Nicotine intake and smoking topography in smokers with bipolar disorder

Williams JM, Gandhi KK, Lu S‐E, Steinberg ML, Benowitz NL. Nicotine intake and smoking topography in smokers with bipolar disorder. Bipolar Disord 2012: 14: 618–627. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Cigarette smoking behavior in bipolar disorder (BPD), including the effects of mood‐stabilizing medications, has not been well characterized. Methods: We compared serum nicotine, nicotine metabolite levels, and smoking topography in 75 smokers with BPD to 86 control smokers (CON). For some comparisons, an additional control group of 75 smokers with schizophrenia (SCZ) were included. Results: There were no differences between the BPD and CON groups in baseline smoking characteristics or serum nicotine or cotinine levels. Fifty‐one smokers with BPD (68.9%) were taking one of the following mood stabilizers: valproic acid, lamotrigine, carbamazepine, oxcarbazepine, lithium, or topiramate. The 3‐hydroxycotinine‐to‐cotinine ratio, a marker of cytochrome P450 2A6 (CYP2A6) metabolic activity, was significantly higher in BPD versus CON and versus SCZ (0.68 versus 0.49 versus 0.54; p = 0.002). The difference between groups, however, was no longer significant when the analysis was repeated with those taking hepatic enzyme‐inducing drugs (carbamazepine, oxcarbazepine, and topiramate) included as a covariate. The time between puffs, or interpuff interval (IPI), was shorter in BPD versus CON by an average of 3.0 sec (p < 0.05), although this was no longer significant when we removed smokers from the analysis of those taking hepatic enzyme inducers. Conclusions: Smokers with BPD are not different from CON on most measures of nicotine intake and smoking topography. We found an increased rate of nicotine metabolism in smokers taking mood stabilizers that are hepatic enzyme inducers, including carbamazepine, oxcarbazepine, and topiramate. Smokers with rapid nicotine metabolism might be expected to smoke more intensely to compensate for the more rapid disappearance of nicotine from the blood and brain, and may have more difficulty in quitting smoking, although this requires further study.     

Stroke prophylaxis in critically-ill patients with new-onset atrial fibrillation

Journal of Thrombosis and Thrombolysis - Despite a high incidence of new onset atrial fibrillation (NOAF) in critically ill patients and its association with short and long-term incidence of...     

In a Model of Neuroinflammation Designed to Mimic Delirium,Quetiapine Reduces Cortisol Secretion and Preserves Reversal Learning in the Attentional Set Shifting Task

Quetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials to criterion, errors, non-locomotion episodes and latency to criterion, serum cortisol and tumor necrosis factor alpha (TNF-α) levels. TNF-α levels were not different between groups at 24 h. Cortisol levels in the LPS + Quetiapine group were reduced compared to LPS + Placebo (P < 0.001) and did not differ from the placebo group (P = 0.15). Analysis between LPS + Quetiapine and LPS + Placebo treated rats demonstrated improvement in the compound discrimination reversal (CD Rev1) (P = 0.016) and the intra-dimensional reversal (ID Rev2) (P = 0.007) discriminations on trials to criterion. LPS + Quetiapine treated rats had fewer errors than LPS + Placebo treated animals in the compound discrimination (CD) (P = 0.007), CD Rev1 (P = 0.005), ID Rev2 (P < 0.001) discriminations. There was no difference in non-locomotion frequency or latency to criterion between the three groups in all discriminations (P > 0.0167). We demonstrated preserved reversal learning, no effect on attentional set shifting and normalized cortisol levels in quetiapine-treated rats in this neuroinflammatory model of delirium. This suggests that quetiapine’s beneficial effects in delirium may be related to the preservation of reversal learning and potential downstream effects related to reduction in cortisol production.

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Percutaneous Radiofrequency Ablation of Appendicular Skeleton Chondroblastoma—an Experience from a Tertiary Care Cancer Center

PurposeTo evaluate safety and long-term efficacy of radiofrequency (RF) ablation in treatment of chondroblastoma.Materials and MethodsThis retrospective analysis comprised 27 consecutive patients with histopathologically proven chondroblastoma treated by RF ablation. The tumors were located in the proximal humerus (n = 6), proximal tibia (n = 8), proximal femur (n = 6), distal femur (n = 5), acromion process (n = 1), and lunate (n = 1). In 19 patients (70.3%), the tumor was in the weight-bearing area of the bone. Clinical response was assessed by comparing pain scores and functional assessment by Musculoskeletal Tumor Society (MSTS) score before and after ablation. Patients were followed for a minimum of 1 year to rule out complications and recurrence.ResultsTechnical success rate was 100%. Mean pain score before the procedure was 7.34 (range, 7–9); all patients experienced a reduction in pain, with 25 (92.6%) patients reporting complete pain relief at 6 weeks. Mean MSTS score before the procedure was 15.4, whereas mean MSTS score at 6 weeks after the procedure was 28.6, suggesting significant functional improvement (P < .0001). Two patients developed osteonecrosis and collapse of the treated bone. There were no recurrences.ConclusionsPercutaneous RF ablation is a safe and effective option for treating chondroblastoma of the appendicular skeleton.     

