22 research outputs found

    Possible Relation of Roseolovirus Infection with Fibromyalgia

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    Publisher Copyright: © 2016 by Svetlana Capenko. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.Fibromyalgia (FM) is a chronic widespread pain disorder that impacts 0.5%-7% of the general population worldwide. The aetiology and pathogenesis of the disease are still unknown. Human herpesvirus-6 and-7 belong to the family Herpesviridae, subfamily Betaherpesvirinae, and genus Roseolovirus and are immunomodulating viruses potentially pathogenic to the nervous system. Presence of anti-HHV-6 and-HHV-7 antibodies and viral genomic sequences, viral loads, HHV-6 variant-specificity, and TNF-α level were studied in 41 FM patients and 50 healthy individuals using polymerase chain reactions, restriction endonuclease analysis and ELISA. There was no difference in the presence of anti-HHV-6 and anti-HHV-7 IgG class antibodies between FM patients and control group individuals. Viral sequences were found in 80.5% of FM patients and in 62.0% of controls. Significantly higher rate of concurrent HHV-6 and HHV-7 infection and higher viral loads in peripheral blood were detected in FM patients compared to the control group individuals. Plasma viremia was detected only in FM patients. Significantly higher TNF-α levels were detected in virus positive FM patients. From all positive cases only in two FM patients HHV-6A was revealed. Significantly higher detection frequency of concurrent HHV-6 and HHV-7 infection, simultaneous HHV-6 and HHV-7 activation, higher viral loads and TNF-α expression levels in primary FM patients than in control group individuals indicate the potential involvement of Roseoloviruses in development of this disorder.Peer reviewe

    Acute parathyroid hormone differentially regulates renal brush border membrane phosphate cotransporters

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    Renal phosphate reabsorption across the brush border membrane (BBM) in the proximal tubule is mediated by at least three transporters, NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Parathyroid hormone (PTH) is a potent phosphaturic factor exerting an acute and chronic reduction in proximal tubule phosphate reabsorption. PTH acutely induces NaPi-IIa internalization from the BBM and lysosomal degradation, but its effects on NaPi-IIc and Pit-2 are unknown. In rats adapted to low phosphate diet, acute (30 and 60min) application of PTH decreased BBM phosphate transport rates both in the absence and the presence of phosphonoformic acid, an inhibitor of SLC34 but not SLC20 transporters. Immunohistochemistry showed NaPi-IIa expression in the S1 to the S3 segment of superficial and juxtamedullary nephrons; NaPi-IIc was only detectable in S1 segments and Pit-2 in S1 and weakly in S2 segments of superficial and juxtamedullary nephrons. PTH reduced NaPi-IIa staining in the BBM with increased intracellular and lysosomal appearance. NaPi-IIa internalization was most prominent in S1 segments of superficial nephrons. We did not detect changes in NaPi-IIc and Pit-2 staining over this time period. Blockade of lysosomal protein degradation with leupeptin revealed NaPi-IIa accumulation in lysosomes, but no lysosomal staining for NaPi-IIc or Pit-2 could be detected. Immunoblotting of BBM confirmed the reduction in NaPi-IIa abundance and the absence of any effect on NaPi-IIc expression. Pit-2 protein abundance was also significantly reduced by PTH. Thus, function and expression of BBM phosphate cotransporters are differentially regulated allowing for fine-tuning of renal phosphate reabsorptio

    The role of HHV-6 and HHV-7 infections in the development of fibromyalgia

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    Funding Information: Funding The work was supported by the project RSU ZP 13/2013: BAssociation of fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome with beta-herpesviruses (HHV-6A, HHV-6B, HHV-7) and parvovirus B19 infection^ (SC). Publisher Copyright: © 2019, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Human herpes virus-6 (HHV-6) and human herpes virus-7 (HHV-7) are immunomodulating viruses potentially affecting the nervous system. We evaluated the influence of HHV-6 and HHV-7 infections on fibromyalgia (FM) clinical course. Forty-three FM patients and 50 control group participants were enrolled. 39.50% (n = 17) FM patients had light A delta and C nerve fiber damage, 27.91% (n = 12) had severe A delta and C nerve fiber damage. 67.44% (n = 29) FM patients had loss of warm sensation in feet, loss of heat pain sensation, and increased cold pain sensation (34.90%, n = 15 in both findings). HHV-6 and HHV-7 genomic sequences in peripheral blood DNA in 23/43 (51.00%) and 34/43 (75.50%) of samples from FM patients and in 3/50 (6.00%) and 26/50 (52.00%) of samples from the control group individuals were detected. Active HHV-6 (plasma viremia) or HHV-7 infection was revealed only in FM patients (4/23, 17.40% and 4/34, 11.80%, respectively). A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). 23/43 patients from the FM group and control group participants HHV-6 and 34/45 HHV-7 did have infection markers. A statistically significant moderate positive correlation was found between A delta and C nerve fiber damage severity and HHV-6 infection (p < 0.01, r = 0.410). No difference was found between detection frequency of persistent HHV-6 and HHV-7 infection between FM patients and the control group. Statistically significant correlation was observed between quantitation of changes in QST thermal modalities and HHV-6 infection. There was no correlation between A delta and C nerve fiber damage and HHV-7 infection.Peer reviewe

