Visualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopyvisualization of Nd3+-doped Laf3 Nanoparticles For Near Infrared Bioimaging via Upconversion Luminescence at Multiphoton Excitation Microscopy

Recent developments in the field of biophotonics facilitate the raise of interest to inorganic nanoparticles (NPs) doped with Nd 3+ ions, because of their near-infrared (NIR) absorption. These NPs are interesting bioimaging probes for deep tissue visualization, while they can also act as local thermometers in biological tissues. Despite the good possibilities for visualization of NPs with Nd 3+ ions in NIR spectral range, difficulties arise when studying the cellular uptake of these NPs using commercially available fluorescence microscopy systems, since the selection of suitable luminescence detectors is limited. However, Nd 3+ ions are able to convert NIR radiation into visible light, showing upconversion properties. In this paper we found optimal parameters to excite upconversion luminescence of Nd 3+ :LaF 3 NPs in living cells and to compare the distribution of the NPs inside the cell culture of human macrophages THP-1 obtained by two methods. Firstly, by detecting the upconversion luminescence of the NPs in VIS under NIR multiphoton excitation using laser scanning confocal microscopy and secondly, using transmission electron microscopy

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Colocalized Structural and Functional Changes in the Cortex of Patients with Trigeminal Neuropathic Pain

Background: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. Methodology/Principal Findings: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. Conclusions: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Insula-specific responses induced by dental pain: a proton magnetic resonance spectroscopy study

OBJECTIVES: To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. METHODS: Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. RESULTS: Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. CONCLUSION: The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed

The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

DA Sychev,1,2 NP Denisenko,1,2 ZM Sizova,2 AV Grachev,3 KA Velikolug4 1Russian Medical Academy of Post-Graduate Education, 2I.M. Sechenov First Moscow State Medical University, 3SM-Clinic, 4Out-patient department Number 51 branch 3, Moscow, Russia Introduction: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. Aim: To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. Methods: We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6&plusmn;11.9 years (range: 15&ndash;88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G&gt;A (CYP2C19*2, rs4244285), CYP2C19 636 G&gt;A (CYP2C19*3, rs4986893) and CYP2C19 -806 C&gt;T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. Results: Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 &ndash; 0.140, CYP2C19*3 &ndash; 0.006, CYP2C19*17 &ndash; 0.274. Conclusion: There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors. Keywords: CYP2C19, proton pump inhibitors, peptic ulcer, Russia

The frequency of SLCO1B1*5 polymorphism genotypes among Russian and Sakha (Yakutia) patients with hypercholesterolemia

Dmitrij Alekseevitch Sychev,1 Grigorij Nikolaevich Shuev,2 Jana Valer&#39;evna Chertovskih,3 Nadezhda Romanovna Maksimova,3 Andrej Vladimirovich Grachev,1 Ol&#39;ga Aleksandrovna Syrkova2 1Department of Internal Medicine and Clinical Pharmacology, Russian Medical Academy of Postgraduate Education, Moscow, 2Faculty of Postgraduate Education, Far Eastern State Medical University, Khabarovsk, 3Genetic Laboratory, Ammosov North-Eastern Federal University, Yakutsk, Russian Federation Introduction: Statins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time, up to 25% of patients cannot tolerate or have to discontinue the statin therapy due to statin-induced myopathy. In a majority of cases, statin-induced myopathy is attributed to SLCO1B1 gene polymorphism. The strongest association between statin-induced myopathy and SLCO1B1 gene polymorphism was described for simvastatin. Our research was focused on the frequency of SLCO1B1*5 genetic variant in the Russian population and in the native population of Sakha (Yakutia).Materials and methods: A total of 1,071 hyperlipidemic Russian and 76 hyperlipidemic Sakha (Yakutian) patients were included in the study. Genotypes of SLCO1B1*5 (c.521T&gt;C, rs4149056) were determined with polymerase chain reaction amplification. The results of our study were compared with data about hyperlipidemic patients in available publications.Results: In the Russian population 665 (62%) patients had TT genotype of SLCO1B1*5, 346 (32%) patients had TC genotype, and in 60 patients (6%) CC variant was found (Hardy&ndash;Weinberg&#39;s chi-square test was 3.1 P=0.21). In comparison with Brazil, France, the People&#39;s Republic of China, Japan, and the native population of Sakha (Yakutia), C-allele, which causes an increased risk of statin-induced myopathy, was found significantly more often in the Russian population. In the native population of Sakha (Yakutia) SLCO1B1 polymorphism was TT &ndash; 62 (82%), TC &ndash; 11 (14%), CC &ndash; 3 (4%) (Hardy&ndash;Weinberg&#39;s chi-square test was 5.13 P=0.077). In comparison with data from Brazil, France, the People&#39;s Republic of China, and Japan, C-allele frequency in the Sakha (Yakutian) population was not significantly different.Conclusion: Thus, we have studied the incidence of pathologic SLCO1B1 c.521C-allele in Russian and Sakha hyperlipidemic patients. The presence of SLCO1B1 C-allele in patients with hyperlipidemia forces us to be more careful in hypolipidemic drug prescription, especially statins, according to a higher risk of statin-induced myopathy development. The fact that SLCO1B1 C-allele is rarer among Sakha patients, could be interesting from the point of studying adverse drug effects frequency and statins&#39; effectiveness.Keywords: Russian, Sakha (Yakutia), pharmacogenetics, SLCO1B1, statins, myopath