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Today, 12 Ιουλίου 2016, 4:09:28 μμ
Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a “metabolically-triggered” low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. Method: We have reviewed >200 articles to discuss the interrelationship between periapical lesions and metabolic disorders including type 2 diabetes mellitus, hypertension, and non-alcoholic fatty liver diseases (NAFLD), and their common pathological background in immunology/osteoimmunology and cytokine biology. Results: An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non-alcoholic steatohepatitis. Conclusion: Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship.
Dissecting the Role of K61/K59 Residue in VPS4 Functions
Today, 12 Ιουλίου 2016, 4:09:29 μμ
ESCRTs (Endosomal Sorting Complexes Required for Transport) are required for the formation of the intraluminal vesicles in the multivesicular bodies and are involved in other topologically similar processes such as cytokinesis, nuclear envelope sealing and viral egress. The final complex ESCRT-III is disassembled by the recruitment and activation of the AAA-ATPase VPS4 to the endosomal membranes. This recruitment is due to the binding of VPS4 N-terminal MIT with MIM1 and MIM2 domains present in the CHMPs proteins. By analyzing different cellular membrane remodeling events in which VPS4 is involved, here we provide evidence that the K61 residue, mapping within the MIT domain of VPS4B (K59 in VPS4A), is involved in VPS4 functioning. Posttranslational modifications of this residue might modulate MIT-MIM2 binding affinity and, as a consequence, VPS4 functions.
Erratum:
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Corrigendum to Manuscript “Pfeifer T, Buchebner M, Chandak PG, Patankar J, Kratzer A, Obrowsky S, Rechberger GN, Kadam RS, Kompella UB, Kostner GM, Kratky D, Levak-Frank S. Synthetic LXR agonist suppresses endogenous cholesterol biosynthesis and efficiently lowers plasma cholesterol. Curr Pharm Biotechnol. 2011 Feb 1;12(2):285-92.” LC-MS internal standard peak areas used in the calculation of brain DMHCA levels in the original manuscript were in error. Brain tissue levels were recalculated using valid internal standard peak areas and the revised Figure 6C is presented below. Thus, brain DMHCA concentration was low and variable at 1.74 +/- 1.15 µg/g tissue but not undetectable, with the concentrations being lower relative to several other tissues.
Electrocardiographic and Cardiac Autonomic Indices - Implications of Sex-Specific Risk Stratification in Women After Acute Myocardial Infarction
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: The debate on whether sex-specific predictive models improve risk stratification after myocardial infarction is ongoing. Methods: This review summarises the current clinical knowledge on sex-specific differences in post-infarction risk stratification parameters. Particular focus is given to electrocardiographic risk factors and indices of cardiac autonomic status. Results: Differences in the underlying pathophysiology between men and women are known. However, clinical findings often lead to uncertain conclusions for a number of risk predictors including, among others, resting heart rate, heart rate variability, heart rate turbulence, QT interval duration, and QRS-T angle. The review links recent findings in prognostic parameters with successful approaches in sex-specific non-invasive risk stratification. Conclusion: Disparities are described in the current clinical opinions on the relevance of investigated parameters in women and possible directions for further research in the field are given.
Potential of Microbial Enzymes in Retting of Natural Fibers: A Review
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Retting may be defined as the separation of bast fibres from the core tissues of the stem. The methods of retting have witnessed technological advances based on intervention of microbial enzymes resulting in better quality of fibers. The traditional methods of retting namely water retting and dew retting suffered from several limitations like poor quality of fibers, comparatively large space and time requirement, dependence on weather conditions, huge manpower involvement, pollution and high cost of drying. The microbial enzymes predominately pectinases are becoming popular for retting of fibers owing to the fact that it results in high quality fiber, save time and is also ecofriendly. The enzymatic retting is now preferred over the traditional methods resulting in formulation of several commercial enzyme preparations like Flaxzyme and Viscozyme. The variability in types of natural fibers, different retting methods, intervention of microbial enzymes for retting of fibers, parameters for efficient retting aresome of the important highlights of this review.
Population Studies of Association Between Lithium and Risk of Neurodegenerative Disorders
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Lithium shows neuroprotective and neurotrophic effects in vitro and in vivo. Due to its involvement in hippocampal neurogenesis and the interaction with beta-amyloid and neurofibrillary tangle metabolism it has been hypothesized that lithium could have the potential to influence the development of dementia. Method: Using the PubMed database and cross-reference search strategies our aim was to specifically identify population (cohort or case-control) studies investigating the association between lithium and dementia. Results: Data from large cohort studies suggest an association between lithium treatment and dementia risk reduction or reduced dementia severity. Studies with smaller sample sizes yield more variable findings. Conclusions: Lithium may reduce the risk of dementia among middle-aged and older people. Beneficial lithium effects are possibly limited to specific types of neurodegenerative processes.
