The Nimodipine-Sparing Effect of Perioperative Dexmedetomidine Infusion During Aneurysmal Subarachnoid Hemorrhage: A Prospective, Randomized, Controlled Trial.

Background: Nimodipine can block the influx of calcium into the vascular smooth muscle cell and prevent secondary ischemia in patients with aneurysmal subarachnoid hemorrhage. However, the reduction of blood pressure after long-term intravenous administration of nimodipine has been associated with neurological deterioration. Yet, no effective solutions have been suggested to address this phenomenon. The use of neuroprotective drug combinations may reduce the risk of sudden blood pressure loss. This prospective, randomized, controlled trial was performed to evaluate the nimodipine-sparing effect of perioperative dexmedetomidine infusion during aneurysmal subarachnoid hemorrhage. Methods: One hundred nine patients who underwent aneurysm embolization were divided into three groups: group C (n = 35, infused with 0.9% sodium chloride at the same rate as other two groups), group D1 (n = 38, dexmedetomidine infusion at 0.5 µg·kg-1 for 10 min, then adjusted to 0.2 µg·kg-1·h-1), and group D2 (n = 36, dexmedetomidine infusion at 0.5 µg·kg-1 for 10 min, then adjusted to 0.4 µg·kg-1·h-1). Patient-controlled analgesia was given for 48 h after surgery. The primary outcome measure was the total consumption of nimodipine during the first 48 h after surgery. The secondary outcome measures were recovery time at post-anesthesia care unit (PACU), postoperative pain intensity scores, dexmedetomidine and sufentanil consumption, hemodynamic, satisfaction of patients and neurosurgeon, neurologic examination (Glasgow Coma Scale, GCS), Bruggemann comfort scale, and adverse effects. Intraoperative hemodynamics were recorded at the following time-points: arrival at the operating room (T1); before intubation (T2); intubation (T3); 5 min (T4), 10 min (T5), and 15 min (T6) after intubation; suturing of femoral artery (T7); end of surgery (T8); extubation (T9); and 5 min (T10), 10 min (T11), and 15 min (T12) after arrival at the PACU. The level of sedation was recorded at 15 min, 30 min, 1 h, and 2 h after extubation. We also recorded the incidence of symptomatic cerebral vasospasm during 7 days after surgery, Glasgow Outcome Score (GOS) at 3 months, and incidence of cerebral infarction 30 days after surgery. Results: The consumption of nimodipine during the first 48 h after surgery was significantly lower in group D2 (P < 0.05). Compared with group C, HR and MAP were significantly decreased from T2 to T12 in group D1 and D2 (P < 0.05). Patients in group D2 showed a significantly decreased MAP from T5 to T9 compared with group D1 (P < 0.05). The consumption of sevoflurane, remifentanil, dexmedetomidine, and nimodipine were all significantly reduced in groups D1 and D2 during surgery (P < 0.05). Compared with group C, MAP was significantly decreased in groups D1 and D2 during the first 48 h after surgery (P < 0.05). Compared with group C, consumption of sufentanil and dexmedetomidine at 1 h, pain intensity at 1 h, and 8 h after surgery were significantly decreased in groups D1 and D2 (P < 0.05). FAS was significantly higher in group D2 at 8 h, 16 h, and 24 h after surgery. LOS was significantly lower only in group D2 at 0.5 h after surgery (P < 0.05). Compared with group C, BCS was significantly higher group D2 at 4 h and 8 h after surgery (P < 0.05). There were no significant differences among the three groups in consumption of propofol, cisatracurium, fentanyl, and vasoactive drugs during operation, recovery time at PACU, satisfaction of patients and neurosurgeon, and number of applied urapidil and GCS during the first 48 h after surgery. The incidence of symptomatic cerebral vasospasm during 7 days after surgery, GOS of 3 months, and cerebral infarction after 30 days were also comparable among the three groups. Conclusions: Dexmedetomidine (infusion at 0.5 µg·kg-1 for 10 min, then adjusted to 0.4 µg·kg-1·h-1 during the surgery) significantly reduced the total consumption of nimodipine during the first 48 h after surgery and promoted early rehabilitation of patients although the incidences of symptomatic cerebral vasospasm, GOS, and cerebral infarction were not reduced.