    Micro-Raman Spectroscopy for Detection of Label-Free and Oil Red O Labeled PEGylated Nanoliposomes in hCmec/D3 Cell Internalization Studies

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    Rapid development of nanomedicines necessitates advancement in internalization techniques which can accurately distinguish between the complex environments of cells and nanocarriers. Internalization (or endocytosis) studies of oil red O labeled and label-free PEGylated-lecithin/cholesterol nanoliposomes was performed using micro-Raman spectroscopy. The C.O stretching vibrations and CCH scissoring bendings of naphthalene ring around 1225 cm.1 as well as the N=N stretching vibrations at 1377 cm.1 are prominent peaks absent from the label-free spectra which can be used for detection of internalized oil red O labeled nanoliposomes. Suitability of oil red O as a liposome marker was confirmed by stability studies of the incorporated dye and automated fluorescence cell counting. The C.C stretching region with a prominent wide band centered at 1080 cm.1 indicative of larger gauche conformer content typical for the lecithin-cholesterol nanoliposomes and the strong maximum at 980 cm.1 associated with O.C.C.N+ stretching vibrations of the liposome polar head groups are important for studying label-free nanoliposome cell internalization

    Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen

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    BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression

    Plant Explants Grown on Medium Supplemented with Fe 3

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    Development of nanotechnology leads to the increasing release of nanoparticles in the environment that results in accumulation of different NPs in living organisms including plants. This can lead to serious changes in plant cultures which leads to genotoxicity. The aims of the present study were to detect if iron oxide NPs pass through the flax cell wall, to compare callus morphology, and to estimate the genotoxicity in Linum usitatissimum L. callus cultures induced by different concentrations of Fe3O4 nanoparticles. Two parallel experiments were performed: experiment A, where flax explants were grown on medium supplemented with 0.5 mg/l, 1 mg/l, and 1.5 mg/l Fe3O4 NPs for callus culture obtaining, and experiment B, where calluses obtained from basal MS medium were transported into medium supplemented with concentrations of NPs identical to experiment A. Obtained results demonstrate similarly in both experiments that 25 nm Fe3O4 NPs pass into callus cells and induce low toxicity level in the callus cultures. Nevertheless, calluses from experiment A showed 100% embryogenesis in comparison with experiment B where 100% rhizogenesis was noticed. It could be associated with different stress levels and adaptation time for explants and calluses that were transported into medium with Fe3O4 NPs supplementation

    Evaluation of the in vitro bee venom release and skin absorption from bioadhesive gel formulation

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    Topical and transdermal drug delivery are one of the most suitable alternative, non-invasive routes for administration of drugs in clinical practice mainly due to the increased patient compliance and reduced systemic drug side effects. Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected, as for example, topical formulations for the treatment of different local skin disorders. Also, significant concentrations of drug could be absorbed by the body regions close to the site of delivery, where regional effects are expected, for e.g., in the muscles, local blood vessels and articulations. Arthritis is a systemic, autoimmune disease characterized by inflammation of joints. Inflammatory cytokines cause activation of the macrophages which leads to swelling of joints, damage to cartilage, bone erosion , functional impairment and stiffness. Bee venom (BV) contains a variety of peptides, including melittin, apamin, adolapin, the mast-cell degranulating peptide, enzymes (phospholipase [PL] A2), biologically active amines (histamine and epinephrine) and nonpeptide components with anti�inflammatory, anti-arthritis, anticoagulant, antimicrobial, anticancer and anti-nociceptive properties. Melittin, a major peptide component of BV shown to have anti-inflammatory and anti�arthritis properties and inhibitory activity on nuclear factor kappaB which is involved in the synthesis of inflammatory mediators and may be essential for the treatment of arthritis using BV. The aim of this study was to evaluate the stability of crude BV as an active ingredient, as well as to evaluate the in vitro release and skin absorption of BV from a designed topical gel formulation

    Thermal Quantitative Sensory Testing in Fibromyalgia Patients

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    Publisher Copyright: © 2015 by Marija Mihailova. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.Fibromyalgia (FM) is a chronic disorder manifested by diffuse musculoskeletal pain, fatigue, sleep, and emotional disturbance. The disorder is probably associated with dysfunction of C and A delta peripheral nerve fibres. Thermal quantitative sensory testing (QST) was used to analyse thinly myelinated A delta fibres and nonmylinated C fibres, which function in the nociceptive sensory system, and the spinothalamic pathway. The observation that FM pain has neuropathic nature increased the value of QST as an additional diagnostic tool. The research group included 51 patients. Somatic symptoms were assessed using the Fatigue Severity Score (FSS), Fibromyalgia Impact Questionnaire (FIQ) and American College of Rheumatology (ACR) 2010 year diagnostic criteria. QST was performed by using thermal stimulus at wrist and feet. QST results were compared with 20 non-FM controls matched for age and sex. FM patients showed significant alteration of thermal perception and pain threshold compared with that in healthy controls, which demonstrated possible neuropathic pain nature in FM patients. Changes were more expressed in warm perception and heat pain threshold, which probably indicates that in FM patients C fibres are more damaged and warm perception and warm pain threshold are more sensitive, which may be used as FM diagnostics. We also found statistically significant negative correlations between warm and cold perception thresholds and between heat and cold pain thresholds, reflecting central sensitization or a defective pain inhibitory system.publishersversionPeer reviewe