Role of microRNA in Regulating Cell Signaling Pathways, Cell Cycle, and Apoptosis in Non-Small Cell Lung Cancer
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Dysregulation in the expression of miRNAs has been observed in various human cancers, including lung cancer. Recent studies have identified the role of a number of miRNAs in regulating key cellular processes and signaling pathways involved in lung tumourigenesis, including cell proliferation, differentiation, angiogenesis, apoptosis, invasion and metastasis. Due to their variable behavior and regulatory role in various nodal junctions in cellular pathways, miRNAs have also been used as potential therapeutic targets and clinical biomarkers in lung cancer. In this non-systematic review, we briefly focus on biogenesis and function of cytoplasmic miRNA and the role of methylation in the regulation of miRNA biogenesis in non-small cell lung cancer (NSCLC). Further, we elaborate the role of differentially expressed miRNAs and their regulatory role on various signaling pathways, cell cycle, and apoptosis in NSCLC.
Quantification of Rat Brain Amino Acids: Analysis of the Data Consistency
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Tissue amino acids are important markers to characterize (patho)physiology. As neurotransmitters or their precursors, they have special significance in brain. However, mass spectrometry (MS)-based quantifications of brain amino acids are rare and inconsistent. </p><p> Methods: To reveal efficient procedures optimal for brain research purposes, free amino acids in the same extracts of rat cerebellum were quantified by published assays employing hybrid triple quadrupole-linear ion trap (QTRAP) MS or amino acid analyzer with ninhydrin derivatization. </p><p> Results: Levels of four amino acids out of 14 quantified by the two methods were established to be perturbed in the QTRAP MS assay, with the ninhydrin-based quantification agreeing well with the published values obtained by non-MS approaches. The overestimation of Glu and Lys and underestimation of Gly and Tyr in brain extracts by QTRAP MS suggest interference of the co-eluting compounds and ion suppression effects, correspondingly. The MS-inherent artifacts presumably contribute to inconsistency of published MS data on the brain amino acid content, as our analysis of different studies indicated that the variability of the MS data greatly exceeds the biological variability. </p><p> Conclusion: Evaluation of potential artifacts of the MS-based quantification of brain amino acids using the ninhydrin detection as a reference method, provides a solution for reliable quantification of the artifact-resistant amino acids, pointing to relatively good performance of the time- and cost-efficient QTRAP MS procedure employed. </p><p>
Implementation of “Quality by Design (QbD)” Approach for the Development of 5-Fluorouracil Loaded Thermosensitive Hydrogel
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. </p><p> Methods: To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. </p><p> Results: Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. </p><p> Conclusion: In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel. </p><p>
Genomic Variations Affecting Biological Effects of Statins
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Statins are inhibitors of hydroxy-methyl-glutaryl coenzymeA (HMG-CoA) reductase, the rate-limiting enzyme involved in de novo cholesterol synthesis. The patient health profile needs to be taken in account during the interpretation of the variability in the outcome of drug therapy, as well as compliance with prescribed pharmacological treatments, and genetic profile. </p><p> Objective: Several genetic polymorphisms playing a role in the different response to lipid lowering therapy have recently been identified. Statins, today are used to reduce Low Density Lipoprotein-Cholesterol (LDL-C), represent the treatment of choice in individuals with increased risk of Cardio-Vascular Disease (CVD), both in primary and secondary prevention of cardiovascular events. Regardless of the usefulness in a wide range of patients, the common interindividual genetic variability, along with phenotypic aspects, lead to resistance and adverse responses. </p><p> Methods: we reviewed on PubMed, inserting as term search “statin and polymorphism”, “statin and pharmacogenomic”, “statin and gene”, “HMG-CoA reductase and gene”. </p><p> Results: A large number of candidate genes and many single nucleotide polymorphisms (SNPs) have been evaluated and related to pharmacokinetic and/or pharmacodynamic of statins. </p><p> Conclusion: Despite these several findings there is still not enough evidence to recommend pharmacogenomic tests before starting statin therapy. </p><p>
Assessment of the Accuracy of Whole Blood/Serum Rapid Point-of-Care HIV Three Dot Test for Oral Fluid Specimens