GBP1 exerts inhibitory effects on acute viral myocarditis by inhibiting the inflammatory response of macrophages in mice.

Viral myocarditis (VMC) is a condition that could potentially progress to dilated cardiomyopathy or congestive heart failure, making it the leading cause of the untimely death in young adults. Interferon-induced GBP1 encodes much of the GTPase induced by interferon gamma in many eukaryotic cells. However, little is known regarding the effect of GBP1 on acute VMC (AVMC). Hence, this aim of this study was to assess the effect of GBP1 on AVMC. Once the AVMC mouse models were established, the functional role of GBP1 was determined in AVMC. Serum levels of IL-6, TNF-α, and TGF-ß, and expression levels of GBP1, MIF, iNOS, and COX-2 were detected, together with the viability and apoptosis of cardiomyocytes. AVMC mice presented with increased levels of TGF-ß, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cell apoptosis, but lower expression of GBP1 and viability of cardiomyocytes. Restored GBP1 or depleted macrophages resulted in decreased levels of TGF-ß, IL-6, TNF-α, MIF, iNOS, and COX-2, as well as cardiomyocyte apoptosis, while increasing cardiomyocyte viability. In conclusion, our results highlight the potential role of GBP1 in inhibiting AVMC development. The experimental results indicate that GBP1 up-regulation and macrophage depletion can alleviate AVMC-related cardial damage by inhibiting inflammatory responses and cardiomyocyte apoptosis while increasing cardiomyocyte viability.

Local thrombolytic therapy in severe cerebral venous sinus thrombosis during puerperium.

This study is to explore and evaluate the efficacy and safety of local thrombolytic therapy in superior sagittal sinus in patients with severe cerebral venous sinus thrombosis during puerperium, as well as the efficacy and safety of anti-platelet aggregation treatment for preventing recurrence. Twelve patients during postpartum period with cerebral venous sinus thrombosis were received local thrombolytic therapy by placing a micro-catheter at the distal end of superior sagittal sinus from January 2008 to December 2013. All the patients accepted mechanical thrombus maceration before local intrasinus thrombolytic therapy, and were treated with low molecular weight heparin in the acute phase. After local thrombolytic therapy, anti-platelet aggregation treatment was performed for 6 months. Follow-up data included lumber puncture, fundus examination and magnetic resonance venography (MRV) once per half year for 6-70 months. At discharge, the intracranial pressure of 12 patients reduced to below 200 mmH2O. DSA or MRV confirmed that superior sagittal sinus of 9 patients were smooth. The cortex venous and deep venous were recovered to normal. Superior sagittal sinus of 3 patients recanalized partly. Cortex venous and deep venous was compensated. The follow-up study indicated that no thrombosis and new neurological symptoms occurred among all patients. Local thrombolytic treatment is safe and effective in patients with severe cerebral venous sinus thrombosis during puerperium. The collateral circulation compensation is the main recovery factor. And it is also safe and effective for anti-platelet aggregation treatment to prevent recurrence of cerebral venous sinus thrombosis.

Postural sway in idiopathic rapid eye movement sleep behavior disorder: a potential marker of prodromal Parkinson's disease.

There is compelling evidence that postural instability occurs at very early clinical stages of Parkinson's disease (PD), making it tempting to speculate that changes in postural sway may even occur at a prodromal phase. Studies estimate that approximately half of patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) will eventually develop PD, so RBD may be an indicator of prodromal PD. This study was undertaken to investigate postural sway and its relation to stereopsis function in patients with RBD. We examined 24 patients with polysomnography-confirmed RBD and 23 healthy, sex-and age-matched control subjects. Postural sway was measured with an accelerometer at the center of mass at the lower spine. Subjects were asked to stand quietly for 30s under two usual conditions (eyes open and eyes closed) and three challenging conditions (eyes open with dual task, eyes closed with dual task, and tandem standing). Stereopsis was assessed using the Titmus fly test. RBD patients showed an increased variability of trunk acceleration and a decrease of smoothness of sway, compared to control subjects. These differences reached significance in the challenging conditions. RBD patients demonstrated significant impairment in stereopsis. There were statistically significant correlations between log seconds of arc of the Titmus test and some sway parameters within the RBD group. RBD patients with abnormal stereopsis showed a significant increase of JERK values compared to patients with normal stereopsis in the challenging conditions. Our results indicate that idiopathic RBD patients, especially with abnormal stereopsis, have subtle signs of postural instability under challenging conditions. Postural sway performance may serve as a biological marker for prodromal PD.

