Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

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Associations between oral sugar clearance,dental caries,and related factors among 71-year-olds

Objective. To investigate the associations between oral sugar clearance and the prevalence of dental decay. Material and Methods. A total of 92 (44 F, 48 M) 71-year-old subjects in Göteborg, Sweden were consecutively chosen from a representative cohort study. The subjects were examined for: 1) caries-related status, 2) oral function, 3) salivary conditions, 4) cariogenic micro-organisms, and 5) oral sugar clearance. A factor analysis was used to investigate the possible existence of latent variables within these five areas. The latent variables from the factor analyses were used to study the associations between clearance and caries in multivariate regression models. Results. Only one latent variable relating to oral sugar clearance was found. In the regression model with the latent variable related to oral sugar clearance as a dependent variable and gender plus the latent variables related to oral function and salivary conditions as an independent variable, there were associations with gender and some latent variables reflecting oral function and one reflecting glucose in saliva (R²=0.20/0.17). Three latent variables relating to caries-related status were found and these were associated with the number of teeth, the percentage of filled tooth surfaces, and the percentage of decayed tooth surfaces (DS%). In the regression analysis using the latent variable associated with DS% as a dependent variable, this variable was related to the latent variables of oral sugar clearance and to some reflecting oral function, as well as glucose in saliva (R²=0.28). Conclusions: Oral sugar clearance appears to be independently associated with the prevalence of dental caries in the elderly.     

Flexion and extension radiographic evaluation for the clearance of potential cervical spine injures in trauma patients

Background

Flexion and extension radiographs are often used in the setting of trauma to clear a cervical spine injury. The utility of such tests, however, remains to be determined. We hypothesized that in patients who underwent a negative computed tomography (CT) cervical spine scan, flexion and extension radiographs did not yield useful additional information.

Methods

We conducted a retrospective chart review of all patients admitted to a Level I trauma center who had a negative CT scan of the cervical spine and a subsequent cervical flexion–extension study for evaluation of potential cervical spine injury. All flexion–extension films were independently reviewed to determine adequacy as defined by C7/T1 visualization and 30° of change in the angle from flexion to extension. The independent reviews were compared to formal radiology readings and the influence of the flexion–extension studies on clinical decision making was also reviewed.

Results

One thousand patients met inclusion criteria for the study. Review of the flexion–extension radiographs revealed that 80 % of the films either did not adequately demonstrate the C7/T1 junction or had less than 30° range of motion. There was one missed injury that was also missed on magnetic resonance imaging. Results of the flexion–extension views had minimal effects on clinical decision making.

Conclusion

Adequate flexion extension films are difficult to obtain and are minimally helpful for clearance of the cervical spine in awake and alert trauma patients.     

早期乳酸清除率评估重型颅脑创伤合并高乳酸血症患者预后的研究

目的评估重型颅脑创伤合并高乳酸血症患者6小时乳酸清除率与预后的关系。方法前瞻性研究．选取余姚市人民医院神经外科和重症医学科病房2010年6月至2012年6月人院的重型颅脑创伤合并高乳酸血症患者38例,测定治疗前及治疗后6小时动脉血乳酸,计算6小时乳酸清除率。以患者人住神经外科或重症医学科病房为研究起点,患者出院（最长随访者为28天）或死亡为研究终点,将患者分为存活组（31例）和死亡组（7例）,以6小时血乳酸清除率10％为界限分为高乳酸清除率（≥10％）维（25例）和低乳酸清除率（〈10％）组（13例）。比较存活组和死亡组6小时乳酸清除率差异,高乳酸清除率组和低乳酸清除率组之间28天死亡率差异。结果各组年龄、性别、治疗前GCS评分、APACHElI评分、基础血乳酸值均无统计学差异;存活组早期乳酸清除率显著高于死亡组[（20．68±14．67）％VS（6．21±10．40）％．P〈O．05];高乳酸清除率组28天死亡率显著低于低乳酸清除率组（8．70％VS62．5％,P〈0．05）;高乳酸清除率组生存率显著高于低乳酸清除率组（92．0％．VS615％,P〈0．05）。结论早期乳酸清除率可作为评估重型颅脑创伤合并高乳酸血症患者预后的指标。     

Effect of Nitric Oxide Synthase Inhibition and Saline Administration on Blood Pressure and Renal Sodium Handling During Experimental Sepsis in Rats