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Saliva rapid point of care HIV tests have proven advantages over blood-based HIV tests in terms of quality, rapidity and convenience. </p><p> Aim: To assess the sensitivity, specificity and reproducibility of saliva samples using the serum/ whole blood rapid test and to compare it with serum specimens. </p><p> Material & Methods: 52 seropositive and 52 seronegative patients were included in the study. Stimulated and unstimulated saliva samples were collected and tested using the serum/ whole blood signal HIV THREE DOT rapid test (span diagnostics). </p><p> Results: The sensitivity, specificity, positive predictive value and negative predictive value of the test was found to be 100% for saliva samples. </p><p> Conclusion: Saliva samples can be used as a substitute to serum/whole blood for HIV testing. It can be done using the serum/whole blood kits which are cheaper and readily available thus broadening the reach of testing programs in resource limited settings. </p><p>
Evaluation of Antimicrobial and Antiviral Activities of Different Venoms
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Animals’ venomous secretions or peptides obtained from those secretions are used in the development of new therapeutic agents. The aims of this study were to investigate antimicrobial and antiviral activity of four different venoms obtained from the frog named Bufo arenarum and the snakes Crotalus atrox, Causus rhombeatus and Naja melanoleuca. </p><p> Methods: Antimicrobial activities of the venoms tested against 9 bacteria, 1 yeast, 1 fungal species and 2 viral species based on micro-well dilution assay and antiviral assay. </p><p> Results: Four different venoms were examined to evaluate the antimicrobial and antiviral activity against 9 bacteria, 1 yeast and 1 fungal and 2 viral species. None of the venoms exhibited anticandidal or antifungal activity. However, all of the four venoms tested were found to have both antibacterial and antiviral activities. </p><p> Conclusion: This is the first study demonstrating that venoms of Crotalus atrox and Bufo arenarum have antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Bacillus subtilis, Aeromonas hydrophila, Aeromonas spp. Antiviral activities of 4 venoms against Poliovirus and Adenovirus were also investigated for the first time. </p><p>
Optimization of Site Targeted Zolmitriptan Delivery Using Polyox N12K and Methacrylic Acid
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Zolmitriptan is the drug of choice for the treatment of migraine with or without aura. Oral bioavailability of drug is 40% due to high first pass metabolism. Elimination half life is 3 hrs and drug degradation occurs in acidic environment of GIT. To overcome these problems present research was aimed to prepare intestinal targeted delivery. This was prepared by compression coating technique as maximum absorption of drug occurs in small intestine. 32 factorial design was applied with independent variables polyox N12K and methacrylic acid. Core tablet consists of croscarmellose sodium as superdisintegrant, avicel as binder, dicalcium phosphate as diluent and zolmitriptan as drug. Outer coating of polyox N12K and methacrylic acid was applied in compression coating. Optimized batch F8 consist of polyox N12K (60%) & methacrylic acid (3%). In-vitro release study in simulated media indicated presence of the tablet in small intestine giving burst release. In-vivo placebo X- ray radiographic technique for F8 showed that tablet was not adhered throughout GIT and bypass stomach. This indicated F8 can be a potential to achieve the targeted site delivery.
Modeling Ensembles of Loop Conformations by Iterative Stochastic Elimination
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Protein models are useful in structure-based protein engineering applications, including designing drugs, redesigning enzyme specificity, and designing new folds in proteins. Predicting loop structures is considered the main challenge in protein 3-D structure modeling. The flexibility of loop regions dictates the need for special attention to their conformations. In this paper, we report on the implementation of iterative stochastic elimination (ISE) optimization technology for the ab initio modeling of protein variable regions (loops). The ISE algorithm was tested on a benchmark of 70 structurally refined loops. The median root-mean-square deviation (RMSD) of the loop residues was 1.5Å, with 80% of the targets conforming to the native with RMSD lower than 2.0Å. The median-backbone, heavy-atom global RMSD of the loop predictions were 0.67Å for short loops (4-6 residues), 0.88Å for medium loops (7-9 residues), 1.68Å for long loops (10-12 residues) and 2.76Å for very long loops (13-16 residues). In addition to the accurate modeling of short, medium and long loops, the current method provided us with ensembles of conformations, which are crucial for studying the dynamic nature of loops, mainly on the surfaces of proteins. The proposed technique could be incorporated into modules for generating homologybased models and for flexible docking.
