BACKGROUND: Prostaglandin I 2 synthesized by endothelial COX (cyclooxygenase) evokes potent vasodilation in some blood vessels but is paradoxically responsible for endothelium-dependent constriction (EDC) in others. Prostaglandin I 2 production and EDC may be enhanced in diseases such as hypertension. However, how PGIS (prostaglandin I 2 synthase) deficiency affects EDC and how this is implicated in the consequent cardiovascular pathologies remain largely unknown. METHODS: Experiments were performed with wild-type, Pgis knockout ( Pgis − / − ) and Pgis /thromboxane-prostanoid receptor gene ( Tp ) double knockout ( Pgis − / − Tp − / − ) mice and Pgis − / − mice transplanted with unfractionated wild-type or Cox-1 − / − bone marrow cells, as well as human umbilical arteries. COX-derived prostanoids were measured by high-performance liquid chromatography-mass spectrometry. Vasomotor responses of distinct types of arteries were assessed by isometric force measurement. Parameters of hypertension, vascular remodeling, and cardiac hypertrophy in mice at different ages were monitored. RESULTS: PGF 2α , PGE 2 , and a trace amount of PGD 2 , but not thromboxane A 2 (TxA 2 ), were produced in response to acetylcholine in Pgis − / − or PGIS-inhibited arteries. PGIS deficiency resulted in exacerbation or occurrence of EDC ex vivo and in vivo. Endothelium-dependent hyperpolarization was unchanged, but phosphorylation levels of eNOS (endothelial nitric oxide synthase) at Ser1177 and Thr495 were altered and NO production and the NO-dependent relaxation evoked by acetylcholine were remarkably reduced in Pgis − / − aortas. Pgis − / − mice developed high blood pressure and vascular remodeling at 16 to 17 weeks and subsequently cardiac hypertrophy at 24 to 26 weeks. Meanwhile, blood pressure and cardiac parameters remained normal at 8 to 10 weeks. Additional ablation of TP (TxA 2 receptor) not only restrained EDC and the downregulation of NO signaling in Pgis − / − mice but also ameliorated the cardiovascular abnormalities. Stimulation of Pgis − / − vessels with acetylcholine in the presence of platelets led to increased TxA 2 generation. COX-1 disruption in bone marrow–derived cells failed to affect the development of high blood pressure and vascular remodeling in Pgis − / − mice though it largely suppressed the increase of plasma TxB 2 (TxA 2 metabolite) level. CONCLUSIONS: Our study demonstrates that the non-TxA 2 prostanoids/TP axis plays an essential role in mediating the augmentation of EDC and cardiovascular disorders when PGIS is deficient, suggesting TP as a promising therapeutic target in diseases associated with PGIS insufficiency.
Ca~(2+) plays a very important role in regulating numerous physiological cellular phenomena and there is a close relation between the change in the concentration of free Ca~(2+) and the function of the cell,signal transmission and the cell injury and death.So it is very important to determine the concentration and the distribution of the intracellular free Ca~(2+).The common fluorescent indicators of intracellular free Ca~(2+) are summarized and the popular methods and their relevant merits and demerits were compared and analyzed.
Background: Posterior cervical atlantoaxial pedicle screw fixation is a very effective treatment for atlantoaxial instability (AAI). However, due to the complex anatomy of the cranial-cervical junction, the accuracy and safety of posterior atlantoaxial pedicle screw placement remains extremely challenging. Objective: To quantitatively evaluate the safety and accuracy of the 3D navigation module to assist the posterior atlantoaxial fixation. Methods: A total of 20 AAI patients were selected between June 2014 and September 2015. The Mimics v10.1 and 3-matic software were used. The 3D navigation module was designed as a double-sided positioning hole guide with a guide rod. All patients underwent posterior atlantoaxial posterior pedicle screw fixation with 3D navigation module. The actual entry point and screw trajectory were measured after operation, which were compared with the ideal entry point and screw trajectory. The Japanese Orthopaedic Association (JOA) score was measured before and after surgery to evaluate the neurological function improvement. The average operation time, blood loss, and frequency of intraoperative fluoroscopy were counted. Results: The posterior atlantoaxial pedicle screw fixation with a 3D navigation module was successfully performed in all patients. A total of 80 atlantoaxial pedicle screws were implanted in the 20 patients. Postoperative CT scan showed that two pedicle screws deviated from the medial aspect of the atlas pedicle cortex and entered the spinal canal approximately 1 mm, without causing neurological complications. There was no significant difference between the ideal and actual entry points or ideal and actual screw trajectories of the atlas and axis (P > 0.05). The preoperative JOA score was 12.45 ± 1.15 and postoperative JOA score was 15.5 ± 0.89, with statistically significant difference (P < 0.05). Conclusion: It was safe and effective to use the 3D navigation module to assist the posterior atlantoaxial pedicle insertion, with a high accuracy of pedicle screw placement. Keywords: atlantoaxial instability, pedicle screw, 3D navigation module, rapid prototyping
Abstract Aims Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here, we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. Methods and results Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalization of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors. Conclusion These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA.
Objective:To detect the synthesis level of prostacyclin(PGI2)in rat aortas with the established method of high performance liquid chromatography-mass spectrometry(HPLC-MS).Methods: HPLC-MS was established to analyze the five kinds of prostaglandin productions derived from cyclooxygenase(COX)mediated metabolism.The PGI2 metabolite 6-keto-PGF1α of aortas isolated from Wistar rats was analyzed.Results: HPLC-MS could be applied to detect the five prostaglandin productions derived from the COX-mediating pathway.The PGI2 metabolite 6-keto-PGF1α produced by Wistar rat aortas was well determined by HPLC-MS.The amount of 6-keto-PGF1α was obviously augmented when stimulated with the endothelial receptor agonist acetylcholine.Conclusion: The method of HPLC-MS is well established to detect 6-keto-PGF1α produced by aortas from Wistar rats.
Objective To study the risk factors of posteriorly dislocated crystalline lenses during manual small incision cataract surgery(MSICS) by beginner at county hospital.Methods Through a questionnaire survey in 50 trainees of Starr MSICS hand-on project,this retrospective analysis included all MSICS procedures with dropped nucleus performed by the trainees.The risk factors,the clinical features and the final outcome of posteriorly dislocated lens nuclei were evaluated.Results There were 9 cases(6 male,3 female) which nuclei were dropped.The ages ranged 62 to 92 years old.All 9 cases were diagnosed as senile cataract,included 2 hypermature cataract,6 big/dark nuclei,3 coexist high myopia and one crystalline lens subluxation.Can-opener capsulotomy was used in all 9 MSICS operations,and the operational process was clumsy and rough.Conclusion For MSICS beginner,the main risk factors of dropped nucleus were extreme elderly patients,hypermature cataract,big/dark nuclei,high myopia and subluxation lens.On the other hand,can-opener capsulotomy and clumsy rough operation were also the important risk factor for dropped nucleus.It was necessary to enhance the training of theory and practice aiming at the risk factors for MSICS beginner.
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