Calcium dependence of chemical carcinogen induced morphological transformation of Syrian hamster embryo cells

The effect of extracellular calcium upon carcinogen induced morphological transformation was evaluated in Syrian hamster embryo cells. Reduction in [Ca²⁺] from 1.8 mM to 0.2 mM throughout the 6 days between exposure of the cells to 2.5 μg benzo[a]pyrene (BP)/ml and examination of the cells for transformation inhibited both cell proliferation and transformation as measured by the frequencies of colony formation and morphological transformation. The transformation frequency among surviving cells, i.e. frequency/cell colony, however, was nearly equivalent indicating that the inhibition of transformation largely resulted from inhibition of cell colony formation. Proliferation and transformation were unaffected when [Ca²⁺] was reduced to 0.2 mM on days 3–6. Reduction to 0.01 mM Ca²⁺ during the same period, however, completely abolished transformation by BP, UV-irradiation or n-acetoxyacetylaminofluorene (AcAAF) without reducing cell proliferation. Thus, the expression of morphological transformation in newly transformed hamster cells is dependent upon extracellular [Ca²⁺] to a greater degree than is cell proliferation.     

尼莫地平对大鼠急性脑缺血再灌注损伤的保护机制

目的探讨尼莫地平对大鼠急性脑缺血再灌注损伤的保护作用。方法将局灶性缺血模型大鼠分为假手术组、缺血组及尼莫地平干预组,测各组大鼠脑组织亚细胞器丙二醛(MDA)、超氧化物歧化酶(SOD)的含量及脑细胞内游离Ca2 浓度。结果脑缺血再灌注后脑组织MDA及Ca2 浓度显著升高,SOD显著降低。尼莫地平能改善这种状况。结论尼莫地平对急性脑缺血再灌注损伤有保护作用,其机制与降低脑细胞MDA、Ca2 浓度升高SOD有关。     

Evidence for the presence of glutamatergic receptors in adult Schistosoma mansoni

Several studies have suggested that L-glutamate is a putative neurotransmitter in helminths. The present study investigated the presence of non-N-methyl-D-aspartate (NMDA) ionotropic receptors for glutamate in four subcellular fractions from adult male Schistosoma mansoni. Low-affinity (K(d)=221+/-80 nM) binding sites for [3H]kainic acid (KA) were detected in the heterogeneous (P(1)) fraction, which contains pieces of unbroken worm tissues, tegument, nuclei, and some vesicles. This binding was inhibited by classical glutamatergic ligands in the following order of potency: KA>L-glutamate>alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)>quisqualate congruent with 6,7-dinitroquinoline-2,3-dione (DNQX). However, neither NMDA, a selective agonist for NMDA receptors, nor DL-threo-beta-hydroxyaspartate (THA) and 1-trans-pyrollidine-2-dicarboxylic acid (PDC), inhibitors of high-affinity glutamate transporters, modified [3H]KA binding to the P(1) fraction. In addition, no specific binding for 10nM [3H]AMPA was detected in any subcellular fraction from S. mansoni. These results suggested the presence of KA receptors in adult male worms. This is supported by the evidence that direct application of 10 microM KA to whole worms produced a corkscrew-like coiling of their bodies, modifying the motility of the worms. The KA-induced response, measured as a decrease of the body area, was time-dependent and reversible. PDC was ineffective at blocking the KA effects, indicating that KA does not depend on high-affinity glutamate transporters to reach its site of action. On the other hand, DNQX, the non-NMDA antagonist, was able to partially inhibit KA-induced responses. As a whole, the present data support the presence of a glutamatergic signaling pathway in this parasite.     

Morphological alterations in dorsal root ganglion neurons and supporting cells of organotypic mouse spinal cord-ganglion cultures exposed to taxol

Expiants of 14-day fetal mouse spinal cord with attached dorsal root ganglia, which had become differentiated over 2–3 weeks in culture, were exposed to 1–2 μM taxol for up to 6 days. The culture medium was supplemented with nerve growth factor (300 units/ml) during exposure to the drug.By 3–6 days in taxol, unusually numerous microtubules were seen in peripheral perikaryal and proximal neuritic regions of ganglion neurons. Microtubules also engirdled massive aggregations of pleomorphic vesicular/cisternal elements in many neurons. These aggregates were visible as unusual ‘clear’ spheroidal regions in the living cells, and were often as large as the nuclei. Some of the elements comprising these striking vesicular/cisternal accumulations appeared to be portions of disrupted Golgi complexes normally polarized around the cytocentrum, as well as hypertrophied smooth endoplasmic reticulum formations. In other neuronal areas, Golgi complexes and other organelles were altered or disrupted to lesser degrees. Ordered microtubular arrays occurred along endoplasmic reticulum cisternae both in neuron somata and neurites. Over time, a plethora of microtubules assembled throughout the perikarya in various orientations apparently unrelated to microtubule organizing centers. Unlike the effects of other plant alkaloids that interact with tubulin, there was no discernible increase in filaments, although their distribution appeared altered. Concentric ordered microtubular-macromolecular lamellated complexes were seen only in neurites. Neuronal nuclei were misshapen, often displaced, and displayed fine structure reminiscent of chromatolysis. Satellite and Schwann cells contained atypically abundant microtubules, abnormal cisternae, disrupted Golgi complexes, and increased lysosomes. Some nuclei displayed abnormal chromatin, and in rare cases even microtubules.We suggest that taxol alters the distribution, integrity, and/or organization of organelle systems in dorsal root ganglion cells by engendering unusually abundant microtubules in abnormal groupings and aberrant locations in these cells.     

Distribution and biomarkers of carbon‐14‐labeled fullerene C60 ([14C(U)]C60) in female rats and mice for up to 30 days after intravenous exposure

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon‐14‐labeled C₆₀ ([¹⁴C(U)]C₆₀). Rodents were administered [¹⁴C(U)]C₆₀ (~0.9 mg kg^?1 body weight) or 5% polyvinylpyrrolidone‐saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [¹⁴C(U)]C₆₀ or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [¹⁴C(U)]C₆₀ was < 2% in urine and feces at any 24 h time points. [¹⁴C(U)]C₆₀ and [¹⁴C(U)]C₆₀‐retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [¹⁴C(U)]C₆₀ exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [¹⁴C(U)]C₆₀ exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [¹⁴C(U)]C₆₀ is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright © 2015 John Wiley & Sons, Ltd.     

Association of lipoprotein(a) with aortic dissection

BackgroundLipoprotein(a) [Lp(a)] is associated with coronary atherosclerotic heart disease, aortic stenosis, stroke, and heart failure. We aimed to determine the relationship between Lp(a) and aortic dissection (AD).MethodsTwo hundred patients with AD were included in our case group. The control group consisted of 200 non‐AD people who were age‐ (±5 years) and gender‐matched to the case group. Data were collected retrospectively, including hypertension, smoking, coronary artery disease, diabetes mellitus, Lp(a), total cholesterol, triglyceride, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. The association between Lp(a) and AD was studied using univariate and multivariate logistic regression analysis.ResultsPatients with AD had greater median Lp(a) concentrations than non‐AD people (152.50 vs. 81.75 mg/L). Lp(a) was associated with AD in a multivariate logistic regression analysis (odds ratio, 8.03; 95% confidence interval, 2.85–22.62), comparing those with Lp(a) quartile 4 with those with Lp(a) quartile 1. Stratified analysis showed that this relationship was observed in both men and women, as well as in older and younger individuals.ConclusionsHigh levels of Lp(a) are strongly associated with AD, independent of other cardiovascular risk factors.