The Pharmacological effects of novel 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamide derivatives on plasma lipid profile of Triton-WR-1339-induced Wistar rats

A novel series of 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) were synthesized. The present study was undertaken to investigate the possible antihyperlipidemic effect of these novel compounds on hyperlipidemic rats. Hyperlipidemia was induced by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg). The tested animals were divided into normal control (NCG), hyperlipidemic control (HCG), compounds 3c-, 3d-, 3e-, 3f-, 3g- and bezafibrate (BF)-treated groups. At a dose of 15 mg/kg, compounds 3c–3g and BF (100 mg/kg) significantly (p < 0.0001) reduced elevated plasma triglycerides levels after 12 and 24 h compared to the hyperlipidemic control group. However, only compounds 3e and 3g obviously showed a significant (p < 0.0001) reduction in plasma total cholesterol levels after 12 and 24 h. Moreover, high-density lipoprotein cholesterol levels were significantly increased in all treated groups. The current study demonstrates that 5-fluoro-N-(9,10-dihydro-9,10-dioxoanthracen-8-yl)-1H-indole-2-carboxamides (3c–3g) have a definite antihyperlipidemic potential and these beneficial activities may contribute to their cardioprotective and antiatherosclerotic role.     

A comparative study on the effect of homobrassinolide and gibberellic acid on lipid peroxidation and antioxidant status in normal and diabetic rats

Dietary content of phytohormones may potentially influence metabolic processes in animal cells. This study therefore aimed to investigate the effect of two plant growth regulators homobrassinolide (HB) and gibberellic acid (GBA) on the antioxidant defense status and lipid peroxidation level in the tissues of normal and streptozotocin- induced diabetic rats. Normal and diabetic rats (Albino –wistar strain) were administered 50μg HB and GBA intradermally each day for seven days and their tissue and blood levels of malondialdehyde (MDA), 4-hydroxy-2-nonenol (4-HNE), reduced glutathione (GSH) content and catalase (CAT) activity were determined. Subchronic treatment of rats with HB reduced lipid perioxidation and elevated antioxidant defense whereas GBA caused enhancement of lipid peroxidation and reduction of antioxidant defense in treated animals compared to the control rats.     

THE INFLUENCE OF MAGNETIC FIELDS ON THE PRIMARY HEALING OF INCISIONAL WOUNDS IN RATS

Our studies were conducted to examine the influence of extremely low frequency magnetic fields (ELF-MF) on skin wound healing in male adults rats. We used 40 Hz and 10 mT sinusoidal fields. We evaluated the rate of wound healing by determining the tissue hydroxyproline concentration and scar imaging in electron microscope. The systemic body response to ELF-MF was detected by analysis of blood morphological and biochemical parameters, such as: RBC, WBC, hemoglobin, hematocrit, reticulocytes, electrolytes, urea, and total protein concentration.

ELF-MF induced the increase of hydroxyproline level in scar tissue and intensified the maternity of collagen seen in the electron microscope. The increase of reticulocyte number in blood confirmed that the healing process in experimental animals was supported by the activation of the oxygen supply and utilization processes, as a result of erythropoietic intensification, without simultaneously upsetting cellular energetic processes. We did not obtain changes in biochemical parameters in blood, such as: electrolytes, urea, and total protein concentration, so we concluded that ELF-MF evoked no negative systemic response.     

Clodronate changes neurobiological effects of pulsed magnetic field on diabetic rats with peripheral neuropathy

Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment.     

脑损伤后大鼠NAAG肽酶基因沉默的神经保护

目的：探索沉默NAALADase基因的方法对骨髓间充质干细胞（BMSC）静脉移植,评价其对大鼠脑损伤后的神经保护作用。方法：体外分离培养BMSC,应用小分子干扰RNA转染方法沉默NAALADase基因的表达。建立脑损伤模型后,48h处死动物取脑组织进行Fluom—JadeB组织荧光染色以及HE染色。结果：HE染色显示沉默NAALADase基因BDNF数目明显增多并且损伤后神经元退变也减少。结论：沉默NAAG肽酶的表达后能有效实现对神经的保护作用。     

Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation

Glyceryl triacetate (GTA), a compound effective at increasing circulating and tissue levels of acetate was used to treat rats subjected to a continual 28 day intra-ventricular infusion of bacterial lipopolysaccharide (LPS). This model produces a neuroinflammatory injury characterized by global neuroglial activation and a decrease in choline acetyltransferase immunoreactivity in the basal forebrain. During the LPS infusion, rats were given a daily treatment of either water or GTA at a dose of 6 g/kg by oral gavage. In parallel experiments, free-CoA and acetyl-CoA levels were measured in microwave fixed brains and flash frozen heart, liver, kidney and muscle following a single oral dose of GTA. We found that a single oral dose of GTA significantly increased plasma acetate levels by 15 min and remained elevated for up to 4 h. At 30 min the acetyl-CoA levels in microwave-fixed brain and flash frozen heart and liver were increased at least 2.2-fold. The concentrations of brain acetyl-CoA was significantly increased between 30 and 45 min following treatment and remained elevated for up to 4 h. The concentration of free-CoA in brain was significantly decreased compared to controls at 240 min. Immunohistochemical and morphological analysis demonstrated that a daily treatment with GTA significantly reduced the percentage of reactive glial fibrillary acidic protein-positive astrocytes and activated CD11b-positive microglia by 40-50% in rats subjected to LPS-induced neuroinflammation. Further, in rats subjected to neuroinflammation, GTA significantly increased the number of choline acetyltransferase (ChAT)-positive cells by 40% in the basal forebrain compared to untreated controls. These data suggest that acetate supplementation increases intermediary short chain acetyl-CoA metabolism and that treatment is potentially anti-inflammatory and neuroprotective with regards to attenuating neuroglial activation and increasing ChAT immunoreactivity in this model.     

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint I. Role of progesterone receptors

Progestins and antiprogestins are widely used therapeutic agents in humans. In many cases, these are indicated for the treatment of reproductive activities. However, progesterone has widespread physiological effects including a reduction of the response to stress. We have reported that 5 min of restraint reduced lordosis behavior of ovariectomized rats hormonally primed with estradiol benzoate. When ovariectomized rats received both estradiol benzoate and progesterone priming, restraint had minimal effects on lordosis. Progesterone influences behavior through classical intracellular progesterone receptor-mediated nuclear events as well as extranuclear events. How these multiple events contribute to the response to stress is unclear. The current project was designed to initiate examination of the mechanisms responsible for progesterone's ability to protect against the effects of the restraint. In the first experiment, ovariectomized rats, primed with 10 μg estradiol benzoate, received 500 μg progesterone 4 h, 1 h, or 30 min before restraint. When progesterone was injected 4 h before restraint, progesterone eliminated the effects of restraint. In contrast, progesterone 30 min before restraint offered no protection. Effects of progesterone 1 h before restraint were equivocal allowing the suggestion that less than 4 h of progesterone priming might be sufficient. In the second experiment, the synthetic progestin, medroxyprogesterone, was shown to mimic effects of progesterone in preventing effects of restraint. Finally, the progesterone receptor antagonist, RU486, attenuated progesterone's protection against restraint. These findings offer evidence that ligand-activated progesterone receptor mechanisms contribute to the maintenance of lordosis behavior in the presence of mild stress.     

去垂体幼鼠的生物学特性与激素水平

目的观察去垂体幼鼠的生物学特性的改变,了解去垂体术后幼鼠体内激素水平。方法 80只4周龄SD幼鼠2 d内经咽旁入路行垂体去除术,术后与20只同批系的正常幼鼠置于相同条件下观察并饲养,隔日记录体重、饮水量、进食量、体长、尾长等,1周时测量体温后,放入代谢笼饲养1d,记录尿量,2周时测量体温并经目眦静脉采血,分离冻存,分批测量生长激素(GH)、类胰岛素生长因子-1(IGF-1)、甲状腺激素(FSH、FT3、FT4)、促肾上腺皮质激素(ACTH)等。结果去垂体术后2周中,生物特性明显改变,体重、身长、尾长增长,与正常大鼠比较,去垂体幼鼠存在生长障碍,体温逐渐下降,进食量减低,饮水量、排尿量增加。血清GH、IGF-1、ACTH、FSH、FT3、FT4降低,与对照组相比差异有显著性(P<0.01)。结论去垂体幼鼠生物特性改变,垂体激素水平显著降低。     

Phylogenetic relationships in the Niviventer-Chiromyscus complex (Rodentia,Muridae) inferred from molecular data,with description of a new species

Based on molecular data for mitochondrial (Cyt b, COI) and nuclear (IRBP, GHR) genes, and morphological examinations of museum specimens, we examined diversity, species boundaries, and relationships within and between the murine genera Chiromyscus and Niviventer. Phylogenetic patterns recovered demonstrate that Niviventer sensu lato is not monophyletic but instead includes Chiromyscus chiropus, the only previously recognized species of Chiropus. To maintain the genera Niviventer and Chiropus as monophyletic lineages, the scope and definition of the genus Chiromyscus is revised to include at least three distinct species: Chiromyscus chiropus (the type species of Chiromyscus), Chiromyscus langbianis (previously regarded as a species of Niviventer), and a new species, described in this paper under the name Chiromyscus thomasi sp. n.     

Preparation of Rat Serum Suitable for Mammalian Whole Embryo Culture

Mammalian whole embryo culture (WEC) is a widely used technique for examining pharmacological toxicity in developing mouse and rat embryos and for investigating the mechanisms of developmental processes. Immediately centrifuged (IC) rat serum is commonly used for WEC and is essential for the growth and development of cultured mouse and rat embryos ex vivo. For the culture of midgestation embryos (i.e., E8.0-12.5 for the mouse, and E10.0-14.5 for the rat), 100% rat serum is the best media for supporting the growth of the embryo ex vivo. To prepare rat serum suitable for WEC, the collected blood should be centrifuged immediately to separate the blood cells from the plasma fraction. After centrifugation, the fibrin clot forms in the upper layer; this clot should be squeezed gently using a pair of sterile forceps and subsequently centrifuged to completely separate the blood cells from the serum. In this video article, we demonstrate our standard protocol for the preparation of optimal IC rat serum, including blood collection from the abdominal aorta of male rats and extraction of the serum by centrifugation.