Much effort has been made in recent years to clarify metabolic and renal function changes in sepsis. A number of studies performed in different models of sepsis have been described. One such model that is frequently used is cecal ligation and puncture (CLP) in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late hypodynamic, hypometabolic phase. The present study evaluated the blood pressure (n = 5) and renal function changes during development of CLP renal failure and to determine the effects of NOS inhibition (L-NAME) and 0.15 M NaCl administration on tail blood pressure and renal function in randomly assigned five groups (n = 10 each): (1) Sham-operated, (2) Sham-operated L-NAME-treated, (3) CLP rats, (4) CLP L-NAME-treated, and (5) CLP 0.15 M NaCl-treated rats. The basal tail blood pressure was not significantly different among the four groups. One week later, arterial pressure was significantly increased in sham-operated L-NAME-treated rats (159 ± 12 mmHg) compared with the other groups (118 ± 9.0 mmHg in nontreated rats, p<0.05). Blood pressure shows a slightly and not significant decrease up to 12 h in L-NAME and 0.15 M NaCl treated rats, which in turn was followed by a significant reduced arterial pressure 18 h after CLP in both groups (L-NAME: 96.0 ± 3.6 mmHg, p<0.05) and NaCl: 82.3 ± 2.4 mmHg, p<0.05) compared to sham-operated groups. The glomerular filtration rate estimated by C_Cr decreases significantly in the CLP untreated group (p<0.001) and did not significantly differ from the sham-operated and L-NAME-treated groups (p = 0.4) during the studies of renal tubule sodium handling. On the other hand, subcutaneous 0.15 M NaCl administration prevented C_Cr decreases in CLP rats (p = 0.25). CLP increased the FE_Na in the sham-operated from: 857.2 ± 85.1 Δ% min^?1 to CLP: 1197.8 ± 119.0 Δ% min^?1. The high FE_Na to CLP was blunted and significantly reduced by previous systemic treatment of animals with L-NAME from sham-operated + L-NAME: 1368.0 ± 72.0 Δ% min^?1 to CLP+L-NAME: 1148.0 ± 60.4 Δ% min^?1 (p<0.01). The enhanced FE_Na in the CLP group were accompanied by a significant increase in proximal sodium reabsorption rejection. The salient findings of the present study suggest that a decrease in the blood pressure and creatinine clearance caused by CLP may benefit from L-NAME and fluid resuscitation during initial bacteremia (first 12 h) by promoting an additional increase of tubule sodium reabsorption in the post-proximal segments of nephrons, but these therapies could not prevent acute renal failure after established endotoxemia.     

Comparison of Cystatin C,Creatinine and Creatinine Clearance vs. GFR for Detection of Renal Failure in Renal Transplant Patients

Background: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. Methods: In a 60‐subject cohort (40 ± 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut‐off (60 and 90 mL/min/1.73 m²). Results: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m² were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. Conclusions: This study provides cut‐off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.     

Effect of maxillary sinus floor augmentation on sinus membrane thickness in computed tomography

Background: Little is known about maxillary sinus compliance, i.e., the intrinsic potential of the sinus membrane to resume its homeostatic status after the surgical trauma caused by sinus floor elevation. The aim of the present study is to investigate the effect of maxillary sinus floor augmentation on sinus membrane thickness. Methods: Within‐patient comparison of computed tomographic scans before bone grafting versus 4 to 6 months after bone grafting was performed. Changes in membrane thickness were evaluated in 65 maxillary sinus floor augmentation procedures via a lateral approach in 35 patients without clinical signs of sinus pathology at any time. Results: Sinus membrane thickness differed significantly before (0.8 ± 1.2 mm) versus after (1.5 ± 1.3 mm) augmentation surgery (P <0.001), with a mean increase of 0.8 ± 1.6 mm (maximum: 4.4 mm). Only 28% of augmented sinuses did not show membrane thickening. In non‐augmented control sinuses, there was no evidence of membrane thickness increase. Conclusions: The results indicate that the maxillary sinus membrane, even in healthy clinical conditions, undergoes morphologic modifications after sinus floor elevation, yet membrane reactions demonstrate significant variability. Future research on the effect of augmentation surgery on maxillary sinus physiology is recommended.     

Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine's discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors.     

Amyloid β inhibits retinoic acid synthesis exacerbating Alzheimer disease pathology which can be attenuated by an retinoic acid receptor α agonist

The retinoic acid receptor (RAR) α system plays a key role in the adult brain, participating in the homeostatic control of synaptic plasticity, essential for memory function. Here we show that RARα signalling is down‐regulated by amyloid beta (Aβ), which inhibits the synthesis of the endogenous ligand, retinoic acid (RA). This results in the counteraction of a variety of RARα‐activated pathways that are key in the aetiopathology of Alzheimer's disease (AD) but which can be reversed by an RARα agonist. RARα signalling improves cognition in the Tg2576 mice, it has an anti‐inflammatory effect and promotes Aβ clearance by increasing insulin degrading enzyme and neprilysin activity in both microglia and neurons. In addition, RARα signalling prevents tau phosphorylation. Therefore, stimulation of the RARα signalling pathway using a synthetic agonist, by both clearing Aβ and counteracting some of its toxic effects, offers therapeutic potential for the treatment of AD.