Synthesis, DNA binding, photo-induced DNA cleavage and cell cytotoxicity studies of a family of light rare earth complexes.

A family of light rare earth complexes, [RE(acac)(3)(dpq)] (RE=La (1), Ce (2), Pr (3), Nd (4), Sm (5)) and [RE(acac)(3)(dppz)].CH(3)OH (RE=La (6), Ce (7), Pr (8), Nd (9), Sm (10) viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)), have been synthesized and structurally characterized. Binding interactions of these complexes with CT-DNA and their photo-induced DNA cleavage activity with pBR 322 DNA are also investigated. These complexes have strong DNA binding interaction (K(b)≈10(5)M(-1) and K(app)≈10(5)M(-1))and the binding propensity to CT-DNA decrease with the order: dppz complexes>dpq complexes. Furthermore, DNA photocleavage experiments indicate that these complexes are efficient DNA cleaving agents in UV-A (365 nm) and ambient light in the absence of any external reagents. Hydroxyl radical (HO(•)) and singlet oxygen ((1)O(2)) are the major cleavage active species from the machanistic studies. Moreover, cell cytotoxicity studies of these complexes on HeLa, K562 and MDA-MB-231 cells indicate that they have the potential to act as effective metal-based anti-cancer drugs.

Synthesis, DNA binding, photo-induced DNA cleavage, cytotoxicity and apoptosis studies of copper(II) complexes.

Two new Cu(II) complexes, [Cu(acac)(dpq)Cl] (1) and [Cu(acac)(dppz)Cl] (2) (acac = acetylacetonate, dpq = dipyrido[3,2-d:20,30-f]quinoxaline, dppz = dipyrido[3,2-a:20,30-c] phenazine), have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes show good binding propensity to calf thymus DNA in the order: 2(dppz) >1(dpq). Furthermore, two complexes exhibit efficient DNA cleavage activity on natural light or UV-A (365 nm) irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. The photo-induced DNA cleavage activity of the dppz complex 2 is found to be more efficient than its dpq analogue. In vitro study of the photocytotoxicity of two complexes on HeLa cells indicate that both of them have the potential to act as effective anticancer drugs, with IC(50) values of 5.25±0.83 µM (1) and 4.40±0.52 µM (2) in the natural light, and 2.57±0.92 µM (1) and 2.18±0.52 µM (2) in UV-A light. In addition, to detect an apoptotic HeLa body, cells were stained with Hoechst 33342 dye.

Synthesis, crystal structure, magnetic property and nuclease activity of a new binuclear cobalt(II) complex.

One new binuclear Co(II) complex of N,N,N',N'-tetrakis(2-benzimidazolylmethyl)-2-hydroxyl-1,3-diaminopropane (HL), [Co(2)L(mu(2)-Cl)](ClO(4))(2) x 3CH(3)CN x C(2)H(5)OC(2)H(5) (1), has been synthesized and its crystal structure and magnetic properties are shown. In 1, each Co(II) atom has a distorted trigonal bipyramidal geometry with a N(3)OCl donor set. The central two Co(II) atoms are bridged by one alkoxo-O atom and one Cl atom with the Co1-Co2 separation of 3.239 A. Susceptibility data of 1 indicate strong intramolecular antiferromagnetic coupling of the high-spin Co(II) atoms. In this paper, the interaction with calf thymus DNA was investigated by UV absorption and fluorescent spectroscopy. Results show the complex binds to ct-DNA with a intercalative mode. The interaction between complex 1 and pBR322 DNA has also been investigated by submarine gel electrophoresis, noticeably, the complex exhibits effective DNA cleavage activity in the absence of any external agents.