Proabsorptive Action of Gum Arabic in Isotonic Solutions Orally Administered to Rats. II. Effects on Solutes Under Normal and Secretory Conditions

Gum arabic (GA) is a natural proteoglycan with proabsorptive capacity attributable to its physico-chemical properties. Previous experiments showed that in rats oral administration of GA in an isotonic solution had a generally positive effect. This study extends the investigation to include acetaminophen and to evaluate whether GA could also act under secretory conditions induced by theophylline. Test solutions were orally administered to rats under CO2 anesthesia and blood concentrations followed for 3 hr. The secretory effects of theophylline were clearly observed for sodium and zinc. Addition of GA resulted in a more rapid rate of glutamate absorption, under normal physiologic conditions, as indicated by the higher area under the curve (AUC). There were no differences in the presence of theophylline. Acetaminophen blood concentrations peaked about 30 min after administration, and the AUC in rats that received GA was higher than in those that got the solution without GA. AUCs for total body water distribution with time and those for glucose concentrations were indistinguishable whether the solutions contained or did not contain either GA or theophylline. The results confirm that oral administration of GA can accelerate absorption of some solutes, including pharmacologic agents.     

聚合酶反应扩增谷氨酸富有蛋白基因片段应用于恶性疟原虫基因分型

目的：建立恶性疟原虫谷氨酸富有蛋白（ＧＬＵＲＰ）基因分型诊断鉴别系统。方法：设计并合成两对针对恶性疟原虫ＧＬＵＲＰ基因的特异引物，采用套式聚合酶链反应（ＰＣＲ）技术，扩增ＧＬＵＲＰ基因Ｒ２多态区目的基因，并应用于泰国Ｂｏｒａｉ疟区恶性疟患者虫株基因分型。结果：在自然感染的恶性疟原虫株群中，ＧＬＵＲＰ基因存在明显的多态性。在１５４份恶性疟感染血样中，共检查出２９０个基因株，它们属于１２种ＤＮＡ片段长度不同的ＧＬＵＲＰ基因型；其中以７７０ｂｐ片段基因型较为常见，１１００ｂｐ片段基因型较少见。４３％以上病人为不同恶性疟原虫基因株混合感染者。在９个月的流行季节中，１２种不同基因株的频率构成比无明显变化。结论：建立ＧＬＵＲＰ基因分型诊断鉴别系统，将有助于疟原虫虫株分类和致病性研究，对疟疾的流行病学研究与防治具有实用意义。     

帕金森病大鼠模型纹状体中谷氨酸、γ-氨基丁酸与多巴胺之间的关系

目的:了解帕金森病大鼠模型纹状体内谷氨酸(glutamate,Glu)、γ-氨基丁酸(gama-aminobutyric acid,GABA)和多巴胺(dopamine,DA)之间的关系,从而进一步探讨帕金森病的发病机制。方法:动物分为溶剂对照组、假手术组和帕金森模型组。大脑右侧黑质致密部和前脑内侧束两点注射6-羟基多巴胺(6-hydroxydopamine,6-OHDA)建立帕金森病大鼠模型,溶剂对照组注入生理盐水,假手术组不注射任何药物,采用脑微透析术于建模后第3,4,5,6周连续动态透析大鼠毁损侧纹状体,结合高效液相色谱(HPLC)动态监测各组谷氨酸、GABA和多巴胺的变化。结果:(1)PD组纹状体内多巴胺含量到第5周仅为溶剂对照组和假手术组的1/5;(2)谷氨酸含量随建模时间逐渐升高,到第6周PD组是溶剂对照组和假手术组的1倍以上;(3)GABA含量呈下降趋势,到第6周约降至溶剂对照组、假手术组的1/2。结论:帕金森病大鼠模型纹状体内谷氨酸的变化与多巴胺分泌可能存在某种联系;GABA含量随建模时间的增加而下降。     

Glutamate in cancers: from metabolism to signaling

Glutamine and glutamate are major bioenergy substrates for normal and cancer cell growth. Cancer cells need more biofuel than normal tissues for energy supply, anti-oxidation activity and biomass production. Genes related to metabolic chains in many cancers are somehow mutated, which makes cancer cells more glutamate dependent. Meanwhile, glutamate is an excitatory neurotransmitter for conducting signals through binding with different types of receptors in central neuron system. Interestingly, increasing evidences have shown involvement of glutamate signaling, guided through their receptors, in human malignancy. Dysregulation of glutamate transporters, such as excitatory amino acid transporter and cystine/glutamate antiporter system, also generates excessive extracellular glutamate, which in turn, activates glutamate receptors on cancer cells and results in malignant growth. These features make glutamate an attractive target for anti-cancer drug development with some glutamate targeted but blood brain barrier impermeable anti-psychosis drugs under consideration. We discussed the relevant progressions and drawbacks in this field herein.     

