Structure and immunohistochemistry of the human lenticulostriate arteries

Background: Data about the structure and immunohistochemistry of the lenticulostriatearteries (LSAs), although very important for medical research and clinicalpractice, have been rarely reported in literature.Materials and methods: Fourty serially sectioned LSAs were stained with hematoxilinand eosin, and prepared for immunohistochemistry.Results: Our examination revealed a typical endothelial lining and a narrow subendothelialspace with subintimal smooth muscle cells occasionally. The internalelastic lamina was fragmented or absent in the smallest LSAs branches. The mediacoat, with a mean diameter of 148.5 μm, contained typical smooth muscle cellswhich formed 14.2 layers on average and showed a positive immune reactions foralfa-actin, desmine, laminin and collagen IV. The thin adventitial coat containedfibroblasts, collagen fibers, and nerve bundles, with the strongest immunopositivityto thyrosin hydroxilase. The immune reactions against CD31 and CD34 proteins,endothelial nitric oxide synthase, S 100 protein, neurofilament protein and synaptophysin,seem to be performed in the LSAs wall for the first time. Similarly,the thickness of the LSAs wall and its coats have never been reported, nor thenumber of the smooth muscle cell layers.Conclusions: Our results related to the structure and immunohistochemistry ofthe LSAs could be important in cerebrovascular pathology, neurology and neurosurgery

Electrochemical synthesis and characterization of basic bismuth nitrate [Bi6O5(OH)3](NO3)5·2H2O: a potential highly efficient sorbent for textile reactive dye removal

A new method of synthesis was developed for the preparation of basic bismuth nitrate [Bi6O5(OH)3](NO3)5·2H2O (ECBBN). Electrochemical synthesis of the material was carried out by galvanostatic electrodeposition from an acidic Bi(III) solution on a Ti substrate and further thermal treatment in air at 200 °C. Characterization of ECBBN was conducted by employing SEM–EDX, N2 adsorption, XRD and FTIR, and its pI was also determined. The analyses showed that the material obtained was pure [Bi6O5(OH)3](NO3)5·2H2O. Morphologically, ECBBN aggregates were composed of crystals, some smaller than 50 nm. Electrochemically synthesized sorbent (ECBBN) was used for the removal of the textile dye Reactive Blue 19 (RB19) from deionized water and model solutions of polluted river water, and it showed considerably superior sorption performance compared to other inorganic sorbents synthesized by conventional methods reported in the literature. A kinetic study suggests that the sorption process is both under reaction and diffusion control. Equilibration of the sorption process was attained in several minutes, i.e. the sorption process is very fast. The sorption equilibrium data were well interpreted by the Langmuir, Redlich–Peterson and Brouers–Sotolongo isotherm. Using Langmuir isotherm, the maximum sorption capacity of ECBBN was reached at pH 2 and was 1049.19 mg g−1

Identification of Candidate Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor Which May Improve Vagus Nerve Stimulation in ChronicTinnitus

Chronic tinnitus is characterized by neuroplastic changes of the auditory cortex. A promising method for therapy of chronic tinnitus is vagus nerve stimulation (VNS) combined with auditory stimulation. The principle of VNS is reversal of pathological neuroplastic changes of the auditory cortex toward physiological neural activity and synchronicity. The VNS mechanism of action in chronic tinnitus patients is prevailingly through the muscarinic neuromodulation of the auditory cortex by the activation of nc. basalis Meynerti. The aim of this study is to propose potential pharmaceutics which may improve the neuromodulatory effects of VNS. The working hypothesis is that M1 receptors have a dominant role in the neural plasticity of the auditory cortex. We propose that allosteric agonists of the muscarinic receptor type 1 (M1) receptor could improve specificity and selectivity of the neuromodulatory effect of VNS on the auditory cortex of chronic tinnitus patients even in the circumstances of lower acetylcholine brain concentration. This intervention would also reinforce the re-learning process of tinnitus (sub) networks by acting on cholinergic memory and learning mechanisms. We performed in silico screening of drug space using the EIIP/AQVN filter and selected 50 drugs as candidates for allosteric modulators of muscarinic receptors. Further filtering of these compounds by means of 3D QSAR and docking revealed 3 approved drugs-bromazepam, estazolam and flumazenil as the most promising candidates for combined chronic tinnitus therapy. These drugs should be further evaluated by biological tests and clinical trials

In Silico Screening of Natural Compounds for Candidates 5HT6 Receptor Antagonists against Alzheimer’s Disease

Alzheimer’s disease (AD), a devastating neurodegenerative disease, is the focus of pharmacological research. One of the targets that attract the most attention for the potential therapy of AD is the serotonin 5HT6 receptor, which is the receptor situated exclusively in CNS on glutamatergic and GABAergic neurons. The neurochemical impact of this receptor supports the hypothesis about its role in cognitive, learning, and memory systems, which are of critical importance for AD. Natural products are a promising source of novel bioactive compounds with potential therapeutic potential as a 5HT6 receptor antagonist in the treatment of AD dementia. The ZINC—natural product database was in silico screened in order to find the candidate antagonists of 5-HT6 receptor against AD. A virtual screening protocol that includes both short-and long-range interactions between interacting molecules was employed. First, the EIIP/AQVN filter was applied for in silico screening of the ZINC database followed by 3D QSAR and molecular docking. Ten best candidate compounds were selected from the ZINC Natural Product database as potential 5HT6 Receptor antagonists and were proposed for further evaluation. The best candidate was evaluated by molecular dynamics simulations and free energy calculations