Pharmacokinetic Considerations of Inhaled Pharmaceuticals for Systemic Delivery
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Systemic pulmonary delivery is considered to have advantages over oral or intravenous administration for certain drugs. </p><p> Methods: In this article, we review the effects of intrinsic drug properties and drug loading carriers on the pharmacokinetic parameters of inhaled drugs in the context of use in systemic pulmonary delivery. </p><p> Results: The delivery of drugs via inhalation can be advisable to achieve a fast onset of action; enhance the systemic bioavailability of drugs with poor oral absorption, including peptides and proteins; avoid invasive administration and improve patient compliance. To optimize the functioning of this delivery system, there is high demand for a systematic understanding of the pharmacokinetic characteristics, which are closely related to the pharmacodynamic and toxicological effects. </p><p> Conclusion: The pharmacokinetic parameters of inhaled drug products are affected by many factors, including physiological and pathological variables and the intrinsic drug and formulation properties. </p><p>
Optimization of the Enzymolysis Conditions for Scorpion Peptides and Evaluation of its Antitumor Activity
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Trypsin, chymotrypsin and elastase were combined to hydrolyze scorpion Buthus marstesii Karsch powders to prepare scorpion peptides (SP). Orthogonal design experiment L<sub>16</sub> (4<sup>4</sup>) was used to optimize variables of enzymolysis temperature, time, pH and enzyme concentration. Degree of hydrolysis (DH) and inhibition rate (IR) of A549 cells were selected as analysis indicators. The optimum enzymolysis conditions were determined as follows: enzymolysis temperature 40°C, time 3h, pH 8.5 and enzyme concentration of each 2000U. The anti-tumor activity of SP was determined on a panel of representative cell lines (A549, MCF7 and EC109) using MTT assay. In vitro, SP significantly inhibited the proliferation of A549, which was more obvious than MCF-7 and EC109. Further experiments on cell apoptosis and cell cycle analysis revealed that SP induce apoptosis and arrest cell cycle progression in S phase.
Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Apathy is an early and common neuropsychiatric syndrome in Alzheimer’s disease (AD) patients. In clinical trials, apathy is associated with decreased motor activity that can be monitored by actigraphy. The triple transgenic mouse AD model (3xTgAD) has been shown to recapitulate the biochemical lesions as well as many of the synaptic and cognitive alterations associated with AD. In the present work we found that these mice also develop an early and consistent apathy-like behavior as evidenced by a drastic decrease in spontaneous activity measured by actimetry. We recently established that these mice also display an intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) appearing early, in absence of Aβ. Interestingly, we found that the apathy-like behavior observed in 3xTgAD mice was temporally associated with C99 accumulation and synaptic alterations. Since it is well known that the genetic background can strongly influence behavior and can induce transcriptional variability in animal models, we decided to determine the influence of genetic background on the above-described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found that the genetic background had no influence on either C99 accumulation or synaptic plasticity alterations, but strongly affected the apathy-like behavior.
The Interaction Between Gender and Diabetes Mellitus in the Coronary Heart Disease Risk
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: Cardiovascular disease (CVD) despite the advances in medical management keeps on as the primary cause of morbidity and mortality for both genders in Western societies. Sex differences though modify the clinical picture as well as the effectiveness of treatment. </p><p> Methods and Results: In this literature review article we searched publications in Englishlanguage on MEDLINE and the Cochrane Database from the beginning of the databases to January 2016. Among the specific key words and phrases we used were Diabetes Mellitus; Gender; Coronary artery disease; Stroke and Cardiovascular disease. Various studies have found that diabetic women have increased risk of coronary heart disease than their male counterparts; however, further research into this field has questioned this finding and there is much controversy among many researchers. Women have a different risk factor profile, are usually treated less effectively than men, and have a variance in the levels of sex hormones throughout their life which complicate the study and understanding of the mechanisms involved in insulin resistance, diabetes mellitus and cardiovascular risk profile. </p><p> Conclusion: The connection between diabetes mellitus and cardiovascular disease is variable according to gender and further studies are needed to elucidate the lenient differentiations in gender specific hormones, risk factor profile, and therapeutic implications between genders. </p><p>
Incidence of Profound Hypogammaglobulinemia and Infection Rate in Lymphoma Patients Following the Combination of Chemotherapy and Rituximab
Today, 12 Ιουλίου 2016, 4:09:29 μμ
Background: The Anti-CD20 monoclonal antibody Rituximab suppresses B-lymphocytes and may induce hypogammaglobulinemia in treated patients. The incidence and clinical significance of rituximab induced hypogammaglobulinemia in lymphoma patients is underestimated. </p><p> Methods: We retrospectively analyzed the rates of hypogammaglobulinemia, infection and infectionrelated mortality in 136 lymphoma patients who were treated with a combination of chemotherapy and rituximab. </p><p> Results: Rituximab given in more than 8 doses (OR 6.05, 95% CI: 1.24-29.5), relative hypogammaglobulinemia at time of lymphoma diagnosis (OR 4.2, 95% CI: 1.26-14.1) and the combination of fludarabine with rituximab (OR 3.4, 95% CI: 1.24-9.47) were factors significantly associated with prolonged (more than 6 months) hypogammaglobulinemia. The combination of fludarabine and rituximab (OR 6.4, 95% CI: 1.49-27.0) and secondarily prolonged hypogammaglobulinemia (OR 4.5, 95% CI: 1.19-18.5) were found to be predictive factors for severe infections and infection-related mortality. </p><p> Conclusion: These data suggest the importance of following serum immunoglobulin levels before and after combination immuno-chemotherapy, particularly in patients with recurrent infections or relapsed/refractory disease. </p><p>
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