scholarly journals Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

2007 ◽  
Vol 81 (17) ◽  
pp. 8996-9003 ◽  
Author(s):  
Che-Szu Chen ◽  
Yi-Chuan Yao ◽  
Shin-Chao Lin ◽  
Yi-Ping Lee ◽  
Ya-Fang Wang ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Early Stage ◽  
Clinical Signs ◽  
Enterovirus 71 ◽  
Severe Infection ◽  
Dependent Manner ◽  
Transmission Route ◽  
Brain Infection ◽  
Reverse Pattern ◽  
Clinical Illness

ABSTRACT Inoculation of enterovirus 71 (EV71) by the oral (p.o.), intramuscular (i.m.), or intracranial route resulted in brain infection, flaccid paralysis, pulmonary dysfunction, and death of 7-day-old mice. The lag time of disease progression indicated that neuroinvasion from the inoculation sites was a prerequisite for the development of the clinical signs. Although EV71 p.o. inoculation led to a persistent viremia and a transient increase in blood-brain barrier permeability at the early stage of the infection, only low levels of virus, which led to neither severe infection nor clinical illness, could be detected in the brain, suggesting that hematogenous transport might not represent a major transmission route. In the spinal cord, following both p.o. and hind limb i.m. inoculation, the virus first appeared and increased rapidly in the lower segments, especially at the anterior horn areas, and then spread to the upper segments and brain in the presence of viremia. A reverse pattern, with the virus being first detected in the upper segment, was observed when the virus was i.m. inoculated in the forelimb. Colchicine, a fast axonal transport inhibitor, but not sciatic nerve transection reduced EV71 neuroinvasion in a dose-dependent manner, indicating a neuronal transmission of the virus.

scholarly journals Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability

2021 ◽  
Vol 14 (4) ◽  
pp. 338
Author(s):  
Yen-Chen Chen ◽  
Jeng-Wei Lu ◽  
Chia-Tsui Yeh ◽  
Te-Yu Lin ◽  
Feng-Cheng Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Early Stage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enterovirus 71 ◽  
Denv Infection ◽  
Immunofluorescence Assay ◽  
Dependent Manner ◽  
Virus Binding ◽  
Virus Serotype

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

Duffy antigen / receptor for chemokines correlates with inflammatory reaction in rats with venous hypertension: implication for the pathogenesis of primary chronic venous disease

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Weibin Huang ◽  
Weiwei Qin ◽  
Lei Lv ◽  
Haoyv Deng ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Early Stage ◽  
Antigen Receptor ◽  
Venous Hypertension ◽  
Skin Tissue ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Dependent Manner ◽  
Time Points ◽  
Duffy Antigen

Background: Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation. Materials and methods: The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected. Results: Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05). Conclusions: A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.

scholarly journals Investigation of an EHV-1 Outbreak in the United States Caused by a New H752 Genotype

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 747
Author(s):  
Nicola Pusterla ◽  
Samantha Barnum ◽  
Julia Miller ◽  
Sarah Varnell ◽  
Barbara Dallap-Schaer ◽  
...  
Keyword(s):  
Early Stage ◽  
Clinical Signs ◽  
Amino Acid Position ◽  
High Viral Load ◽  
The United States ◽  
Neurological Deficits ◽  
Diagnostic Challenge ◽  
Genotype I ◽  
Flunixin Meglumine ◽  
Nasal Secretions

Here we report on an EHV-1 outbreak investigation caused by a novel genotype H752 (histidine in amino acid position 752 of the ORF 30 gene). The outbreak involved 31 performance horses. Horses were monitored over a period of 35 days for clinical signs, therapeutic outcome and qPCR results of EHV-1 in blood and nasal secretions. The morbidity of the EHV-1 outbreak was 84% with 26 clinically infected horses displaying fever and less frequently anorexia and distal limb edema. Four horses showed mild transient neurological deficits. Clinically diseased horses experienced high viral load of EHV-1 in blood and/or nasal secretions via qPCR, while subclinically infected horses had detectable EHV-1 mainly in nasal secretions. The majority of infected horses showed a rise in antibody titers to EHV-1 during the outbreak. All 31 horses were treated with valacyclovir, while clinically infected horses further received flunixin meglumine and sodium heparin. This investigation highlights various relevant aspects of an EHV-1 outbreak caused by a new H752 genotype: (i) importance of early detection of EHV-1 infection; (ii) diagnostic challenge to assess H752 genotype; (iii) apparent benefit of valacyclovir use in the early stage of the outbreak; and (iv) weekly testing of blood and nasal secretions by qPCR in order to monitor individual infection status and lift quarantine.