    Opinion of Liepaja residents on the reasons for rejection and delay of vaccination against COVID - 19

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    MāszinībasVeselības aprūpeNursing StudiesHealth CareVakcīnu pieņemšana ir būtiska pietiekama imunizācijas līmeņa sasniegšanai pandēmijas laikā. Mērķis. Noskaidrot un salīdzināt Liepājas iedzīvotāju viedokli par vakcinācijas pret COVID-19 noraidīšanas un vilcināšanās iemesliem. Metode. Aptaujātie 115 pilngadīgi Liepājas iedzīvotāji, sadalīti grupās atkarībā no COVID-19 vakcinācijas statusa, aizpildīja tiešsaistes anketu, kur jānovērtē piekrišana piedāvātajiem 16 vakcinācijas pret COVID-19 noraidīšanas/vilcināšanās iemesliem. Rezultāti. Respondentu viedokļi mērķa grupās atšķiras. Nevakcinētie respondenti tendēti piekrist ar uzticību saistītajiem iemesliem, bet vakcinētie – ar pašu saslimšanu saistītajiem. Darba raksturojums. Apskatīta COVID-19 vakcinācijas noraidīšanas/vilcināšanās problemātika. Darba sastāvs: 33 lappuses, 24 attēli, 12 pielikumi, 26 literatūras avoti.Vaccine acceptance is essential to achieve sufficient level of immunization during a pandemic. Objective. To assess and compare the opinion of Liepaja residents about the reasons for rejection and delay of vaccination against COVID-19. Methods. The surveyed 115 adult residents of Liepaja, divided into groups according to the COVID-19 vaccination status, filled in an online questionnaire, where the acceptance of the proposed 16 reasons for rejecting/delaying vaccination against COVID-19 had to be assessed. Results. Respondents’ opinion vary in target groups. Unvaccinated respondents tend to agree with trust related reasons, while vaccinated respondents tend to agree with the reasons related to the disease itself. Study description. The issue of COVID-19 vaccine hesitancy was assessed. Contents: 33 pages, 24 figures, 12 appendices, 26 references

    HCV prototype vaccine based on hepatitis B core virus-like particles

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    HCV prototipa vakcīna izveidota uz hepatīta B kora vīrusveidīgo daļiņu pamata Darba anotācija Šajā pētījumā C termināli saīsinātie HBc ekspresijas vektori tika izmantoti dažādu hepatīta C vīrusa (HCV) proteīnu (kora, E2 un NS3) fragmentu eksponēšanai. Visas izveidotās konstrukcijas inducēja relatīvi augstu rekombinanto proteīnu sintēzes līmeni E.coli šūnās, kaut gan ne visi himērie proteīni bija spējīgi pašsavākties vīrusveidīgajās daļiņās (VLPs). HBcCterm/HVR1tetramer VLPs izrādījās par visefektīvāko HBc/HCV imunogēnu no visām testētajām konstrukcijām. Tās spēja inducēt HCV specifisku imūno atbildi, kā humorālu, tā arī T šūnu proliferatīvo. Interesanti rezultāti tika iegūti ar HBcCterm/NS3/327-482 himēro proteīnu, jo tika sasniegta tikai humorāla HCV specifiska imūnā atbilde. HCV specifiskas T šūnu atbildes trūkums lika secināt par HBcCterm/NS3/327-482 konstrukcijas T šūnu neatkarīgās imūnās atbildes indukciju.HCV prototype vaccine based on hepatitis B core virus-like particles Abstract In the current study the C-terminally truncated HBc expression vectors were used for exposure of different hepatitis C virus (HCV) protein (core, E2, and NS3) fragments. All created chimeric constructs directed high level of recombinant protein synthesis in E.coli. However, not all chimeric proteins were able to self-assemble into virus-like particles (VLPs). HBcCterm/HVR1tetramer VLPs turned out to be a much more efficient immunogen of all HBc/HCV proteins tested. They were able to induce specific anti-HCV immune response, both humoral and T cell proliferative. Interesting results were acquired with the HBcCterm/NS3/327-482 chimeric protein, which induced only humoral HCV-specific response. The absence of the HCVspecific T cell proliferative response suggests induction of a T cell independent pathway of immune response by this construct
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