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Viruses Jul 2023Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested...
Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.
Topics: Animals; Chick Embryo; Hydroxycholesterols; Marek Disease; Chickens; Interferon-alpha; Antiviral Agents; Interferon Type I; Virus Replication
PubMed: 37631994
DOI: 10.3390/v15081652 -
Trials Oct 2022To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of...
BACKGROUND
To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility. This study will determine the efficacy of high-intensity endurance exercise as first-line therapy for persons diagnosed with PD within 3 years, and untreated with symptomatic therapy at baseline.
METHODS
This is a multicenter, randomized, evaluator-blinded study of endurance exercise training. The exercise intervention will be delivered by treadmill at 2 doses over 18 months: moderate intensity (4 days/week for 30 min per session at 60-65% maximum heart rate) and high intensity (4 days/week for 30 min per session at 80-85% maximum heart rate). We will randomize 370 participants and follow them at multiple time points for 24 months. The primary outcome is the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score (Part III) with the primary analysis assessing the change in MDS-UPDRS motor score (Part III) over 12 months, or until initiation of symptomatic antiparkinsonian treatment if before 12 months. Secondary outcomes are striatal dopamine transporter binding, 6-min walk distance, number of daily steps, cognitive function, physical fitness, quality of life, time to initiate dopaminergic medication, circulating levels of C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF). Tertiary outcomes are walking stride length and turning velocity.
DISCUSSION
SPARX3 is a Phase 3 clinical trial designed to determine the efficacy of high-intensity, endurance treadmill exercise to slow the progression of PD as measured by the MDS-UPDRS motor score. Establishing whether high-intensity endurance treadmill exercise can slow the progression of PD would mark a significant breakthrough in treating PD. It would have a meaningful impact on the quality of life of people with PD, their caregivers and public health.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04284436 . Registered on February 25, 2020.
Topics: Antiparkinson Agents; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Clinical Trials, Phase III as Topic; Dopamine Plasma Membrane Transport Proteins; Exercise; Exercise Therapy; Humans; Multicenter Studies as Topic; Parkinson Disease; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36203214
DOI: 10.1186/s13063-022-06703-0 -
Biological Trace Element Research Mar 2022Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se... (Review)
Review
Selenium (Se) is an important microelement with numerous positive effects on human health and diseases. It is important to specify that the status and consumption of Se are for a specific community as the levels of Se are extremely unpredictable between different populations and regions. Our existing paper was based on the impacts of Se on human health and disease along with data on the Se levels in Middle Eastern countries. Overall, the findings of this comprehensive review show that the consumption and levels of Se are inadequate in Middle Eastern nations. Such findings, together with the growing awareness of the importance of Se to general health, require further work primarily on creating an acceptable range of blood Se concentration or other measures to determine optimal Se consumption and, consequently, to guarantee adequate Se supplementation in populations at high risk of low Se intake.
Topics: Humans; Nutritional Status; Selenium; Selenoproteins
PubMed: 33884538
DOI: 10.1007/s12011-021-02716-z -
Polish Archives of Internal Medicine Feb 2022The first modern description of respiratory syndrome of aspirin hypersensitivity was published over half of the century ago, but the pathogenesis of the disease is still... (Review)
Review
The first modern description of respiratory syndrome of aspirin hypersensitivity was published over half of the century ago, but the pathogenesis of the disease is still elusive. Just a few years after discovery how aspirin works, Andrew Szczeklik and his co‑workers described that asthmatics with aspirin hypersensitivity cross‑react to the whole class of nonsteroidal anti‑inflammatory drugs. It took rest of his life to seek for an answer on how this disease, nowadays referred to as N ‑ERD, develops and how it can be treated. In the meantime, cysteinyl leukotrienes, leukotriene modifying drugs, and novel subpopulations of lymphocytes were discovered. This review on aspirin hypersensitivity documents a progress in our understanding of mechanisms of hypersensitivity to nonsteroidal anti‑inflammatory drugs. Current concepts about origin of the disease integrate advances in the field of allergology and inflammatory mechanisms of asthma. However, pharmacological inhibition of prostaglandin biosynthesis by nonsteroidal anti‑inflammatory drugs has a pivotal role in these investigations. Presented is a central role of prostaglandin E2 , a double‑faced lipid immunoregulatory mediator whose deficiency is related to the administration of an anti‑inflammatory drug. Discussed are cysteinyl leukotrienes, the most reliable biomarkers of aspirin hypersensitivity and cells of innate immunity capable of leukotrienes production. Involvement of blood platelets and recently described mucosal basophils are areas of ongoing studies in the disease. Aspirin hypersensitivity is an acquired condition; therefore, the search for genetic predisposition using classic association studies was inconclusive. There is a new hope to explain mechanisms of aspirin hypersensitivity by studies of innate lymphoid cells, which have a central role in the regulation of respiratory mucosa function in asthma.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Asthma, Aspirin-Induced; Humans; Immunity, Innate; Leukotrienes; Lymphocytes
PubMed: 35226440
DOI: 10.20452/pamw.16219 -
Nature Medicine Apr 2024Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's...
Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (≥60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (≥60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.
Topics: Humans; Male; Female; Middle Aged; Parkinson Disease; Tremor; Antiparkinson Agents; Monoamine Oxidase; Disease Progression
PubMed: 38622249
DOI: 10.1038/s41591-024-02886-y -
Journal of Veterinary Research Dec 2020Marek's disease (MD) is a tumourous disease caused by Marek's disease virus (MDV) and most commonly described in poultry. The aim of the study was to determine the...
INTRODUCTION
Marek's disease (MD) is a tumourous disease caused by Marek's disease virus (MDV) and most commonly described in poultry. The aim of the study was to determine the occurrence of Marek's disease virus infections in Poland and analyse clinical cases in the years 2015-2018.
MATERIAL AND METHODS
The birds for diagnostic examination originated from 71 poultry flocks of various types of production. Birds were subjected to anatomopathological examination post mortem, during which liver and spleen sections and other pathologically changed internal organs were taken. These sections were homogenised with generally accepted methods, then total DNA was isolated and amplified with a real-time PCR. A pair of primers complementary to the MDV genome region encoding the gene were used.
RESULTS
MDV infection was found predominantly in broiler chicken flocks (69.01%), and also in layer breeder (9.85%) and commercial layer flocks (7.04% each).
CONCLUSION
The results of research conducted in the years 2015-2018 clearly indicate that the problem of MDV infections is still current.
PubMed: 33367138
DOI: 10.2478/jvetres-2020-0079 -
Neurology Apr 2023The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson... (Clinical Trial)
Clinical Trial
BACKGROUND AND OBJECTIVES
The University of Pennsylvania Smell Identification Test (UPSIT) is commonly used to assess olfaction and screen for early detection of disorders including Parkinson (PD) and Alzheimer disease. Our objective was to develop updated percentiles, based on substantially larger samples than previous norms, to more finely discriminate age- and sex-specific UPSIT performance among ≥50-year-old adults who may be candidates for studies of prodromal neurodegenerative diseases.
METHODS
The UPSIT was administered cross-sectionally to participants recruited between 2007-2010 and 2013-2015 for the Parkinson Associated Risk Syndrome (PARS) and Parkinson's Progression Markers Initiative (PPMI) cohort studies, respectively. Exclusion criteria included age <50 years and a confirmed or suspected PD diagnosis. Demographics, family history, and prodromal features of PD including self-reported hyposmia were collected. Normative data including mean, SDs, and percentiles were derived by age and sex.
RESULTS
The analytic sample included 9,396 individuals (5,336 female and 4,060 male), aged 50-95 years, who were predominantly White, non-Hispanic US residents. UPSIT percentiles were derived and are provided across 7 age categories (50-54, 55-59, 60-64, 65-69, 70-74, 75-79, and ≥80 years) for female and male participants separately; relative to existing norms, subgroups included between 2.4 and 20 times as many participants. Olfactory function declined with age and was better among women than men; accordingly, the percentile corresponding to a given raw score varied markedly by age and sex. UPSIT performance was comparable among individuals with vs without first-degree family history of PD. Comparisons of self-reported hyposmia vs UPSIT percentiles indicated a strong association (χ < 0.0001) but minimal agreement (Cohen simple kappa [95% CI]: = 0.32 [0.28-0.36] for female participants; 0.34 [0.30-0.38] for male participants).
DISCUSSION
Updated age/sex-specific UPSIT percentiles are provided for ≥50-year-old adults who reflect a population likely to be recruited into studies of prodromal neurodegenerative diseases. Our findings highlight the potential advantages of evaluating olfaction relative to age and sex instead of in absolute terms (i.e., based on raw UPSIT scores) or based on subjective (i.e., self-reported) measures. This information addresses the need to support studies of disorders including PD and Alzheimer disease by providing updated normative data from a larger sample of older adults.
