Shc (p66ShcRNAi). High-fat diet feeding of wild-type mice amplified surface P-selectin expression on platelets stimulated by the thrombin receptor agonist protease-activated receptor-4 (PAR4), and increased aggregation of platelets induced by thrombin. These exaggerated platelet responses induced by high-fat diet feeding were significantly blunted in p66ShcRNAi mice. Finally, thrombin-stimulated platelet reactive oxygen species were suppressed in p66ShcRNAi mice.

Conclusions

Hypercholesterolemia stimulates p66Shc expression in platelets, promoting platelet oxidative stress, hyperreactivity and hyperaggregation via p66Shc.     

Experimental atherosclerosis: a historical overview

Almost one-hundred years ago the first evidence of experimental atherosclerosis was reported. Over the past century, significant advances have been made in the development of animal models of human coronary artery disease. In this minireview, induction of atherosclerotic lesions in several animal models including rodents (mice, rabbits, rats, hamsters, guinea pigs), avian (pigeons, chickens, quail), swine, carnivora (dogs, cats), and non-human primates is discussed. The limitations and advantages of the animal models of atherosclerosis have been summarized. The transgenic/knockout animal models have greatly enhanced our understanding of atherosclerosis. Compared to wild-type counterparts, the knockout/transgenic animals develop atherogenesis faster without a need for a highly atherogenic diet. Although almost all investigations support a causal role for increased plasma cholesterol levels in the development of atherosclerotic vascular disease, an increasing body of evidence indicates serious invqlvement of other factors including oxidative stress, inflammation, infection and other emerging risk factors.     

Coppery titi monkey (Plecturocebus cupreus) pairs display coordinated behaviors in response to a simulated intruder

Mate guarding and coordinated behaviors between partners are important for the maintenance of monogamous pair bonds. To study the effects of a perceived unfamiliar social intruder on females' behavior, we used coppery titi monkeys (Plecturocebus cupreus). We examined the effects of male aggressive temperament on females' behavior and the effects of each behavior performed by the male on the same female behavior. Using a mirror, we simulated a social intruder in the home territory and scored behaviors using an established ethogram. Based on our analysis of self-directed behaviors, females do not recognize themselves in the mirror. We then used general linear mixed models to predict percent change in females' behaviors as a function of (a) males' temperament, (b) males' behavior, and (c) an interaction between males' temperament and behavior. Male temperament did not significantly predict female behavior for any of our best fitting models. For percent change in female lip-smacking, male lip-smacking significantly predicted female lip-smacking (β = 0.74, SE = 0.22, t = 3.39; p = .004). There was a positive correlation between male and female agonistic behaviors such as back-arching/tail-lashing (β = 0.51, SE = 0.23, t = 2.22; p = .04) and for anxiety-related behaviors such as leaving the partner (β = 0.50, SE = 0.19, t = 2.68; p = .015), locomotion duration (β = 0.19, SE = 0.06, t = 2.98; p = .02), and locomotion frequency (β = 0.71, SE = 0.14, t = 5.17; p < .001). These findings on coordination of pair-mate behaviors may explain how titi monkeys display pair bond strength and ensure their reproductive success.     

Role of lupeol and lupeol linoleate on lipemic-oxidative stress in experimental hypercholesterolemia

Epidemiological studies have shown that there is a positive correlation between the incidence of coronary heart disease (CHD) and the blood cholesterol level. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on blood lipid status and oxidant stress in heart and hemolysate, male albino Wistar rats were fed high cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. A significant increase (p<0.05) in plasma total cholesterol (4.22 fold) and triglycerides (1.7 fold) was observed in HCD fed rats, along with elevated LDL (3.56 fold) and VLDL (1.99 fold) cholesterol and decreased HDL cholesterol (34.14%). Treatment with lupeol and its derivative normalized the lipid profile. The significant increase (p<0.05) in lipid peroxidation (LPO) was paralleled by significantly diminished (p<0.05) activities of antioxidant enzymes (SOD, CAT and GPx) and decreased (p<0.05) concentration of antioxidant molecules (GSH, Vit C and Vit E) in cardiac tissue and hemolysate of HCD fed rats. The oxidative tissue injury in hypercholesterolemic rats was substantiated by the increase in cardiac marker, serum CPK and the drop in its activity in the heart tissue. Lupeol and lupeol linoleate treatment decreased the LPO levels and increased enzymatic and nonenzymatic antioxidants. CPK activity in the treated group was comparable with that of the control. These observations highlight the beneficial effects of the triterpene, lupeol and its linoleate ester derivative, in ameliorating the lipidemic-oxidative abnormalities in the early stage of hypercholesterolemic atherosclerosis.     

