黄芩苷、丹参酮ⅡA、三七皂苷R1对过氧化氢所致大鼠海马神经元损伤的保护作用

目的:探讨黄芩苷、丹参酮ⅡA、三七皂苷R1对过氧化氢所致的大鼠海马神经元损伤的保护作用.方法:采用新生1d SD大鼠海马神经元原代培养,以H2O2(50μM)造成细胞损伤模型,将黄芩苷、丹参酮ⅡA、三七皂苷R1的高(20μg/ml)和低(0.2μg/ml)两个剂量加入到培养细胞液中.在4h时,检测细胞形态及释放出的LDH活性变化,观察到上述药物对海马神经元损伤的直接保护作用.结果:低剂量黄芩苷和三七皂苷R1与模型组比较,未见明显差异,三种组分高剂量和丹参酮ⅡA低剂量组与模型组比较,均有明显差异.结论:黄芩苷、丹参酮ⅡA、三七皂苷R1对过氧化氢所致的大鼠海马神经元损伤具有一定的保护作用.     

Bilobed oblong porous coated acetabular components in revision total hip arthroplasty

Thirty-eight oblong bilobed noncustom uncemented, porous-coated titanium acetabular components were used to reconstruct failed hip arthroplasties with large superior segmental acetabular bone deficiencies. No structural bone grafts were used. All patients were followed up for 2 to 5 years (mean, 3 years) after the operation. One patient (whose socket rested primarily on a structural bone graft from a previous procedure) had revision surgery for acetabular loosening. No other patients have had revision surgery or had another ipsilateral hip operation. At latest followup, 35 patients had no or mild pain and two patients had moderate pain. Two implants migrated more than 2 mm in the first year, then stabilized. On the latest radiographs, two implants had bead shedding, but there was no measurable migration or change in position. For selected patients with large superolateral acetabular bone deficiencies, this implant facilitated a complex reconstruction, provided good clinical results, and showed satisfactory stability at early to midterm followup in most patients.     

Distinguishing craniomorphometric characteristics and severity in metopic synostosis patients

The decision about which metopic synostosis patients should undergo surgery remains controversial. Multiple measures for radiographic severity have been developed in order to determine the optimal criteria for treatment. The aim of this study was to perform an extensive craniomorphometric analysis of patients who underwent surgery for metopic synostosis to validate and compare the various severity scales developed for this non-syndromic craniosynostosis. A comparative morphometric analysis was performed using computed tomography scans of preoperative metopic synostosis patients (n = 167) and normal controls (n = 44). Measurements included previous and newly developed metopic severity indices. Volumetric and area analyses were used to determine the degree of anterior cranial area and potential volume restrictions. Of the severity indices measured, the frontal angle, endocranial bifrontal angle (EBF), adjusted EBF (aEBF), anterior cranial fossa angle, horizontal cone angle, and bitemporal/biparietal distance ratio were significantly different in the metopic subjects relative to controls overall. However, metopic index, orbital rim angle, foramen ovale distance, and cranial volume exhibited no significant difference from controls. Only the frontal angle and aEBF correlated with the changes in anterior cranial dimensions observed in metopic synostosis. In conclusion, the frontal angle and aEBF provide the most accurate measures of severity in metopic synostosis.     

Survival of pre-viable preterm infants in the United States: A systematic review and meta-analysis

The objective of this paper is to review observational studies that addressed the survival of pre-viable gestations in the United States. We searched PubMed, Ovid, CINAHL, and Web of Knowledge for studies reporting survival of infants born at <24 gestational weeks and/or <500 g in the United States and published between January 2003 and January 2013. The full texts of 70 articles were examined and a total of 15 studies qualified and were selected. We analyzed fixed-effect and random-effects models for eight studies on survival to discharge. Pooled survival to discharge in the random-effects model was 45.9% (95% CI: 41.1–51.7) and 39.7% in the fixed-effect model (95% CI: 38.8–40.7). Studies differed by pre-viable survival measures and epochs (1985–2009). Protective factors included antenatal corticosteroids, neonatal resuscitation, and intensive care. The current survival threshold for pre-viable infants warrants reconsideration of the limits of viability. Protective factors that enhance survival should be considered in the management of these infants.     

Repeated episodes of chronic intermittent ethanol promote insensitivity to devaluation of the reinforcing effect of ethanol

Studies in animal models have shown that repeated episodes of alcohol dependence and withdrawal promote escalation of drinking that is presumably associated with alterations in the addiction neurocircuitry. Using a lithium chloride-ethanol pairing procedure to devalue the reinforcing properties of ethanol, the present study determined whether multiple cycles of chronic intermittent ethanol (CIE) exposure by vapor inhalation also alters the sensitivity of drinking behavior to the devaluation of ethanol's reinforcing effects. The effect of devaluation on operant ethanol self-administration and extinction was examined in mice prior to initiation of CIE (short drinking history) and after repeated cycles of CIE or air control exposure (long drinking history). Devaluation significantly attenuated the recovery of baseline ethanol self-administration when tested either prior to CIE or in the air-exposed controls that had experienced repeated bouts of drinking but no CIE. In contrast, in mice that had undergone repeated cycles of CIE exposure that promoted escalation of ethanol drinking, self-administration was completely resistant to the effect of devaluation. Devaluation had no effect on the time course of extinction training in either pre-CIE or post-CIE mice. Taken together, these results are consistent with the suggestion that repeated cycles of ethanol dependence and withdrawal produce escalation of ethanol self-administration that is associated with a change in sensitivity to devaluation of the reinforcing properties of ethanol.     

Effects of a novel Nodal-targeting monoclonal antibody in melanoma

Nodal is highly expressed in various human malignancies, thus supporting the rationale for exploring Nodal as a therapeutic target. Here, we describe the effects of a novel monoclonal antibody (mAb), 3D1, raised against human Nodal. In vitro treatment of C8161 human melanoma cells with 3D1 mAb shows reductions in anchorage-independent growth and vasculogenic network formation. 3D1 treated cells also show decreases of Nodal and downstream signaling molecules, P-Smad2 and P-ERK and of P-H3 and CyclinB1, with an increase in p27. Similar effects were previously reported in human breast cancer cells where Nodal expression was generally down-regulated; following 3D1 mAb treatment, both Nodal and P-H3 levels are reduced. Noteworthy is the reduced growth of human melanoma xenografts in Nude mice treated with 3D1 mAb, where immunostaining of representative tumor sections show diminished P-Smad2 expression. Similar effects both in vitro and in vivo were observed in 3D1 treated A375SM melanoma cells harboring the active BRAF(V600E) mutation compared to treatments with IgG control or a BRAF inhibitor, dabrafenib. Finally, we describe a 3D1-based ELISA for the detection of Nodal in serum samples from cancer patients. These data suggest the potential of 3D1 mAb for selecting and targeting Nodal expressing cancers.