TRIAL REGISTRATION INFORMATION
NCT00387075 and NCT01141023.
Topics: Aged; Female; Humans; Male; Middle Aged; Alzheimer Disease; Anosmia; Olfaction Disorders; Parkinson Disease; Smell; Cross-Sectional Studies
PubMed: 36849448
DOI: 10.1212/WNL.0000000000207077 -
Viruses Dec 2022Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses....
Marek's disease virus (MDV) infection results in Marek's disease (MD) in chickens, a lymphoproliferative and oncogenic deadly disease, leading to severe economic losses. The spleen and bursa are the most important lymphoid and major target organs for MDV replication. The immune response elicited by MDV replication in the spleen and bursa is critical for the formation of latent MDV infection and reactivation. However, the mechanism of the host immune response induced by MDV in these key lymphoid organs during the latent and reactivation infection phases is not well understood. In the study, we focused on the replication dynamics of a vaccine MDV strain MDV/CVI988 and a very virulent MDV strain MDV/RB1B in the spleen and bursa in the latent and reactivation infection phases (7-28 days post-inoculation [dpi]), as well as the expression of some previously characterized immune-related molecules. The results showed that the replication ability of MDV/RB1B was significantly stronger than that of MDV/CVI988 within 28 days post-infection, and the replication levels of both MDV strains in the spleen were significantly higher than those in the bursa. During the latent and reactivation phase of MDV infection (7-28 dpi), the transcriptional upregulation of chicken IL-1β, IL6, IL-8L1 IFN-γ and PML in the spleen and bursa induced by MDV/RB1B infection was overall stronger than that of MDV/CVI988. However, compared to MDV/RB1Binfection, MDV/CVI988 infection resulted in a more effective transcriptional activation of CCL4 in the latent infection phase (7-14 dpi), which may be a characteristic distinguishing MDV vaccine strain from the very virulent strain.
Topics: Animals; Cytokines; Spleen; Marek Disease; Chickens; Herpesvirus 2, Gallid; Marek Disease Vaccines; Latent Infection
PubMed: 36680047
DOI: 10.3390/v15010006 -
Virology Feb 2023Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and...
Marek's disease, caused by herpes virus infection, is a highly contagious disease characterized by latent infection. Here, we aimed to study the pathology, viremia and apoptosis during the Marek's Disease Virus (MDV) latency in vaccinated chickens. Vaccinated chickens were inoculated with the MD5 strain and were dissected at different time points. The viremia occurs in the spleen and thymus during the latency period of MD5 infection, however, lesions can be observed in the liver tissue. The latency-associated early gene of MDV, i.e., ICP4, was highly expressed in the spleen and thymus during the early latency. Compared with the early cytolytic stage, apoptosis of splenocytes was remarkably downregulated in the latency period. This study suggests that MDV latency could occur in the spleen and thymus in vaccinated chickens and there is a negative correlation between the MDV latency and apoptosis of spleen. MDV latency can resist the apoptosis of spleen.
Topics: Animals; Marek Disease; Chickens; Viremia; Herpesvirus 2, Gallid; Apoptosis
PubMed: 36696868
DOI: 10.1016/j.virol.2023.01.003 -
Veterinarni Medicina Nov 2023Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The...
Marek's disease (MD) is a huge problem for researchers due to the significant losses in bird flocks, but more importantly, the virus's mutagenic potential. The purpose of this study was to describe non-classical gross lesions observed in broilers and laying hens that suggest the disease emergence and re-emergence. The survey was conducted on 10 broiler and 4 laying hen flocks. All of the dead birds were necropsied in order to obtain a comprehensive diagnosis of lesions, analysing both macroscopic and microscopic alterations. Marek's disease occurred in 80% of cases in broilers and 100% of cases in layer hens. The disease struck 26-day-old broilers and hens at 2 weeks of age, causing a total mortality of 6% and 15%, respectively. There were no clinical indications of the classical neurological form of the disease in either rearing type, and tumour lesions were mostly detected in the liver, spleen, and ovarian follicles in layers, and in the proventriculus in broilers. These findings demonstrated that MD is widespread and that its resurgence is primarily manifested in visceral rather than neurological manifestations. Despite MD immunization, biosecurity remains critical.
PubMed: 38163046
DOI: 10.17221/75/2023-VETMED