Masked excitatory action of noradrenaline on rat islet β-cells via activation of phospholipase C

The effect of noradrenaline (NE) on rat islet -cells was examined. NE reduced insulin secretion from rat islets exposed to extracellular solutions containing glucose at 5.5 or 16.6 mM. In islets treated with pertussis toxin (PTX), however, NE increased insulin secretion. The NE-induced augmentation of insulin secretion was inhibited by prazosin. In intact islets, NE increased phospholipase C (PLC) activity, an effect that was prevented by treatment of islets with U-73122. NE elevated intracellular [Ca²⁺] ([Ca²⁺]_i) in isolated -cells independently of PTX. Although this NE effect was inhibited by prazosin, phenylephrine did not mimic it. The [Ca²⁺]_i response to NE was also prevented by the treatment of cells with U-73122. NE produced depolarization of -cells followed by nifedipine-sensitive action potentials. NE reduced the whole-cell membrane currents through ATP-sensitive K⁺ channels (K_ATP), responsible for the depolarization. This NE effect was prevented by treatment of -cells with U-73122 or BAPTA/AM. Although at least some of our results imply the presence of ₁-adrenoceptors, -cells were not stained by a polyclonal IgG antibody recognizing all adrenergic ₁-receptor subtypes so far identified. These results suggest that an interaction of NE with an unknown type of receptor activates rat islet -cells via a PLC-dependent signal pathway. This effect is, however, masked by the inhibitory action via a PTX-sensitive pathway also activated by NE.     

己酮可可碱对小鼠急性脑缺血的保护作用研究

目的　研究己酮可可碱 (PentoxifyllinePTX)对急性脑缺血所致小鼠大脑功能改变的保护作用。 方法　采用双侧颈总动脉不完全和完全结扎法及小鼠快速断头法 ,观察小鼠在急性脑缺血时的所产生的神经症状、存活时间和脑细胞的改变及己酮可可碱 (PTX)的保护作用。结果　 2 5、5 0mg·kg -1的PTX可以显著减少急性不完全性脑缺血致小鼠神经症状的发生 ,减少小鼠大脑细胞的坏死百分率 ;可以显著延长急性完全性脑缺血小鼠断头张口喘气时间并能增加小鼠耐缺氧的存活时间。结论　PTX对小鼠急性完全和不完全性脑缺血具有保护作用。     

己酮可可碱对溃结鼠NF-κB,IL-1β基因表达的影响

目的 观察PTX对UC大鼠肠黏膜组织NF-κB和IL-1β表达的影响,并探讨其机理.方法 将45只雄性Wistar大鼠随机分为对照组、模型组、治疗组,每组15只,模型组和治疗组用应用TNBS建立UC模型,3d后,治疗组给予PTX治疗,其余两组则给予等量生理盐水,持续5d.评价各组大鼠结肠组织大体及组织病理学改变,免疫组化法检测NF-кB,IL-1β蛋白在肠黏膜中的定位及表达,应用RT-PCR法检测IL-1β mRNA的表达.结果 ①大鼠结肠组织大体形态学及组织病理学评分：治疗组及对照组症状好于模型组,差异有统计学意义（P〈0.05）;②模型组NF-кB,IL-1β阳性细胞表达水平及IL-1β mRNA的表达明显增高,且明显高于治疗组和对照组（P〈0.05）,给予PTX治疗后NF-кB,IL-1β及其mRNA的表达明显降低,且与对照组无明显差异（P〉0.05）.结论 NF-кB,IL-1β与UC关系密切,PTX可能通过抑制NF-κB的活性,减少IL-1β等细胞因子的表达而起到抗炎作用.     

急性ST段抬高型心肌梗死患者血浆PTX3水平与GRACE评分的相关性研究

目的 研究急性ST段抬高型心肌梗死(STEMI)患者血浆PTX3水平与全球急性冠状动脉事件注册(GRACE)风险评分的相关性,评价PTX3对急性心肌梗死的早期诊断及远期预后的评估价值.方法 急性ST段抬高型心肌梗死患者86例,依据患者入院时GRACE评分分值将患者分为低危组(32例)、中危组(26例)、高危组(28例),另选30名体检健康成人作为正常对照组,入院后1h内采集血液标本,送检肌钙蛋白、心肌酶等常规化验;应用酶联免疫法测血浆PTX3水平.结果 急性心肌梗死患者血浆PTX3水平明显高于正常对照组(P＜0.05).高危组患者血浆PTX3高于中、低危组(P＜0.05),中危组患者血浆PTX3高于低危组,但差异无统计学意义(P＞0.05).STEMI患者PTX3水平与年龄、GRACE评分、Killip分级、肌钙蛋白T呈正相关(P＜0.05).多元线性回归分析显示PTX3与GRACE评分中的Killip分级独立相关(P＜0.05).结论 PTX3可作为心肌坏死的早期分子指标,是急性ST段抬高型心肌梗死患者不良心血管事件发生的有效独立预测因子.     

Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis

The acute phase protein pentraxin 3 (PTX3) is a pattern recognition receptor involved in regulation of the host immune response. This relatively newly discovered member of the pentraxin superfamily elicits both immunostimulatory and immunoregulatory functions preventing autoimmune pathology and orchestrated clearance of pathogens through opsonization of damage- and pathogen-associated molecular patterns (DAMP/PAMP). Thus, PTX3 has been described as a possible evolutionary precursor to immunoglobulins. While shown to provide protection against specific bacterial and fungal pathogens, persistent elevation of PTX3 levels following initial onset of infection appear to predict poor patient outcome and may contribute to disease sequelae such as tissue damage and coagulopathy. Measurement of PTX3 following onset of sepsis may improve patient risk assessment and thus be useful in guiding subsequent therapeutic interventions including steroidal anti-inflammatory and altered antibiotic therapies. In this review, we summarize the role of PTX3 in inflammatory syndromes and its utility as a marker of sepsis disease severity.     

Signals of cell death and tissue turnover during physiological pregnancy,pre-eclampsia,and autoimmunity

Apoptosis normally occurs in the human placenta. As a consequence, cell blebs, post-apoptotic debris (also referred to as syncytial knots) and membrane microparticles are released into the blood of pregnant women. These events become prominent during the best-characterized pregnancy complication, pre-eclampsia. An excessive or deregulated cell death, which results in the generation of an overwhelming burden of apoptotic material, alarms the immune system. This plays a role in the pathogenesis of systemic connective tissue diseases and possibly of small vessels vasculitis. Infiltration of leukocytes and activation of endothelial cells and platelets are hallmarks of normal pregnancy, indicating that physiologic pregnancy is a condition characterized by an activation of the innate immune system. Conversely, a failure in the physiologic termination of inflammatory events is probably a requirement for pre-eclampsia to develop. Here, we discuss recent findings suggesting a link between deregulated disposal of placental debris, the generation of endogenous pro-inflammatory signals (alarmins) and the widespread vascular inflammation that characterizes on one hand pre-eclampsia and on the other systemic autoimmune diseases.     

Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery

Abstract

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core–shell structures and particle sizes ranging from 1 to 4?µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core–shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX?+?ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core–shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.     

Lipid based nanocarriers: a translational perspective

Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside.