Pulpal and periradicular response to caries: current management and regenerative options

The pulp-dentin complex is a strategic and dynamic barrier to various insults that plague the dentition. Researchers have yet to understand the complete potential of this shifting junction and its components. The most common cause of injury to the pulp-dentin complex is carious breakdown of enamel and dentin. In recent years, there has been a change in restorative management of caries. The emphasis is on strategies to preserve dentin and protect the pulp. This article provides a brief review of the effect of caries on the pulp, of subsequent events on the periradicular tissues, and of current understanding of treatment modalities.     

Evaluation of the effect of pentoxifylline on sleep‐deprivation induced memory impairment

In this study, we examined the ability of Pentoxifylline (PTX) to prevent sleep deprivation induced memory impairment probably through decreasing oxidative stress. Sleep deprivation was chronically induced 8 h/day for 6 weeks in rats using modified multiple platform model. Concurrently, PTX (100 mg/kg) was administered to animals on daily basis. After 6 weeks of treatment, behavioral studies were conducted to test the spatial learning and memory using the Radial Arm Water Maze. Additionally, the hippocampus was dissected; and levels/activities of antioxidant defense biomarkers glutathione reduced (GSH), glutathione oxidized (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), were assessed. The results show that chronic sleep deprivation impaired short‐ and long‐term memories, which was prevented by chronic treatment with PTX. Additionally, PTX normalized sleep deprivation‐induced reduction in the hippocampus GSH/GSSG ratio (P < 0.05), and activities of GPx, catalase, and SOD (P < 0.05). In conclusion, chronic sleep deprivation induces memory impairment, and treatment with PTX prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus. © 2013 Wiley Periodicals, Inc.     

Novel KCNQ2 Mutation in a Large Emirati Family With Benign Familial Neonatal Seizures

Mutations in voltage-gated potassium channel Kv7.2 are responsible for benign familial neonatal seizures type 1, a rare monogenic autosomal dominant inherited epilepsy syndrome. We describe a novel mutation (c.1126_1127delA) in exon 9 of KCNQ2, the gene encoding for the Kv7.2 channel, in a large Emirati family with benign familial neonatal seizures type 1. The mutation leads to a frameshift at amino acid position 376, triggering loss of function and haploinsufficiency. Patients with this mutation manifest repeated clonic seizures with normal interictal electroencephalograms and favorable prognoses. Signs occur within the first days of age, lingering well into puberty. KCNQ2 mutation screening, alongside genetic counseling, should be included in diagnostic evaluations of neonatal epileptic patients, potentially sparing the need for unnecessary investigations and treatment. To our knowledge, this report is the first of a KCNQ2 mutation in an Emirati family with benign familial neonatal seizures type 1.     

Enhancement of levodopa stability when complexed with β-cyclodextrin in transdermal patches

Abstract

Levodopa is a promising candidate for administration via the transdermal route because it exhibits a short plasma half-life and has a small window of absorption in the upper section of the small intestine. The aim of this study was to prepare stable levodopa transdermal patches. Both xanthan gum and Carbopol 971 polymers were selected with ethylcellulose constituting the backing layer of the prepared patches. The effect of adding β-cyclodextrin on the prepared patches was investigated. The uniformity in thickness, weight and content of the studied patches was acceptable. Physicochemical characterization revealed that there was no interaction between levodopa and the applied polymer. The results proved that levodopa precipitated as an amorphous form in carbopol patches. Controlled drug release was achieved for all the tested patches over a 6?h period. However, increased permeation was achieved for the carbopol patches. Although cyclodextrin did not enhance levodopa permeation, the stability study confirmed that levodopa stability was enhanced when complexed with β-cyclodextrin. The cumulative amount of drug released from carbopol patches is slightly higher than that of xanthan patches. The optimal stability was achieved in the carbopol/levodopa:β-cyclodextrin patch. The levodopa-β-cyclodextrin complex was successfully characterized using X-ray diffraction, NMR analysis and molecular dynamics simulations. In conclusion, carbopol/levodopa:β-cyclodextrin patches can be considered as a promising stable and effective transdermal drug-delivery system.     

Metformin Eased Cognitive Impairment Induced by Chronic L-methionine Administration: Potential Role of Oxidative Stress

Chronic administration of L-methionine leads to memory impairment, which is attributed to increase in the level of oxidative stress in the brain. On the other hand, metformin is a commonly used antidiabetic drug with strong antioxidant properties. In the current study, we tested if chronic metformin administration prevents memory impairment induced by administration of L-methionine. In addition, a number of molecules related to the action of metformin on cognitive functions were examined. Both metformin and L-methionine were administered to animals by oral gavage. Testing of spatial learning and memory was carried out using radial arm water maze (RAWM). Additionally, hippocampal levels or activities of catalase, thiobarbituric acid reactive substances (TBARs), glutathione peroxidase (GPx), glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG ratio were determined. Results showed that chronic L-methionine administration resulted in both short- and long- term memory impairment, whereas metformin treatment prevented such effect. Additionally, L-methionine treatment induced significant elevation in GSSG and TBARs, along with reduction in GSH/GSSG ratio and activities of catalase, and GPx. These effects were shown to be restored by metformin treatment. In conclusion, L-methionine induced memory impairment, and treatment with metformin prevented this impairment probably by normalizing oxidative stress in the hippocampus.     

Survival Results After Implantation of Intrapericardial Third‐Generation Centrifugal Assist Device: An INTERMACS‐Matched Comparison Analysis

Reports on third‐generation centrifugal intrapericardial pumps (HeartWare International, Inc., Framingham, MA, USA) have shown better survival results than the previous‐generation devices. However, outcomes depending on the preoperative level of stability can substantially differ, resulting in a limited analysis of potentialities and drawbacks of a given device. In the present study we sought to compare in our single‐center experience the survival results of this third‐generation device with previous left ventricular systems taking into account the different preoperative Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels. Between February 1993 and March 2012, 287 patients underwent assist device implantation in our university hospital (INTERMACS Level 1‐2 = 158 patients; INTERMACS Level 3‐4‐5 = 129 patients). Assist devices implanted were: Group A (HVAD HeartWare, n = 52), group B (previous continuous‐flow ventricular assist device [VAD], InCor [Berlin Heart, Berlin, Germany], n = 37; VentrAssist [VentraCor, Inc., Chatswood, NSW, Australia], n = 7; DeBakey [MicroMed Cardiovascular, Inc., Houston, TX, USA], n = 32), and group C (pulsatile systems, n = 159). After cumulative support duration of 54 436 days and a mean follow‐up of 6.21 ± 7.46 months (range 0–45.21 months), log‐rank analysis revealed a survival for group A of 82.0%, 70.4%, and 70.4%; for group B of 84.0%, 48.2%, 33.7%; and for group C of 71.6%, 46.1%, 33.8%, at 1, 12, and 24 months respectively, with a significantly (P = 0.013) better outcome for group A. When stratifying the survival on the basis of INTERMACS level, no significant survival improvement was observed among all patients who underwent VAD implantation in INTERMACS 1‐2 (P = 0.47). However, among patients who underwent elective VAD implantation (INTERMACS 3‐4‐5), group A had a significantly better outcome (P = 0.005) compared with the other INTERMACS‐matched groups (B,C) with a survival rate of 88.8% in group A versus 34.2% in group B and 45.6% in group C at 24 months, respectively. Elective HVAD system implantation shows improved survival benefit over the other INTERMACS‐matched devices. Moreover, preoperative unstable hemodynamics resulted in a poor prognosis independently from the pump generation.     

Comparison between short- and long-acting erythropoiesis-stimulating agents in hemodialysis patients: target hemoglobin,variability, and outcome

Purpose

Maintaining target hemoglobin (Hb) with minimal variability is a challenge in hemodialysis (HD) patients. The aim of this study is to compare the long- and short-acting erythropoietin-stimulating agents such as Aranesp and Eprex in achieving these targets.

Methods

Randomized, prospective, open-labeled study of 24 weeks includes stable patients on HD >3 months, age >18 years, and on Eprex for >3 months. Patients were randomized into two groups: A-(Aranesp group):HD patients on Eprex Q TIW or BIW were converted to Aranesp Q weekly, by using the conversion factor of 200:1 and those on Eprex Q weekly to Aranesp Q 2 weeks; B-(Eprex group):patients continued on Eprex treatment. Hemoglobin target was set at (105–125 g/l). Primary end points were percentage of patients achieving target Hb, hemoglobin variability, and number of dose changes in each group.

Results

This study consisted of 139 HD patients: 72 in the Aranesp and 67 in the Eprex—mean (SD) age 54 (16.2) years, 77 (55 %) males. About 46 % were diabetic. Target Hb achieved in 64.8 % of the Aranesp and 59.7 % in the Eprex (p = 0.006). Hb variability was less frequent in the Aranesp group (p = 0.2). Mean number of dose changes was 1.3 (0.87) in the Aranesp and 1.9 (1.2) in the Eprex (p < 0.001). There was 1 vascular access thrombosis in the Aranesp and 8 in the Eprex (p < 0.001). There was no difference in hospitalization and death number between the 2 groups.

Conclusions

Aranesp Q weekly or every 2 weeks is more efficient in achieving target Hb, with less dose changes and minor vascular access complications.     

Autophagy: An adaptive metabolic response to stress shaping the antitumor immunity

Several environmental-associated stress conditions, including hypoxia, starvation, oxidative stress, fast growth and cell death suppression, modulate both cellular metabolism and autophagy to enable cancer cells to rapidly adapt to environmental stressors, maintain proliferation and evade therapies. It is now widely accepted that autophagy is essential to support cancer cell growth and metabolism and that metabolic reprogramming in cancer can also favor autophagy induction. Therefore, this complex interplay between autophagy and tumor cell metabolism will provide unique opportunities to identify new therapeutic targets. As the regulation of the autophagic activity is related to metabolism, it is important to elucidate the exact molecular mechanism which drives it and the functional consequence of its activation in the context of cancer therapy. In this review, we will summarize the role of autophagy in shaping the cellular response to an abnormal tumor microenvironment and discuss some recent results on the molecular mechanism by which autophagy plays such a role in the context of the anti-tumor immune response. We will also describe how autophagy activation can behave as a double-edged sword, by activating the immune response in some circumstances, and impairing the anti-tumor immunity in others. These findings imply that defining the precise context-specific role for autophagy in cancer is critical to guide autophagy-based therapeutics which are becoming key strategies to overcome tumor resistance to therapies.     

Effect of a Contrast Modulation System on Contrast Media Use and the Rate of Acute Kidney Injury After Coronary Angiography

Objectives

The aim of the AVERT (AVERT Clinical Trial for Contrast Media Volume Reduction and Incidence of CIN) trial was to test the efficacy of the AVERT system to reduce the contrast media volume (CMV) used during coronary angiographic procedures without impairing image quality and to prevent contrast-induced acute kidney injury (CI-AKI) in patients at risk for CI-AKI.