二甲亚砜对人表皮的核酸和蛋白质合成的影响

用体外培养的人的伪表皮作为模型，进行药物毒理学作用的研究，观察了二甲亚砜（ＤＭＳＯ）在不同浓度和不同接触时间条件下，对人的伪表皮细胞脱氧核糖核酸（ＤＮＡ）、核糖核酸（ＲＮＡ）和蛋白质合成的影响：随着接触时间的延长，ＤＮＡ、ＲＮＡ和蛋白质合成均受抑制。低浓度条件下（１％），ＤＮＡ、ＲＮＡ和蛋白质合成增加；在１５～５０％浓度下，ＤＮＡ和蛋白质合成抑制，而ＲＮＡ合成仍增加；在高浓度条件下（７０％～１００％），ＤＮＡ、ＲＮＡ和蛋白质合成均明显抑制。     

Behavioral effects of vehicles: DMSO, ethanol, Tween-20, Tween-80, and emulphor-620

Experimental drugs and compounds that do not easily dissolve in water or saline are frequently combined with vehicles like solvents, detergents, or vegetable oils. Yet very little has been reported on the behavioral effects of vehicles. In this study, we assessed the effects of a vegetable oil (emulphor-620), two detergents (Tween-20 and Tween-80), and two solvents [dimethyl sulphoxide (DMSO) and ethanol] on the locomotor activity in CD2F1 male mice. Locomotor activity was monitored for 12 h after vehicle administration (IP). The concentrations for each vehicle were expressed as percent of vehicle in saline (v/v). Emulphor-620 did not affect locomotor activity at any concentration tested (2%, 4%, 8%, 16%, and 32%). Tween-20 significantly decreased locomotor activity at a concentration of 16% and Tween-80 at 32%. DMSO significantly decreased locomotor activity at concentrations of 32% and 64%. In contrast, ethanol produced a biphasic behavioral response: increased activity at a concentration of 16% and decreased activity at a concentration of 32%. These results will facilitate the selection and concentration of vehicles to be used in combination with experimental drugs or test agents.     

Development of the retinal pathway to the pretectum of the cat

The development of retinal projections to the pretectal complex of prenatal and early postnatal cats has been examined using the anterograde transport of horseradish peroxidase and tritiated amino acids. As early as embryonic day 38, the entire dorsal pretectum is penetrated by retinal ganglion cell axons. At this stage the bilateral complement of retinal efferents appears to be dispersed uniformly within the pretectal anlage. A week later, on embryonic day 46, indistinct foci of peroxidase reaction product can be discerned within 2 of the primordial nuclei: the nucleus of the optic tract and the olivary nucleus. By embryonic day 56, five distinct bilateral fields of retinal fiber termination are apparent within the following regions:

(i) the nucleus of the optic tract;

(ii) the pretectal olivary nucleus;

(iii) the posterior pretectal nucleus;

(iv) the anterior pretectal nucleus; and

(v) the medial pretectal nucleus. Four days before birth, on embryonic day 61, crossed and uncrossed retinal arbors are partially segregated within the nucleus of the optic tract and the pretectal olivary nucleus.

The early postnatal retinal connection to the pretectum has an overall pattern virtually indistinguishable from that of the mature cat. The ontogeny of the retinal influx to the pretectum is similar to that of the retinocollicular projection.⁶¹ However, the development of retinal projections to the pretectum and superior colliculus appears to lag behind those to the dorsal lateral geniculate nucleus.⁴⁹ These differences may reflect temporal and spatial gradients in the maturation of three major classes of retinal ganglion cells.     