Spontaneous pericardial mesothelioma in a rhesus monkey.

Spontaneous tumors in nonhuman primates are of great importance. A spontaneous pericardial mesothelioma was observed in an 18-year-old female rhesus monkey. Grossly, the visceral pericardium was multifocally irregular and thickened with tan discoloration and was soft in consistency. Histologically, the pericardium contained highly in-folded branching fronds lined by a single layer of cuboidal cells. Tumor invaded into approximately half of the thickness of the atrial and ventricular muscles. Tumor penetration was not observed into the atrial or ventricular cavity. Within the myocardium, neoplastic cells formed glandular structures which were lined by cuboidal to columnar cells. Neoplastic cells were weakly positive with PAS and strongly positive for colloid iron and alcian blue. Immunohistochemically, neoplastic cells were positive for both vimentin and cytokeratin and negative with CEA and Leu-M1, indicating mesothelial origin. To the best of the authors' knowledge, this is the first report of a spontaneous pericardial mesothelioma in a rhesus monkey.     

C反应蛋白与动脉粥样硬化

人类C反应蛋白 (C reactiveprotein ,CRP)是在感染和组织损伤时血浆浓度快速、急剧升高的主要的急性期蛋白。CRP可以激活补体和加强吞噬细胞的吞噬而起调理作用 ,从而清除入侵机体的病原微生物和损伤、坏死、凋亡的组织细胞 ,在机体的天然免疫过程中发挥重要的保护作用。关于CRP的研究已经有 70多年的历史 ,传统观点认为CRP是一种非特异的炎症标志物 ,但近十年的研究揭示了CRP直接参与了炎症与动脉粥样硬化等心血管疾病 ,并且是心血管疾病最强有力的预示因子与危险因子     

过氧化物酶体增殖物激活受体与动脉粥样硬化

过氧化物酶体增殖物激活受体 (peroxisomeproliferator activatedreceptors ,PPARs)是核受体超家族中的一类配体依赖的核转录因子 ,包括α、β/δ和γ三种亚型 ,在脂肪细胞分化、能量代谢和炎症过程中都发挥重要的作用。最近的研究显示 ,PPARs的活化不仅可以改善包括糖尿病、高血压和肥胖等在内的胰岛素抵抗综合征 ,而且还直接作用于血管壁 ,从而减缓动脉粥样硬化的进程。本综述将就PPARs的结构、功能、与动脉粥样硬化发病机制和治疗相关的最新研究进展进行简要介绍。     

氧化型胆固醇与动脉粥样硬化的关系

氧化型胆固醇是胆固醇氧化衍生物,多达上百种。氧化型胆固醇存在于胆固醇膳食,高胆固醇血症的血浆和动脉组织、人动脉粥样硬化斑块和斑块内的泡沫细胞,以及氧化型低密度脂蛋白中。大量实验表明氧化型胆固醇对与动脉粥样硬化形成有关的细胞（如血管内皮细胞,平滑肌细胞以及单核／巨噬细胞等）具有毒性作用,提示,氧化型胆固醇在动脉粥样硬化的发生和演变中具有不可忽视的作用。     

Recovery of fine motor performance after ischemic damage to motor cortex is facilitated by cell therapy in the rhesus monkey

Abstract

We investigated the efficacy on recovery of function following controlled cortical ischemia in the monkey of the investigational cell drug product, CNTO 0007. This drug contains a cellular component, human umbilical tissue-derived cells, in a proprietary thaw and inject formulation. Results demonstrate significantly better recovery of motor function in the treatment group with no difference between groups in the volume or surface area of ischemic damage, suggesting that the cells stimulated plasticity.     

LOX-1 deletion and macrophage trafficking in atherosclerosis

Background

Atherosclerosis is associated with macrophage accumulation. LOX-1 has been shown to induce macrophage attachment, and its deletion (LOX-1 knockout, KO) reduces atherosclerosis in LDLr KO mice fed a high cholesterol diet. We examined differences in macrophage trafficking in age-matched wild type, LOX-1 KO, LDLr KO, and LDLr/LOX-1 double KO mice.