scholarly journals Wolman’s disease presenting with secondary hemophagocytic lymphohistiocytosis: a case report from Saudi Arabia and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fahad Alabbas ◽  
Ghaleb Elyamany ◽  
Talal Alanzi ◽  
Tahani Bin Ali ◽  
Fatma Albatniji ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Metabolic Disorder ◽  
Clinical Signs ◽  
Failure To Thrive ◽  
Severe Infection ◽  
Signs And Symptoms ◽  
Immune Deficiency Syndrome ◽  
Autoimmune Disorder ◽  
Deficiency Syndrome ◽  
Homozygous Deletion

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal syndrome that is characterized by strong activation of the immune system from hyperinflammatory cytokines. Symptoms of HLH patients include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. Inherited HLH is classified as primary, whereas secondary HLH (sHLH) occurs when acquired from non-inherited reasons that include severe infection, immune deficiency syndrome, autoimmune disorder, neoplasm, and metabolic disorder. Wolman’s disease (WD) is a rare and fatal infantile metabolic disorder caused by lysosomal acid lipase deficiency, that exhibits similar clinical signs and symptoms as HLH. This paper reports the case of an infant diagnosed with WD and who presented with sHLH. Case presentation A 4-month-old infant presenting with hepatosplenomegaly, failure to thrive, and other abnormalities. WD diagnosis was confirmed by the presence of the LIPA gene homozygous deletion c.(428 + 1_967-1)_(*1_?)del. The infant also met the HLH-2004 diagnostic criteria. Conclusions Metabolic disorder such as WD should be investigated in infants fulfilling the HLH criteria to diagnose the underlying condition. More studies are needed to understand the link between WD and sHLH and to identify appropriate therapies.

scholarly journals Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cleo C. L. van Aanhold ◽  
Manon Bos ◽  
Katrina M. Mirabito Colafella ◽  
Marie-Louise P. van der Hoorn ◽  
Ron Wolterbeek ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Early Stage ◽  
Vascular Inflammation ◽  
Angiogenesis Inhibitor ◽  
Serum Levels ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Soluble Thrombomodulin ◽  
Filtration Barrier ◽  
Glomerular Endothelium

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

scholarly journals Phenotype of the Aging-Dependent Spontaneous Onset of Hearing Loss in DBA/2 Mice

2021 ◽  
Vol 8 (3) ◽  
pp. 49
Author(s):  
Min-Soo Seo ◽  
Byeonghyeon Lee ◽  
Kyung-Ku Kang ◽  
Soo-Eun Sung ◽  
Joo-Hee Choi ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Early Stage ◽  
Auditory Brainstem ◽  
Dependent Manner ◽  
Intrinsic Properties ◽  
Hearing Ability ◽  
Brainstem Response ◽  
Long Term Observation ◽  
Spontaneous Onset

DBA/2 mice are a well-known animal model for hearing loss developed due to intrinsic properties of these animals. However, results on the phenotype of hearing loss in DBA/2 mice have been mainly reported at an early stage in mice aged ≤7 weeks. Instead, the present study evaluated the hearing ability at 5, 13, and 34 weeks of age using DBA/2korl mice. Auditory brainstem response test was performed at 8–32 KHz at 5, 13, and 34 weeks of age, and hearing loss was confirmed to be induced in a time-dependent manner. In addition, histopathological evaluation at the same age confirmed the morphological damage of the cochlea. The findings presented herein are the results of the long-term observation of the phenotype of hearing loss in DBA/2 mice and can be useful in studies related to aging-dependent hearing loss.

scholarly journals The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer

2021 ◽  
Vol 14 (3) ◽  
pp. 209
Author(s):  
Zachary Heinzman ◽  
Connor Schmidt ◽  
Marek K. Sliwinski ◽  
Nalin C. W. Goonesekere
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Early Stage ◽  
Dependent Manner ◽  
Strong Inhibitor ◽  
Tissue Samples ◽  
Reverse Transcription Pcr ◽  
Tumor Stages ◽  
Early Tumor

The high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of pancreatic cancer cell lines and in early-stage paired patient tissue samples (normal and diseased) by quantitative reverse transcription-PCR (qRT-PCR). We also investigated the effect of 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (PGG) as a therapeutic agent for PC. We find that GNMT is markedly downregulated (p < 0.05), in a majority of PC cell lines. Similar results are observed in early-stage patient tissue samples, where GNMT expression can be reduced by a 100-fold or more. We also show that PGG is a strong inhibitor of PC cell proliferation, with an IC50 value of 12 ng/mL, and PGG upregulates GNMT expression in a dose-dependent manner. In conclusion, our data show that GNMT has promise as a biomarker and as a therapeutic target for PC.

scholarly journals The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons

2021 ◽  
Vol 16 ◽  
pp. 263310552110202
Author(s):  
Sean X Naughton ◽  
Wayne D Beck ◽  
Zhe Wei ◽  
Guangyu Wu ◽  
Peter W Baas ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Cortical Neurons ◽  
Acetylcholinesterase Inhibitors ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Cortical Neurons ◽  
Toxicological Mechanism

Among the various chemicals that are commonly used as pesticides, organophosphates (OPs), and to a lesser extent, carbamates, are most frequently associated with adverse long-term neurological consequences. OPs and the carbamate, pyridostigmine, used as a prophylactic drug against potential nerve agent attacks, have also been implicated in Gulf War Illness (GWI), which is often characterized by chronic neurological symptoms. While most OP- and carbamate-based pesticides, and pyridostigmine are relatively potent acetylcholinesterase inhibitors (AChEIs), this toxicological mechanism is inadequate to explain their long-term health effects, especially when no signs of acute cholinergic toxicity are exhibited. Our previous work suggests that a potential mechanism of the long-term neurological deficits associated with OPs is impairment of axonal transport (AXT); however, we had not previously evaluated carbamates for this effect. Here we thus evaluated the carbamate, physostigmine (PHY), a highly potent AChEI, on AXT using an in vitro neuronal live imaging assay that we have previously found to be very sensitive to OP-related deficits in AXT. We first evaluated the OP, diisopropylfluorophosphate (DFP) (concentration range 0.001-10.0 µM) as a reference compound that we found previously to impair AXT and subsequently evaluated PHY (concentration range 0.01-100 nM). As expected, DFP impaired AXT in a concentration-dependent manner, replicating our previously published results. In contrast, none of the concentrations of PHY (including concentrations well above the threshold for impairing AChE) impaired AXT. These data suggest that the long-term neurological deficits associated with some carbamates are not likely due to acute impairments of AXT.

scholarly journals Osteoarthritis in pet guinea pigs: an update on diagnosis, treatment and management

2021 ◽  
Vol 26 (6) ◽  
pp. 100-106
Author(s):  
Emma Keeble
Keyword(s):  
Quality Of Life ◽  
Early Diagnosis ◽  
Guinea Pigs ◽  
Advanced Disease ◽  
Early Stage ◽  
Clinical Signs ◽  
Nutritional Supplements ◽  
Lifestyle Changes ◽  
Early Age

This article reviews the current literature on osteoarthritis in pet and laboratory guinea pigs. The associated clinical signs, diagnosis and treatment of osteoarthritis in pet guinea pigs will be discussed, with options for analgesia detailed. This condition is thought to be common in pet guinea pigs, even from an early age in some genetic lines, although osteoarthritis often goes undiagnosed in this species until advanced disease is present, posing a major welfare concern. Increasing awareness of this condition in veterinary practitioners should aid early diagnosis in pets and help improve their quality of life. Prevention may be possible using oral protective nutritional supplements to slow down the progression of this disease at an early stage. Lifestyle changes are also discussed for the management of this condition in pet guinea pigs.

Markers of the early stage of rheumatoid arthritis

2016 ◽  
Vol 51 (4) ◽  
pp. 305-314
Author(s):  
Beata Polińska ◽  
Joanna Matowicka-Karna ◽  
Halina Kemona
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Population ◽  
Early Stage ◽  
Clinical Signs ◽  
High Sensitivity ◽  
Unknown Etiology ◽  
Serological Tests ◽  
Citrullinated Peptide ◽  
Peptide Antibodies

Rheumatoid arthritis (RA) is a chronic, autoimmune connective tissue disease of unknown etiology. RA affects about 1% of the human population, women suffer three times more often than men, with the peak incidence between the age of 40 to 50. The up-to-date criteria from 2010 for the diagnosis of RA include: occurrence and duration of clinical signs, indicators of inflammation and serological tests. Neopterin, a protein released by macrophages, is a sensitive indicator of inflammation and the severity of RA. Regarding the serological tests, anti-cyclic citrullinated peptide antibodies represent a well-known marker with the specificity for RA of about 98%. The antibodies may be present in the serum of patients even a few years before the first clinical signs of the disease, heralding erosive changes in the joints and more severe course of RA. The literature also contains reports about autoantibodies anti-CarP and anti-Sa/ anti-MCV, which may occur in people with pain and swelling of joints and precede full-blown development of RA as well as reflect disease activity. Serological diagnosis of RA may be supported by some genetic tests based on PCR for detecting mutations e.g. C1858T in the PNPN22 gene. In turn, the quantitative analysis of different classes of miRNAs seems justified in order to better classify patients showing symptoms of RA. Further studies are needed that take into account the role of different markers in the development of RA, and confirm the high sensitivity and specificity of these markers in the diagnosis of the disease.

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