One characteristic of heart failure (HF) is increased sympathetic activation. The paraventricular nucleus (PVN) of the hypothalamus (involved in control of sympathetic outflow) has been shown to have increased neuronal activation during HF. This study examined the influence of endogenous GABA input (inhibitory in nature) into the PVN on renal sympathetic nerve discharge (RSND), arterial blood pressure (BP), and heart rate (HR) in rats with HF induced by coronary artery ligation. In alpha-chloralose- and urethane-anesthetized rats, microinjection of bicuculline (a GABA antagonist) into the PVN produced a dose-dependent increase in RSND, BP, and HR in both sham-operated control and HF rats. Bicuculline attenuated the increase in RSND and BP in HF rats compared with control rats. Alternatively, microinjection of the GABA agonist muscimol produced a dose-dependent decrease in RSND, BP, and HR in both control and HF rats. Muscimol was also less effective in decreasing RSND, BP, and HR in HF rats than in control rats. These results suggest that endogenous GABA-mediated input into the PVN of rats with HF is less effective in suppressing RSND and BP compared with control rats. This is partly due to the post-release actions of GABA, possibly caused by altered function of post-synaptic GABA receptors in the PVN of rats with HF. Reduced GABA-mediated inhibition in the PVN may contribute to increased sympathetic outflow, which is commonly observed during HF.

ObjectiveTo investigate the incidences of deep vein thrombosis (DVT) before and after operation in inpatients with hip fractures in both lower extremities.Patients and methodsWe collected the clinical data of 463 patients with lower extremities fractures who presented at Xi’an Honghui Hospital between July 1, 2014, and October 31, 2016 and met all the inclusion criteria. Doppler ultrasonography was used to diagnose DVT. The patients were examined preoperatively and postoperatively and divided into the thrombosis and non-thrombosis group according to the ultrasonographic findings. We divided the DVT cases into central, peripheral, and mixed thromboses.ResultsThe incidence of preoperative DVT was 34.98%, and the prevalence of DVT on the uninjured side was 13.60%. This composition ratio increased to 57.23% postoperatively, and the prevalence of DVT on the uninjured side was 25.05%. Age (odds ratio [OR], 1.03; 95% CI: 1.01–1.04; P=0.002), venous thrombosis at admission (OR, 4.05; 95% CI, 2.30–7.13; P=0.000), and the days between the fracture and the operation (OR, 1.10; 95% CI, 1.02–1.20; P=0.020) were the independent risk factors of preoperative DVT. Coronary heart disease (OR, 1.85; 95% CI: 1.18–2.89; P=0.007), venous thrombosis at admission (OR, 22.35; 95% CI: 6.78–73.60; P=0.000), days between fracture and operation (OR, 1.06; 95% CI: 1.01–1.11; P=0.021), and blood loss (OR, 1.002; 95% CI: 1.000–1.003; P=0.014) were independent risk factors of postoperative DVT.ConclusionThe actual incidence of DVT after hip fracture may be underestimated. The incidences of preoperative and postoperative DVTs and the incidence of DVT on the uninjured limb were high.

Early detection of Alzheimer's disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates (K = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a promising potential as theranostic agents for the diagnosis and therapy of AD.

Paclitaxel (Taxol) is a microtubule-stabilizing compound that is used for cancer chemotherapy. However, Taxol administration is limited by serious side effects including cardiac arrhythmia, which cannot be explained by its microtubule-stabilizing effect. Recently, neuronal calcium sensor 1 (NCS-1), a calcium binding protein that modulates the inositol-1,4,5-trisphosphate receptor (InsP 3 R), was described as a binding partner of Taxol and as a substrate of calpain. We examined calcium signaling processes in cardiomyocytes after treatment with Taxol to investigate the basis of Taxol-induced cardiac arrhythmia. After treating isolated neonatal rat ventricular myocytes with a therapeutic concentration of Taxol for several hours live cell imaging experiments showed that the frequency of spontaneous calcium oscillations significantly increased. This effect was not mimicked by other tubulin-stabilizing agents. However, it was prevented by inhibiting the InsP 3 R. Taxol treated cells had increased expression of NCS-1, an effect also detectable after Taxol administration in vivo. Short hairpin RNA mediated knock down of NCS-1 decreased InsP 3 R dependent intracellular calcium release, whereas Taxol treatment, that increased NCS-1 levels, increased InsP 3 R dependent calcium release. The effects of Taxol were ryanodine receptor independent. At the single channel level Taxol and NCS-1 mediated an increase in InsP 3 R activity. Calpain activity was not affected by Taxol in cardiomyocytes suggesting a calpain independent signaling pathway. In short, our study shows that Taxol impacts calcium signaling and calcium oscillations in cardiomyocytes through NCS-1 and the InsP 3 R.