Novel peptidomimetic peptide deformylase (PDF) inhibitors of Mycobacterium tuberculosis

Emergence of MDR‐TB and XDR‐TB led to the failure of available anti‐tubercular drugs. In order to explore, identify and develop new anti‐tubercular drugs, novel peptidomimetic series of Mtb–peptide deformylase (PDF) inhibitors was designed and synthesized. In vitro antimycobacterial potential of compounds was established by screening of compounds against Mycobacterium tuberculosis H37Rv strain using MABA. Among them, ester series of compounds 4a , 4b , 4c , 4d , and 4e were found most active, with compound 4c being highly active and exhibiting minimum inhibitory concentration of 6.25 µg/ml against M. tb H37Rv strain. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on Mtb‐peptide deformylase (PDF), which is involved in the mycobacterium protein synthesis.     

Novel anionic polymer as a carrier for CNS delivery of anti-Alzheimer drug

Natural and plant-based polymers could be used for control release of drugs and also helps in targeting drug to the site of action. The main objective of present work was to check the feasibility of plant-based, namely, mango gum polymeric nanoparticles (NPs) as a carrier for central nervous system (CNS) delivery using model drug donepezil (DZP). The NPs were prepared by modified ionic gelation method and emulsion cross-linking method. Zeta sizer results showed that the diameter of NPs was about 90–130?nm. The polymeric DZP-loaded NPs were almost spherical in shape, as revealed by transmission electron microscopy (TEM). On increasing concentration of NPs suspension from 50?μg/ml to 5000?μg/ml there was no significant increase in % hemolysis. In vivo studies showed that brain targeting was achieved. So on the basis of above results, the extracted water soluble fraction of mango gum is a suitable candidate for brain delivery in the form of nanoformulations.     

Early investigational tubulin inhibitors as novel cancer therapeutics

Introduction: Microtubules represent one of the most logical and strategic molecular targets amongst the current targets for chemotherapy, alongside DNA. In the past decade, tubulin inhibitors as cancer therapeutics have been an area of focus due to the improved understanding and biological relevance of microtubules in cellular functions. Fueled by the objective of developing novel chemotherapeutics and with the aim of establishing the benefits of tubulin inhibition, several clinical trials have been conducted with others ongoing.

Area covered: At present, the antitubulin development pipeline contains an armful of agents under clinical investigation. This review focuses on novel tubulin inhibitors as cancer therapeutics. The article covers the agents which have completed the phase II studies along with the agents demonstrating promising results in phase I studies.

Expert opinion: Countless clinical trials evaluating the efficacy, safety and pharmacokinetics of novel tubulin inhibitors highlights the scientific efforts being paid to establish their candidature as cancer therapeutics. Colchicine binding site inhibitors as vascular disrupting agents (VDAs) and new taxanes appear to be the most likely agents for future clinical interest. Numerous agents have demonstrated clinical benefits in terms of efficacy and survival in phase I and II studies. However conclusive benefits can only be ascertained on the basis of phase III studies.     

Spectral Clustering for Unsupervised Segmentation of Lower Extremity Wound Beds Using Optical Images

Chronic lower extremity wound is a complicated disease condition of localized injury to skin and its tissues which have plagued many elders worldwide. The ulcer assessment and management is expensive and is burden on health establishment. Currently accurate wound evaluation remains a tedious task as it rely on visual inspection. This paper propose a new method for wound-area detection, using images digitally captured by a hand-held, optical camera. The strategy proposed involves spectral approach for clustering, based on the affinity matrix. The spectral clustering (SC) involves construction of similarity matrix of Laplacian based on Ng-Jorden-Weiss algorithm. Starting with a quadratic method, wound photographs were pre-processed for color homogenization. The first-order statistics filter was then applied to extract spurious regions. The filter was selected based on the performance, evaluated on four quality metrics. Then, the spectral method was used on the filtered images for effective segmentation. The segmented regions were post-processed using morphological operators. The performance of spectral segmentation was confirmed by ground-truth pictures labeled by dermatologists. The SC results were additionally compared with the results of k-means and Fuzzy C-Means (FCM) clustering algorithms. The SC approach on a set of 105 images, effectively delineated targeted wound beds yielding a segmentation accuracy of 86.73 %, positive predictive values of 91.80 %, and a sensitivity of 89.54 %. This approach shows the robustness of tool for ulcer perimeter measurement and healing progression. The article elucidates its potential to be incorporated in patient facing medical systems targeting a rapid clinical assistance.