二甲亚砜对小鼠腹水型网状细胞肉瘤ARS细胞的分化诱导

小鼠ARS腹水型网状细胞肉瘤瘤株加1.5、2.0、2.5%DMSO体外培养,被诱导出现了巨噬细胞样分化。细胞及核缩小,尤以核缩小为著,核质比值下降。2.5%DMSO的作用最显著,核仁缩小仅见于2.5%组。核质比值小于0.5,且核仁亦缩小的细胞近似巨噬细胞。2.5%DMSC使非特异性酯酶阳性细胞增多;Po1ystyrene胶乳颗粒吞噬百分数和吞噬指数亦增高。透射电镜观察,2.5%DMSO处理的、核质比值小于0.5的ARS细胞内,细胞器丰富,Golgi复合体发达,次级溶酶体增多。扫描电镜观察,对照组的大细胞多,表面有多数密集的细长微绒毛。2.5%DMSO处理的ARS,大细胞减少,小细胞增多,微绒毛明显缩短减少。这种小细胞与光镜和透射电镜下观察的小细胞一致,是分化程度较高的巨噬细胞样细胞。2.5%DMSO处理的ARS细胞核分裂指数显著下降。     

Lucigenin-dependent chemiluminescence as a new assay for NAD(P)H-oxidase activity in particulate fractions of human polymorphonuclear leukocytes

The enzyme responsible for the respiratory burst in human neutrophils is an oxidase that catalyzes the reduction of oxygen to superoxide anion (O-2). Superoxide anion production may be measured by chemiluminescence (CL) in the presence of lucigenin (10,10'-dimethyl-9,9'- biacridinium dinitrate). We established an assay of the oxidase, by measuring the CL of particulate fractions of PMN in the presence of lucigenin . This CL required the addition of NAD(P)H and was very low in fractions of resting cells. In particulate fractions of PMNs stimulated with PMA selectively, the NADPH-dependent CL was found to be increased. CL was linear with protein concentrations up to 100 micrograms and was shown to be at least 10 times more sensitive for the detection of O-2 than the assay based on the spectrophotometric determination of superoxide mediated cytochrome c reduction. CL was abolished by inactivating the enzyme at 56 degrees C.     

Proper Fitting and Use of Crutches

In brief: Injured athletes who need crutches must be fitted correctly and taught their proper use to help prevent further injury, undue complications, and discouragement. Crutches should reach to about two finger widths below the armpit, and the handgrip should be adjusted so the elbow is flexed 25° to 30° with the wrist straight. The weight should be supported through the palms on the handgrips. The three-point gait is used when only one foot, ankle, or knee is injured. Proper instruction is extremely important for negotiating stairs.     

Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy-quinocetone metabolite in porcine adrenocortical cells in vitro

Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway.     

Toxicology of 3-epi-deoxynivalenol,a deoxynivalenol-transformation product by Devosia mutans 17-2-E-8

Microbial detoxification of deoxynivalenol (DON) represents a new approach to treating DON-contaminated grains. A bacterium Devosia mutans 17-2-E-8 was capable of completely transforming DON into a major product 3-epi-DON and a minor product 3-keto-DON. Evaluation of toxicities of these DON-transformation products is an important part of hazard characterization prior to commercialization of the biotransformation application. Cytotoxicities of the products were demonstrated by two assays: a MTT bioassay assessing cell viability and a BrdU assay assessing DNA synthesis. Compared with DON, the IC₅₀ values of 3-epi-DON and 3-keto-DON were respectively 357 and 3.03 times higher in the MTT bioassay, and were respectively 1181 and 4.54 times higher in the BrdU bioassay. Toxicological effects of 14-day oral exposure of the B6C3F₁ mouse to DON and 3-epi-DON were also investigated. Overall, there were no differences between the control (free of toxin) and the 25 mg/kg bw/day or 100 mg/kg bw/day 3-epi-DON treatments in body and organ weights, hematology and organ histopathology. However, in mice exposed to DON (2 mg/kg bw/day), white blood cell numbers and serum immunoglobulin levels were altered relative to controls, and lesions were observed in adrenals, thymus, stomach, spleen and colon. Taken together, in vitro and in vivo studies indicate that 3-epi-DON is substantially less toxic than DON.