The Claustrum in the Squirrel Monkey

The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies dramatically across mammals, raising the question of whether there might also be differences in CLA organization, circuitry, and function. Species variations in the shape of the CLA are well documented. Studies in multiple species have identified subsets of neurochemically distinct interneurons; some data suggest species variations in the nature, distribution, and numbers of different neurochemically identified neuronal types. We have studied the CLA in a smooth-brained primate, the squirrel monkey, using Nissl-stained sections and immunohistochemistry. We found that the shape of the CLA is different from that in other primates. We found several different neurochemically defined populations of neurons equally distributed throughout the CLA. Immunoreactivity to GAD_65/67 and GABA_A receptors suggest that GABAergic interneurons provide widespread inhibitory input to CLA neurons. Immunoreactivity to glutamate transporters suggests widespread and overlapping excitatory input from cortical and possibly subcortical sources. Comparison of CLA organization in different species suggests that there may be major species differences both in the organization and in the functions of the CLA. Anat Rec, 303:1439–1454, 2020. © 2019 American Association for Anatomy     

Antinociceptive activity of Syzygium cumini leaves ethanol extract on orofacial nociception protocols in rodents

Context: Syzygium cumini (L.) Skeels (Myrtaceae) is a tree with dark purple fruits, popularly known as “jambolão” or “jambolan”. In folk medicine, this plant is used for the treatment of diabetes and inflammatory conditions.

Objective: We investigated the antinociceptive effect of ethanol extract (EE) from S. cumini leaves on orofacial nociception.

Material and methods: The antinociceptive effects of the EE obtained from the leaves of S. cumini were evaluated in mice using formalin- and glutamate-induced orofacial nociception.

Results: ESI-MS/MS analyses demonstrated that major constituents in the analyzed samples coincided with the mass of the phenolic acids and flavonoids. In pharmacological approach, pre-treatment with EE (100, 200, or 400?mg/kg, p.o.) significantly reduced (p?p?G-nitro-l-arginine (l-NOARG). The extract, all doses, also caused a marked inhibition (p?p?glutamate-induced orofacial nociception (38.8, 51.7, and 54.7%) when compared with the control group. No effect was observed with the rota-rod model.

Conclusions: We can suggest that the antinociceptive effect of the EE is mediated by peripheral mechanisms, possibly involving K_ATP channels and the nitric oxide pathways. These effects appear to be related to the presence of flavonoids compounds, such as quercetin.     

N-Stearoyltyrosine Protects Against Glutamate-Induced Oxidative Toxicity by an Apoptosis-Inducing Factor (AIF)-Mediated Caspase-Independent Cell Death Pathway

N-Stearoyltyrosine (NsTyr), a synthesized anandamide (AEA) analogue, could exert potent neuroprotective effects on cerebral ischemia models both in vivo and in vitro via intervening in multiple injuries. Glutamate, a major excitatory neurotransmitter, plays a critical role during stroke/cerebral ischemia. In this study, we explored the protective effects of NsTyr on glutamate neurotoxicity in PC12 cells and investigated its underlying mechanisms. NsTyr treatment attenuated glutamate-induced oxidative toxicity in a dose-dependent manner and the best performance was observed at 10 μΜ. NsTyr treatment suppressed glutamate-induced upregulation of lipoxygenase 12/15 (LOX 12/15) activity and reactive oxygen species (ROS) elevation, attenuated the increase of BH3-interacting domain death agonist (Bid) in the mitochondria, prevented the loss of mitochondria membrane potential and consequently inhibited apoptosis-inducing factor (AIF) translocation into the nucleus. The results demonstrated that NsTyr could protect cells against AIF-mediated caspase-independent cell death induced by glutamate, which may be due to the blockage of Bid-mediated mitochondrial damage via reducing LOX 12/15 activity and ROS accumulation.     

ShcC proteins: Brain aging and beyond

To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.