Methods

Sections of aortas of mice fed high cholesterol diet were collected at weeks 0, 4, 8, 12 and 19 and analyzed by immunohistochemistry and flow cytometry.

Results

In the LDLr KO mice aorta, CD68 positivity (macrophage accumulation) increased over time up to 12 weeks, and then the accumulation fell modestly but significantly. The periaortal fat and adventitia showed more CD68 positivity than the media and intima. This pattern was also evident in the non-atherosclerotic areas. Importantly, LOX-1 KO and LDLr–LOX-1 double KO mice showed diminished CD68 positivity in comparison to wild type and LDLR KO mice, respectively. Further, macrophages from LOX-1 KO mice revealed a marked reduction in migration (vs. macrophages from wild type mice) in in vitro migration assay.

Conclusions

LOX-1 deletion translates into reduction in macrophage trafficking in the aorta of LDLr KO mice. Most of the macrophage trafficking appears in the subadventitial regions.     

Accumulation of calcium in the arteries of Japanese monkey

To examine whether the calcium accumulation in the arteries is related to the way of walk or not, the calcium contents were determined in various arteries of Japanese monkeys of quadrupedal walk by inductively coupled plasma-atomic emission spectrometry. Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. Age-related changes of the calcium content were examined in various monkey arteries. Significant relationships between age and calcium content were found in the arteries, such as the axillary, brachial, radial, subclavian, common carotid, common iliac, and femoral arteries, but not statistically in the thoracic and abdominal aortas, ulnar, external iliac, internal iliac, popliteal, and tibial arteries. The average contents of calcium were compared between the two groups of the monkeys below 14 yr and over 24 yr of age. Below 14 yr, the calcium content was a little higher in the arteries, such as the common, external and internal iliac, and femoral arteries than that of the other ones. Over 24 yr, the calcium content increased remarkably in the arteries, such as the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries. The calcium contents of the thoracic aorta, common, internal and external iliac, common carotid, and subclavian arteries increased by more than two times over 24 yr compared with those below 14 yr. In a comparison between the calcium contents of the arteries in the anatomically corresponding regions of the upper and lower limbs, no statistically significant differences were found in the subjects over 24 yr as well as the subjects 2–29 yr of age. The calcium accumulation in the arteries of monkeys with aging was different from those in the arteries of humans, because in the case of human, a very high accumulation of calcium occurred in the arteries of the lower limb with aging in comparison with those in the upper limbs. Therefore, it is likely that different ways of walk or different species are partly affected in the calcium accumulation in the arteries with aging.     

Influence of selenomethionine and vitamin E on the antioxidative system in animals with experimentally induced hypercholesterolemia

The aim of this study was to investigate the effect of combined therapy of vitamin E and selenomethionine to pro/ antioxidant status in experimental hypercholesterolemia. Thirty male rabbits were included in the study and randomized into five groups consisting of the control group (standard diet) and four experimental groups staying on a diet rich in cholesterol (0.5 g/100 g diet): cholesterol group and groups supplemented cholesterol with selenomethionine (12.5 μg/kg body mass/24 h) or vitamin E (10 mg of Dl-α-tocopherol/kg body mass/24 h) or combination of the above antioxidants for 3 mo. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) as well as the concentration of malondialdehyde (MDA) was estimated in the blood during every month of experiment. Increased activity of SOD and GPX with a decreased concentration of MDA in comparison to the cholesterol diet was found mainly in the combination of study antioxidants. The supplementation of the cholesterol diet with combined doses of vitamin E and selenomethionine appears to prevent the lesions induced by experimental hypercholesterolemia much more efficiently than single doses of the above.     

慢性炎症、自身免疫和动脉粥样硬化

动脉粥样硬化是一种炎症性疾病。在粥样斑块中存在许多免疫细胞,而且在不稳定斑块中尤为丰富。近年来对动脉粥样硬化中免疫细胞的聚集,分化和激活有了更深入的了解。流行病研究发现了多种与其相关的病毒和细菌感染。通过研究初步研究了几个自身性抗原,并提出了自身免疫假说。根据这些新的认识,提出了免疫调节和预防接种等心血管疾病的预防和治疗策略。这必将极大地提高对动脉粥样硬化的研究和防治水平。