Common molecular mechanism of the hepatic lesion and the cardiac parasympathetic regulation in chronic hepatitis C infection: a critical role for the muscarinic receptor type 3

Background: The pathophysiological overlapping between Sjorgens Syndrome (SS) and HCV, presence of anti-muscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R. Results: To identify HCV protein which possibly is crossreactive with M3R or which binds to this receptor, we performed the Informational Spectrum Method (ISM) analysis of the HCV proteome. This analysis revealed that NS5A protein represents the most probable interactor of M3R or that this viral protein could elicit antibodies which modulate function of this receptor. Further detailed structure/function analysis of NS5A and M3R performed by the ISM method extended with other Digital Signal processing (DSP) approaches revealed domains of these proteins which participate in their crossreactivity or in their direct interaction, representing promising diagnostic and therapeutic targets. Conclusions: Application of the ISM with other compatible bioinformatics methods offers new perspectives for identifying diagnostic and therapeutic targets for complicated forms of HCV and other viral infections. We show how the electron-ion interaction potential (EIIP) amino-acid scale used in the ISM combined with a robust, high performance hydrophobicity scale can provide new insights for understanding protein structure/function and protein-protein interactions

Synthesis and characterization of new Ti–Bi2O3 anode and its use for reactive dye degradation

This paper reports the synthesis, characterization and application of a Ti–Bi2O3 anode for the electrochemical decolorization of the textile dye Reactive Red 2. The anode was synthesized by electrodeposition on a Ti substrate immersed in an acidic bismuth (III) solution at constant potential, followed by calcination in air at 600 °C. Thermogravimetric Analysis (TGA), Energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) analysis revealed that the electrodeposited material was predominantly metallic bismuth, which was oxidized to pure α-Bi2O3 during the calcination in air. SEM micrographs revealed that the Bi2O3 coat at the anode surface was inhomogeneous and porous. Reactive Red 2 was completely electrochemically decolorized at the synthesized anode in the presence of H2O2. The applied current density, H2O2 and Na2SO4 concentration, medium pH and initial dye concentration affected the dye decolorization rate. The optimal process parameters were found to be as follows: an applied current density of 40 mA cm−2 using a mixture of 10 mmol dm−3 H2O2 and 10 mmol dm−3 Na2SO4 at pH 7. The dye decolorization rate was shown to decrease as its initial concentration increased. The decolorization reactions were found to follow pseudo-first order kinetics

Levels of Presepsin and Midregion-Proadrenomedullin in Septic Patients with End-Stage Renal Disease after Cardiovascular Surgery: 1-Year Follow Up Study

Background: Procalcitonin (PCT) is a marker for sepsis diagnosis, identification of bacterial infection and monitoring of antibiotic therapy. It has been shown that PCT is not a good choice in patients with hemodialysis. Therefore, we have explored two biomarkers: a) presepsin, and, b) midregion-proadrenomedullin (MR-proADM) in patients having End-Stage Renal Disease (ESRD). Patients and Methods: We prospectively enlisted 20 patients, who underwent cardiovascular surgery and had been on dialysis. The diagnosis of sepsis has been established clinically and confirmed by PCT. Blood samples were taken before and after dialysis. Additionally, plasma and sera of 10 healthy blood donors without any complications were used as controls. Results: Presepsin plasma concentrations (4368 ± 3088 vs. 694.1 ± 239.1 pg/mL) were significantly higher in patients with sepsis compared with controls (p0.05) with no significance between alive and deceased (p=0.53) patients. Adjustments have shown that the difference for MR-proADM level is due to the random sampling variability (p=0.989), whereas difference for presepsin remained highly significant (p<0.001). Conclusions: Our results indicate that the accuracy of new biomarkers is equal to that of PCT in patients with ESRD. Presepsin might be as good marker in repeated measurements, before and after dialysis, as it is PCT. © 2014 Maravic-Stojkovic V, et al

From functional food to medicinal product: Systematic approach in analysis of polyphenolics from propolis and wine

In the last decade we have been working on standardization of propolis extract and determination of active constituents of wine those are rich in polyphenolics and have nutritional as well as therapeutic value. Here we are summarizing our results and providing overview on systematic approach how to analyse natural products rich in flavonoids and phenolic acids

Association of acute Babesia canis infection and serum lipid, lipoprotein, and apoprotein concentrations in dogs

Background: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis: Dogs with B. canis-induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals: Twenty-nine client-owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods: Observational cross-sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA-1 (radioimmunoassay) and SAA was determined. Results: Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1-716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0-4.2 μg/mL) (P lt .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89-7.64 mmol/L versus 6.15 mmol/L, 4.2-7.4 mmol/L) (P =.02), phospholipid (4.64 mmol/L, 2.6-6.6 mmol/L versus 5.72 mmol/L, 4.68-7.0 mmol/L) (P =.02), and α-lipoproteins (77.5%, 27.7%-93.5% versus 89.2%, 75.1%-93.5%) (P =.04), and higher ApoA-1 (1.36 U, 0.8-2.56 U versus 0.95 U, 0.73-1.54 U) concentrations (P =.02). Serum amyloid A correlated with high-density lipoproteins (HDLs) diameter (rho =.43; P =.03) and ApoA-1 (rho =.63, P lt .001). Conclusions and Clinical Importance: Major changes associated with B. canis-induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA-1 and SAA concentration increase is a unique still unexplained pathophysiological finding

Impact of specific functional groups in flavonoids on the modulation of platelet activation

Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationships of flavonoids upon the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents